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  • 1. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, nr 5, s. 1587-1598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 2.
    Bergström, Ulrica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Fracture mechanisms and fracture pattern in men and women aged 50 years and older: a study of a 12-year population-based injury register, Umeå, Sweden2008Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 19, nr 9, s. 1267-1273Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Summary: In a study of a 12-year population-based injury register, Umeå, Sweden, we analyzed the fracture mechanisms and fracture pattern in men and women 50 years and older. Low-energy trauma was responsible for the major and costliest part of the fracture panorama, but the pattern differs between age groups.

    Introduction: Osteoporosis-related fracture is a major health problem: the number of hip fractures is expected to double to 2030. While osteoporosis is one of many risk factors, trauma is almost always involved. Therefore, we analyzed injury mechanisms in patients aged over 50.

    Methods: We registered injury mechanism, cause, diagnosis in all trauma patients at Umeå University hospital, Sweden. This population-based register (1993–2004) comprises a total of 113,668 injuries (29,189 fractures). Patients ≥50 years contributed to 13,279 fractures.

    Results: Low-energy trauma (fall <1 m) caused 53% of all fractures ≥50 years and older. In those over 75 low-energy trauma caused >80%. The seasonal variation of fractures was maximally 25%. With increasing age, proximal fractures became more common, in both upper and lower extremities. Proximal locations predominate in older age groups.

    Conclusions: Low-energy trauma was responsible for the largest and costliest part of the fracture panorama. In fact, almost all fractures in middle-aged and old people were caused by low-energy mechanisms; thus, most fractures in these patients have a fragility component, and the contribution of osteoporosis-related fractures is more important than previously thought. A better understanding of injury mechanisms also in low-energy trauma is a prerequisite for preventive interventions.

  • 3. Bergström, Ulrica
    et al.
    Björnstig, Ulf
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
    Svensson, Olle
    Fracture panorama in Umeå2006Ingår i: Läkartidningen, ISSN 0023-7205, Vol. 103, nr 40, s. 2967-8Artikel i tidskrift (Refereegranskat)
  • 4.
    Bergström, Ulrica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    The hip fracture incidence curve is shifting to the right: a forecast of the age-quake2009Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, nr 5, s. 520-524Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The number of hip fractures has doubled in the last 30–40 years in many countries. Age-adjusted incidence has been reported to be decreasing in Europe and North America, but is there a decreasing trend in all age groups? Patients and methods This population-based study included all hip-fracture patients over 50 years of age (a total of 2,919 individuals, 31% of whom were men) admitted to Umeå University Hospital, Sweden, from 1993 through 2005. Results The incidence of hip fracture declined between the periods 1993–1996 and 2001–2005: from 706 to 625 hip fractures per 105 women and from 390 to 317 hip fractures per 105 men. However, there was a 114% increase in the number of fractures in women aged 90 or older (12 and 25 hip fractures/year, respectively, in the two time periods). For the period 2001–05, women ≥ 90 years of age accounted for almost the same numbers of hip fractures as women aged 75–79 (27 fractures/year). The rate increased during this period, from 2,700 per 105 women to 3,900 per 105 women > 90 years. In men there were declining trends for both relative and absolute numbers. Interpretation Although age-adjusted incidence declined in the population > 50 years of age, absolute fracture rate and incidence increased in the very old. Women over 90 now have the same absolute number of hip fractures every year as women aged 75–79 years. There was a right-shift in hip fracture distribution towards the oldest old, probably due to an increased number of octo/nonagenarians, a new population of particularly frail old people that hardly existed earlier. Better health among septuagenarians may also have delayed the age at which fractures occurred. This changing pattern will strain orthopedic and geriatric resources even more.

  • 5. Borgström, Fredrik
    et al.
    Zethraeus, Niklas
    Johnell, Olof
    Lidgren, Lars
    Ponzer, Sari
    Svensson, Olle
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Abdon, Peter
    Ornstein, Ewald
    Lunsjö, Karl
    Thorngren, Karl Göran
    Sernbo, Ingemar
    Rehnberg, Clas
    Jönsson, Bengt
    Costs and quality of life associated with osteoporosis-related fractures in Sweden.2006Ingår i: Osteoporos International, ISSN 0937-941X, Vol. 17, nr 5, s. 637-50Artikel i tidskrift (Refereegranskat)
  • 6.
    Brax-Olofsson, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lorentzon, Ronny
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Lindström, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Periosteal transplantation to the rabbit patella.2007Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 15, nr 5, s. 560-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.

  • 7. Conaway, H Herschel
    et al.
    Persson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Halén, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Lie, Anita
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Lerner, Ulf H
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Retinoids inhibit differentiation of hematopoietic osteoclast progenitors2009Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, nr 10, s. 3526-3538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.

  • 8.
    Conaway, H. Herschel
    et al.
    Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
    Pirhayati, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Persson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindholm, Catharina
    Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg.
    Henning, Petra
    Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg.
    Tuckermann, Jan
    Tissue-specific Hormone Action, Leibniz Institute for Age Research, Fritz Lipmann Institute, D-07745 Jena, Germany.
    Lerner, Ulf H.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Retinoids Stimulate Periosteal Bone Resorption by Enhancing the Protein RANKL: a Response Inhibited by Monomeric Glucocorticoid Receptor2011Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, s. 31425-31436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RAR alpha/beta/gamma) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RAR alpha enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RAR beta/gamma or RAR gamma had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RAR alpha antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on 45Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RAR alpha receptors, a response that can be inhibited by monomeric GR.

  • 9. Conaway, Herschel H
    et al.
    Persson, Emma
    Halén, Marie
    Granholm, Susanne
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson, Ulrika
    Lie, Anita
    Lerner, Ulf H
    Retinoids inhibit differentiation of hematopoetic osteoclast progenitors2009Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, nr 10, s. 3526-3538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.

