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Although oral bisphosphonates are highly effective in preventing fractures, some patients will still suffer a fracture while on treatment. In fact, it is important to explain to the patient that any anti-fracture treatment is indeed capable of reducing, but not aborting the risk for fractures. The following study from Spain quantified the remaining risk of fracture while on bisphosphonate therapy [1].


The SIDIAP database was searched to identify new users of oral bisphosphonates in 2006–2007. SIDIAP includes pharmacy invoice data and primary-care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were: Paget disease, < 40 years of age, and any anti-osteoporosis treatment in the previous year. [i]A priori[/i] defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, pre-existing co-morbidities, and medications. Fractures were considered if they appeared after at least 6 months after treatment initiation. Fractures while on treatment were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥ 80%). Only 7449/21,385 (34.8%) participants completed > 6 months of therapy. Incidence of ‘fracture while on treatment’ was 3.4/100 person-years (95% confidence interval (CI) 3.1–3.7). Predictors of these among patients persisting and adhering to treatment included: older age (sub-hazard ratio (SHR) for 60 to < 80 years 2.18; 95% CI 1.70–2.80; for ≥ 80 years, SHR 2.5; 95% CI 1.82–3.43), previous fracture (SHR 1.75; 95% CI 1.39–2.20 and SHR 2.49; 95% CI 1.98–3.13 in the last 6 months and longer, respectively), underweight (SHR 2.11; 95% CI 1.14–3.92), inflammatory arthritis (SHR 1.46; 95% CI 1.02–2.10), use of proton pump inhibitors (SHR 1.22; 95% CI 1.02–1.46), and vitamin D deficiency (SHR 2.69; 95% CI 1.27–5.72). Thus, even among high compliers, 3.4% of oral bisphosphonate users will fracture every year. Older age, underweight, vitamin D deficiency, proton pump inhibitor use, previous fracture and inflammatory arthritides are associated with increased fracture risk.


  • Amos Pines
    Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


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