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  • 151.
    Li, Wenrong
    et al.
    Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Hirvasniemi, Jukka
    Center for Machine Vision and Signal Analysis, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Saarakkala, Simo
    Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Comparison of bone texture between normal individuals and patients with Kashin-Beck disease from plain radiographs in knee2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17510Article in journal (Refereed)
    Abstract [en]

    To compare tibial bone texture between Kashin-Beck disease (KBD) patients and normal individuals from plain radiographs using an advanced image analysis. Plain knee radiographs were obtained from KBD patients (n = 49) and age-matched healthy controls (n = 98). KBD were graded with diagnostic criteria WS/T 207-2010. The textural values related to bone structure from medial and lateral tibial subchondral and trabecular bones were evaluated using entropy of Laplacian-based image (ELap), entropy of local binary patterns (ELBP), homogeneity indices (HI) of local angles (HIMean, HIPerp and HIParal), and fractal dimensions from horizontal (FDHor) and vertical (FDVer) structures. KBD patients were shorter in height and lighter in weight, and their tibial width was wider than controls. Anatomical angle of KBD patients showed more genu valgus. Total KBD patients and subgroups had higher ELap, HIMean, HIPerp and HIParal in detected tibial subchondral and trabecular bones than controls, except ELap in lateral subchondral bone. ELBP, FDHor and FDVer from the detected tibial bone in KBD patients and subgroups were lower than controls, except FDVer in lateral trabecular bone. Our results indicate that micro-scale in bone texture in KBD-affected knees can be quantitatively examined from plain radiographs using an advanced image analysis.

  • 152. Lieber, Richard L
    et al.
    Pontén, Eva
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Burkholder, Thomas J
    Fridén, Jan
    Sarcomere length changes after flexor carpi ulnaris-to-extensor digitorum communis tendon transfer1996In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 21, no 4, p. 612-618Article in journal (Refereed)
    Abstract [en]

    Sarcomere length was measured intraoperatively on five patients undergoing tendon transfer of the flexor carpi ulnaris (FCU) to the extensor digitorum communis (EDC) for radial nerve palsy. The most significant result was that the absolute sarcomere length and sarcomere length operating range of the FCU increased after transfer into the EDC (p <.001). Preoperatively, with the wrist fully extended and fingers flexed, FCU sarcomere length was 4.22 +/- .24 mu m and decreased to 3.19 +/- .05 mu m as the wrist was fully flexed. This represented an overall sarcomere length range of 1.03 mu m After the tendon transfer using standard recommended techniques, all sarcomere lengths were significantly longer (p <.001). Specifically, sarcomeres were 0.74 +/- .14 mu m longer with the muscle in its fully lengthened position (4.96 +/- .43 mu m with the wrist and digits flexed) and 0.31 +/- .16 mu m longer with the FCU in the fully shortened position (3.50 +/- .06 mu m with the wrist and digits extended). At these sarcomere lengths, the FCU muscle was predicted to develop relatively high force only during movement involving synergistic wrist flexion and finger extension. Under the conditions of the procedures performed, the transferred FCU muscle was predicted to produce maximum force over the range of about 30 degrees of wrist flexion and 0 degrees of finger flexion to 70 degrees of wrist extension and 90 degrees of finger flexion. While this is acceptable, a more desirable result was predicted to occur if the muscle was transferred at a longer length. In this latter case, greater stretch of the FCU during transfer (increasing sarcomere length to about 5 mu m) was predicted to improve the transfer. The more highly stretched FCU was predicted to result in maximum force as the wrist and fingers progressed from about 60 degrees of wrist extension and 0 degrees of finger flexion to 80 degrees of wrist extension and 70 degrees of finger flexion. These results quantify the relationship between the passive tension chosen for transfer, sarcomere length, acid the estimated active tension that can be generated by the muscle. The results also demonstrate the feasibility of using intraoperative laser diffraction during tendon transfer as a guide for optimal placement of the transferred muscle.

  • 153. Lionikaite, Vikte
    et al.
    Henning, Petra
    Drevinge, Christina
    Shah, Furqan A.
    Palmquist, Anders
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Windahl, Sara H.
    Lerner, Ulf H.
    Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation2019In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 4, p. 5237-5247Article in journal (Refereed)
    Abstract [en]

    Increased vitamin A consumption is associated with decreased cortical bone mass and increased fracture risk in humans. Rodent studies have demonstrated that hypervitaminosis A increases cortical bone resorption, whereas the importance of the effects on bone formation is less well defined. We used an experimental model of increased bone formation by loading of the tibiae to investigate the effect of vitamin A on bone formation. Control [retinol activity equivalents (RAE) 4.5 µg/g chow] or vitamin A (RAE 60 µg/g chow) diets were given to female C57BL/6N mice for 4 wk, after which the tibiae were subjected to axial loading on alternate days for 2 wk, while the diets were continued. Vitamin A inhibited the loading-induced increase in trabecular and cortical bone volume. This was attributed to inhibition of loading-induced increase in osteoblast number and activity, and expression of osteoblastic genes Sp7Alpl, and Col1a1 in cortical bone. Vitamin A, loading, and combination thereof also resulted in site-specific effects on bone composition measured by Raman spectroscopy. In summary, a clinically relevant dose of vitamin A suppresses the loading-induced gain of bone mass by decreasing bone formation. These observations may have implications for regulation of bone mass caused by physical activity and the risk of osteoporosis in humans.—Lionikaite, V., Henning, P., Drevinge, C., Shah, F. A., Palmquist, A., Wikström, P., Windahl, S. H., Lerner, U. H. Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation.

    Bone remodeling is a continuous process throughout life that is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts (1, 2). With age, the balance of remodeling is often disrupted, and bone resorption exceeds formation, leading to decreased bone mass and, eventually, osteoporosis and fractures (3–5). Although preventative measures can be taken to delay the onset and magnitude of bone loss (e.g., diet and exercise), bone loss can also be exacerbated by drugs such as glucocorticoids and vitamins such as vitamin A (retinol) if consumed in excess.

    Vitamin A is found in foods such as meat, dairy products, and vegetables. A balanced diet is sufficient to maintain the nutritional needs; however, fortification of products as well as supplementation with vitamins leads to an increased risk of hypervitaminosis A and is becoming an increasing problem (6). Excess vitamin A consumption and elevated serum retinol levels have been associated with increased bone fragility and fracture risk in humans (7–10). This association indicates that increased vitamin A intake may be a risk factor for secondary osteoporosis.

    The current recommended daily allowance for vitamin A consumption in adults is 900 and 700 µg retinol activity equivalents (RAE) per day in men and women, respectively (11). The upper tolerable limit of maximum vitamin A consumption that does not pose ill effects is 3000 µg/d (11). Supplements, whether single-ingredient or multimineral or multivitamin when combined with food or each other, often contain over 100% of the recommended daily allowance of 1 or more nutrients (12). Besides professional athletes (13), the elderly (aged 60 y and over) are the highest users of supplements (12). For this reason, supplementation of vitamin A or constituents high in vitamin A (e.g., liver oil), in addition to an already balanced diet, may exacerbate bone loss.

    In experimental rat studies, a 142-fold increase in vitamin A intake (RAE vitamin A 510 µg/g chow) has been illustrated to induce hypervitaminosis A and vitamin A toxicity determined by serum retinol status, reduced food intake, and reduction in weight gain (14–16). In rats receiving oral gavage of a 200–500-fold increase of vitamin A levels (RAE vitamin A 3000–7500 µg/d), spontaneous long-bone fractures have been reported (17). Short-term hypervitaminosis A in rodents decreases cortical bone because of an increased number of osteoclasts on the periosteal bone (14, 17–19) and a decreased number on the endocortical bone (14).

    The effects of vitamin A on bone formation have been less well studied. In 2 studies, rats fed hypervitaminosis A diet containing 1700 IU (RAE vitamin A 510 µg/g chow) for 7 d have decreased osteoblast activity and number on the periosteal bone of the femur (15) and on the pericranial side of the calvaria (16). In another study, mice given daily injections of 125 µg/kg of the retinoid Ro 13-6295 for 4 d had a reduced number of osteoblasts with no effect on their activity (19).

    Although the doses of vitamin A used in rodent studies are high, they are not necessarily reflective of human consumption in either quantity or duration. More recently, we have shown that a clinically relevant dose of vitamin A (RAE 60 µg/g chow), which is only 13 times higher than control diet, decreased periosteal bone formation after 1 wk and also increased endocortical bone formation after 1 and 4 wk of treatment in mice (20). Thus, via concomitant increase in bone resorption and decrease in bone formation, excess vitamin A can lead to decreased bone strength (14, 21) and increased risk of fractures (8, 9, 22–24).

    Bone strength is dependent on size, architecture, and composition. Loading of the skeleton during physical activity leads to recruitment of bone-forming osteoblasts in order to adapt the bones to the applied strain, thereby increasing bone strength (25). Bone is composed of organic (mainly collagen type 1 fibers) and inorganic (hydroxyapatite, calcium, phosphate) compounds that reflect the quality of the bone. Axial mechanical loading of the tibia in rodents is the gold standard of studying bone response to load (26). It is also a good model of impact sports and can be used against a background of various dietary supplements. Often it is noted that the opportune time to enhance bone strength and reduce the risk of fractures later in life is during childhood and puberty; however, implementation of exercise in postmenopausal women has also shown increases in bone mineral density (BMD) at the lumbar spine and femoral neck (27–31).

    We hypothesized that a clinically relevant dose of vitamin A may inhibit the bone-forming effects of mechanical loading in mice, in addition to activation of bone resorption. Therefore, we assessed the loading response in bone with and without prior and concurrent treatment with a clinically relevant dose of vitamin A.

  • 154.
    Liu, Huan
    et al.
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Yang, Lei
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Yu, Fang Fang
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Wang, Sen
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Wu, Cuiyan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Guo, Xiong
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, no 5, p. 616-624, article id 27919783Article, review/survey (Refereed)
    Abstract [en]

    The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA.

  • 155.
    Lyrén, Per-Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of applied educational science, Departement of Educational Measurement.
    Atroshi, Isam
    Lunds universitet; Hässleholm och Kristianstad sjukhus.
    Using item response theory improved responsiveness of patient-reported outcomes measures in carpal tunnel syndrome2012In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 65, no 3, p. 325-334Article in journal (Refereed)
    Abstract [en]

    Objective To compare responsiveness based on item response theory (IRT) with that based on conventional scoring for two patient-reported outcomes measures in carpal tunnel syndrome (CTS); the short disabilities of the arm, shoulder, and hand (QuickDASH) measure, and the 6-item CTS symptoms scale (CTS-6).

    Study Design and Setting Prospective cohort study of patients with CTS undergoing carpal tunnel release at one orthopedic department. Of 455 consecutive patients, 343 completed the QuickDASH and the CTS-6 before and within 1 year after surgery. IRT-based and conventional scores were compared in subgroups according to global rating of change in hand status and treatment satisfaction. The effect size (ES) and the area under the receiver operating characteristic (ROC) curve were used as measures of responsiveness.