  • 10.
    Crnalic, Sead
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Hildingsson, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Löfvenberg, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer2013Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, nr 4, s. 809-815Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Spinal cord compression is an oncological and surgical emergency. Delays in referral and diagnosis may influence functional outcome. It is therefore important to identify patients who will regain or maintain ability to walk after surgery. The aim of the present study was to examine current practice for referral and diagnosis of prostate cancer patients with spinal cord compression and to identify prognostic factors for neurological outcome after surgery.

    Patients and methods. The study includes 68 consecutive patients with prostate cancer who underwent surgery due to neurological compromise.  Intervals from onset of neurological symptoms to referral, diagnosis, and treatment were analyzed in relation to functional outcome. The prognostic significance of preoperative clinical parameters on gait function one month after surgery was evaluated.

    Results. Patients who were referred from local hospitals had longer delay to surgery than those who directly presented to the cancer centre (p=0.004). The rate of diagnosis with MRI increased through the week and peaked on Friday, with few patients being diagnosed during weekends. Ability to walk before surgery, hormone-naive prostate cancer, and/or shorter time from loss of ambulation were associated with more favorable neurological outcome. In patients with hormone-refractory disease who were unable to walk before surgery regaining of ambulation was associated with: duration of paresis <48 hours (p=0.005), good preoperative performance status (p=0.04), preoperative PSA serum level <200 ng/ml (p=0.03), and surgery with posterior decompression and stabilization (p=0.03).

    Conclusion. Early diagnosis and rapid treatment of spinal cord compression in prostate cancer patients is crucial for neurological recovery. Rising of awareness for the condition among patients at risk and among physicians is mandatory as well as improvement of local and regional guidelines for treatment.

  • 11.
    Crnalic, Sead
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Hörnberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lerner, Ulf H
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Tieva, Åse
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients2010Ingår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 17, nr 4, s. 885-895Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.

  • 12.
    Edmundsson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Toolanen, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Intermittent claudication in diabetes mellitus due to chronic exertinal compartment syndrome of the leg: an observation study of 17 patients2008Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, nr 4, s. 534-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Intermittent claudication in diabetes mellitus is commonly associated with arterial disease but may occur without obvious signs of peripheral circulatory impairment. We investigated whether this could be due to chronic exertional compartment syndrome (CECS).

    Patients and methods: We report on 17 patients (3 men), mean age 39 (18–72) years, with diabetes mellitus—12 of which were type 1—and leg pain during walking (which was relieved at rest), without clinical signs of peripheral arterial disease. The duration of diabetes was 22 (1–41) years and 12 patients had peripheral neuropathy, retinopathy, or nephropathy. The leg muscles were tender and firm on palpation. Radiography, scintigraphy, and intramuscular pressure measurements were done during exercises to reproduce their symptoms.

    Results: 16 of the 17 patients were diagnosed as having CECS. The intramuscular pressures in leg compartments were statistically significantly higher in diabetics than in physically active non‐diabetics with CECS (p < 0.05). 15 of the 16 diabetics with CECS were treated with fasciotomy. At surgery, the fascia was whitish, thickened, and had a rubber‐like consistency. After 1 year, 9 patients rated themselves as excellent or good in 15 of the 18 treated compartments. The walking time until stop due to leg pain increased after surgery from less than 10 min to unlimited time in 8 of 9 patients who were followed up.

    Interpretation: Intermittent claudication in diabetics may be caused by CECS of the leg. The intramuscular pressures were considerably elevated in diabetics. One pathomechanism may be fascial thickening. The results after fasciotomy are good, and the increased pain‐free walking time is especially beneficial for diabetics.

  • 13.
    Einarsdottir, Elisabet
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Carlsson, Anna
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Minde, Jan
    Toolanen, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Solders, Göran
    Holmgren, Gösta
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Holmberg, Dan
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Holmberg, Monica
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception.2004Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 13, nr 8, s. 799-805Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identification of genes associated with pain insensitivity syndromes can increase the understanding of the pathways involved in pain and contribute to the understanding of how sensory pathways relate to other neurological functions. In this report we describe the mapping and identification of the gene responsible for loss of deep pain perception in a large family from northern Sweden. The loss of pain perception in this family is characterized by impairment in the sensing of deep pain and temperature but with normal mental abilities and with most other neurological responses intact. A severe reduction of unmyelinated nerve fibers and a moderate loss of thin myelinated nerve fibers are observed in the patients. Thus the cases in this study fall into the class of patients with loss of pain perception with underlying peripheral neuropathy. Clinically they best fit into HSAN V. Using a model of recessive inheritance we identified an 8.3 Mb region on chromosome 1p11.2-p13.2 shared by the affected individuals in the family. Analysis of functional candidate genes in the disease critical region revealed a mutation in the coding region of the nerve growth-factor beta (NGFB) gene specific for the disease haplotype. This NGF mutation seems to separate the effects of NGF involved in development of central nervous system functions such as mental abilities, from those involved in peripheral pain pathways. This mutation could therefore potentially provide an important tool to study different roles of NGF, and of pain control.

  • 14.
    Eklund, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Neovius, Martin
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Variation in fracture rates by country may not be explained by differences in bone mass2009Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 85, nr 1, s. 10-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is unclear whether the high fracture incidence in Sweden compared with other countries is related to low bone mass. We present and compare bone mineral density (BMD, g/cm(2)) at the femoral neck in a mainly osteoporotic referral population consisting of 2,031 men and 6,932 women with that of previous population-based cohorts. BMD measurements were collected at a single study center in Sweden, and data on validated hip fractures were collected from the corresponding health-care district and the cohort investigated. The BMD values of our cohort were similar to those of population-based cohorts from other countries. In contrast, the total incidence of hip fractures in 80-year-old women and men in the health-care district where our BMD measurements were performed was high (1.8% and 0.9%, respectively). The correlation between age and BMD was more negative in men aged 20-49 years than in women of the same age group (-0.011 vs. -0.006 g/cm(2) yearly, P < 0.001). In contrast, at 50-80 years of age, more negative regression coefficients were seen in women (-0.007 vs. -0.004 g/cm(2) yearly, P < 0.001 for comparison). In conclusion, a low BMD may not be the key factor explaining Sweden's comparatively high fracture incidence. In our cross-sectional data, age trends in BMD at the femoral neck differ between men and women. It would be highly interesting to further study the underlying causes of the global variations in fracture incidence rates.

