Can bisphosphonates reduce risk of death in osteoporotic patients?

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Although bisphosphonates are currently considered first-line treatment for osteoporosis, the mechanism by which the drugs impact survival is not fully understood. A recent study in the Journal of Bone and Mineral Research aimed to determine whether the association between bisphosphonates and survival is mediated by a reduction in rate of bone loss.

The research included 1743 women 50 years and older who were participating in the Canadian Multicentre Osteoporosis Study (CaMos). Participants had at least two bone mineral density (BMD) measurements and either used one of the available bisphosphonates (alendronate, risedronate, or etidronate) or did not use any bone-related medication. A standardized interview-administered questionnaire was administered at baseline (1995-97) and included information on lifestyle factors, demographics, comorbidities, and medication use. 

Femoral neck and lumbar spine areal BMD were measured, via x-ray, at baseline and then again in years 3, 5, and 10. A linear regression model was used to calculate the annual percent change in BMD for each individual participant. Self-reports of incident clinical fractures were obtained yearly and at clinical visits. 

During follow-up (median 15 years), 454 (26%) women experienced an incident fracture and 241 (14%) died. BMD declined at the site of the femoral neck with a median of -0.38%/year (IQR -1.00 to 0.22%) and slightly increased at the lumbar spine with a median of +0.22%/year (IQR -0.39 to 0.92). 

Women were classified according to treatment as nitrogen bisphosphonate (nBP) (n=387), etidronate users (n=337) and non-users (NoRx) (n=1019). All bisphosphonate users had several factors associated with poorer survival: significantly lower femoral neck BMD, weight, and more prior fractures than individuals taking no treatment. 

The nBP (271 pairs) and etidronate groups (327 pairs) were matched 1:1 by propensity score to nontreated participants. nBP use was associated with significant mortality risk reduction (HR = 0.61 [95% CI 0.39-0.96]). However, etidronate use was not significantly associated with the reduction (1.35 [95% CI 0.86-2.11]). 

Rapid bone loss was associated with more than a 2-fold increased mortality risk compared with no loss. Medication analysis revealed that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. 

The authors suggested that this study provides evidence that treatment with bisphosphonates is associated with reduction in risk not only of fracture risk but also of mortality compared to that seen in nontreated individuals. They noted that mortality rates were directly related to greater bone loss in the nontreated groups. Ob/gyns may want to discuss incorporating bisphosphonates into the treatment plans for their osteoporotic patients. The authors suggested that future mechanistic studies into osteoporosis, antiresorptive treatment, and survival should be the next steps.