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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.

Author(s)

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

Citations

  1. Prieto-Alhambra D, Pagès-Castellà A, Wallace G, et al. Predictors of fracture while on treatment with oral bisphosphonates: A population-based cohort study. J Bone Miner Res 2013 Jun 12. Epub ahead of print
    http://www.ncbi.nlm.nih.gov/pubmed/23761350
  2. Liberman UA, Weiss SR, Bröll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 1995;333:1437-43.
    http://www.ncbi.nlm.nih.gov/pubmed/7477143
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  8. Olsen KR, Hansen C, Abrahamsen B. Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs-an analysis using national health databases. Osteoporos Int 2013 Apr 20. Epub ahead of print.
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  9. Lee YK, Ha YC, Choi HJ, et al. Bisphosphonate use and subsequent hip fracture in South Korea. Osteoporos Int 2013 May 17.
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  10. Migliore A, Broccoli S, Massafra U, Cassol M, Frediani B. Ranking antireabsorptive agents to prevent vertebral fractures in postmenopausal osteoporosis by mixed treatment comparison meta-analysis. Eur Rev Med Pharmacol Sci 2013;17:658-67.
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