  • 15.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Physical activity in middle-aged women and hip fracture risk: the UFO study2011Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 22, nr 2, s. 499-505Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Summary: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women.

    Introduction: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture.

    Methods: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years.

    Results: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05–0.53 for walking and OR 0.19; 95% CI; 0.08–0.46, OR 0.17, 95% CI; 0.05–0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women.

    Conclusion: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.

  • 16.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Active commuting reduces the risk of wrist fractures in middle-aged women: the UFO study2013Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, nr 2, s. 533-540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.

    INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.

    METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.

    RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.

    CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.

  • 17. Estrada, Karol
    et al.
    Styrkarsdottir, Unnur
    Evangelou, Evangelos
    Hsu, Yi-Hsiang
    Duncan, Emma L
    Ntzani, Evangelia E
    Oei, Ling
    Albagha, Omar ME
    Amin, Najaf
    Kemp, John P
    Koller, Daniel L
    Li, Guo
    Liu, Ching-Ti
    Minster, Ryan L
    Moayyeri, Alireza
    Vandenput, Liesbeth
    Willner, Dana
    Xiao, Su-Mei
    Yerges-Armstrong, Laura M
    Zheng, Hou-Feng
    Alonso, Nerea
    Eriksson, Joel
    Kammerer, Candace M
    Kaptoge, Stephen K
    Leo, Paul J
    Thorleifsson, Gudmar
    Wilson, Scott G
    Wilson, James F
    Aalto, Ville
    Alen, Markku
    Aragaki, Aaron K
    Aspelund, Thor
    Center, Jacqueline R
    Dailiana, Zoe
    Duggan, David J
    Garcia, Melissa
    Garcia-Giralt, Natàlia
    Giroux, Sylvie
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Khusainova, Rita
    Kim, Ghi Su
    Kooperberg, Charles
    Koromila, Theodora
    Kruk, Marcin
    Laaksonen, Marika
    Lacroix, Andrea Z
    Lee, Seung Hun
    Leung, Ping C
    Lewis, Joshua R
    Masi, Laura
    Mencej-Bedrac, Simona
    Nguyen, Tuan V
    Nogues, Xavier
    Patel, Millan S
    Prezelj, Janez
    Rose, Lynda M
    Scollen, Serena
    Siggeirsdottir, Kristin
    Smith, Albert V
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Trompet, Stella
    Trummer, Olivia
    van Schoor, Natasja M
    Woo, Jean
    Zhu, Kun
    Balcells, Susana
    Brandi, Maria Luisa
    Buckley, Brendan M
    Cheng, Sulin
    Christiansen, Claus
    Cooper, Cyrus
    Dedoussis, George
    Ford, Ian
    Frost, Morten
    Goltzman, David
    González-Macías, Jesús
    Kähönen, Mika
    Karlsson, Magnus
    Khusnutdinova, Elza
    Koh, Jung-Min
    Kollia, Panagoula
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Ljunggren, Osten
    Lorenc, Roman S
    Marc, Janja
    Mellström, Dan
    Obermayer-Pietsch, Barbara
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Reid, David M
    Riancho, José A
    Ridker, Paul M
    Rousseau, François
    Lagboom, P Eline S
    Tang, Nelson LS
    Urreizti, Roser
    Van Hul, Wim
    Viikari, Jorma
    Zarrabeitia, María T
    Aulchenko, Yurii S
    Castano-Betancourt, Martha
    Grundberg, Elin
    Herrera, Lizbeth
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Kwan, Tony
    Li, Rui
    Luben, Robert
    Medina-Gómez, Carolina
    Th Palsson, Stefan
    Reppe, Sjur
    Rotter, Jerome I
    Sigurdsson, Gunnar
    van Meurs, Joyce BJ
    Verlaan, Dominique
    Williams, Frances MK
    Wood, Andrew R
    Zhou, Yanhua
    Gautvik, Kaare M
    Pastinen, Tomi
    Raychaudhuri, Soumya
    Cauley, Jane A
    Chasman, Daniel I
    Clark, Graeme R
    Cummings, Steven R
    Danoy, Patrick
    Dennison, Elaine M
    Eastell, Richard
    Eisman, John A
    Gudnason, Vilmundur
    Hofman, Albert
    Jackson, Rebecca D
    Jones, Graeme
    Jukema, J Wouter
    Khaw, Kay-Tee
    Lehtimäki, Terho
    Liu, Yongmei
    Lorentzon, Mattias
    McCloskey, Eugene
    Mitchell, Braxton D
    Nandakumar, Kannabiran
    Nicholson, Geoffrey C
    Oostra, Ben A
    Peacock, Munro
    Pols, Huibert AP
    Prince, Richard L
    Raitakari, Olli
    Reid, Ian R
    Robbins, John
    Sambrook, Philip N
    Sham, Pak Chung
    Shuldiner, Alan R
    Tylavsky, Frances A
    van Duijn, Cornelia M
    Wareham, Nick J
    Cupples, L Adrienne
    Econs, Michael J
    Evans, David M
    Harris, Tamara B
    Kung, Annie Wai Chee
    Psaty, Bruce M
    Reeve, Jonathan
    Spector, Timothy D
    Streeten, Elizabeth A
    Zillikens, M Carola
    Thorsteinsdottir, Unnur
    Ohlsson, Claes
    Karasik, David
    Richards, J Brent
    Brown, Matthew A
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John PA
    Kiel, Douglas P
    Rivadeneira, Fernando
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture2012Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, s. 491-501Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

  • 18.
    Farhang, Mehdy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Mukka, Sebastian
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Sayed-Noor, Arkan S.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    The trend of radiological severity of hip fractures over a 30 years period: a cohort study2019Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 20, nr 1, artikel-id 358Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Despite advances in operative techniques and preoperative care, proximal femur fractures (PFF) still represent a great public health problem. Displacement and fracture stability have been assumed as important determinants of treatment modality and outcome in such fractures. Purpose of this study was to determine whether the radiological severity of PFF fractures has increased over time.

