Bisphosphonates and Hip Fracture in People With Osteoporosis or Osteopenia

hip fracture
hip fracture
Researchers investigated whether hip fractures could be prevented with bisphosphonates in people with osteoporosis or osteopenia.

A systematic review and meta-analysis found zoledronic acid, risedronate, and alendronate therapies reduced the incidence of hip fracture among patients with osteoporosis or osteopenia. These findings were published in the Journal of Investigative Medicine.

Investigators from Chengdu BOE Hospital in China searched medical publication databases (PubMed, Embase, and the Cochrane Library) through January 2021 for randomized placebo-controlled clinical trials of bisphosphonate for the treatment and prevention of osteoporosis and fracture. A total of 17 trials met the inclusion criteria.

The study populations comprised 15,346 individuals who received placebo and 19,586 who received bisphosphonate therapy. Most studies used the bisphosphonate intervention zoledronic acid (ZOL; n=5) followed by alendronate (n=4), risedronate (n=3), etidronate (n=2), clodronate (n=1), ibandronate (n=1), and pamidronate (n=1).

Overall, the incidence of hip fracture (IHF) was significantly reduced by bisphosphonate (risk ratio [RR], 0.66; 95% CI, 0.56-0.77; P <.00001); I2, 0%).

Stratified by intervention, there was evidence to support ZOL (RR, 0.60; 95% CI, 0.46-0.78; P =.0002; I2, 0%), alendronate (RR, 0.61; 95% CI, 0.40-0.95; P =.03; I2, 0%), and risedronate (RR, 0.74; 95% CI, 0.59-0.94; P =.01; I2, 0%) for reducing hip fracture incidences, but there was no evidence to support clodronate, etidronate, ibandronate, or pamidronate.

Among a subset of study individuals aged ³55 years (bisphosphonate: n=5144; placebo: n=4162), bisphosphonate significantly reduced the incidence of hip fracture (RR, 0.63; 95% CI, 0.43-0.93; P =.02; I2, 0%). However, stratified by individual interventions, no significant effect was observed for etidronate (RR, 0.50; 95% CI, 0.05-5.25; P =.56), ibandronate (RR, 0.59; 95% CI, 0.26-1.31; P =.19), or alendronate (RR, 0.65; 95% CI, 0.41-1.03; P =.07; I2, 0%).

A similar finding for was observed among the population aged ³65 years (bisphosphonate: n=5368; placebo: n=5356) in which bisphosphonate therapy reduced IHF  (RR, 0.60; 95% CI, 0.44-0.81; P =.0010; I2, 0%).  Zolendronic acid was associated with a significant reduction in hip fracture incidence (RR, 0.60; 95% CI, 0.44-0.82; P =.001; I2, 0%) but not alendronate (RR, 0.50; 95% CI, 0.09-2.71; P =.42).

The Begg’s and Egger’s tests for publication bias were not significant (t, -1.79; 95% CI, -0.87 to 0.75; P =.093).

The researchers acknowledged several limitations of the study, including a lack of published information regarding men with osteoporosis or osteopenia, and that some of the studies included in their analysis may have been inadequately reported.

“Systematic reviews and meta-analyses showed that bisphosphonates (especially zolendronic acid, alendronate, and risedronate) could significantly decrease the incidence rate of hip fracture,” the study authors concluded. “Zolendronic acid-mediated reduction of the incidence rate of hip fracture might not be influenced by age, but it should be confirmed in populations aged ≥70 years old.”


Zhao S, Zhao W, Du D, et al. Effect of bisphosphonate on hip fracture in patients with osteoporosis or osteopenia according to age: a meta-analysis and systematic review. J Investig Med. Published online December 10, 2021. doi:10.1136/jim-2021-001961