    Results The mean value for the IRT-based QuickDASH estimate was −0.09 (standard deviation [SD] = 1.13) preoperatively and −2.14 (SD = 1.79) postoperatively (ES = −1.8) and for the CTS-6 estimate was 0.29 (SD = 1.36) preoperatively and −3.87 (SD = 2.3) postoperatively (ES = −3.1), indicating very large improvement. The ES for the QuickDASH and CTS-6 were very large (−2.4 and −3.8), respectively, in the group with the largest perceived improvement and decreased with lower perceived improvement. The ES was consistently larger with IRT-based scoring than conventional scoring. The AUC for the QuickDASH and CTS-6 exceeded 0.85.

    Conclusion IRT-based scoring showed high responsiveness for the QuickDASH and CTS-6, and the ES were larger than those estimated using conventional scoring.

  • 156.
    Lysholm, Jack
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Henriksson, Marketta
    Tegner, Yelverton
    In memoriam Jan Gillquist 1934-20162016In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 24, no 9, p. 2719-2720Article in journal (Other academic)
  • 157.
    Långsjö, Teemu
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland; Department of Radiology, Vaasa Central Hospital, Vaasa, Finland.
    Vasara, Anna
    Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland.
    Hyttinen, Mika
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Kaukinen, Antti
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio,.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Quantitative analysis of collagen network structure and fibril dimensions in cartilage repair with autologous chondrocyte transplantation.2010In: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 192, no 6, p. 351-360, article id 20664251Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to undertake a stereological analysis to quantify the dimensions of the collagen network in the repair tissue of porcine joints after they had been subjected to autologous chondrocyte transplantation (ACT).

    METHOD: ACT was used to repair cartilage lesions in knee joints of pigs. Electron-microscopic stereology, immunostaining for type II collagen, and quantitative polarized-light microscopy were utilized to study the collagen fibrils in the repair tissue 3 and 12 months after the operation.

    RESULTS: The collagen volume density (V(V)) was lower in the repair tissue than in normal cartilage at 3 months (20.4 vs. 23.7%) after the operation. The collagen surface density (S(V), 1.5·10(-2) vs. 3.1·10(-2) nm(2)/nm(3)) and V(V) increased with time in the repair tissue (20.4 vs. 44.7%). Quantitative polarized-light microscopy detected a higher degree of collagen parallelism in the repair tissue at 3 months after the operation (55.7 vs. 49.7%). In contrast, 1 year after the operation, fibril parallelism was lower in the repair tissue than in the control cartilage (47.5 vs. 69.8%).

    CONCLUSION: Following ACT, V(V) and S(V) increased in the repair tissue with time, reflecting maturation of the tissue. One year after the operation, there was a lower level of fibril organization in the repair tissue than in the control cartilage. Thus, the newly synthesized collagen fibrils in the repair tissue appeared to form a denser network than in the control cartilage, but the fibrils remained more randomly oriented.

  • 158.
    Löfvenberg, Richard
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Chronic lateral instability of the ankle joint: natural course, pathophysiology and steroradiographic evaluation of conservative and surgical treatment1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic lateral instability of the ankle (CLI), defined as frequent sprains and recurrent giving way, difficulty in walking and running on uneven surface, is often connected with pain and swollen ankles. It occurs in 10 to 20 percent after acute ankle injuries. Mechanical instability of the talocrural and subtalar joint, peroneal weakness and impaired proprioception has been suggested as etiological factors.

    Aim.

    To investigate the natural course in conservatively treated patients with CLI.

    To assess the mechanical stability in patients with CLI by measuring the three dimensional motions in the talus, the fibula and the calcaneus in relation to the tibia during different testing procedures pre- and postoperatively.

    To determine if CLI is associated with proprioceptive deficiency.

    Patients and Methods.

    This Thesis includes 127 ankles in 78 patients (30 women, 48 men) with CLI.

    Thirty-seven patients were followed up 20 years after their first contact with the orthopaedic department because of CLI. Forty-six ankles were evaluated radiographically and the result was compared with a gender- and age - matched control-material.

    The neuromuscular response to a sudden angular displacement of the ankles was studied in 15 ankles in 13 patients using EMG.

    Thirty-six patients entered a prospective study using roentgen stereophotogrammetric analysis (RSA) in which the ankles were tested at manual adduction, adduction with predetermined torque, with and without external support and at drawer tests (40 N and 160N). Twenty-seven patients were followed five years postoperatively.

    Result.

    After 20 years 22 patients, conservatively treated still suffered from instability of the ankle and ten had recurrent giving way symptoms even on plane surface. Six ankles in the patient group and four in the control group displayed osteoarthritic changes

    Prolonged ipsilateral reaction time (m. per. long, and m. tib. ant.) was found in patients with CLI indicating proprioceptive insufficiency.

    Increased talar adduction and a tendency toward increased total translation of the talar center was found in ankles with CLI. Concomitant fibular rotations and translations were found but with no conclusive deviation in the ankles with symptoms. The talo-calcaneal adduction reached the same level in the patient and control groups regardless of symptoms. External support (ankle brace) increased the talar stability. The use of predetermined torque and constrained testing procedure did not add information compared with the manual test

    Twenty-five patients graded the result as excellent or good five years after lateral ligament reconstruction. Talar stability (decreased adduction and translation) was increased two years postoperatively and was improved or remained the same at five years without comprising the range of motion.

    Conclusion.

    In more than half the cases symptoms of CLI did not resolve spontaneously. Minor degenerative changes was found after twenty years, but not to a greater extent than in a control group. CLI was associated with proprioceptive insufficiency and talocrural but not subtalar instability. Increased ankle stability can be obtained by the use of an ankle brace and by an anatomical ligament reconstruction.

  • 159.
    Lötjönen, Pauno
    et al.
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Julkunen, Petro
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland: Department of Biosciences, Applied Biotechnology and Biocenter Kuopio, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Physics, University of Kuopio, Kuopio, Finland.
    Nieminen, Heikki
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Strain-dependent modulation of ultrasound speed in articular cartilage under dynamic compression.2009In: Ultrasound in Medicine and Biology, ISSN 1879-291X, Vol. 35, no 7, p. 1177-1184, article id 19427104Article in journal (Refereed)
    Abstract [en]

    Mechanical properties of articular cartilage may be determined by means of mechano-acoustic indentation, a clinically feasible technique for cartilage diagnostics. Unfortunately, ultrasound speed varies in articular cartilage during mechanical compression. This can cause significant errors to the measured mechanical parameters. In this study, the strain-dependent variation in ultrasound speed was investigated during dynamic compression. In addition, we estimated errors that were induced by the variation in ultrasound speed on the mechano-acoustically measured elastic properties of the tissue. Further, we validated a computational method to correct these errors. Bovine patellar cartilage samples (n = 7) were tested under unconfined compression. Strain-dependence of ultrasound speed was determined under different compressive strains using an identical strain-rate. In addition, the modulation of ultrasound speed was simulated using the transient compositional and structural changes derived from fibril-reinforced poroviscoelastic (FRPVE) model. Experimentally, instantaneous compressive strain modulated the ultrasound speed (p < 0.05) significantly. The decrease of ultrasound speed was found to change nonlinearly as a function of strain. Immediately after the ramp loading ultrasound speed was found to be changed -0.94%, -1.49%, -1.84%, -1.87%, -1.89% and -2.15% at the strains of 2.4%, 4.9%, 7.3%, 9.7%, 12.1% and 14.4%, respectively. The numerical simulation revealed that the compression-related decrease in ultrasound speed induces significant errors in the mechano-acoustically determined strain (39.7%) and dynamic modulus (72.1%) at small strains, e.g., at 2.4%. However, at higher strains, e.g., at 14.4%, the errors were smaller, i.e., 12.6% for strain and 14.5% for modulus. After the proposed computational correction, errors related to ultrasound speed were decreased. By using the correction, with e.g., 2.4% strain, errors in strain and modulus were decreased from 39.7% to 7.2% and from 72.1% to 35.3%, respectively. The FRPVE model, addressing the changes in fibril orientation and void ratio during compression, showed discrepancy of less than 1% between the predicted and measured ultrasound speed during the ramp compression.

  • 160.
    Ma, Wei-Juan
    et al.
    Medical College of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Xi'an, Shaanxi, China.
    Guo, Xiong
    Medical College of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Xi'an, Shaanxi, China.
    Liu, Jiang-Tao
    Medical College of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Xi'an, Shaanxi, China.
    Liu, Rui-Yu
    Medical College of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Xi'an, Shaanxi, China.
    Hu, Jian-Wen
    Research Center for Proteome Analysis, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
    Sun, An-Guo
    Research Center for Proteome Analysis, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
    Yu, Yue-Xiang
    Shaanxi Provincial Institute For Endemic Disease Control, Xi'an, Shaanxi, China.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
    Proteomic changes in articular cartilage of human endemic osteoarthritis in China.2011In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 11, no 14, p. 2881-90, article id 21681992Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a chronic endemic osteochondropathy with unclear pathogenesis. It is a degenerative disease similar to osteoarthritis, but with different manifestations of cartilage damage. The aim of this investigation was to show the protein changes in KBD cartilage and to identify the candidate proteins in order to understand the pathogenesis of the disease. Proteins were extracted from the media of primary cell cultures of KBD and normal chondrocytes, and separated by two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). MALDI-TOF/TOF analysis revealed statistically significant differences in 27 proteins from KBD chondrocyte cultures, which consisted of 17 up-regulated and ten down-regulated proteins. The results were further validated by Western blot analysis. The proteins identified are mainly involved in cellular redox homeostasis and stress response (MnSOD, Hsp27, Peroxiredoxin-1, and Cofilin-1), glycolysis (PGK-1, PGM-1, α-enolase), and cell motility and cytoskeletal organization (Actin, Calponin-2, and Keratin). These KBD-associated proteins indicate that cytoskeletal remodeling, glycometabolism, and oxidative stress are abnormal in KBD articular cartilage.

  • 161. Maduri, Rodolfo
    et al.
    Bobinski, Lukas
    Neurosurgical Service, Department of Clinical Neurosciences, University Hospital of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland..
    Duff, John Michael
    Image Merge Tailored Access Resection (IMTAR) of Spinal Intradural Tumors. Technical Report of 13 Cases.2017In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 98, p. 594-602Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Standard translaminar approaches for intradural extramedullary (IDEM) tumors require extensive soft tissue dissection and partial facet removal. Ventral lesions may necessitate wider bone resection with subsequent possible spinal instability. Any manipulation of an already compromised spinal cord may lead to neurological injury. We describe an image-guided minimal access technique for IDEM tumor resection.

    METHODS: Retrospective chart review of 13 consecutive patients after institutional ethics committee approval. We superimpose preoperative magnetic resonance imaging data with intraoperative 3-dimensional fluoroscopic images, allowing to simultaneously visualize osseous anatomy and the soft tissue lesion using appropriate windowing. We then plan optimal angle of trajectory to the tumor, which defines the skin incision and the transmuscular trajectory. A tubular retractor is placed to span the tumor. Microsurgical tumor resection is then carried out using this angle of approach.

    RESULTS: Thirteen patients (mean age. 57 years; male-to-female ratio, 10:3) were operated on during 28 months. Gross total resection was achieved in all patients. Neurological improvement occurred in 12 of the 13 patients. There was no neurological deficit outside of the expected sensory loss due to intentional nerve root sacrifice. No mechanical pain nor tumor recurrence were noted during the follow-up (mean, 16 months; range, 2-30 months).

