Dataset Information

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

ABSTRACT: We investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.

Purpose

To investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index.

Methods

Norwegian women aged 50-89 in 2005-2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis.

Results

Of 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91-0.99) for bisphosphonate use and 0.60 (95% CI: 0.47-0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29-0.61) compared with the unexposed population.

Conclusions

In population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

SUBMITTER: Riska BSL

PROVIDER: S-EPMC10382386 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Riska Brit Solvor Lyse BSL Gunnes Nina N Stigum Hein H Finnes Trine E TE Meyer Haakon E HE Omsland Tone K TK Holvik Kristin K

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20230427 8

We investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.<h4>Purpose</h4>To investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for ...[more]

PMID: 37100950

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Project description:The knowledge about why hip fracture rates in Norway have declined is sparse. Concurrent with decreasing hip fracture rates, the rates of total hip replacements (THRs) have increased. We wanted to investigate if hip fracture rates continued to decline, and whether the increase in THRs had any influence on this decline, assuming that living with a hip prosthesis precludes fracture of the operated hip. Information on hip fractures in Norway 1999-2019 was available from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database and population size were available in official population tables from Statistics Norway. Primary THRs (for any cause except hip fracture) 1989-2019 were obtained from the Norwegian Arthroplasty Register. We calculated the annual age-standardized incidence rates of hip fracture by sex for the period 1999-2019. The hip fracture rates in a scenario with no hip prostheses were calculated by subtracting 0.5 persons from the population at risk for each prevalent hip prosthesis, considering that each person has two hips at risk of fracture. We estimated how much of the decline could be attributed to the increased prevalence of hip prostheses. From 1999 to 2019, age-standardized incidence rates of hip fracture decreased by 27% in women and 20% in men. The rates remained stable in those under 70 years and decreased in those 70 years and above. Excluding replaced hips from the population at risk led to higher incidence rates, and this impact was considerably larger at higher ages. The increased prevalence of hip prostheses over the period accounted for approximately 18% (20% in women and 11% in men) of the observed decline in hip fracture rates. In conclusion, the incidence of hip fractures continued to decline, and the increasing number of people living with hip prostheses contributed significantly to the observed declining time trends. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:Norway is an elongated country with large variations in climate and duration of winter season. It is also a high-risk country for osteoporotic fractures, in particular hip fractures, which cause high mortality. Although most hip fractures occur indoors, there is a higher incidence of both forearm and hip fractures during wintertime, compared with summertime. In a nationwide longitudinal cohort study, we investigated whether cold ambient (outdoor) temperatures could be an underlying cause of this high incidence and mortality. Hospitalized/outpatient forearm fractures (International Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code S52) and hospitalized hip fractures (ICD-10 codes S72.0-S72.2) from 2008 to 2018 were retrieved from the Norwegian Patient Registry. Average monthly ambient temperatures (degrees Celsius, °C) from the years 2008 to 2018 were provided by the Norwegian Meteorological Institute and linked to the residential area of each inhabitant. Poisson models were fitted to estimate the association (incidence rate ratios [IRRs], 95% confidence intervals [CIs]) between temperature and monthly incidence of total number of forearm and hip fractures. Flexible parametric survival models (hazard ratios [HR], 95% CI) were used to estimate the association between temperature and post-hip fracture mortality, taking the population mortality into account. Monthly temperature ranged from -20.2°C to 22.0°C, with a median of -2.0°C in winter and 14.4°C in summer. At low temperatures (<0°C) compared to ≥0°C, there was a 53% higher risk of forearm fracture (95% CI, 51%-55%) and 21% higher risk of hip fracture (95% CI, 19%-22%), adjusting for age, gender, calendar year, urbanization, residential region, elevation, and coastal proximity. When taking the population mortality into account, the post-hip fracture mortality in both men (HR 1.08; 95% CI, 1.02-1.13) and women (HR 1.09; 95% CI, 1.04-1.14) was still higher at cold temperatures. There was a higher risk of forearm and hip fractures, and an excess post-hip fracture mortality at cold ambient temperatures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:Fall prevention programs have shown inconclusive results concerning hip fracture reduction. We found that fallers with poor health, low societal participation, and use of psychotropics/painkillers had a threefold to fivefold increased hip fracture risk compared to non-fallers without these risk factors. This may help target fall prevention towards high-risk individuals.IntroductionTo investigate whether self-reported information on health, societal participation, and drug use in older people, easily obtainable by health care providers, contribute to predict future hip fracture beyond self-reported falls.MethodsWe used data from 3801 women and 6439 men aged 70-79 years participating in population-based studies in five counties in Norway 2000-2003. Height and weight were measured. Socioeconomic status, lifestyle, health status, and history of falling were self-reported through questionnaires. Falls last year were dichotomized into one or more versus no falls. Hip fractures were identified by linkage to hospital data with follow-up through 2013. Hazard ratios (HR) with 95% confidence intervals (95% CI) for hip fracture by combinations of risk factors with history of falling were estimated using Cox proportional hazards regression.ResultsMore women (32.4%) than men (27.7%) reported one or more falls during the previous year, and 17.9% of women (n = 682) and 8.9% of men (n = 572) suffered a hip fracture during median 11.6 years of follow-up. Poor health, low societal participation, and use of psychotropics/analgesics among fallers were strong predictors of hip fracture. The presence of all three risk factors and history of falling was associated with HR 2.92 (95% CI 2.10-4.05) for hip fracture in women and HR 4.60 (95% CI 2.71-7.81) in men compared to non-fallers without these factors.ConclusionOur study indicates that self-assessment of health, information about activities outside home, and drug use among fallers far better identify high risk of hip fracture in older people than information about falls alone.

