The Endocrine Society published a 2019 and an updated 2020 guideline for the pharmacological management of osteoporosis in postmenopausal women. The guidelines include a meta-analysis accessing each individual agent's effect on vertebral fracture, non-vertebral fracture, and hip fracture. When compared to placebo treatment, a significant reduction in vertebral fractures was observed with abaloparatide, alendronate, zoledronic acid, denosumab, and teriparatide. A significant reduction in hip fractures was also observed for alendronate, zoledronic acid, and denosumab, but not abaloparatide or teriparatide; a clearly superior agent was not identified. Choice of therapy is recommended based on availability, cost, tolerability, and patient preference for postmenopausal women with a high risk of fracture. While a difference in effect may have been observed between agents in the meta-analysis, the clinical impact may not be substantial. Therefore, numerical differences may be misleading in regard to the prevention of the three fractures. [1], [2], [3]
The American Association of Clinical Endocrinologists/American College of Endocrinology published 2020 guidelines for the management of postmenopausal osteoporosis. For pharmacologic treatment, the guidelines consider alendronate, zoledronate, and denosumab to have broad-spectrum anti-fracture efficacy and should be considered as first-line options. If patients are at very high-risk of fracture, then abaloparatide, teriparatide, denosumab, and zoledronate may be considered. The evidence of fracture risk reduction was judged on a binary yes/no response based on chosen evidence. [4]
As discussed before, the primary measurement of efficacy with pharmacologic agents for osteoporosis is the prevention of fractures. This outcome can be interpreted as the response rate, but the results also vary between individual studies and meta-analyses, making it difficult to present a numerical result. Highlighted clinical trials from review articles report percent reduction rates of fracture which will be summarized. The efficacy of denosumab was reported in the FREEDOM trial enrolling 7,868 postmenopausal women, which reported a reduction in the relative risk of new radiographic vertebral fractures, clinically diagnosed vertebral fractures, and multiple new vertebral fractures of 68%, 69%, and 61%, respectively. For teriparatide, a 21-month randomized study reported that the relative risk of vertebral fracture in the 20 mcg and 40 mcg group compared to placebo was 0.35 and 0.31, respectively, which is converted as 65% and 69% reduced risk. The converted non-vertebral fracture rate was 53% and 54% for 20 and 40 mcg, respectively. These examples are only snapshot comparisons between landmark clinical trials which may vary depending on the inclusion of other studies and emerging evidence. [5], [6], [7]
A 2012 systematic review and network meta-analysis evaluated the comparative effectiveness of various pharmacological agents in preventing fragility fractures. This analysis incorporated data from 116 randomized controlled trials, involving a total of 139,647 participants, predominantly postmenopausal women. The study focused on a comparative analysis of bisphosphonates, teriparatide, selective estrogen receptor modulators (SERMs), denosumab, and the combination of calcium and vitamin D. Of the agents, teriparatide demonstrated the highest probability of effectiveness in reducing the risk of hip, vertebral, and nonvertebral fractures, although the differences from denosumab and various bisphosphonates like zoledronate and alendronate were not statistically significant. The study found calcium and vitamin D, when administered separately, to be ineffective but effective in combination for reducing hip fracture risk. Overall, the analysis underscored that while teriparatide, bisphosphonates, and denosumab are highly effective in reducing fracture risk, the differences in efficacy among these agents are marginal. Consequently, the decision-making process should also consider the potential harms and costs associated with these treatments. [8]