    METHODS: In a cohort study, the plain radiographs of all patients with PFF aged over 50 years who were admitted to Umeå University Hospital in 1981/82, 2002 and 2012 were recruited to examine the types of fractures.

    RESULTS: The ratio of undisplaced to displaced femoral neck (FN) fractures was 30 to 70% in 1981/82, 28 to 72% in 2002 and 25 to 75% in 2012. The ratio of stable to unstable intertrochanteric (IT) fractures was 64 to 36% in 1981/82, 68 to 32% in 2002 and 75 to 25% in 2012. The ratio of simple to comminute subtrochanteric fractures was 35 to 65% in 1981/82, 16 to 84% in 2002 and 12 to 88% in 2012. In both FN and IT fractures we found no statistical difference among these 3 study periods, p = 0.67 and p = 0.40. In subtrochanteric fractures we saw a tendency towards more comminute subtrochanteric fractures (1981/82 to 2012), p = 0.09.

    CONCLUSIONS: We found no significant increment in the radiological severity of FN and IT over a 30 years' period. However, there was tendency towards an increase in comminute subtrochanteric fractures.

  • 19.
    Haney, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Löfvenberg, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Optimize perioperative health and begin with insistence on pre-operative smoking cessation2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 2, s. 133-134Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    Hedström, Erik M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Michno, Piotr
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Epidemiology of fractures in children and adolescents2010Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, nr 1, s. 148-153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose Fractures are most common in youth and in the elderly, with differences in incidence over time and between regions. We present the fracture pattern in a population of youths 19 years of age, who were seen at Umeå University Hospital, Sweden.

    Material and methods All injuries seen at the hospital have been recorded in a database since 1993. The data include variables such as age, sex, date, type of injury, mechanism of injury, and treatment. For the period 1993–2007, there were 10,203 injury events that had resulted in at least 1 fracture.

    Results The incidence for the whole period was 201/104 person years. The incidence increased by 13% during the period 1998–2007, when we were able to control for registration errors. The most common fracture site was the distal forearm. The most common type of injury mechanism was falling. The peak incidence occurred at 11–12 years in girls and at 13–14 years in boys, with a male-to-female incidence ratio of 1.5. We found variations in mechanisms and activities at injury with age, and over time.

    Interpretation Fractures are caused by a combination of intrinsic and extrinsic factors that vary with age. We believe the increase in incidence is partly explained by changes in children's activity patterns over time. Further research may help to identify preventive measures to reduce the number of fractures, in particular those involving hospital care, surgical treatment, and—most importantly—long-term impairment.

    Read More: http://informahealthcare.com/doi/abs/10.3109/17453671003628780

  • 21.
    Hedström, Erik M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Michno, Piotr
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Epidemiology of fractures in children and adolescents: Increased incidence over the past decade: a population-based study from northrn Sweden2010Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, nr 1, s. 148-153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose Fractures are most common in youth and in the elderly, with differences in incidence over time and between regions. We present the fracture pattern in a population of youths <= 19 years of age, who were seen at Umeå University Hospital, Sweden. Material and methods All injuries seen at the hospital have been recorded in a database since 1993. The data include variables such as age, sex, date, type of injury, mechanism of injury, and treatment. For the period 1993-2007, there were 10,203 injury events that had resulted in at least 1 fracture. Results The incidence for the whole period was 201/10<sup>4</sup> person years. The incidence increased by 13% during the period 1998-2007, when we were able to control for registration errors. The most common fracture site was the distal forearm. The most common type of injury mechanism was falling. The peak incidence occurred at 11-12 years in girls and at 13-14 years in boys, with a male-to-female incidence ratio of 1.5. We found variations in mechanisms and activities at injury with age, and over time. Interpretation Fractures are caused by a combination of intrinsic and extrinsic factors that vary with age. We believe the increase in incidence is partly explained by changes in children's activity patterns over time. Further research may help to identify preventive measures to reduce the number of fractures, in particular those involving hospital care, surgical treatment, and-most importantly-long-term impairment.

  • 22.
    Hovelius, Lennart
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Sandström, Björn
    Olofsson, Anders
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Rahme, Hans
    The effect of capsular repair, bone block healing, and position on the results of the Bristow-Laterjet procedure (study III): long-term follow-up in 319 shoulders2012Ingår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 21, nr 5, s. 647-660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background We evaluated the results of the May modification of the Bristow-Latarjet procedure (“coracoid in standing position”) in 319 shoulders with respect to (1) coracoid healing and position and (2) surgical treatment of the joint capsule.

    Methods From 1980 until 2004, all shoulders with a Bristow-Latarjet repair were registered at our hospital. This study consists of 3 different cohorts with respect to follow-up. Series 1, 118 shoulders operated on during 1980 through 1985, had 15 years’ radiographic and clinical follow-up. Series 2, 167 shoulders that had surgery during 1986 through 1999, underwent retrospective follow-up by a questionnaire and scores—Western Ontario Shoulder Instability Index; Disabilities of the Arm, Shoulder and Hand; and Subjective Shoulder Value—after 10 to 23 years. Series 3, 34 shoulders treated during 2000 through 2004, with an added modified Bankart repair (“capsulopexy”) in 33 shoulders, were prospectively followed up for 5 to 8 years with the same questionnaire and scores as series 2.