    CONCLUSIONS: Image merge tailored access resection appears to be at least equivalent in terms of tumor resection, blood loss, and complications to other tubular techniques. It may reduce risks of neurological deficit and spine instability. Image merge tailored access resection is a novel application of merging intraoperative fluoroscopic images with preoperative magnetic resonance images for tailored IDEM resection.

  • 162.
    Mahmood, Sarwar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Sundsvall and Norrland University Hospitals.
    Mukka, Sebastian S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Sundsvall and Norrland University Hospitals.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Sundsvall and Norrland University Hospitals.
    Sayed-Noor, Arkan S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Sundsvall and Norrland University Hospitals.
    The Influence of Leg Length Discrepancy after Total Hip Arthroplasty on Function and Quality of Life: a Prospective Cohort Study2015In: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 30, no 9, p. 1638-1642Article in journal (Refereed)
    Abstract [en]

    We investigated whether patients with lengthening (> 9 mm), restoration (between 9 mm lengthening and 5 mm shortening) or shortening (> 5 mm) of the operated leg after total hip arthroplasty (THA) had different function (WOMAC score), quality of life (EQ-5D), residual hip pain, use of shoe lift and walking aid and leg length discrepancy (LLD) awareness, 12-15 months postoperatively. All patients had a significant postoperative improvement in WOMAC and EQ-5D regardless the LLD. However, the lengthening group showed less improvement in WOMAC, more use of shoe lift, residual hip pain and LLD awareness compared with the other two groups. No differences in EQ-5D were found. In spite of the improvement in function and quality of life, lengthening had adverse effects and should therefore be avoided.

  • 163.
    Mahmood, Sarwar S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Al-Amiry, Bariq
    Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
    Mukka, Sebastian S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Sundsvall and Norrland University Hospitals.
    Baea, Saida
    Department of Radiology, Sundsvall Teaching Hospital, Sundsvall, Sweden.
    Sayed-Noor, Arkan S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Department of Orthopaedics, Sundsvall Teaching Hospital, Sundsvall, Sweden .
    Validity, reliability and reproducibility of plain radiographic measurements after total hip arthroplasty2015In: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 44, no 3, p. 345-351Article in journal (Refereed)
    Abstract [en]

    In total hip arthroplasty (THA), radiographic preoperative planning and postoperative evaluation of acetabular component, femoral offset (FO) and leg length discrepancy (LLD) require good validity, interobserver reliability and intraobserver reproducibility. In this study, we evaluated the validity of the Sundsvall method of FO measurement and the interobserver reliability and intraobserver reproducibility of measurement of FO, LLD, acetabular cup inclination and anteversion. Ninety patients with primary unilateral osteoarthritis (OA) were included in this prospective study. On postoperative radiographs FO by the Sundsvall method (femoral axis-pelvic midline), FO by a standard method (femoral axis-hip rotational centre-teardrop point), LLD (inter-teardrop line-lesser trochanter), acetabular cup inclination (on AP view the angle between the cup rim and transischial line) and anteversion (on lateral view the angle between the face of acetabulum and a line perpendicular to the horizontal plane) were measured. The interobserver reliability and intraobserver reproducibility were calculated for three independent observers. The concurrent validity and degree of prediction of the Sundsvall method are measured by comparing its results with the standard method. The interobserver reliability of all measurements was excellent (ICC > 0.80), except for LLD, which was substantial (ICC = 0.79). The intraobserver reproducibility of all measurements was excellent (ICC > 0.80). The concurrent validity of the Sundsvall method compared to the standard method was good with a positive correlation. The Sundsvall method is as reliable as the standard method. The evaluated radiographic measurement methods have the required validity and reliability to be used in clinical practice.

  • 164.
    Mahmood, Sarwar S.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall and Norrland University Hospitals.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Wretenberg, Per
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Sayed-Noor, Arkan S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall and Norrland University Hospitals.
    Association between changes in global femoral offset after total hip arthroplasty and function, quality of life, and abductor muscle strength: A prospective cohort study of 222 patients2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 1, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Background and purpose - There is no consensus on the association between global femoral offset (FO) and outcome after total hip arthroplasty (THA). We assessed the association between FO and patients? reported hip function, quality of life, and abductor muscle strength.

    Patients and methods - We included 250 patients with unilateral hip osteoarthritis who underwent a THA. Before the operation, the patient?s reported hip function was evaluated with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of life was evaluated with EQ-5D. At 1-year follow-up, the same scores and also hip abductor muscle strength were measured. 222 patients were available for follow-up. These patients were divided into 3 groups according to the postoperative global FO of the operated hip compared to the contralateral hip, as measured on plain radiographs: the decreased FO group (more than 5 mm reduction), the restored FO group (within 5 mm restoration), and the increased FO group (more than 5 mm increment).

    Results - All 3 groups improved (p < 0.001). The crude results showed that the decreased FO group had a worse WOMAC index, less abductor muscle strength, and more use of walking aids. When we adjusted these results with possible confounding factors, only global FO reduction was statistically significantly associated with reduced abductor muscle strength. The incidence of residual hip pain and analgesics use was similar in the 3 groups.

    Interpretation - A reduction in global FO of more than 5 mm after THA appears to have a negative association with abductor muscle strength of the operated hip, and should therefore be avoided.

  • 165. Masci, Lorenzo
    et al.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    van Schie, Hans T. M.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. Pure Sports Medicine Clinic; ISEH, University College London Hospitals.
    How to diagnose plantaris tendon involvement in midportion Achilles tendinopathy: clinical and imaging findings2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, article id 97Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of this investigation was to evaluate if clinical assessment, Ultrasound + Colour Doppler (US + CD) and Ultrasound Tissue Characterisation (UTC) can be useful in detecting plantaris tendon involvement in patients with midportion Achilles tendinopathy. Methods: Twenty-three tendons in 18 patients (14 men, mean age: 37 years and 4 women: 44 years) (5 patients with bilateral tendons) with midportion Achilles tendinopathy were surgically treated with a scraping procedure and plantaris tendon removal. For all tendons, clinical assessment, Ultrasound + Colour Doppler (US + CD) examination and Ultrasound Tissue Characterisation (UTC) were performed. Results: At surgery, all 23 cases had a plantaris tendon located close to the medial side of the Achilles tendon. There was vascularised fat tissue in the interface between the Achilles and plantaris tendons. Clinical assessment revealed localised medial activity-related pain in 20/23 tendons and focal medial tendon tenderness in 20/23 tendons. For US + CD, 20/23 tendons had a tendon-like structure interpreted to be the plantaris tendon and localised high blood flow in close relation to the medial side of the Achilles. For UTC, 19/23 tendons had disorganised (type 3 and 4) echopixels located only in the medial part of the Achilles tendon indicating possible plantaris tendon involvement. Conclusions: US + CD directly, and clinical assessment indirectly, can detect a close by located plantaris tendon in a high proportion of patients with midportion Achilles tendinopathy. UTC could complement US + CD and clinical assessment by demonstrating disorganised focal medial Achilles tendon structure indicative of possible plantaris involvement.

  • 166.
    Mellner, Carl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Studies on the complications and prediction of mortality after hip fracture surgery2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An elderly patient who sustains a hip fracture has increased morbidity and mortality. Scandinavia presents the highest incidence annually of hip fractures worldwide. 

    Femoral neck fracture (FNF) of the hip accounts for 50% of all hip fractures in geriatric patients. Intertrochanteric and subtrochanteric femoral fracture accounts for the other 50%. Hip fracture patients are plagued with a high 1-year mortality rate ranging from 8% to 36%. Complications of hip fracture surgery after arthroplasty generally include periprosthetic fracture (PPF), periprosthetic joint infection (PJI), and dislocation. 

    Treatent regarding FNF has improved in the last decade. Arthroplasties are currently the standard treatment for displaced FNFs in the elderly. The surgical treatment of PPF can be technically demanding, with a high frequency of complications due to deep infection, dislocation and intraoperative fractures. Some prosthetic designs have been reported.

    PJIs are associated with prolonged antibiotic treatment, multiple revision surgeries, prolonged hospital stays, late aseptic loosening and poor functional outcome for the patients. A widely accepted treatment of choice for acute deep PJIs comprises debridement, antibiotics and implant retention (DAIR).

    There are currently several models for predicting mortality with the aim of identifying and optimizing patients at risk. The Sernbo score was initially developed as a guidance tool for the orthopedic surgeon in decision making in hip fracture surgery.

    Study I: This was a prospective cohort study of patients with FNFs treated with hemiarthroplasty or total arthroplasty. The aim of this study was to compare the risk for PPF between the straight, highly, polished, tapered (CPT) stem and the matte anatomic SPII stem. It was found that the CPT stem imposed a higher risk of postoperative PPF.

    Study II: This was a retrospective multicenter cohort study of patients with FNFs treated with total or hemiarthroplasty. The aim of this study was to compare the risk for PPF between the straight, highly polished, tapered Exeter stem and the matte anatomic SPII stem. It was found that Exeter stem imposed a higher risk of sustaining a PPF.

    Study III: This was a retrospective cohort study of patients treated with a primary hip arthroplasty (hemi- or total hip) for a displaced FNF. The primary aim of this study was to identify the frequency of PJI and to evaluate the success rate of DAIR. The secondary aim was to analyze the risk factors for developing PJI. It was found that DAIR had a high short- term success rate and that the need for repeated bandage changes indicates an increased risk of PJI and should prompt early surgical intervention.

    Study IV: This was a retrospective study with the aim of validating the Sernbo score for predicting mortality after hip replacement for a displaced FNF in elderly patients. The Sernbo score (based on age, habitat, walking aids and mental state) can be used to stratify patients into groups with different one-year mortality rates. The score can be calculated using information obtained during routine orthopedic patient assessments.The Sernbo score was found to identify patients at high risk of dying in the first postoperative year.

    Study V: This was a retrospective registry study. All patients who sustained a hip fracture and registered in “Rikshöft” (a Swedish database for hip fracture) were included. The aim of this study was to validate the Sernbo score for predicting mortality after hip fracture in elderly patients on a registry-based level. It was found that the Sernbo score can be used to stratify patients into groups with different one-year mortality rates.

  • 167.
    Mellner, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Eisler, Thomas
    Börsbo, Johannes
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Brodén, Cyrus
    Morberg, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The Sernbo score predicts 1-year mortality after displaced femoral neck fractures treated with a hip arthroplasty2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 402-406Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Displaced femoral neck fractures (FNFs) are associated with high rates of mortality during the first postoperative year. The Sernbo score (based on age, habitat, mobility, and mental state) can be used to stratify patients into groups with different 1-year mortality. We assessed this predictive ability in patients with a displaced FNF treated with a hemiarthroplasty or a total hip arthroplasty. Patients and methods - 292 patients (median age 83 (65-99) years, 68% female) with a displaced FNF were included in this prospective cohort study. To predict 1-year mortality, we used a multivariate logistic regression analysis including comorbidities and perioperative management. A receiver operating characteristic (ROC) analysis was used to evaluate the predictive ability of the Sernbo score, which was subsequently divided in a new manner into a low, intermediate, or high risk of death during the first year. Results - At 1-year follow-up, the overall mortality rate was 24%, and in Sernbo's low-, intermediate-, and high-risk groups it was 5%, 22%, and 51%, respectively. The Sernbo score was the only statistically significant predictor of 1-year mortality: odds ratio for the intermediate-risk group was 4.2 (95% Cl: 1.5-12) and for the high-risk group it was 15 (95% CI: 5-40). The ROC analysis showed a fair predictive ability of the Sernbo score, with an area under the curve (AUC) of 0.79 (95% CI: 0.73-0.83). Using a cutoff of less than 11 points on the score gave a sensitivity of 61% and a specificity of 83%. Interpretation - The Sernbo score identifies patients who are at high risk of dying in the first postoperative year. This scoring system could be used to better tailor perioperative care and treatment in patients with displaced FNF.

