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Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures., Introduction: Patients with diabetes have an increased risk of femoral fractures, but little is known about the risk of atypical femoral fractures (AFFs). The aim of this study was to identify the risk of subtrochanteric and femoral shaft (ST/FS) fractures and estimate the risk of AFFs in patients with type 1 (T1D) and type 2 diabetes (T2D)., Methods: From the nationwide Danish National Patient Register, we identified patients with T1D (n = 19,896), T2D (n = 312,188), and sex- and aged-matched controls without diabetes (n = 996,252) from the general population and all ST/FS fractures (n = 7509). Data were analyzed using a Cox proportional-hazards model and the incidence rate and rate ratio of ST/FS fractures were estimated., Results: The incidence rate of ST/FS fractures in T1D was 52.14 events per 100,000 person years and 73.21 per 100,000 person years in T2D. T1D was associated with an increased risk of ST/FS (HR 2.07 (95% CI 1.68-2.56)), whereas T2D was not (HR 0.99 (95% CI 0.94-1.10)). Previous ST/FS fractures were associated with an increased risk of subsequent ST/FS fractures (HR 6.95 (95% CI 6.00-8.05)) and the use of bisphosphonates with an increased risk of ST/FS fractures (HR 1.72 (95% CI 1.54-1.91))., Conclusion: Patients with T1D have a higher risk of ST/FS fractures compared with sex- and age-matched controls. Since a proportion of ST/FS fractures are classified as AFFs, this could point towards the fact that AFFs also are increased in patients with T1D, but not T2D.

This study evaluated the 2-year persistence with teriparatide in the Netherlands. Analyses showed that the risk of non-persistence was 28% lower in patients who were followed according to an additional educational and motivational support program., Introduction: Until recently, teriparatide (TPTD) was a third-line treatment option for severe osteoporosis in the Netherlands, which could only be prescribed by medical specialists based on a specific medical statement. We aimed to determine whether an educational and motivational support program (EMSP) increased 2-year treatment persistence with TPTD in patients with severe osteoporosis., Methods: We evaluated persistence in 1573 Dutch patients treated with TPTD from January 2013 until January 2018. From January 2013 onwards, all patients received a basic support program (BSP) consisting of an educational home visit to initiate TPTD treatment and phone calls (at 1, 2.5 and 8 weeks). Since May 2015, all patients received the EMSP consisting of the BSP extended with evaluation of medication adherence during phone calls, an additional phone call (at 12 months), and motivational letters at 9 and 14 months., Results: The EMSP showed a statistically significantly higher 2-year persistence (78%) with TPTD as compared with the BSP (72%). Reasons for treatment discontinuation were comparable between groups, except for the proportion of patients who had stopped TPTD administration due to side effects, which was significantly lower in the EMSP group (8% vs. 15% in BSP, p < 0.001). Overall, the risk of non-persistence was 28% lower in the EMSP compared with the BSP group (HR: 0.72; 95% CI: 0.55-0.93)., Conclusion: The introduction of the EMSP has demonstrated to improve the persistence with TPTD, resulting in 78% of the patients being persistent with TPTD during the 2-year treatment period.