    Results Of 319 shoulders, 16 (5%) had 1 or more redislocations and 3 of these (1%) had revision surgery because of remaining instability. One or more subluxations were reported in 41 shoulders (13%). The worst scores were found in 16 shoulders with 2 or more subluxations (P < .001). Radiographs showed bony healing in 246 of 297 shoulders (83%), fibrous union in 34 (13%), migration by 0.5 cm or more in 14 (5%), and no visualization in 3 (1%). Five of six shoulders that had the transplant positioned 1 cm or more medial to the glenoid rim had redislocations (83%, P = .001). Shoulders with migrated transplants did not differ from those with bony or fibrous healing with respect to redislocations and subluxations. When just a horizontal capsular shift was added to the transfer, the recurrence rate (redislocations or subluxations) decreased, with 2 of 53 (4%)compared with 37 of 208 (18%) with just anatomic closure of the capsule (P = .005), and the Western Ontario Shoulder Instability Index score improved (92 vs 85.6, P = .048). In total, for 307 of 319 shoulders (96%), patients were satisfied or very satisfied at final follow-up.

    Conclusion The open Bristow-Latarjet procedure yields good and consistent results, with bony fusion of the coracoid in 83%. A position of the coracoid 1 cm or more medial to the rim meant significantly more recurrences. The rate of recurrences decreased and subjective results improved when a horizontal capsular shift was added to the coracoid transfer.

  • 23.
    Hovelius, Lennart
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Vikerfors, Ola
    Olofsson, Anders
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Rahme, Hans
    Bristow-Latarjet and Bankart: a comparative study of shoulder stabilization in 185 shoulders during a seventeen-year follow-up2011Ingår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 20, nr 7, s. 1095-1101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In 2 Swedish hospitals, 88 consecutive shoulders underwent Bankart repair (B), and 97 consecutive shoulders underwent Bristow-Latarjet repair (B-L) for traumatic anterior recurrent instability.

    Materials and methods: Mean age at surgery was 28 years (B-L group) and 27 years (B group). All shoulders had a follow-up by letter or telephone after a mean of 17 years (range, 13-22 years). The patients answered a questionnaire and completed the Western Ontario Shoulder Index (WOSI), Disability of Arm Shoulder and Hand (DASH), and SSV (Simple Shoulder Value) assessments.

    Results: Recurrance resulted revision surgery in 1 shoulder in the B-L group and in 5 shoulders in the B group (P=.08). Redislocation or subluxation after the index operation occurred in 13 of 97 B-L shoulders and in 25 of 87 of B shoulders (after excluding 1 patient with arthroplasty because of arthropathy, P=.017). Of the 96 Bristow shoulders, 94 patients were very satisfied/satisfied compared with 71 of 80 in the B series (P=.01). Mean WOSI score was 88 for B-L shoulders and 79 for B shoulders (P=.002). B-L shoulders also scored better on the DASH (P=.002) and SSV (P=.007). Patients had 11 degrees loss of subjectively measured outward rotation with the arm at the side after B-L repair compared with 19 degrees after Bankart (P=.012). The original Bankart, with tunnels through the glenoid rim, had less redislocation(s) or subluxation(s) than shoulders done with anchors (P=.048).

    Conclusions: Results were better after the Bristow-Latarjet repair than after Bankart repairs done with anchors with respect to postoperative stability and subjective evaluation. Shoulders with original Bankart repair also seemed to be more stable than shoulders repaired with anchors.

    Level of evidence: Level III, Retrospective Case Control Study, Treatment Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees.

  • 24. Johansson, Helena
    et al.
    Kanis, John A
    Ljunggren, Östen
    Ström, Oskar
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Mellström, Dan
    10-årsrisken för fraktur. Stöd i behandlingen av osteoporos, enligt preliminära svenska riktlinjer.2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 7, s. 336-339Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    Risken för fraktur beräknas med FRAX för män och kvinnor, för olika åldrar, för olika BMI och med följande riskvariabler: tidigare osteoporotisk fraktur, höftfraktur hos föräldrar, aktuell rökning, längre tids peroral behandling med kortison någon gång i livet, förekomst av reumatoid artrit, förekomst av andra sjukdomstillstånd som orsakar osteoporos, aktuell alkoholkonsumtion ≥3 enheter och bentäthetsmätning.

    FRAX finns fritt tillgängligt på Internet.

    I denna artikel beskrivs bakgrunden till FRAX och dess användning vid diagnostik och behandling av osteoporos.

  • 25.
    Lundström, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Stenvall, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Karlsson, Stig
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Englund, Undis
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Borssén, Bengt
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Postoperative delirium in old patients with femoral neck fracture: a randomized intervention study.2007Ingår i: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 19, nr 3, s. 178-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs. We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures.

    METHODS: One hundred and ninety-nine patients, aged 70 years and over (mean age+/-SD, 82+/-6, 74% women), were randomly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward. The intervention consisted of staff education focusing on the assessment, prevention and treatment of delirium and associated complications. The staff worked as a team, applying comprehensive geriatric assessment, management and rehabilitation. Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale, and delirium was diagnosed according to DSM-IV criteria.

    RESULTS: The number of days of postoperative delirium among intervention patients was fewer (5.0+/-7.1 days vs 10.2+/-13.3 days, p=0.009) compared with controls. A lower proportion of intervention patients were delirious postoperatively than controls (56/102, 54.9% vs 73/97, 75.3%, p=0.003). Eighteen percent in the intervention ward and 52% of controls were delirious after the seventh postoperative day (p<0.001). Intervention patients suffered from fewer complications, such as decubitus ulcers, urinary tract infections, nutritional complications, sleeping problems and falls, than controls. Total postoperative hospitalization was shorter in the intervention ward (28.0+/-17.9 days vs 38.0+/-40.6 days, p=0.028).

    CONCLUSIONS: Patients with postoperative delirium can be successfully treated, resulting in fewer days of delirium, fewer other complications, and shorter length of hospitalization.