  • 168.
    Mellner, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Eisler, Thomas
    Knutsson, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Early periprosthetic joint infection and debridement, antibiotics and implant retention in arthroplasty for femoral neck fracture2017In: HIP International, ISSN 1120-7000, E-ISSN 1724-6067, Vol. 27, no 4, p. 349-353Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Periprosthetic joint infection (PJI) is a severe complication of hip arthroplasty for femoral neck fractures (FNF). Debridement, antibiotics and implant retention (DAIR) is recommended in early PJI in association with stable implants. Few studies have evaluated the outcome of DAIR in this fragile population.The purpose of this study was to analyse risk factors for PJI and the short-term outcome of DAIR in FNF patients treated with a hip arthroplasty.

    METHODS: A consecutive series of 736 patients (median age 81 years, 490 women, 246 men) had been treated with either a total hip arthroplasty or a hemi hip arthroplasty for a displaced FNF at our institution. 33 (4.5%) of the hips developed an early (&lt;6 weeks post operatively) PJI and 28 (3.8%) of these patients were treated according to the DAIR-protocol. Regression analyses were performed to assess risk factors for developing a PJI.

    RESULTS: DAIR eradicated the PJI in 82% (23/28) of patients at a median follow-up of 31 (SD 29.8) months of the infected hips.The logistic regression analysis indicated that 2 or more changes of the primary dressing due to wound bleeding was associated with an increased risk for developing PJI (OR 4.9, 95% 1.5 to 16.1, p = 0.01).

    CONCLUSIONS: The short-term success-rate of DAIR was unexpectedly favourable in this fragile patient population; the results being on par with that after PJI in osteoarthritis patients. The need for repeated bandage changes postoperatively indicates an increased risk for PJI and should prompt early surgical intervention.

  • 169.
    Mellner, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hedström, Margareta
    Hommel, Ami
    Sköldenberg, Olof
    Eisler, Thomas
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    The modified Sernbo score as a predictor of 1-year mortality after hip fracture: A registry study on 55,716 patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose

    Patients sustaining a hip fracture have a high mortality rate during the first postoperative year and the Sernbo score may stratify patients into a high, intermediate and low risk of death during this period. We added gender with the aim to improve the original score (i.e. a modified score), and assessed its predictive properties on patients from the National Swedish Hip Fracture Register.

    Patients and Methods

    55,716 hip fracture patients, 69% women, older than 65 years at surgery (registered between 2010-2015) with complete Sernbo scores and mortality data were studied. Receiver Operating Characteristics analyses (ROC) were used. Validation of Sernbo score.

    Results

    The over-all 1-year mortality rate was 26% - and 6%, 17% and 42% in the low, intermediate and high risk groups respectively. The ROC analysis indicated a predictive ability of the Modified-Sernbo score, with an AUC of 0.72 (CI 0.71–0.73). ROC analysis of the original Sernbo Score showed an AUC 0.70 (CI 95% 0.70-0.71).

    Conclusion

    The Modified-Sernbo score identifies patients at high-risk of death during the first year postoperatively, slight improvement when adding sex to the score and validated on national level. This scoring system could be used to tailor peri- and postoperative care and treatment in patients with hip fracture.

  • 170.
    Mellner, Carl
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Mohammed, Jabbar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Larsson, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Esberg, Sandra
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Szymanski, Maciej
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hellström, Nils
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Chang, Cecilia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Berg, Hans E.
    Sköldenberg, Olof
    Knutsson, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Morberg, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Increased risk for postoperative periprosthetic fracture in hip fracture patients with the Exeter stem than the anatomic SP2 Lubinus stemManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The purpose of this study was to compare the cumulative incidence of postoperative periprosthetic fracture (PPF) in a cohort of femoral neck fracture (FNF) patients treated with two commonly used cemented stems: either a collarless, polished, tapered Exeter stem or the anatomic Lubinus SP2 stem.

    Methods: In this retrospective multicenter cohort study of a consecutive series of patients, we included 2527 patients 60 years and above with an FNF who were treated with either hemiarthroplasty or total hip arthroplasty using either a polished tapered Exeter stem or an anatomic Lubinus SP2 stem. The incidence of PPF was assessed at a minimum of 2 years postoperatively.

    Results: The incidence of PPF was assessed at a median follow-up of 47 months postoperatively. Forty patients (1.6%) sustained a PPF at a median of 27 months (range, 0-96 months) postoperatively. Two of the operatively treated fractures were Vancouver A (5%), 7 were Vancouver B1 (18%), 11 were Vancouver B2 (27%), 7 were Vancouver B3 (18%), and 13 were Vancouver C (32%). The cumulative incidence of PPF was 2.3% in the Exeter group compared with 0.7% in the SP2 group (p<0.001). The HR was 5.5 (95% CI, 2.4-12.8, p≤0.01), using the SP2 group as the denominator. Six of 40 (15%) patients needed revision surgery after initial treatment of the PPF.Conclusions: The Exeter stem was associated with a higher risk for PPF than the Lubinus SP2 stem. We suggest that the tapered Exeter stem should be used with caution in the treatment of FNF.

  • 171.
    Minde, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Andersson, T
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Fulford, M
    Department of Internal Medicine, Gällivare Hospital, Gällivare, Sweden.
    Aguirre, M
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Nennesmo, I
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Remahl, I Nilsson
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Solders, G
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    A novel NGFB point mutation: a phenotype study of heterozygous patients2009In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, no 2, p. 188-195Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients. METHODS: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy. RESULTS: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Adelta) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found. CONCLUSIONS: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.

  • 172. Modig, Karin
    et al.
    Erdefelt, Annelie
    Mellner, Carl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Cederholm, Tommy
    Talbäck, Mats
    Hedström, Margareta
    "Obesity Paradox" Holds True for Patients with Hip Fracture2019In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 101, no 10, p. 888-895Article in journal (Refereed)
    Abstract [en]

    Background: Hip fractures are associated with high mortality and reduced quality of life. Studies have reported a high body mass index (BMI) as being positively associated with survival when linked to old age and some chronic diseases. This phenomenon is called the “obesity paradox.” The association between BMI and survival after hip fracture has not been thoroughly studied in large samples, nor has to what extent the association is altered by comorbidities, sex, and age. The objective of this study was to investigate the association of BMI with survival after hip fracture and with the probability of returning to living at home after hip fracture.

    Methods: This cohort study was based on data from a prospectively maintained national registry of patients with hip fracture. A total of 17,756 patients ‡65 years of age who were treated for hip fracture during the period of 2013 to 2016, and followed until the end of 2017, were included. BMI was clinically assessed at hospital admission, comorbidity was measured with the American Society of Anesthesiologists (ASA) score, and the date of death was retrieved from a national database. Self-reported data on living arrangements were assessed on admission and 4 months after fracture. Multivariable regression models were used to estimate the associations.

    Results: Despite ASA scores being similar among all BMI groups, obese patients had the highest 1-year survival and patients with a BMI of <22 kg/m2 had the lowest. Adjustment for potential confounders strengthened the associations. For the chance of returning to living at home, no advantage was seen for obese patients, but patients with a BMI of <22 kg/m2 had clearly worse odds compared with patients who were of normal weight, overweight, or obese.

    Conclusions: The obesity paradox appears to be true for hip fracture patients aged 65 and older. Attention should be given to patients with malnutrition and underweight status rather than to those with overweight status or obesity when developing the orthogeriatric care.

  • 173.
    Mohammed, Jabbar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hedbeck, Carl-Johan
    Chammout, Ghazi
    Gordon, Max
    Sköldenberg, Olof
    Reduced periprosthetic fracture rate when changing from a tapered polished stem to an anatomical stem for cemented hip arthroplasty: an observational prospective cohort study with a follow-up of 2 years2019In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 90, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Straight collarless polished tapered stems have been linked to an increased risk for periprosthetic femur fractures in comparison with anatomically shaped stems, especially in elderly patients. Therefore, we evaluated the effect of an orthopedic department's full transition from the use of a cemented collarless, polished, tapered stem to a cemented anatomic stem on the cumulative incidence of postoperative periprosthetic fracture (PPF). Patients and methods - This prospective single-center cohort study comprises a consecutive series of 1,077 patients who underwent a cemented hip arthroplasty using either a collarless polished tapered stem (PTS group, n = 543) or an anatomic stem (AS group, n = 534). We assessed the incidence of PPF 2 years postoperatively and used a Cox regression model adjusted for age, sex, ASA class, cognitive impairment, BMI, diagnosis, and surgical approach for outcome analysis. Results - Mean age at primary surgery was 82 years (49-102), 73% of the patients were female, and 75% underwent surgery for a femoral neck fracture. The PPF rate was lowered from 3.3% (n = 18) in the PTS group to 0.4% (n = 2) in the AS group. The overall complication rate was also lowered from 8.8% in the PTS group to 4.5% in the AS group. In the regression model only cognitive dysfunction (HR 3.8, 95% CI 1.4-10) and the type of stem (PTS vs AS, HR 0.1, CI 0.0-0.5) were correlated with outcome. Interpretation - For elderly patients with poor bone quality use of cemented anatomic stems leads to a substantial reduction in periprosthetic fracture rate without increasing other complications.

  • 174.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Aspects on treatment of femoral neck fractures: studies on treatment methods, surgical approach and external validity2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Femoral neck fracture (FNF) is a great challenge for today´s health care and is associated with high mortality and morbidity in the elderly.  In the short term several studies in the literature have demonstrated improved hip function, quality of life and fewer re-operations in elderly patients treated with total hip arthroplasty (THA) instead of internal fixation (IF). There are few reports on the long-term outcome comparing IF and THA. The vast majority of orthopaedic departments in Sweden use the direct lateral (DL) or posteriolateral (PL) approaches for hip arthroplasty. The PL approach has been linked to an increased risk of dislocation of the prosthesis and a higher rate of revision surgery in comparison to the DL approach. There are few reports focusing on radiological risk factors for prosthetic dislocation and patient reported hip function comparing the two surgical approaches for hip arthroplasty in FNF.

    The randomized controlled trial (RCT) is the gold standard for evaluating medical or surgical interventions. An RCT of high quality has to be internally and externally valid. Internal validity refers to a correct study design to avoid bias skewing the results. External validity (EV) refers to whether the results will be clinically relevant to a definable group of patients and can be extrapolated to the general health care situation. There are only a few reports in the orthopaedic literature focusing on the EV of published studies and none in the field of hip fractures.

    Study I: This is a RCT of 100 patients with a displaced FNF comparing THA and IF. Follow-up evaluations were performed at three months and 1, 2, 4, 11 and 17 years. It was found that the Harris hip score (HHS) was higher and the rate of reoperations lower for patients treated with THA.

