Comparing Effectiveness of Osteoporosis Drugs on Risk of Fracture in 2 Countries

Researchers aimed to compare the clinical effectiveness of oral anti-osteoporosis drugs based on the observed risk of fracture while receiving treatment through primary care in the United Kingdom and Spain.

Data for the study came from 2 primary care records databases covering patients in the National Health Service (Clinical Practice Research Datalink, CPRD) in the United Kingdom and Catalan healthcare (Information System for Research in Primary Care, SIDIAP) in Spain during 1995-2014 and 2006-2014, respectively. A total of 163,950 United Kingdom and 145,236 Catalan patients were identified.

The retrospective study included these drugs:

• Bisphosphonates, which inhibit osteoclastic bone resorption and appear to promote survival of osteocytes and osteoblasts.
• Strontium ranelate (SR), which inhibits osteoclasts, which decreases bone resorption, while stimulating the formation of new bone tissue.
• Selective estrogen receptor modulators (SERMs), which bind to estrogen receptors and inhibit bone resorption, decreasing bone turnover as assessed by biochemical markers.

The oral bisphosphonates included in this study were risedronate and ibandronate, as these are the most commonly prescribed in both countries. Among SERMs, raloxifene was the most widely prescribed drug in both datasets, but bazedoxifene users were also identified and included in SIDIAP.

Treatment-naïve incident users of anti-osteoporosis drugs were included and followed until treatment cessation, switching, death, transfer out, or study completion. The authors considered hip fracture while on treatment as the main outcome and major osteoporotic fractures (hip, clinical spine, wrist, and proximal humerus) as the secondary outcome.

Users of alendronate made up the reference group and were compared with those on oral bisphosphonates, SR, and SERMs.

Hip (sub-hazard ratio [SHR] [95% CI] 1.04 [0.77—1.40]) and major osteoporotic (SHR [95% CI] 1 [0.78–1.27]) fracture risks were similar among oral bisphosphonates compared with alendronate users. Both hip (SHR [95% CI] 1.26 [1.14–1.39]) and major osteoporotic (SHR [95% CI] 1.06 [1.02–1.12]) fracture risk were higher in SR compared with alendronate users. SERM users had a reduced hip (SHR [95% CI] 0.75 [0.60–0.94]) and major osteoporotic (SHR [95% CI] 0.77 [0.72–0.83]) fracture risk compared with alendronate users.

The authors said head-to-head randomized controlled trials are needed to confirm their findings, which found a 26% excess hip fracture risk among SR compared with matched alendronate users, in line with placebo-controlled randomized controlled trial findings. Conversely, in a lower-risk population, SERM users had a 25% reduced hip fracture risk compared with alendronate users.

Reference

Khalid S, Calderon-Larrañaga S, Hawley S, et al. Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on “real-world” data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database. [published online October 9, 2018]. Clin Epidemiol. doi: 10.2147/CLEP.S164112