Bone anabolic treatments better than bisphosphonates for fracture prevention among postmenopausal women.

A new study found that bone anabolic therapies can be used for post-menopausal women with high risk for bone fractures as they were found to be superior to bisphosphonates in preventing clinical and vertebral fractures, regardless of the baseline risk factors. The study results were published in the journal The BMJ. 

Osteoporosis is a common condition seen in post-menopausal women. There are multiple treatment algorithms for the management of it. Though most of them target bone mineral density, preventing fractures is the most relevant one. As previous literature has shown multiple treatment options researchers conducted a systematic review, network meta-analysis, and meta-regression analysis of various randomized clinical trials to review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterize the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. 

Between January 1996 and November 2021, data were extracted from all randomized controlled trials from Medline, Embase, and Cochrane Library to identify all non-Asian postmenopausal women with no age restriction, with interventions targeting bone quality in a broad perspective. 69 trials were included (>80 000 patients). Measuring clinical fractures was the primary outcome. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all-cause mortality, adverse events, and serious cardiovascular adverse events. 

Key findings: 

• Bisphosphonates, parathyroid hormone receptor agonists, and romosozumab had a protective effect on clinical fractures compared with placebo.
• The odds of reducing clinical fractures were less for bisphosphonates when compared with parathyroid hormone receptor agonists, 
• Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures. 
• All the included treatments showed some effect on the vertebral fractures compared with placebo.
• In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures.
• Baseline risk indicators did not affect the various treatment regimens, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age.
• No harmful outcomes were seen.
• Due to reporting restrictions, the accuracy of the impact estimates was moderate to low for each outcome, nominally suggesting a high likelihood of bias and imprecision. 

Thus, the majority of postmenopausal osteoporosis therapies that have been approved have been effective in preventing all types of fractures, with head-to-head studies favoring bone anabolic therapy over bisphosphonates in preventing clinical and vertebral fractures.  

Further reading: Händel MN, Cardoso I, von Bülow C, et al. Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. BMJ. 2023;381:e068033. Published 2023 May 2. doi: 10.1136/bmj-2021-068033