    Study II: This is a prospective cohort study of 185 hips, comparing the DL and the PL approaches in patients treated with a hemiarthroplasty (HA) for a displaced FNF. Follow-up was after 1 year. There was no difference in patient reported outcome between the groups measured with the HHS and WOMAC index. The PL approach resulted in a higher re-operation rate while the DL approach in a higher incidence of limping.

    Study III: This is a retrospective cohort study of 373 patients with a cemented bipolar HA using a PL approach for a FNF with a follow-up ranging from 6 months to 7 years. Radiographs and all surgical records were reviewed regarding femoral offset (FO), leg length discrepancy (LLD) and Wiberg angle. Patients with recurrent dislocations had a decreased postoperative FO, LLD and shallower acetabulum on the operated side compared with their controls.

    Study IV: This is a prospective cohort study of 840 hips comparing patients included in a RCT with those that did not give their informed consent (NC) or did not fulfill the criteria for participating in the trial (MS). Patients in the NC and MS groups had an increased mortality rate in comparison to those included in the study. We did not find any differences in hip function between these groups.

    The main conclusions of this thesis are:

    • Healthy and lucid elderly patients with good hip function preoperatively, should be treated with THA for a displaced FNF.
    • The DL approach is favourable in treating displaced FNF with HA due to its decreased risk of reoperation but with an identical hip function outcome as the PL approach.
    • Care should be taken to restore the LLD and FO otherwise this may increase the risk of recurrent dislocation of a HA.
    • Our findings suggest that trial participants had a lower mortality rate than non-participants but the functional outcome of non-participants appeared to be satisfactory. This is important to take into consideration when extrapolating study results to a health care system.
  • 175.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hassany, Hamid H.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Geometrical restoration and component positioning after hip arthroplasty for femoral neck fracture2016In: Acta Orthopaedica Belgica, ISSN 0001-6462, Vol. 82, no 3, p. 557-562Article in journal (Refereed)
    Abstract [en]

    In this study, the restoration of leg length and global femoral offset and positioning of the femoral stem and acetabular cup of hemiartroplasty (HA) and total hip arthroplasty (THA) after femoral neck fracture (FNF) were compared at the postoperative radiographs between 181 hips operated using the direct lateral (DL) approach and 127 hips operated using the posterolateral (PL) approach. Regarding HA, the DL approach was associated with lengthening of the operated leg (5.7 mm vs. 2.1 mm), p = 0.001. The PL approach had more varus stem position (23% vs. 12%, p = 0.03) and the DL approach had more stems with C-position (58% vs. 32%, p = 0.001). Regarding THA, the DL approach showed increased cup anteversion (28 degrees vs. 21 degrees), p = 0.016, and a decrease in FO (-5.9 mm vs. -2.0 mm, p = 0.04). Surgeons caring for FNF patients are to be aware of the differences in geometrical restroration and component positioning between the two approaches.

  • 176.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Knutsson, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Krupic, Ferid
    Sayed-Noor, Arkan S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The influence of cognitive status on outcome and walking ability after hemiarthroplasty for femoral neck fracture: a prospective cohort study2017In: European Journal of Orthopaedic Surgery & Traumatology, ISSN 1633-8065, E-ISSN 1432-1068, Vol. 27, no 5, p. 653-658Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Femoral neck fracture (FNF) is a devastating injury with serious medical and social consequences. One-third of these patients have some degree of impaired cognitive status. Despite this, a high proportion of hip fracture trials exclude patients with cognitive impairment (CI). We aimed to evaluate whether moderate to severe CI could predict walking ability, quality of life, functional outcome, reoperations and mortality in elderly patients with displaced FNF treated with hemiarthroplasty (HA).

    METHODS: This cohort study included a consecutive series of 188 patients treated with HA for a displaced FNF. Patients were assessed for estimated preoperative and 1 year postoperatively with regard to walking ability, cognitive status, quality of life with EQ-5D and hip function with Harris hip score.

    RESULTS: There were 188 patients who met the inclusion criteria. A total of 130 patients were in the control group, and 58 were in the CI group. At 1-year follow-up, 31 patients (24%) had died in the control group and 22 patients (38%) had died in the cognitive impaired group. This difference in reoperation and mortality rate was statistically significant (log-rank test, p = 0.016). The CI had a significantly higher incidence of being non-walker (28 vs. 4%, OR 9.2, p = 0.001). The EQ-5D was higher in the control group, while the Harris hip score was comparable in the two groups.

    CONCLUSIONS: Moderate to severe CI was associated with a high incidence of non-walking ability, worse quality of life, high mortality and re-operation rate after femoral neck fractures treated with HA.

  • 177.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Knutsson, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Majeed, Ammar
    Sayed-Noor, Arkan S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Reduced revision rate and maintained function after hip arthroplasty for femoral neck fractures after transition from posterolateral to direct lateral approach2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 6, p. 627-633Article in journal (Refereed)
    Abstract [en]

    Background and purpose The direct lateral (DL) approach to the hip for femoral neck fractures (FNF) has been shown to reduce the rate of dislocation and reoperations. We evaluate the effect of transition from the posterolateral (PL) to DL approach on reoperation and dislocation rates and patients' reported outcome.

    Patients and methods In a prospective cohort study between 2012 and 2015, we enrolled 362 patients (median age 83 years, 70% women, mean follow-up 25 months) with a displaced FNF. The first group of 146 patients were operated using the PL and the second group of 216 patients with a DL approach, after change of our routines. A multivariable Cox regression analysis was used to evaluate factors associated with dislocation and reoperation. A generalized linear model was used to evaluate the functional outcome by comparing WOMAC and Harris hip scores between the 2 groups.

    Results The reoperation rate was reduced from 13% in the PL to 6% in the DL group and the dislocation rate from 13% to 4%. Cox proportional hazard analysis identified the PL approach as the only factor associated with an increased risk of reoperation (hazard ratio =2.5, 95% CI 1.2-5.2). Age, sex, ASA classification, type of arthroplasty, cognitive dysfunction, or the experience of the surgeon had no effect on the risk of reoperation. Patient-reported outcome was similar between the 2 groups.

    Interpretation In patients with FNF we have reduced the reoperation and dislocation rates by changing the surgical approach used for hip arthroplasty without affecting the patient-reported functional outcome.

  • 178.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Lindqvist, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Peyda, Sara
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Broden, Cyrus
    Mahmood, Sarwar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hassany, Hamid
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Dislocation of bipolar hip hemiarthroplasty through a postero-lateral approach for femoral neck fractures: A cohort study2015In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 39, no 7, p. 1277-1282Article in journal (Refereed)
    Abstract [en]

    Purpose To analyze postoperative global femoral offset (FO), leg length discrepancy (LLD) and Wiberg angle as risk factors for prosthetic dislocation after treatment with bipolar hemiarthoplasty (HA) through a postero-lateral approach for femoral neck fracture (FNF). Methods Three hundred and seventy three patients treated with a cemented bipolar HA through a postero-lateral approach between January 2006 and December 2013 were included in a cohort study with a follow-up time ranging from 6 months to 7 years. Radiographs and all surgical records were reviewed regarding Global FO, LLD and Wiberg angle. We compared stable hips without dislocation to those with either a single dislocation and those with recurrent instability. Results Three hundred and twenty eight hips fulfilled the inclusion criteria and were analyzed in the study. The incidence of prosthetic dislocation was 10.7 % (36/373). The mean time from surgery to first dislocation was 3.9 months (0-47) and 62.5 % had recurrent dislocations. Patients with dislocation had a statistically significantly decreased postoperative global FO (-6.4 mm vs. -2.8 mm, p = 0.04), LLD (-2 vs. 1.5 mm, p = 0.03) and smaller Wiberg angle (40A degrees vs. 46A degrees, p = 0.01) on the operated side compared with the rest of cohort. In comparison to age and sex-matched control groups from the cohort, the difference in the radiographic parameters were significant in patients with recurrent dislocations but not in patients with a single dislocation. Conclusion Patients with recurrent dislocations had a decreased postoperative global FO, shorter leg and shallower acetabulum on the operated side compared with their controls. These factors might decrease the soft-tissue tension around the operated hip and predispose to dislocation.

  • 179.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mahmood, Sarwar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Kadum, Bakir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sköldenberg, O
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Direct lateral vs posterolateral approach to hemiarthroplasty for femoral neck fractures2016In: Orthopaedics & Traumatology: Surgery & Research, ISSN 1877-0568, E-ISSN 1877-0568, Vol. 102, no 8, p. 1049-1054Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Adopting the direct lateral (DL) instead of the posterolateral (PL) approach in hip arthroplasty for femoral neck fracture (FNF) patients could lower the rate of prosthetic dislocation. However, little is known about how the approach influences the functional outcome.

    HYPOTHESIS: We hypothesized that both approaches would give comparable results.

    MATERIAL AND METHODS: In a prospective cohort study, we enrolled 185 hips (183 patients, 128 women, median age 84 years) with a displaced FNF. Subjects were assigned to treatment using DL (n=102) or PL approach (n=83) with a hemiarthroplasty (HA). Functional outcome was assessed by Harris Hip Score (HHS), Western Ontario and McMaster Universities Arthritis (WOMAC) index, pain numeric rating scale (PNRS) for pain, mortality and hip complications. Patients were followed-up after 1 year.

    RESULTS: The HHS was 71 (SD 18) in the DL group and 72 (SD 17) in the PL group (P=0.59). We found no difference in WOMAC, PNRS and mortality. Seven patients (6.9%) in the DL group and 11 patients (13.3%) in the PL group had undergone a major reoperation (adjusted OR 0.51; 95% CI, 0.18-2.07; P=0.23).

    DISCUSSION: In this prospective cohort study, patients treated with HA for FNF using either the DL or PL approaches had comparable functional outcome after 1 year. The PL approach had a tendency towards a higher reoperation rate.

    TYPE OF STUDY: Prospective cohort study.

    LEVEL OF PROOF: Level 2.

  • 180.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mahmood, Sarwar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sjödén, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Dual mobility cups for preventing early hip arthroplasty dislocation in patients at risk: experience in a county hospital2013In: Orthopedic Reviews, ISSN 2035-8237, E-ISSN 2035-8164, Vol. 5, no 10, p. 48-51Article in journal (Refereed)
    Abstract [en]

    Dislocation remains a major concern after hip arthroplasty. We asked whether dual mobility cups (DMC) would improve early hip stability in patients with high risk of dislocation. We followed 34 patients (21 females, 13 males) treated between 2009 and 2012 with cemented DMC for hip revisions caused recurrent hip prosthetic dislocation or as a primary procedure in patients with high risk of instability. Functional outcome and quality of life were evaluated using Harris Hip Score and EQ-5D respectively. We found that the cemented DMC gave stability in 94%. Seven patients (20%) were re-operated due to infection. One patient sustained a periprosthetic fracture. At follow-up (6 to 36 months, mean 18), the mean Harris hip score was 67 (standard deviation: 14) and mean EQ-5D was 0.76 (standard deviation: 0.12). We concluded that treating patients with high risk of dislocation with DMC can give good stability. However, complications such as postoperative infection can be frequent and should be managed carefully.

