DSEN Abstract
Drugs for the Treatment and Prevention of Osteoporosis in Post-menopausal Women: A Systematic Review and Network Meta-analysis

Summary and key messages

We conducted a comprehensive systematic review and network meta-analysis to summarize the comparative benefits and harms of oral and intravenous bisphosphonates.
The systematic review was limited by the quality of the included studies and planned analyses were not feasible for all outcomes.

The findings from this review support conclusions that, after 12 months or longer, there are benefits to bisphosphonates drugs in post-menopausal women with a high fracture risk that may outweigh the identified harms.
Intravenous bisphosphonates may provide a treatment alternative to oral bisphosphonates, although evidence for postmenopausal women who fail to adhere to oral schedules, are intolerant of, or contraindicated to, oral drugs is sparse.

Authors: Shuching Hsieh, Shannon E. Kelly, Carine Zheng, Joan Peterson, Wenfei Liu, Becky Skidmore, Zemin Bai, Said Yousef, George A. Wells

For more information, please contact:
George A. Wells
gawells@ottawaheart.ca

Osteoporosis is a loss of bone density often associated with aging that can cause painful fractures, disability and deformity. Osteoporotic fractures are known to lead to significant morbidity and mortality. Bisphosphonates are recommended as first-line treatments for osteoporosis in postmenopausal women for prevention of fractures.
There are newer drug options available and there is uncertainty about which bisphosphonate drug offers optimal treatment or prevention in women with varying risk levels for fracture.

The objective of this project was to summarize benefits and harms of the bisphosphonate drugs available in Canada for the treatment or prevention of osteoporosis in postmenopausal women.

We performed a systematic review and a network meta-analysis to synthesize available randomized controlled trials (RCTs) of oral and intravenous bisphosphonate drugs available in Canada. The primary efficacy outcome was radiographic vertebral fractures at one year or longer.

This review included 133 unique RCTs, among which 48 RCTs were conducted in primary prevention populations of postmenopausal women, and 85 RCTs conducted in secondary prevention populations classified as having a higher risk of fracture. Data were available for four bisphosphonates: alendronate, risedronate, etidronate and zoledronic acid.
Benefits varied by population, intervention and fracture outcome.
In primary prevention populations, no atrial fibrillation, osteonecrosis of the jaw or atypical femoral fracture events were observed for these rare or unusual outcomes in any of the included studies reporting these outcomes.
In secondary prevention populations of postmenopausal women, there was insufficient data to detect meaningful differences between treatments for rare or unusual outcomes, including osteonecrosis of the jaw, atypical femoral fractures and atrial fibrillation, and for many subgroups of interest.

Report: Canada's Drug Agency; HE0023