Zoledronic acid may provide fracture protection in postmenopausal osteoporosis

Issue: November 2010

ASBMR Annual Meeting

TORONTO — Data from two studies highlight an apparent role for zoledronic acid in effectively reducing fracture risk in postmenopausal women.

Results of a study of more than 1,200 postmenopausal osteoporotic women show that annual zoledronic acid (Reclast, Novartis) maintained bone loss at 6 years.

In women who stopped zoledronic acid after 3 years, the bone mineral density decreased significantly but remained well above baseline levels (difference between groups at 6 years, 1.04%; P=.0009). Women who remained on zoledronic acid for 6 years reduced their risk for new morphometric spine fractures by 52% compared with those who stopped treatment at 3 years (P=.04).

In both groups, bone markers were maintained over 6 years within the normal postmenopausal range. In patients who discontinued zoledronic acid after 3 years, there was no evidence of accelerated bone loss.

The long-term study, which extended the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) by 3 years, is a multicenter, double blind, randomized, placebo-controlled study to evaluate the long-term efficacy and safety of zoledronic acid for postmenopausal osteoporosis. After 3 years, women were randomly assigned to zoledronic acid infusion (n=616) or annual placebo infusion (n=617) for 3 additional years.

Analysis of fracture risk reduction

Jane Cauley, PhD, and colleagues conducted a preplanned analysis of 7,736 women with postmenopausal osteoporosis who were included in HORIZON-PFT. They found that zoledronic acid appears to decrease the risk for postmenopausal osteoporotic fractures irrespective of absolute fracture risk.

“The clinical message is that, overall, zoledronic acid reduces fracture consistent across all categories of fracture risk,” Cauley, professor of epidemiology at University of Pittsburgh Graduate School of Public Health, told Endocrine Today.

Researchers examined fracture decrease by predicted risk for fracture, and categorized patients by 5-year hip fracture risk using a risk fracture score known as the FRACTURE Index, which is comprised of seven variables, including age, bone mineral density T-score and fracture risk after age 50 years. The risk score ranges from 1 to 11. Continuous models showed that a one-unit rise in fracture score was associated with 1.29 increased odds for hip fracture and 1.11 increased odds for any clinical fracture.

For this analysis, Cauley and colleagues grouped risk scores into tertiles and derived the relative risk for hip, non-vertebral and all clinical fractures in women assigned to zoledronic acid vs. placebo.

According to the results, zoledronic acid had a consistent impact on fracture reduction for vertebral (P=.26), non-vertebral (P=.72) and all clinical fracture (P=.96) across categories of absolute fracture risk.

Regarding hip fracture, the researchers observed a trend toward a greater decrease in risk among women at the lowest risk for fracture (P=.056). However, Cauley cautioned making “too much” of the hip fracture finding because “it was not statistically significant.” – by Louise Gagnon

For more information:

Black DM. Concurrent oral session 12: Osteoporosis therapy and complications. #1070.

Cauley JA. Concurrent oral session 17: Osteoporosis treatment. #1102. Both presented at: American Society of Bone and Mineral Research 2010 Annual Meeting; Oct. 15-19, 2010; Toronto.

The finding was that irrespective of the risk for fracture in the patient population zoledronic acid was similarly effective in reducing fracture risk. The major limitation of the study is that all women in the study had osteoporosis, so the range during which fracture risk was assessed was skewed to the higher end.

– Michael McClung, MD
Director, Oregon Osteoporosis Center

Follow EndocrineToday.com on Twitter.