  • 181.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Mellner, Carl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Knutsson, Bjorn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Skoldenberg, Olof
    Substantially higher prevalence of postoperative periprosthetic fractures in octogenarians with hip fractures operated with a cemented, polished tapered stem rather than an anatomic stem A prospective cohort study involving 979 hips2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 3, p. 257-261Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Recent studies have demonstrated a high incidence of postoperative periprosthetic femoral fracture (PPF) in elderly patients treated with 2 commonly used cemented, polished tapered stems. We compared the prevalence and incidence rate of PPF in a consecutive cohort of octagenerians with femoral neck fractures (FNFs) treated with either a collarless, polished tapered (CPT) stem or an anatomic matte stem (Lubinus SP2). Patients and methods - In a multicenter, prospective cohort study, we included 979 hips in patients aged 80 years and above (72% females, median age 86 (80-102) years) with a femoral neck fracture as indication for surgery. 69% of the patients were classified as ASA class 3 or 4. Hip-related complications and repeat surgery were assessed at a median follow-up of 20 (0-24) months postoperatively. Results - 22 hips (2.2%) sustained a PPF at a median of 7 (0-22) months postoperatively; 14 (64%) were Vancouver B2 fractures. 7 of the 22 surgically treated fractures required revision surgery, mainly due to deep infection. The cumulative incidence of PPFs was 3.8% in the CPT group, as compared with 0.2% in the SP2 group (p < 0.001). The risk ratio (RR) was 16 (95% CI: 2-120) using the SP2 group as denominator. Interpretation - The CPT stem was associated with a higher risk of PPF than the SP2 stem. We suggest that the tapered CPT stem should not be used for the treatment of femoral neck fractures in patients over 80 years.

  • 182.
    Mukka, Sebastian S.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Andersson, Göran N.
    Hultenby, Kjell R.
    Sköldenberg, Olof G.
    Nordahl, Joakim P.
    Eisler, Thomas M.
    Osteoclasts in periprosthetic osteolysis: the charnley arthroplasty revisited2017In: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 32, no 10, p. 3219-3227Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periprosthetic osteolysis by polyethylene wear debris-triggered osteoclasts is viewed as the main pathophysiological pathway in aseptic loosening in total hip arthroplasty. The present aim was to study osteoclast occurrence in osteolytic lesions in early and late revisions of the Charnley low-friction torque arthroplasty (CLFA).

    METHODS: Biopsies of the soft interface membrane and the adjacent bone were taken from osteolytic lesions during revision of 16 loose CLFA, early (2-6 years) or late (>10 years) after primary surgery. By light microscopy (LM), cell-dense regions with signs of osteoclast-mediated bone resorption were selected for transmission electron microscopy. Three additional patients were studied in LM for osteoclast markers (tartrate-resistant acid phosphatase and Cathepsin K).

    RESULTS: LM disclosed a low-grade chronic inflammation and birefringent particles in most sections. Multiple conglomerates of tartrate-resistant acid phosphatase positive and Cathepsin K positive mononuclear and multinucleated cells were found deep in the fibrous interface membrane. Transmission electron microscopy showed traces of polyethylene-like particles in 67%-100% of the cells. Osteoclast-like cells exhibiting resorptive activity were few (mean, 0.7%; standard deviation, 0.2%), and multinucleated cells, possibly osteoclast precursor cells, located immediately on the bone were also scarce (mean, 2.7%; standard deviation, 5.3%). Multinucleated (odds ratio, 3.0; 95% confidence interval, 1.7-5.5) and macrophage-like cells (odds ratio, 3.6; 95% confidence interval, 2.2-5.6) were typically located deeper in the inflammatory interface membrane with a pathologic appearance with distension and abundance of phagocytic vacuoles. There were no systematic differences in cell populations between early or late revisions.

    CONCLUSION: Despite probable ongoing osteoclastogenesis in the osteolytic lesions, there were few sites of osteoclast-mediated bone resorption. These findings attach a contributing biological explanation to the longevity of the CLFA.

  • 183.
    Mukka, Sebastian S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    An update on surgical approaches in hip arthoplasty: lateral versus posterior approach2014In: HIP International, ISSN 1120-7000, E-ISSN 1724-6067, Vol. 24, no Supplement 10, p. S7-S11Article, review/survey (Refereed)
    Abstract [en]

    In this update we searched the literature about the outcome of the lateral versus posterior approach in hip arthoplasty for osteoarthritis (OA) and femoral neck fracture (FNF) patients. The available evidence shows that the use of posterior approach in OA patients is associated with lower mortality and better functional outcome while the use of lateral approach in FNF patients gives lower dislocation rate. We recommend therefore the use of posterior approach in OA patients and lateral approach in FNF patients.

  • 184.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sjöholm, Pontus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Chammout, Ghazi
    Kelly-Pettersson, Paula
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sköldenberg, Olof
    External Validity of the HOPE-Trial Hemiarthroplasty Compared with Total Hip Arthroplasty for Displaced Femoral Neck Fractures in Octogenarians2019In: JBJS Open Access, ISSN 2472-7245, Vol. 4, no 2, p. 1-7, article id e0061Article in journal (Refereed)
    Abstract [en]

    Background: Randomized controlled trials (RCTs) are the most reliable way of evaluating the effect of new treatments by comparing them with previously accepted treatment regimens. The results obtained from an RCT are extrapolated from the study environment to the general health care system. The ability to do so is called external validity. We sought to evaluate the external validity of an RCT comparing the results of total hip arthroplasty with those of hemiarthroplasty for the treatment of displaced femoral neck fractures in patients ≥80 years of age.

    Methods: This prospective, single-center cohort study included 183 patients ≥80 years of age who had a displaced femoral neck fracture. All patients were screened according to the inclusion and exclusion criteria for an RCT comparing total hip arthroplasty and hemiarthroplasty. The population for this study consisted of patients who gave their informed consent and were randomized into the RCT (consenting group, 120 patients) as well as those who declined to give their consent to participate (non-consenting group, 63 patients). The outcome measurements were mortality, complications, and patient-reported outcome measures. Follow-up was carried out postoperatively with use of a mailed survey that included patient-reported outcome questionnaires.

    Results: We found a statistically significant and clinically relevant difference between the groups, with the non-consenting group having a higher risk of death compared with the consenting group. (hazard ratio, 4.6; 95% confidence interval, 1.9 to 11.1). No differences were found between the groups in terms of patient-reported outcome measures or surgical complications.

    Conclusions: This cohort study indicates a higher mortality rate but comparable hip function and quality of life among eligible non-consenters as compared with eligible consenters when evaluating the external validity of an RCT in patients ≥80 years of age with femoral neck fracture.

    Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

  • 185.
    Mukka, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sjöholm, Pontus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Perisynakis, Nikolaos
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wahlström, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Rahme, Hans
    Kadum, Bakir
    Radial head arthroplasty for radial head fractures: a clinical and radiological comparison of monopolar and bipolar radial head arthroplasty at a mean follow-up of 6 years2018In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to compare clinical and radiographic outcomes of bipolar and monopolar radial head arthroplasty in treatment of radial head fracture at a mean follow-up of 6 years.

    METHODS: A retrospective multicentre cohort study of 30 patients treated for unreconstructable radial head fractures. Patients were treated either with a cemented bipolar or an uncemented monopolar radial head arthroplasty. All patients included were evaluated with patient-rated outcome questionnaire, physical examination, and radiographic evaluation at a mean of 6 years (range, 2-12 years) postoperatively.

    RESULTS: There was no statistical difference in QuickDASH between the bipolar or monopolar groups. The majority of patients had no to little pain during rest. Neither flexion nor extension of the injured arm was significantly affected by the type of prosthesis. None of the patients in the bipolar group had any secondary surgery at the time of follow-up. In the monopolar group, four patients required removal of the arthroplasty. Signs of ulnohumeral degenerative changes were seen in the majority of patients in both groups (55% in the monopolar group, 92% in the bipolar group).

    CONCLUSION: In this retrospective cohort study comparing a bipolar and a monopolar radial head arthroplasty for treatment of radial head fractures, we found comparable functional outcome but more revision procedures in the monopolar group at a mean follow-up of 6 years.

  • 186. Naili, Josefine
    et al.
    Esbjörnsson, Anna-Clara
    Iversen, Maura
    Schwarz, Michael
    Hedström, Margareta
    Häger, Charlotte
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Broström, Eva
    The impact of symptomatic knee osteoarthritis on gait pattern and its association with performance-based measures and patient-reported outcomes2017In: Knee (Oxford), ISSN 0968-0160, E-ISSN 1873-5800, Vol. 24, no 3, p. 536-546Article in journal (Refereed)
    Abstract [en]

    Background: Limited knowledge exists regarding the impact of symptomatic knee osteoarthritis (OA) on the overall gait pattern; and whether gait deviations are associated with performance based measures (PBMs) and patient-reported outcomes (PROs). This cross-sectional study evaluated overall gait patterns in patients with knee OA using the Gait Deviation Index for kinematics (GDI) and kinetics (GDI-kinetic), and explored associations between gait deviations, PBMs, and PROs. Methods: Forty patients with knee OA and 25 age and gender-matched controls underwent three-dimensional gait analysis. Participants performed the Timed Up and Go (TUG), Five Times Sit-to-Stand (5STS), and Single Limb Mini Squat (SLMS) tests and completed a disease specific PRO. Associations between gait deviations, PBMs, and PROs were assessed by Pearson's correlation and multiple linear regression. Results: Patients with OA demonstrated significantly lower GDI and GDI-kinetic scores of the OA and contralateral limbs compared to controls; with GDI-kinetic scores on the contralateral limb more impacted than the OA limb. On the contralateral limb, GDI-kinetic score significantly correlated with TUG (r = -0.42) and 5STS (r = -033), while on the OA limb with TUG (r = -0.68), 5STS (r = -0.38), SLMS (r = -0.38), activities of daily living (r = -0.35) and Knee-related Quality of Life (r = -035). No significant associations existed between kinematic GDI scores, PBMs and PROs. Conclusion: The overall gait pattern, as represented by GDI and GDI-kinetic scores, in patients with symptomatic knee OA is affected both on the painful OA limb and the contralateral limb. The GDI and GDI-kinetic scores provide different information regarding function that is not revealed by PBMs or PROs.

  • 187.
    Nilsson, Kjell G.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Kinematics and fixation of total knee arthroplasties: a clinical, radiographic, scintimetric, and roentgen stereophotogrammetric evaluation1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aseptic loosening of the tibial component is an important cause of failure after total knee arthroplasty. Bone destruction often claimed to be caused by the cement makes the revision difficult. In order to treat younger patients, uncemented fixation has been introduced, but the etiology to loosening is multifactorial and only partly known. Early detection of implant migration facilitates research in this field but is difficult using conventional techniques. In this study modified versions of roentgen stereophotogrammetric analysis (RSA) were developed to obtain accurate and standardized evaluations facilitating comparison between prosthetic designs. The method was used to record the efficacy of cemented and uncemented fixation of different designs of the tibial component, to determine the accuracy of scintimetry in the detection of early aseptic loosening, and to analyse the in vivo kinematics of knee arthroplasties with different design and stability between the joint surfaces.