Introduction: Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs (AOD)., Methods: We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py)., Results: In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 2.3 to 169.7 per 10,000py), followed by a plateau and a 12% decrease in the last three years. In men, a less steep increase from 1990 to 2007 (from 1.4 to 45.3 per 10,000py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85-89years (248.9 per 10,000py in women and 119.3 in men). There were marked differences between ethnic groups and regions. Bisphosphonates were the most frequently prescribed AODs: etidronate till 2000, and then subsequently alendronate., Conclusion: We have demonstrated marked secular changes in rates of anti-osteoporosis drug prescription over the last two decades. The plateau (and decrease amongst women) in rates in recent years, set against an ever ageing population, is worrying, suggesting that the well-documented care gap in osteoporosis treatment persists. The differences in prescription rates by geographic location and ethnicity raise intriguing questions in relation to underlying fracture rates, provision of care and health behaviour., Summary: We studied the prescription incidence of anti-osteoporosis drugs (AOD) from 1990 to 2012 in the UK CPRD. Overall AOD prescription incidence showed a strong increase from 1990 to 2006, followed by a plateau in both sexes and a decrease amongst women in the last three years., Competing Interests: R.Y. van der Velde, C. E. Wyers, E. Teesselink, P. P. M. M. Geusens, J. P. W van den Bergh, F. de Vries, C. Cooper, N. C. Harvey, T. P. van Staa report no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: The probability of initiating with anti-osteoporosis therapy increased from 7 % in 2000 to 46 % in 2010. This improvement was greater for patients over the age of 75 years. Men, those overweight, having dementia or exposed to antipsychotics, sedatives/hypnotics or opioid analgesics were significantly less likely to receive anti-osteoporosis drugs., Introduction: The objective of this study was to examine trends and determinants of anti-osteoporosis drug prescribing after hip fracture in the UK between 2000 and 2010., Methods: Data were extracted from the UK Clinical Practice Research Datalink for patients ≥50 years who had a first hip fracture between 2000 and 2010 and who did not currently (≤6 months prior) receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid hormone, calcitonin and raloxifene) (n = 27,542). The cumulative incidence probability of being prescribed anti-osteoporosis drugs within 1 year after hip fracture was estimated by Kaplan-Meier life-table analyses. Determinants for treatment initiation were estimated by Cox proportional hazards models., Results: The probability of being prescribed any anti-osteoporosis drug after hip fracture increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in patients ≥75 years. The increase in prescribing of anti-osteoporosis drugs was complemented by a similar increase in vitamin D/calcium provision. Cumulative incidence of receiving anti-osteoporosis therapy was greater at any given point in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 % in 2010). In addition to male gender, multivariable Cox regression identified reduced likelihood of receiving anti-osteoporosis drugs for those being overweight, having dementia and exposed to psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics., Conclusion: Although the prescribing of anti-osteoporosis drugs after hip fracture has increased substantially since 2000, the overall rate remained inadequate, particularly in men. With the continuing increase in the absolute number of hip fractures, further research should be made into the barriers to optimise osteoporosis management.

Unlabelled: Long-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., Introduction: The 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., Methods: A 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., Results: Persistence 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., Conclusions: This 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.

Unlabelled: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low., Introduction: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline., Methods: This randomised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D)., Results: The group assigned to the intervention was slightly younger than the control group (68.7 ± 15.4 vs. 65.9 ± 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients ≥70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered., Conclusion: This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population, but there was an increase in men and the elderly. However, the proportion of GIOP-treated patients remained low.

Background: Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling., Objective: To evaluate the risk of fracture in incident MS patients drawn from a dedicated MS registry compared with population-based controls., Methods: We conducted a population-based cohort study (1996-2007) utilising the Danish National Health Registers that were linked to the Danish MS Registry and the Danish MS Treatment Registry. Incident MS patients (2963 cases) were 1:6 matched by year of birth, gender, calendar time and region to persons without MS (controls). Cox proportional hazards models and logistic regression were used to estimate the risk of fracture in MS. Time-dependent adjustments were made for age, history of diseases and drug use., Results: Compared with controls, patients with MS had no overall increased risk of fracture (adjusted hazard ratio (adj. HR): 1.0, 95% CI: 0.9-1.2). However, the risk of femur/hip fracture (adj. HR: 1.9, 95% CI: 1.1-3.4) was significantly increased compared to controls. As compared with unexposed patients, MS patients who had been exposed to a short course of methylprednisolone in the prior year had no significantly increased risk of osteoporotic fracture (adj. HR: 1.2, 95% CI: 0.5-2.9). Disabled MS patients with Expanded Disability Status Scale [EDSS] scores between 6 and 10, had a 2.6-fold increased risk of osteoporotic fracture (adjusted odds ratio (adj. OR): 2.6, 95% CI: 1.0-6.6) compared to patients with an EDSS score between 0 and 3., Conclusion: Patients with MS had a higher risk of femur/hip fracture than controls. Disability status is probably more important than glucocorticoid use in the aetiology of MS and osteoporotic fracture.

