Bisphosphonates are currently considered as first-line therapy for osteoporosis worldwide with much evidence of the drug's ability to reduce the risk of vertebral and non-vertebral fractures. Recently, bisphosphonates have also been associated with improved survival.
The first evidence of a positive association between bisphosphonate use and survival came from an RCT study showing that zoledronic acid was associated with a 28% reduced risk of death compared to placebo. Subsequently, a meta-analysis of anti-osteoporosis drugs from 8 RCTs (including risedronate, zoledronic acid, denosumab, and strontium ranelate) found a combined benefit (~11%) of these drugs on mortality risk.
The mechanisms by which bisphosphonates impact survival are not fully understood. Several hypotheses have been proposed to explain this effect, including through a decrease in the rate of subsequent fractures or a decrease in the rate of bone loss. Excessive bone loss is associated with an increased risk of mortality, both in the general population and post-fracture.
A study was conducted to determine whether the association between bisphosphonate and mortality was mediated by a reduction in bone loss rates. The population-based Canadian Multicentre Osteoporosis Study included 1,743 women aged ≥50 years. Bisphosphonate users were stratified into nitrogen bisphosphonate (nBP; alendronate or risedronate) and etidronate users and non-users (NoRx). There were 271 matched pairs of nBP and NoRx and 327 matched pairs of etidronate and NoRx.
The results showed that the use of nBP, but not etidronate, was associated with a significantly reduced risk of death (HR=0.61 for nBP and 1.35 for etidronate). Rapid bone loss was associated with more than 2-fold increased risk of death compared to no bone loss. Mediation analysis showed that 39% of the association of nBP with mortality was attributed to a reduced rate of bone loss. These findings provide insight into the mechanism of the relationship between nBP and its benefit on survival in osteoporosis patients.
Conclusion:
The use of nitrogen bisphosphonate (such as alendronate or risedronate) in women is associated with better survival and a significant reduction in bone loss.
Image: Illustration (Source: Pressfoto-Freepik)
Reference:
1. Bliuc D, Tran T, van Geel T, Adachi JD, Berger C, van den Bergh J, et al. Reduced bone loss is associated with reduced mortality risk in subjects exposed to nitrogen bisphosphonates: A mediation analysis. J Bone Miner Res. 2019 Nov;34(11):2001-11.
2. Bolland MJ, Grey AB, Gamble GD, Reid IR. ffect of osteoporosis treatment on mortality: A meta-analysis. J Clin Endocrinol Metab. 2010 Mar;95(3):1174-81.