Project description:BackgroundHip fractures are a common and serious consequence of osteoporosis, and hip fracture patients are at high risk for recurrence. Appropriate pharmacotherapy reduces this risk and is associated with reduced mortality after hip fracture, but a care gap exists for fracture prevention in these patients. This evaluation determined rates of osteoporosis treatment and bone mineral density (BMD) testing in hip fracture patients following discharge from a rehabilitation unit.MethodsA prospective cohort study of hip fracture patients aged ? 50 on an inpatient rehabilitation unit in 2008 and 2011. Patients were seen by a nurse specialist, and encouraged to see their family physician for further assessment and treatment. Physicians were sent a letter indicating the need to follow up with their patient. Patients were contacted following discharge from hospital to determine treatment rates.ResultsOf 310 eligible hip fracture patients admitted to the rehabilitation unit in the years studied, 207 patients were reached post-discharge and provided data. Of patients who were not previously taking osteoporosis medication, 59% of patients from the 2008 cohort, and 42% of patients from the 2011 cohort had osteoporosis treatment initiated by six months following discharge. By 2 months following discharge, 46% of patients in the 2008 cohort had a new BMD performed or scheduled, while this was true for 14% of patients from the 2011 cohort. 35% of patients in 2011 had not seen their family physician by 2 months following discharge.ConclusionsRates for osteoporosis treatment and BMD testing were higher than those reported in the literature for patients not enrolled in case manager programs. BMD testing declined from 2008 to 2011. Lower treatment rates may be due to concerns regarding reports of possible association between bisphosphonate use and atypical fractures. Improving rates of patient follow-up with family physicians will be important for increasing hip fracture treatment rates after discharge.

Project description:UnlabelledLong-term persistence with anti-osteoporosis drugs and determinants for discontinuation among fracture patients were examined. Persistence was 75.0 and 45.3 % after 1 and 5 years, respectively. Those aged ≥80 years were at increased risk of early discontinuation. Within 1 year after discontinuation, 24.3 % restarted therapy, yet 47.0 % persisted for 1 year.IntroductionThe risk of osteoporotic fracture can effectively be reduced with use of anti-osteoporosis drugs. However, little is known about persistence with these drugs after fracture where subsequent fracture risk is high. The aims were to determine long-term persistence with anti-osteoporosis drugs among fracture patients, including its determinants, and to describe restart and subsequent persistence.MethodsA cohort study was conducted within the Dutch PHARMO Database Network. Patients aged ≥50 years (n = 961) who received anti-osteoporosis drugs within 1 year after fracture, but not in the preceding year, were included (2002-2011). Persistence (defined as the proportion on treatment) and the proportion restarting after discontinuation were estimated using Kaplan-Meier analyses. Time-dependent Cox regression was used to identify determinants of non-persistence including age, sex, initial dosage regime, fracture type, comorbidities, and drug use.ResultsPersistence with anti-osteoporosis drugs was 75.0 % (95 % confidence interval (CI) 72.0-77.7) and 45.3 % (95 % CI 40.4-50.0) after 1 and 5 years, respectively. A significant determinant of non-persistence was age ≥80 years (reference 50-59 years: adjusted hazard ratio [adj. HR] 1.65; 95 % CI 1.15-2.38). This effect was not constant over time (≤360 days following initiation: adj. HR 2.07; 95 % CI 1.27-3.37; >360 days: adj. HR 1.08; 95 % CI 0.62-1.88). Within 1 year after discontinuation, 24.3 % (95 % CI 20.1-29.2) restarted therapy, yet 47.0 % persisted for 1 year.ConclusionsThis study identified suboptimal persistence with anti-osteoporosis drugs among fracture patients. Major target groups for measures aimed to improve persistence may be those aged >80 years and those restarting therapy.

Project description:Importance:Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown. Objective:To estimate hip fracture risk associated with concurrent exposure to multiple FADs. Design, Setting, and Participants:This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019. Exposure:Receipt of prescription FADs. Main Outcomes and Measures:Hip fracture hospitalization. Results:A total of 11.3 million person-years were observed, reflecting 2 646 255 individuals (mean [SD] age, 77.2 [7.3] years, 1 615 613 [61.1%] women, 2 136 585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2 827 284 person-years (25.1%) involved receipt of 1 FAD; 1 322 296 (11.7%), 2 FADs; and 954 506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P < .001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P < .001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P < .001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P < .001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P < .001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P < .001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P < .001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P < .001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P < .001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P < .001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P < .001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P < .001). Conclusions and Relevance:Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.

Dataset Information

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Purpose

Methods

Results

Conclusions

Publications

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

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