  • 26.
    Minde, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    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 universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Holmberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Toolanen, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    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 patients2009Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 2, s. 188-195Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Minde, Jan
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Holmberg, Monica
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Solders, Göran
    Toolanen, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Orthopedic aspects of familial insensitivity to pain due to a novel nerve growth factor beta mutation.2006Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, nr 2, s. 198-202Artikel i tidskrift (Refereegranskat)
  • 28.
    Minde, Jan
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Toolanen, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Andersson, Thomas
    Nennesmo, Inger
    Remahl, Ingela Nilsson
    Svensson, Olle
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Solders, Göran
    Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study.2004Ingår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 30, nr 6, s. 752-760Artikel i tidskrift (Refereegranskat)
  • 29.
    Nilsson Sommar, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Lundh, Thomas
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hip Fracture Risk and Cadmium in Erythrocytes: A Nested Case-Control Study with Prospectively Collected Samples2014Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 94, nr 2, s. 183-190Artikel i tidskrift (Refereegranskat)
    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.

  • 30. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Kruk, Marcin
    Lewis, Joshua R
    Patel, Millan S
    Scollen, Serena
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    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 universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    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 locus2014Ingår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, nr 2, s. 122-131Artikel i tidskrift (Refereegranskat)
    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.

  • 31.
    Olofsson, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Stenvall, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lundström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Carlsson, Maine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Englund, Undis
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Berglund, Monica
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Vårdprogram för patienter med höftfrakturer, andra upplagan: ortoped-geriatriskt preoperativt vårdprogram för alla patienter med höftfraktur och postoperativt vårdprogram för patienter över 80 år med cervikala och basocervikala höftfrakturer som behandlas vid Norrlands universitets sjukhus i Umeå2008Rapport (Övrigt vetenskapligt)
  • 32.
    Olofsson, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Stenvall, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lundström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Mental status and surgical methods in patients with femoral neck fracture2009Ingår i: Orthopedic Nursing, ISSN 0744-6020, E-ISSN 1542-538X, Vol. 28, nr 6, s. 305-313Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: About one third of hip-fractured patients have dementia and thus may have difficulties adhering to postoperative instructions. Hip replacement is the most common treatment when a femoral neck fracture is displaced in healthy older people, whereas for those with dementia and other severe comorbidities, internal fixation (IF) is generally recommended.

    PURPOSE: To evaluate complications, functional outcome, and mortality for both surgical methods, IF and hemiarthroplasty (HAP), in older patients suffering from femoral neck fracture with or without dementia. SAMPLE: One hundred eighty patients, aged 70 years or older, who were operated on using IF (n = 69) in undisplaced femoral neck fracture and HAP (n = 111) if the fractures were displaced.

    DATA COLLECTION: Mental state was assessed using the Mini-Mental State Examination and Organic Brain Syndrome scale, and dementia and delirium were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Outcomes of mortality, complications, functional ability, and quality of life were measured.

    FINDINGS: There was no difference in complications or mortality at 4 months and 1 year for the IF or HAP groups. Patients with and without dementia, operated on with HAP, had a better functional outcome after 1 year than those operated on with IF. The result of this study indicates that dementia per se is not a reason for disqualifying those patients from the most appropriate surgical method.

  • 33.
    Olofsson, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Stenvall, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lundström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Malnutrition in hip fracture patients: an intervention study.2007Ingår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 16, nr 11, s. 2027-2038Artikel i tidskrift (Refereegranskat)
  • 34. Rydholm, Anders
    et al.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Happy birthday, Acta!2010Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, nr 1, s. 1-2Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 35.
    Röding, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lysholm, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Trauma recidivism at an emergency department of a Swedish medical center2016Ingår i: Injury Epidemiology, ISSN 0176-3733, E-ISSN 2197-1714, Vol. 3, artikel-id 22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To inform targeted prevention, we studied patterns of trauma recidivism and whether a first injury predicts the risk for a recurrent injury.

    METHODS: In a population-based study of 98,502 adult injury events 1999-2012, at the emergency department of Umeå University Hospital, Sweden, we compared non-recidivists with recidivists in terms of patients' sex, age, type of injury and severity of the injury.

    RESULTS: Thirty-six percent of all patients suffered recurrent injuries, which were associated with a higher proportion of inpatient care and more hospital days. Young men and elderly women were at the highest risk for trauma recidivism. At 20 to 24 years, men had a 2.4 (CI 95 % 2.3-2.5) higher risk than women, a 90 years old woman had almost a 10-fold higher risk for another moderate/severe injury than a 20 years old one. A fracture were associated with a hazard ratio of 1.28 (CI 95 % 1.15-1.42) among men younger than 65 years and 1.31 (CI 95 % 1.12-1.54) for men older than 65 years for a subsequent moderate/severe injury. For women younger than 65 years a fracture was associated with a hazard ratio of 1.44 (CI 95 % 1.28-1.62) for a subsequent moderate/severe injury. A sprain carries a higher risk for a new moderate/severe injury for both men and women and in both age groups; the hazard ratio was 1.13 (CI 95 % 1.00-1.26) for men younger than 65 years, 1.42 (CI 95 % 1.01-1.99) for men older than 65 years, 1.19 (CI 95 % 1.05-1.35) for women younger than 65 years and 1.26 (CI 95 % 1.02-1.56) for women older than 65 years. A higher degree of injury severity was associated with a higher risk for a new moderate/severe injury.

    CONCLUSION: Trauma recidivism is common and represents a large proportion of all injured. Age and sex are associated with the risk for new injury. Injury types and severity, also have implications for future injury.

  • 36.
    Stenvall, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lundström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Englund, Undis
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Borssén, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture.2007Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 18, nr 2, s. 167-175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture.

    METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged >or=70 years.

    RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 - 0.76, p=0.006] for the total sample and 0.07 (95% CI: 0.01-0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group.

    CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia.

