Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates: A Binational Population-Based Cohort Study

Abstract

Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two or more fractures while on treatment (!2 FWOT) among users with high adherence. Fractures were considered from 6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informacio per al Desenvolupament de l'Investigacio en Atencio Primaria (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backwardstepwise selection (p-entry 0.049; p-exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of !2 FWOT among patients having persisted with treatment !6 months with overall medication possession ratio (MPR) !80%. Incidence of !2 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of !2 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR) ¼ 2.28 (95% CI, 1.11 to 4.68) and SHR ¼ 2.61 (95% CI, 0.98 to 6.95), respectively, for 65 to <80 years; and SHR ¼ 3.19 (95% CI, 1.33 to 7.69) and SHR ¼ 4.88 (95% CI, 1.74 to 13.7), respectively, for !80 years. Further significant predictors of !2 FWOT identified within only one cohort were dementia, SHR ¼ 4.46 (95% CI, 1.02 to 19.4) (SIDIAP); and history of recent or older fracture, SHR ¼ 3.40 (95% CI, 1.50 to 7.68) and SHR ¼ 2.08 (95% CI: 1.04-4.15), respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain multiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent/old fracture and dementia within one but not both populations. Additional and/or alternative strategies should be investigated for these patients.

Comparison of Osteoporosis Pharmacotherapy Fracture Rates: Analysis of a MarketScan® Claims Database Cohort

“…It is worth keeping in mind that most studies evaluating risk factors looked at general populations, whereas our cohort included only patients currently being treated for osteoporosis. Similar results have also been found by studies that have identified risk factors for treatment failure while on an osteoporosis medication ( 17 , 18 ). Given the significant magnitude of risk found in this study and other for patients who have had a recent fall or fracture, it may be worth considering more intensive therapy for these patients, including possibly using multiple agents when initiating therapy.…”

Anti-Osteoporosis Medication Prescriptions and Incidence of Subsequent Fracture Among Primary Hip Fracture Patients in England and Wales: An Interrupted Time-Series Analysis

“…Using routinely collected data with no individual validation of fracture events is another limitation; however, validation of hip and vertebral fracture coding has been carried out previously and has been shown to be accurate. (31) Our definition of second hip fracture is based on previous work (32) and incorporates a 6-month washout from the index fracture to minimize the inclusion of recoding events, although such occurrences cannot be ruled out.…”

Dried plum diet protects from bone loss caused by ionizing radiation

“…Extensive research focuses on both understanding the fundamental underlying mechanisms and finding suitable treatments for such patients. However, major health concerns remain, such as secondary drug effects, osteonecrosis of the jaw and atypical femoral fractures 18 19 20 21 , motivating continued search for osteoprotective treatments against bone loss.…”