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  • 1.
    Bergman, Jonathan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. School of Sport Sciences, UiT Arctic University of Norway, Postboks 1621, 9509, Alta, Norway..
    Hommel, A.
    Department of Care Sciences, Malmö University, 20506, Malmö, Sweden..
    Kivipelto, M.
    Division of Clinical geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Plan 7, 14183, Huddinge, Sweden. Research and Development Unit, Stockholm Sjukhem, Mariebergsgatan 22, 11219, Stockholm, Sweden..
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Bisphosphonates and mortality: confounding in observational studies?2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, no 10, p. 1973-1982Article in journal (Refereed)
    Abstract [en]

    Summary: Numerous observational studies suggest that bisphosphonates reduce mortality. This study showed that bisphosphonate use is associated with lower mortality within days of treatment, although the association was not significant until the second week. Such an early association is consistent with confounding, although an early treatment effect cannot be ruled out.

    Introduction: The purpose of this study was to examine whether confounding explains why numerous observational studies show that bisphosphonate use is associated with lower mortality. To this end, we examined how soon after treatment initiation a lower mortality rate can be observed. We hypothesized that, due to confounding, the association would be observed immediately.

    Methods: This was a retrospective cohort study of hip fracture patients discharged from Swedish hospitals between 1 July 2006 and 31 December 2015. The data covered 260,574 hip fracture patients and were obtained from the Swedish Hip Fracture Register and national registers. Of the 260,574 patients, 49,765 met all eligibility criteria and 10,178 were pair matched (bisphosphonate users to controls) using time-dependent propensity scores. The matching variables were age, sex, diagnoses, prescription medications, type of hip fracture, type of surgical procedure, known or suspected dementia, and physical functioning status.

    Results: Over a median follow-up of 2.8 years, 2922 of the 10,178 matched patients died. The mortality rate was 7.9 deaths per 100 person-years in bisphosphonate users and 9.4 deaths in controls, which corresponded to a 15% lower mortality rate in bisphosphonate users (hazard ratio 0.85, 95% confidence interval 0.79–0.91). The risk of death was lower in bisphosphonate users from day 6 of treatment, although the association was not significant until the second week.

    Conclusion: Bisphosphonate use was associated with lower mortality within days of treatment initiation. This finding is consistent with confounding, although an early treatment effect cannot be ruled out.

  • 2.
    Bergman, Jonathan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Alendronate use and the risk of nonvertebral fracture during glucocorticoid therapy: a retrospective cohort study2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 306-313Article in journal (Refereed)
    Abstract [en]

    Context: Glucocorticoids increase the risk of nonvertebral fracture, but no clinical trial has shown that nonvertebral fractures can be prevented by co-administration of an anti-osteoporotic drug.

    Objective: To estimate the effect of alendronate on the risk of nonvertebral fracture in older adults taking oral glucocorticoids.

    Design: Retrospective cohort study using national Swedish registers.

    Setting: Hospitalized care and ambulatory specialist care.

    Patients: Among adults aged 50 years or older (N=3,347,959), we identified those who initiated oral glucocorticoid therapy from 2006 through 2011 (≥2.5 mg/day of prednisone or equivalent for ≥91 days). The final analysis included 16,890 alendronate users and 16,890 nonusers, who were matched using time-dependent propensity scores.

    Main Outcome Measure: Nonvertebral fracture. This was not pre-specified.

    Results: Over a median follow-up of 14.5 months, the incidence rate of nonvertebral fracture was 2.0 cases per 100 person-years in alendronate users and 2.4 cases in nonusers. This difference corresponded to a 16% lower rate in users (hazard ratio 0.84, 95% confidence interval 0.75 to 0.94). For hip fractures specifically, the rate was 34% lower in alendronate users relative to nonusers (hazard ratio 0.66, 95% confidence interval 0.55 to 0.78). The association of alendronate use with a lower risk of nonvertebral fracture was strongest in patients who received high doses of glucocorticoid.

    Conclusion: Alendronate use was associated with a lower risk of nonvertebral fracture, including hip fracture. Similar, but not statistically significant, associations have been reported in meta-analyses of clinical trials.