  • 37.
    Stenvall, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lundström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Inpatient falls and injuries in older patients treated for femoral neck fracture.2006Ingår i: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 43, nr 3, s. 389-399Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A prospective inpatient study was performed at the Orthopedic and Geriatric Departments at the Umeå University Hospital, Sweden, to study inpatient falls, fall-related injuries, and risk factors for falls following femoral neck fracture surgery. Ninety-seven patients with femoral neck fracture aged 70 years or older were included, background characteristics, falls, injuries, and other postoperative complications were assessed and registered during the hospitalization. There were 60 postoperative falls among 26/97 patients (27%). The postoperative fall event rate was 16.3/1000 Days (95% CI 12.2-20.4). Thirty two percent of the falls resulted in injuries, 25% minor, and 7% serious ones. In multiple regression analyses, delirium after Day 7, HRR 4.62 (95% CI 1.24-16.37), male sex 3.92 (1.58-9.73), and sleeping disturbances 3.49 (1.24-9.86), were associated with inpatient falls. Forty-five percent of the patients were delirious the day they fell. Intervention programs, including prevention and treatment of delirium and sleeping disturbances, as well as better supervision of male patients, could be possible fall prevention strategies. Improvement of the quality of care and rehabilitation, with the focus on fall prevention based on these results, should be implemented in postoperative care of older people.

  • 38.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    The classic: Walldius, Börje: “Arthroplasty of the Knee Using an Endoprosthesis: 8 Years’ Experience”, Acta Orthopaedica Scandinavica, 1960; 30: 1, 137–1482010Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, nr 1, s. 21-33Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 39.
    Svensson, Olle
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Modin, Göran
    Akademiska sjukhuset, Uppsala.
    Rökstopp inför operation en patientsäkerhetsfråga2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 35, s. 2020-2021Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 40. Thor, Johan
    et al.
    Herrlin, Bo
    Wittlöv, Karin
    Skår, John
    Brommels, Mats
    Svensson, Olle
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Ortopedi.
    Getting going together: can clinical teams and managers collaborate to identify problems and initiate improvement?2004Ingår i: Q Manag Health Care, ISSN 1063-8628, Vol. 13, nr 2, s. 130-42Artikel i tidskrift (Refereegranskat)
  • 41.
    Unneby, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi. Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi. Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Femoral nerve block in a representative sample of elderly people with hip fracture: a randomised controlled trial2017Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 48, nr 7, s. 1542-1549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The number of elderly people with hip fracture and dementia is increasing, and many of these patients suffer from pain. Opioids are difficult to adjust and side effects are common, especially with increased age and among patients with dementia. Preoperative femoral nerve block is an alternative pain treatment. Aim: To investigate whether preoperative femoral nerve block reduced acute pain and opioid use after hip fracture among elderly patients, including those with dementia. Patients and methods: In this randomised controlled trial involving patients aged >= 70 years with hip fracture (trochanteric and cervical), including those with dementia, we compared femoral nerve block with conventional pain management, with opioid use if required. The primary outcome was preoperative pain, measured at five timepoints using a visual analogue scale (VAS). Preoperative opioid consumption was also registered. Results: The study sample comprised 266 patients admitted consecutively to the Orthopaedic Ward. The mean age was 84.1 (+/- 6.9) years, 64% of participants were women, 44% lived in residential care facilities, and 120 (45.1%) had dementia diagnoses. Patients receiving femoral nerve block had significantly lower self-rated pain scores from baseline to 12 h after admission than did controls. Self-rated and proxy VAS pain scores decreased significantly in these patients from baseline to 12 h compared with controls (p < 0.001 and p = 0.003, respectively). Patients receiving femoral nerve block required less opioids than did controls, overall (2.3 +/- 4.0 vs. 5.7 +/- 5.2 mg, p < 0.001) and in the subgroup with dementia (2.1 +/- 3.3 vs. 5.8 +/- 5.0 mg, p < 0.001). Conclusion: Patients with hip fracture, including those with dementia, who received femoral nerve block had lower pain scores and required less opioids before surgery compared with those receiving conventional pain management. Femoral nerve block seems to be a feasible pain treatment for elderly people, including those with dementia. 

  • 42.
    Wadsten, Mats Å
    et al.
    Department of Orthopaedic Surgery. Sundsvall Hospital.
    Sayed-Noor, Arkan S
    Department of Orthopaedic Surgery. Sundsvall Hospital.
    Sjödén, Göran O
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Buttazzoni, Gunnar G
    Department of Orthopaedic Surgery. Östersund Hospital.
    The Buttazzoni Classification of Distal Radial Fractures in Adults: interobserver and Intraobserver Reliability2009Ingår i: Hand, ISSN 1558-9447, Vol. 4, nr 3, s. 283-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite the fact that distal radial fracture is the commonest fracture, there is a little evidence-based knowledge about the value of its classification to guide management and predict prognosis. The available classification systems are either complicated or weakly applicable in clinical practice. Older's classification is the most reliable, but does not cover all radial fracture types. We evaluated the interobserver and intraobserver reliability of a new classification system which is a modification of Older's classification covering all radial fracture types. Two hundred and thirty-two consecutive adult patients with acute distal radial fractures were blindly evaluated according to the new classification by three orthopedic surgeons twice with 1-year interval. The interobserver reliability was measured using the Fleiss kappa coefficient, and the intraobserver reliability was measured using the Cohen's kappa coefficient. The new classification showed fair to substantial interobserver and intraobserver reliability, i.e., results comparable to the reliability of commonly used classification systems. The reliability was better for younger patients and when evaluation was carried out by hand-surgery-interested orthopedic surgeons. The new classification system is simple, covers all radial fracture types, and has an acceptable reliability. Further studies are needed to judge its ability to direct management and predict prognosis.