Objective: To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs)., Methods: The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of "current" and "no exposure." The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation., Results: Patients who intermittently received high-dose GCs (daily dose > or =15 mg) and had no or little previous exposure to GCs (cumulative exposure < or =1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose > or =30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49-6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08)., Conclusion: Intermittent use of high-dose oral GCs (daily dose > or =15 mg and cumulative exposure < or =1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high-dose GCs (daily dose > or =15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

The use of inhaled corticosteroids has been associated with a dose-related increased risk of fracture. This may be related to systemic absorption. However, several studies have found that patients with more severe reductions in pulmonary function had reduced bone mineral density, independent of inhaled corticosteroids. The objective of this study was to evaluate the relationship between disease severity and fracture risk. A large case-control study (108,754 cases) was conducted using data from the UK General Practice Research Database. It was found that higher doses of inhaled corticosteroids were associated with greater risks of fracture. The crude odds ratio of fracture among patients exposed to >1,600 microg beclomethasone equivalents per day was 1.95 (95% confidence interval (CI) 1.68-2.27). When adjustments were made for disease severity and use of bronchodilators, the initial dose-response relationship between inhaled corticosteroids and fracture risk disappeared (adjusted odds ratio of 1.19 (95% CI 1.01-1.41)). In conclusion, patients with severe obstructive airway disease are at risk of fracture. However, adequate adjustment for disease severity is essential when the association between the use of inhaled corticosteroids and risk of osteoporotic fracture is studied in observational research.

Summary: Chronic kidney disease (CKD) is a risk factor for fractures. However, in hip fracture patients, CKD G3-G5 was associated with a higher mortality risk and not associated with a higher risk of subsequent non-hip fractures compared to eGFR > 60 ml/min. The higher mortality risk may, as competing risk, explain our findings. Introduction: Chronic kidney disease (CKD) is a known risk factor for fragility fractures. Patients aged 50+ with a recent fragility fracture have an increased risk of subsequent fractures. Our aim was to evaluate the association between CKD stages G3–G5 versus estimated glomerular filtration rate (eGFR) > 60 ml/min and the risk of a new non-hip fracture or fragility fracture in patients with a first hip fracture. Methods: Population-based cohort study using the UK general practices in the Clinical Practice Research Datalink. Associations between CKD stage and first subsequent fracture were determined using Cox proportional hazard analyses to estimate hazard ratios (HRs). To explore the potential competing risk of mortality, cause-specific (cs) HRs for mortality were estimated. Results: CKD G3–G5 was associated with a lower risk of any subsequent non-hip fracture (HR: 0.90, 95%CI: 0.83–0.97), but not with the risk of subsequent major non-hip fragility fracture. CKD G3-G5 was associated with a higher mortality risk (cs-HR: 1.05, 95%CI: 1.01–1.09). Mortality risk was 1.5- to 3-fold higher in patients with CKD G4 (cs-HR: 1.50, 95%CI: 1.38–1.62) and G5 (cs-HR: 2.93, 95%CI: 2.48–3.46) compared to eGFR > 60 ml/min. Conclusions: The risk of a subsequent major non-hip fragility fractures following hip fracture was not increased in patients with CKD G3–G5 compared to eGFR > 60 ml/min. Mortality risk was higher in both hip fracture and non-hip fracture patients with CKD G4 and G5. The higher mortality risk may, as competing risk, explain our main finding of no increased or even decreased subsequent fracture risk after a hip fracture in patients with CKD G3–G5. [ABSTRACT FROM AUTHOR]