  • 3.
    Bergman, Jonathan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Bisphosphonate use after clinical fracture and risk of new fracture2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 4, p. 937-945Article in journal (Refereed)
    Abstract [en]

    Summary: Among older adults with a previous fracture, treatment for osteoporosis was initially associated with a higher risk of new fracture. However, the relative risk of new fracture decreased over time, a trend that is consistent with a beneficial effect, as treatment for osteoporosis is prescribed to reduce high fracture risks.

    Introduction: The purpose of this study was to examine whether bisphosphonate use is associated with a lower risk of new fracture after a clinical fracture in older adults.

    Methods: Data were available for 3,329,400 adults in Sweden who were aged ae<yen> 50 years between 2006 and 2011. During this period, 260,353 sustained a clinical fracture and were naïve to bisphosphonates at the time. Those who subsequently received a bisphosphonate were matched to up to three others on sex, year of birth, and type and year of initial fracture. The final cohort comprised 83,104 adults (26.3% bisphosphonate users).

    Results: During the period from initial fracture to initiation of bisphosphonate treatment, the incidence rate of any new clinical fracture was higher in those who later became bisphosphonate users than in those who remained nonusers (175.1 vs. 75.9 per 1000 person-years; hazard ratio 2.30, 95% confidence interval 2.19 to 2.41). Similarly, during the first 6 months of treatment, the incidence rate was higher in bisphosphonate users than in nonusers (128.8 vs. 90.2 per 1000 person-years; hazard ratio 1.41, 95% confidence interval 1.32 to 1.51). However, this difference decreased over time: by months 12 to 18, the incidence rate was similar in users and nonusers (59.3 vs. 55.3 per 1000 person-years; hazard ratio 1.03, 95% confidence interval 0.91 to 1.16).

    Conclusions: There was a decrease in the relative risk of new fracture during bisphosphonate treatment, a trend that is consistent with a beneficial treatment effect, as bisphosphonates are prescribed to reduce high fracture risks.

  • 4.
    Bergman, Jonathan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. School of Sport Sciences, UiT Arctic University of Norway, Postboks 1621, 9509, Alta, Norway.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Epidemiology of osteonecrosis among older adults in Sweden2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, no 5, p. 965-973Article in journal (Refereed)
    Abstract [en]

    Summary: This study estimated the incidence of osteonecrosis in a Swedish, nationwide cohort of older adults. Osteonecrosis was approximately 10 times more common than in previous studies. The strongest risk factors were dialysis, hip fracture, osteomyelitis, and organ transplantation, but only hip fractures could have contributed substantially to the disease burden.

    Introduction: The aim of this study was to estimate the incidence of osteonecrosis in a Swedish, nationwide cohort of older adults and in a large number of risk groups in that cohort.

    Methods: In this retrospective cohort study, we included everyone who was aged 50 years or older and who was living in Sweden on 31 December 2005. We used Swedish national databases to collect data about prescription medication use, diagnosed medical conditions, and performed medical and surgical procedures. The study outcome was diagnosis of primary or secondary osteonecrosis at any skeletal site. The strength of risk factors was assessed using age- and sex-standardized incidence ratios (SIRs).

    Results: The study cohort comprised 3,338,463 adults. The 10-year risk of osteonecrosis was 0.4% (n = 13,425), and the incidence rate was 4.7 cases/10000 person-years (95% confidence interval [CI], 4.6 to 4.7 cases). The strongest risk factors for osteonecrosis were hip fracture (SIR, 7.98; 95% CI, 7.69–8.27), solid organ transplantation (SIR, 7.14; 95% CI, 5.59–8.99), dialysis (SIR, 6.65; 95% CI, 5.62–7.81), and osteomyelitis (SIR, 6.43; 95% CI, 5.70–7.23). A history of hip fracture was present in 21.7% of cases of osteonecrosis, but osteomyelitis, dialysis, and solid organ transplantation were present in only 0.5 to 2% of cases.

    Conclusions: Osteonecrosis was approximately 10 times more common than a small number of previous population-based studies have suggested. The strongest risk factors for osteonecrosis were dialysis, hip fracture, osteomyelitis, and solid organ transplantation, but only hip fractures could have contributed substantially to the disease burden.

  • 5.
    Bergman, Jonathan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. School of Sport Sciences, Arctic University of Norway, Tromsø, Norway.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Overestimation of the Limitations of Randomized Controlled Trials2019In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681Article in journal (Refereed)
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