  • 43. Zheng, Hou-Feng
    et al.
    Forgetta, Vincenzo
    Hsu, Yi-Hsiang
    Estrada, Karol
    Rosello-Diez, Alberto
    Leo, Paul J.
    Dahia, Chitra L.
    Park-Min, Kyung Hyun
    Tobias, Jonathan H.
    Kooperberg, Charles
    Kleinman, Aaron
    Styrkarsdottir, Unnur
    Liu, Ching-Ti
    Uggla, Charlotta
    Evans, Daniel S.
    Nielson, Carrie M.
    Walter, Klaudia
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    McCarthy, Shane
    Eriksson, Joel
    Kwan, Tony
    Jhamai, Mila
    Trajanoska, Katerina
    Memari, Yasin
    Min, Josine
    Huang, Jie
    Danecek, Petr
    Wilmot, Beth
    Li, Rui
    Chou, Wen-Chi
    Mokry, Lauren E.
    Moayyeri, Alireza
    Claussnitzer, Melina
    Cheng, Chia-Ho
    Cheung, Warren
    Medina-Gomez, Carolina
    Ge, Bing
    Chen, Shu-Huang
    Choi, Kwangbom
    Oei, Ling
    Fraser, James
    Kraaij, Robert
    Hibbs, Matthew A.
    Gregson, Celia L.
    Paquette, Denis
    Hofman, Albert
    Wibom, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Tranah, Gregory J.
    Marshall, Mhairi
    Gardiner, Brooke B.
    Cremin, Katie
    Auer, Paul
    Hsu, Li
    Ring, Sue
    Tung, Joyce Y.
    Thorleifsson, Gudmar
    Enneman, Anke W.
    van Schoor, Natasja M.
    de Groot, Lisette C. P. G. M.
    van der Velde, Nathalie
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Kemp, John P.
    Christiansen, Claus
    Sayers, Adrian
    Zhou, Yanhua
    Calderari, Sophie
    van Rooij, Jeroen
    Carlson, Chris
    Peters, Ulrike
    Berlivet, Soizik
    Dostie, Josee
    Uitterlinden, Andre G.
    Williams, Stephen R.
    Farber, Charles
    Grinberg, Daniel
    LaCroix, Andrea Z.
    Haessler, Jeff
    Chasman, Daniel I.
    Giulianini, Franco
    Rose, Lynda M.
    Ridker, Paul M.
    Eisman, John A.
    Nguyen, Tuan V.
    Center, Jacqueline R.
    Nogues, Xavier
    Garcia-Giralt, Natalia
    Launer, Lenore L.
    Gudnason, Vilmunder
    Mellstrom, Dan
    Vandenput, Liesbeth
    Amin, Najaf
    van Duijn, Cornelia M.
    Karlsson, Magnus K.
    Ljunggren, Osten
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rousseau, Francois
    Giroux, Sylvie
    Bussiere, Johanne
    Arp, Pascal P.
    Koromani, Fjorda
    Prince, Richard L.
    Lewis, Joshua R.
    Langdahl, Bente L.
    Hermann, A. Pernille
    Jensen, Jens-Erik B.
    Kaptoge, Stephen
    Khaw, Kay-Tee
    Reeve, Jonathan
    Formosa, Melissa M.
    Xuereb-Anastasi, Angela
    Akesson, Kristina
    McGuigan, Fiona E.
    Garg, Gaurav
    Olmos, Jose M.
    Zarrabeitia, Maria T.
    Riancho, Jose A.
    Ralston, Stuart H.
    Alonso, Nerea
    Jiang, Xi
    Goltzman, David
    Pastinen, Tomi
    Grundberg, Elin
    Gauguier, Dominique
    Orwoll, Eric S.
    Karasik, David
    Davey-Smith, George
    Smith, Albert V.
    Siggeirsdottir, Kristin
    Harris, Tamara B.
    Zillikens, M. Carola
    van Meurs, Joyce B. J.
    Thorsteinsdottir, Unnur
    Maurano, Matthew T.
    Timpson, Nicholas J.
    Soranzo, Nicole
    Durbin, Richard
    Wilson, ScottG.
    Ntzani, Evangelia E.
    Brown, Matthew A.
    Stefansson, Kari
    Hinds, David A.
    Spector, Tim
    Cupples, L. Adrienne
    Ohlsson, Claes
    Greenwood, Celia M. T.
    Jackson, Rebecca D.
    Rowe, David W.
    Loomis, Cynthia A.
    Evans, David M.
    Ackert-Bicknell, Cheryl L.
    Joyner, Alexandra L.
    Duncan, Emma L.
    Kiel, Douglas P.
    Rivadeneira, Fernando
    Richards, J. Brent
    Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, nr 7571, s. 112-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

  • 44. Önnerfjord, Patrik
    et al.
    Khabut, Areej
    Reinholt, Finn P
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Heinegård, Dick
    Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups2012Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 23, s. 18913-18924Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human synovial joints display a characteristic anatomic distribution of arthritis, e.g. rheumatoid arthritis primarily affects the metacarpophalangeal and proximal finger joints, but rarely the distal finger joints, whereas osteoarthritis occurs in the distal and proximal finger joints. Pelvospondylitis has a selective localization to the spine and sacroiliac joints. Is this tropism due to differences between the cartilages at the molecular level? To substantiate this concept the present study provides a background detailed compositional analysis by relative quantification of extracellular matrix proteins in articular cartilages, meniscus, intervertebral disc, rib, and tracheal cartilages on samples from 5-6 different individuals using an optimized approach for proteomics. Tissue extraction followed by trypsin digestion and two-dimensional LC separations coupled to tandem mass spectrometry, relative quantification with isobaric labeling, iTRAQ (TM), was used to compare the relative abundance of about 150 proteins. There were clear differences in protein patterns between different kinds of cartilages. Matrilin-1 and epiphycan were specific for rib and trachea, whereas asporin was particularly abundant in the meniscus. Interestingly, lubricin was prominent in the intervertebral disc, especially in the nucleus pulposus. Fibromodulin and lumican showed distributions that were mirror images of one other. Analyses of the insoluble residues from guanidine extraction revealed that a fraction of several proteins remained unextracted, e.g. asporin, CILP, and COMP, indicating cross-linking. Distinct differences in protein patterns may relate to different tissue mechanical properties, and to the intriguing tropism in different patterns of joint pathology.

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