    Forty-three arthroplasties with comparatively high inherent stability of the joint surfaces were randomized to cemented or uncemented fixation of the tibial component. In all groups micromovements were rather large, but with no differences between the cemented and uncemented components. The preoperative diagnosis (arthrosis OA, n=25; rheumatoid arthritis RA, n=18) did not influence the magnitude of micromotion.

    20 arthroplasties with the same design as above but equipped with an intramedullary stem, were randomized to cemented or uncemented fixation in patients with RA. Cement improved the fixation. Uncemented stemmed components displayed micromovements seemingly larger than unstemmed ones.

    34 arthroplasties with an unconstrained design of the joint area and fixed to the tibia with four pegs were randomized to cemented or uncemented fixation in patients with OA. When used uncemented 4 screws were added. Compared with previously investigated designs small micromotions were recorded, and especially in the cemented cases. Uncemented components with thin polyethylene inserts displayed larger initial micromotions. The preoperative deformity influenced the direction of the micromotion.

    33 knees were followed prospectively with RSA and scintimetry to evaluate any correlation between these methods. Low activity under the tibial component at 2 years implied prosthetic stability, whereas high activity indicated instability or high bone remodelling caused by the preoperative malalignment.

    The in vivo kinematics in three different designs of knee arthroplasties were analyzed during active flexion and extension without weight-bearing. Each type of prosthesis displayed design-specific abnormalities when compared with a normal material. Pronounced posterior tibial translations were recorded during flexion regardless whether the posterior cruciate ligament had been sacrificed or not. Data from the kinematic and the fixation studies suggest that movements restricted by the design of the joint area are transmitted to the bony interface with design-specific micromotions as the result.

    Analysis of knee joint kinematics during extension and weight-bearing revealed small alterations compared with non-weight-bearing. Evaluation of the three-dimensional movements in terms of helical axis rotations and translations confirmed the constrained or unconstrained in vivo behaviour of the designs under study. This analysis also facilitated the interpretation of the kinematic behaviour of the prosthetic knees and may be of value in the evaluation of new designs.

  • 188.
    Nilsson, Kjell G
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Henricson, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Norgren, Bo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Dalén, Tore
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Uncemented HA-coated implant is the optimum for the TKA in the young patient2006In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 448, p. 129-139Article in journal (Refereed)
    Abstract [en]

    Fixation of the tibial component in total knee arthroplasty in younger patients remains controversial. We evaluate the results of three different types of fixation of the Profix total knee arthroplasty in a randomized controlled trial of 97 consecutive knees (85 patients) with osteoarthrosis or inflammatory arthritis with 2-year followup of all patients. We randomized patients to three different types of fixation of the tibial component: cemented, uncemented (HA coated) with screws, or uncemented (HA coated) without screws. We performed clinical evaluations and radiostereometric analysis at 6 weeks, and 3, 6, 12 and 24 months postoperatively. The knees in the uncemented groups migrated more than those in the cemented group during the first 3 months, but at 2 years we observed no differences. The uncemented implants displayed all migration within the first 3 months. The cemented implants did not stabilize but had continuously increasing migration during the followup. Cementless implants without screws did not migrate more than implants with screws and displayed similar pattern of migration, indicating screws do not improve fixation. Uncemented fixation using hydroxyapatite-coated implants without screws seems to be the best solution for the younger patient.

  • 189.
    Nilsson, Kjell G.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Umeå University Hospital, S-901 85 Umeå, Sweden.
    Theodoulou, Annika
    Mercer, Graham
    Quinn, Stephen J.
    Krishnan, Jeganath
    Mid-term migration of a cementless, porous acetabular cup: A 5 year Radiostereometric analysis2017In: Journal of Orthopaedics, ISSN 0972-978X, E-ISSN 0972-978X, Vol. 14, no 4, p. 454-460Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the study was to determine the 5 year migratory and wear patterns, adverse events and clinical outcomes of a cementless, porous acetabular cup. Methods: RSA imaging of a cohort of 11 patients was retrospective analysed at 5 years post Total Hip Arthroplasty (THA). Changes in pain, function and symptoms of the hip at 5 years post-THA were compared to preoperative and 2 year postoperative assessments on the Harris Hip Score (HHS) and Hip dysfunction and Osteoarthritis Outcome Score (HOOS). Results: The majority of cup migration occurred up to 6 months and stabilised thereafter (6 months to 5 years, p = 0.091-0.866, Wilcoxon Signed Rank test). The direction of rotation around the 3 axes was evenly distributed among the cups between anterior-posterior rotation, internal-external rotation and increased-decreased inclination. The majority of the cups translated proximally, at an average migration of 0.36 mm (+/- 95% CI 0.17) at 5-years post-THA. Following initial bedding in, up to 6 months, there was no detectable polyethylene wear between 6 months and 5 years. At 5 years postoperatively, a statistically significant difference was observed across all HOOS subscales in comparison to preoperative values, with higher means reported at 5 years (p < 0.001). The total mean HHS displayed a statistically significant improvement, increasing from 'poor' preoperatively to 'good' at 5 years post-THA. Conclusion: Following initial migration between discharge and 6 months, the cementless porous acetabular cup demonstrated a tendency for stabilisation from 6 months up to 5 years post-THA, suggesting good mid-term fixation. Additionally, improvements in clinical outcome measures of pain, function and quality-of-life remained high following THA at 5 years post-surgery. 

  • 190.
    Nilsson Sommar, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Lundh, Thomas
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hip Fracture Risk and Cadmium in Erythrocytes: A Nested Case-Control Study with Prospectively Collected Samples2014In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 94, no 2, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study's biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95 % confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95 % CI 0.77-2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95 % CI 1.18-3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95 % CI 1.29-8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.

  • 191.
    Ning, Yujie
    et al.
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, PR China.
    Wang, Xi
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, PR China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, PR China.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, PR China..
    Changes in the NF-κB signaling pathway in juvenile and adult patients with Kashin-Beck disease2019In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 379, no 2, p. 140-149Article in journal (Refereed)
    Abstract [en]

    To investigate the pathogenesis of Kashin-Beck disease (KBD), we compared the common signaling pathways in peripheral blood mononuclear cells (PBMCs) obtained from healthy juvenile and adults and KBD patients, and also from osteoarthritis (OA) patients. The PBMCs from 12 KBD and 12 healthy juvenile, and those from 20 adult KBD patients and 12 healthy donors were separately collected among the people living in the KBD endemic area. The patients were distinguished according to the national diagnosis criteria. Total RNAs were extracted for the determination of gene expressions by microarray analysis. Ingenuity Pathways Analysis (IPA) was employed to identify the signaling pathways significantly affected by juveniles' and adults' KBD, and OA. The expressions of NFκB-p65, cIAP2 and RANKL in the articular cartilage from both juvenile and adults were detected by immunohistochemistry. NF-κB signaling, apoptosis signaling, death receptor signaling and IL-6 signaling pathways were revealed to be the common affected signaling pathways in the juvenile and adult KBD and the OA. BIRC3 and EGR1 were identified as two common differentially expressed genes. The percentages of positive staining of NFκB-p65, cIAP2 and RANKL were reduced in adult KBD patients but significantly increased in juvenile KBD patients. NF-κB, one of the common signaling pathways between adult and juvenile KBD, was less prominent in the adult KBD patients.

  • 192.
    Nordstrand, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bovinder Ylitalo, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology. Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute for Medicine, Sahlgrenska Academy at University of Gothenburg.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bone Cell Activity in Clinical Prostate Cancer Bone Metastasis and Its Inverse Relation to Tumor Cell Androgen Receptor Activity2018In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 4, article id 1223Article in journal (Refereed)
    Abstract [en]

    Advanced prostate cancer frequently metastasizes to bone and induces a mixed osteoblastic/osteolytic bone response. Standard treatment for metastatic prostate cancer is androgen-deprivation therapy (ADT) that also affects bone biology. Treatment options for patients relapsing after ADT are limited, particularly in cases where castration-resistance does not depend on androgen receptor (AR) activity. Patients with non-AR driven metastases may, however, benefit from therapies targeting the tumor microenvironment. Therefore, the current study specifically investigated bone cell activity in clinical bone metastases in relation to tumor cell AR activity, in order to gain novel insight into biological heterogeneities of possible importance for patient stratification into bone-targeting therapies. Metastasis tissue obtained from treatment-naïve (n = 11) and castration-resistant (n = 28) patients was characterized using whole-genome expression analysis followed by multivariate modeling, functional enrichment analysis, and histological evaluation. Bone cell activity was analyzed by measuring expression levels of predefined marker genes representing osteoclasts (ACP5, CTSK, MMP9), osteoblasts (ALPL, BGLAP, RUNX2) and osteocytes (SOST). Principal component analysis indicated a positive correlation between osteoblast and osteoclast activity and a high variability in bone cell activity between different metastases. Immunohistochemistry verified a positive correlation between runt-related transcription factor 2 (RUNX2) positive osteoblasts and tartrate-resistant acid phosphatase (TRAP, encoded by ACP5) positive osteoclasts lining the metastatic bone surface. No difference in bone cell activity was seen between treatment-naïve and castration-resistant patients. Importantly, bone cell activity was inversely correlated to tumor cell AR activity (measured as AR, FOXA1, HOXB13, KLK2, KLK3, NKX3-1, STEAP2, and TMPRSS2 expression) and to patient serum prostate-specific antigen (PSA) levels. Functional enrichment analysis indicated high bone morphogenetic protein (BMP) signaling in metastases with high bone cell activity and low tumor cell AR activity. This was confirmed by BMP4 immunoreactivity in tumor cells of metastases with ongoing bone formation, as determined by histological evaluation of van Gieson-stained sections. In conclusion, the inverse relation observed between bone cell activity and tumor cell AR activity in prostate cancer bone metastasis may be of importance for patient response to AR and/or bone targeting therapies, but needs to be evaluated in clinical settings in relation to serum markers for bone remodeling, radiography and patient response to therapy. The importance of BMP signaling in the development of sclerotic metastasis lesions deserves further exploration.

  • 193.
    Nordström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Prevention of bone loss with exercise2012In: Diet, nutrients and bone health, CRC Press, 2012, p. 493-508Chapter in book (Refereed)
  • 194.
    Nordström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    The effect of detraining on bone2011In: Open Bone Journal, ISSN 1876-5254, no 3, p. 22-30Article in journal (Refereed)
    Abstract [en]

    Physical activity has been recommended for the treatment and even prevention of osteoporosis. This is because physical activity can potentially increase bone mass and strength in the early years of life and reduce the risk of falling in older populations. However, a key question that remains to be answered is whether a high bone mineral density (BMD) resulting from physical activity is sustained despite decreased activity. The aim of this review is to describe the effects of decreased levels of physical activity on bone.A comprehensive search of Medline, EMBASE, and the Cochrane controlled trials register was conducted. Previous studies have reported that benefits from prior physical activity seem to be eroded after cessation of this activity, at least for bone sites that are rich in trabecular bone such as the clinically important proximal femur. In bone sites rich in cortical bone, there appeared to be long-term beneficial effects of physical activity.In conclusion, bone gain through physical activity is lost in bone sites rich in trabecular bone if the activity is not maintained. However, current knowledge is limited and further prospective research into the effect of detraining is recommended.

