medwireNews: Findings from a systematic review suggest that long-term drug treatment is associated with a reduction in fracture risk among women with osteoporosis, with different agents having varying long-term safety profiles.
Howard Fink (Minneapolis VA Health Care Center, Minnesota, USA) and colleagues analyzed data from 48 studies with low or medium risk of bias, including 35 placebo-controlled trials in which all participants were postmenopausal women, and 13 observational studies in which 84–100% of participants were women. Study participants were aged an average of 72 years.
As reported in the Annals of Internal Medicine, 4 years of treatment with alendronate versus placebo was associated with a significantly reduced risk for clinical fractures among women with osteoporosis defined by bone mineral density (BMD) and no prior vertebral fracture, as well as a significantly lower risk for radiographic vertebral fractures in those with BMD-defined osteopenia or osteoporosis and no prior fracture.
Zoledronic acid treatment for 6 years significantly lowered the risk for clinical, clinical vertebral, and nonvertebral fractures compared with placebo among women with osteopenia or osteoporosis, while 4–8 years of raloxifene was associated with a significant reduction in the risk for clinical and radiographic vertebral fractures, but not nonvertebral or hip fractures.
“In women with osteoporosis, indications for long-term raloxifene therapy may be limited because it reduced only vertebral fractures, whereas both long-term use of zoledronic acid and that of alendronate also reduced nonvertebral fractures,” write Fink and team.
The researchers also found that an average 5.6 years of estrogen–progestin and 7.1 years of unopposed estrogen were associated with a significantly reduced clinical fracture risk versus placebo. They note that “[e]vidence was insufficient” to compare fracture risk associated with long-term denosumab treatment.
In the safety analysis, long-term treatment with bisphosphonates was associated with an increased risk for two rare adverse events, namely atypical femoral fracture and osteonecrosis of the jaw, while long-term hormone therapy was associated with an elevated risk for serious harms, including cardiovascular disease and cognitive impairment.
“Estimating the balance between the potential antifracture benefits and harms of long-term use of bisphosphonates is challenging,” note Fink and co-authors. Based on the studies included in the systematic review, they calculated that for every 1000 women treated with alendronate for 4 years or zoledronic acid for 6 years compared with placebo, around 50–70 more women will avoid a clinical fracture and an additional two will have an atypical femoral fracture.
The researchers point out a number of limitations of their systematic review, including many treatment comparisons having only one trial, and limited generalizability of the findings beyond healthy postmenopausal women.
They also say that “[e]vidence was limited on factors that may modify the effects of long-term ODT [osteoporosis drug treatment] and ODT holidays.”
The team concludes that “[t]o guide future decisions about osteoporosis treatment, considerable new research is warranted,” including comparisons of sequential treatments, studies involving men and people with comorbidities, and further investigation of drug holidays.
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