  • 195.
    Nordström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Tervo, Taru
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Högström, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    The effect of physical activity on bone accrual, osteoporosis and fracture prevention2011In: Open Bone Journal, ISSN 1876-5254, no 3, p. 11-21Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity has been recommended for the prevention and even treatment of osteoporosis because it potentially can increase bone mass and strength during childhood and adolescence and reduce the risk of falling in older populations. However, few reports have systematically investigated the effect of physical activity on bone in men and women of different ages.

    Purpose: The goal of this study was to review the literature relating to the effect of physical activity on bone mineral density in men and women of various ages.

    Method: This review systematically evaluates the evidence for the effect of physical activity on bone mineral density. Cochrane and Medline databases were searched for relevant articles, and the selected articles were evaluated.

    Results: The review found evidence to support the effectiveness of weight bearing physical activity on bone accrual during childhood and adolescence. The effect of weight bearing physical activity was site-specific. In contrast, the role of physical activity in adulthood is primarily geared toward maintaining bone mineral density. The evidence for a protective effect of physical activity on bone is not as solid as that for younger individuals.

    Conclusions: The effect of weight bearing physical activity is seen in sites that are exposed to loading. There also seems to be a continuous adaptive response in bone to loading. Additional randomized, controlled studies are needed to evaluate the effect of physical activity in the elderly.

  • 196.
    Nordström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. School of Sports Science, UiT The Arctic University of Norway, Tromsö, Norway..
    Use of short-acting and long-acting hypnotics and the risk of fracture: a critical analysis of associations in a nationwide cohort2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965Article in journal (Refereed)
    Abstract [en]

    Summary: Numerous observational studies suggest that hypnotics increase the risk of fractures, and long-acting hypnotics are suggested to be especially harmful. This study showed that the highest risk of fracture was found before start of treatment and remained after end of therapy, suggesting that the increased risk during treatment is influenced by other factors, such as underlying disease.

    Introduction: The purpose of this study was to evaluate associations between the use of short-acting and long-acting hypnotics and the risk of fracture.

    Methods: Four cohorts were formed from all individuals living in Sweden aged ≥ 50 years in 2005 (n = 3,341,706). In the first cohort, individuals prescribed long-acting propiomazine (n = 233,609) were matched 1:1 with controls. In the second cohort, individuals prescribed short-acting z-drugs (zopiclone, zolpidem, and zaleplon, n = 591,136) were matched 1:1 with controls. The third and fourth cohorts consisted of full sibling pairs with discordant propiomazine (n = 83,594) and z-drug (n = 153,314) use, respectively.

    Results: The risk of fracture was greatest among users of hypnotics in the 90 days before the initiation of treatment, both for propiomazine (odds ratio [OR], 2.52; 95% confidence interval [CI], 2.28–2.79) and z-drugs (OR, 4.10; 95% CI, 3.86–4.35) compared with that in matched controls. Furthermore, this risk was significantly reduced after the initiation of treatment with propiomazine (OR, 1.42; 95% CI, 1.27–1.60) and z-drugs (OR, 1.67; 95% CI, 1.56–1.80) and remained the first year following the last prescribed dose both for propiomazine (OR, 1.28, 95% CI, 1.21–1.36) and z-drugs (OR, 1.19, 95% CI, 1.16–1.23). The pattern was similar in the sibling cohorts, with the greatest risk of fracture seen in the 90 days before treatment with hypnotics was initiated.

    Conclusion: The use of short-acting and long-acting hypnotics is associated with an increased risk of fracture. This risk was highest before initiation of treatment and remained after end of therapy. The results suggest that the increased risk during treatment is influenced by other factors such as underlying disease.

  • 197.
    Nordström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Type of physical activity, muscle strength, and pubertal stage as determinants of bone mineral density and bone area in adolescent boys.1998In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 13, no 7, p. 1141-8Article in journal (Refereed)
    Abstract [en]

    The present study was conducted to evaluate the influence of different types of weight-bearing physical activity, muscle strength, and puberty on bone mineral density (BMD, g/cm2) and bone area in adolescent boys. Three different groups were investigated. The first group consisted of 12 adolescent badminton players (age 17.0 +/- 0.8 years) training for 5.2 +/- 1.9 h/week. The second group consisted of 28 ice hockey players (age 16.9 +/- 0.3 years) training for 8.5 +/- 2.2 h/week. The third group consisted of 24 controls (age 16.8 +/- 0.3 years) training for 1.4 +/- 1.4h/week. The groups were matched for age, height, and pubertal stage. BMD, bone mineral content (BMC, g), and the bone area of the total body, lumbar spine, hip, femur and tibia diaphyses, distal femur, proximal tibia, and humerus were measured using dual-energy X-absorptiometry. When adjusting for the difference in body weight between the groups, the badminton players were found to have significantly higher BMD (p < 0.05) of the trochanter and distal femur compared with the ice hockey players despite a significantly lower weekly average training. The badminton players had higher BMD compared with the control with the control group at all weight-bearing BMD sites, except at the diaphyses of the femur and tibia and lumbar spine. The independent predictors of bone density were estimated by adjusting BMC for the bone area in a multivariate analysis among all subjects (n = 64). Accordingly, the bone density of all sites except the spine was significantly related to muscle strength and height, and the bone density of the total body, neck, trochanter, distal femur, and proximal tibia was significantly related to type of physical activity (beta = 0.09-0.33, p < 0.05). The bone area values at different sites were strongly related to muscle strength and height and less strongly related to the type of physical activity and pubertal stage. In conclusion, it seems that during late puberty in adolescent boys the type of weight-bearing physical activity is an important determinant of bone density, while the bone area is largely determined by parameters related to body size. The higher BMD at weight-bearing sites in badminton players compared with ice hockey players, despite significantly less average weekly training, indicates that physical activity including jumps in unusual directions has a great osteogenic potential.

  • 198.
    Nordström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Toots, Annika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Thorngren, Karl-Göran
    Hommel, Ami
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bisphosphonate Use After Hip Fracture in Older Adults: A Nationwide Retrospective Cohort Study2017In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 18, no 6, p. 515-521Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate the association between bisphosphonate use and the risk of new fracture in a nationwide cohort of individuals with previous hip fractures, with emphasis on individuals above 80 years of age.

    DESIGN, SETTING, AND PARTICIPANTS: From a nationwide cohort with hip fracture (2006-2012) (n = 93, 601), each individual prescribed bisphosphonates after hip fracture (n = 5845) was matched with up to three individuals not prescribed bisphosphonates, resulting in a cohort of 21,363 individuals.

    MAIN OUTCOME MEASURE: A new hip fracture.

    RESULTS: During a mean follow-up period of 2.98 (range, 0.02-8) years, 4581 fractures occurred in the cohort. Before the initiation of bisphosphonate therapy, individuals later prescribed bisphosphonates had an increased risk of hip fracture (multivariable adjusted odds ratio [OR], 2.63; 95% confidence interval [CI], 2.23-3.24) compared with controls. In the period after bisphosphonate therapy initiation, individuals prescribed bisphosphonates had a lower risk of hip fracture (multivariable adjusted hazard ratio [HR], 0.76; 95% CI, 0.65-0.90) compared with controls. Similar effects were seen after the initiation of bisphosphonates in individuals aged more than 80 years (HR, 0.79; 95% CI, 0.62-0.99). In contrast, the initiation of bisphosphonate therapy did not influence the risk of injurious falls not resulting in fracture (HR, 0.95; 95% CI, 0.86-1.05).

    CONCLUSION: Bisphosphonate use was associated with a decreased risk of hip fracture in this nationwide cohort of older men and women, with similar risk reductions in individuals older than 80 years.

  • 199. Oei, Ling
    et al.
    Hsu, Yi-Hsiang
    Styrkarsdottir, Unnur
    Eussen, Bert H
    de Klein, Annelies
    Peters, Marjolein J
    Halldorsson, Bjarni
    Liu, Ching-Ti
    Alonso, Nerea
    Kaptoge, Stephen K
    Thorleifsson, Gudmar
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Kruk, Marcin
    Lewis, Joshua R
    Patel, Millan S
    Scollen, Serena
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Trompet, Stella
    van Schoor, Natasja M
    Zhu, Kun
    Buckley, Brendan M
    Cooper, Cyrus
    Ford, Ian
    Goltzman, David
    González-Macías, Jesús
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Lorenc, Roman S
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Reid, David M
    Riancho, José A
    Slagboom, P Eline
    Garcia-Ibarbia, Carmen
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Luben, Robert
    Medina-Gómez, Carolina
    Arp, Pascal
    Nandakumar, Kannabiran
    Palsson, Stefan Th
    Sigurdsson, Gunnar
    van Meurs, Joyce B J
    Zhou, Yanhua
    Hofman, Albert
    Jukema, J Wouter
    Pols, Huibert A P
    Prince, Richard L
    Cupples, L Adrienne
    Marshall, Christian R
    Pinto, Dalila
    Sato, Daisuke
    Scherer, Stephen W
    Reeve, Jonathan
    Thorsteinsdottir, Unnur
    Karasik, David
    Richards, J Brent
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John P A
    Kiel, Douglas P
    Rivadeneira, Fernando
    Estrada, Karol
    A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus2014In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, no 2, p. 122-131Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.

    AIM: To identify CNVs associated with osteoporotic bone fracture risk.

    METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.

    RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.

    CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

  • 200.
    Olkku, Anu
    et al.
    School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Leskinen, Jarkko
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hynynen, Kullervo
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland; Department of Medical Biophysics, University of Toronto and Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Canada.
    Mahonen, Anitta
    chool of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Finland; Bone and Cartilage Research Unit, University of Eastern Finland, Kuopio, Finland.
    Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells.2010In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 47, no 2, p. 320-330, article id 20435172Article in journal (Refereed)
    Abstract [en]

    The benefit from an ultrasound (US) exposure for fracture healing has been clearly shown. However, the molecular mechanisms behind this effect are not fully known. Recently, the canonical Wnt signaling pathway has been recognized as one of the essential regulators of osteoblastogenesis and bone mass, and thereby considered crucial for bone health. Mechanical loading and fluid shear stress have been reported to activate the canonical Wnt signaling pathway in bone cells, but previous reports on the effects of therapeutic US on Wnt signaling in general or in bone, in particular, have not been published yet. Therefore, activation of Wnt signaling pathway was assayed in human osteoblastic cells, and indeed, this pathway was found to be activated in MG-63 cells through the phosphoinositol 3-kinase/Akt (PI3K/Akt) and mTOR cascades following a single 10 min US exposure (2 W, 1.035 MHz). In addition to the reporter assay results, the Wnt pathway activation was also observed as nuclear localization of beta-catenin. Wnt activation showed also temperature dependence at elevated temperatures, and the expression of canonical Wnt ligands was induced under the thermal exposures. However, existence of a specific, non-thermal US component was evident as well, perhaps evidence of a potential dual action of therapeutic US on bone. Neither US nor heat exposures affected cell viability in our experiments. In summary, this is the first study to report that Wnt signaling cascade, important for osteoblast function and bone health, is one of the pathways activated by therapeutic US as well as by hyperthermia in human osteoblastic cells. Our results provide evidence for the potential molecular mechanisms behind the beneficial effects of US on fracture healing. Combinations of US, heat, and possible pharmacological treatment could provide useful flexibility for clinical cases in treating various bone disorders.

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