NEW YORK (Reuters Health)—Treatment-related changes in bone formation markers predict vertebral-fracture reduction with anti-resorptive drug therapy, according to a meta-regression analysis of 14 clinical trials.
“These results may be useful for the development of new osteoporosis treatments or when considering new populations or dosing regimens with existing treatments,” Dr. Douglas C. Bauer from the University of California, San Francisco, told Reuters Health by email.
Drugs used to prevent and treat osteoporosis typically cause short-term changes in bone-turnover markers, but few studies have linked these changes to subsequent fracture reduction.
Dr. Bauer and colleagues in the Foundation for the National Institutes of Health (FNIH) Bone Quality Project analyzed individual-level data from 28,000 participants enrolled in 14 fracture-endpoint trials (11 of bisphosphonate and three of selective estrogen receptor modulator) in order to determine whether short-term changes in bone-turnover markers (BTMs) predict fracture outcomes.
In general, greater reductions in BTMs with therapy were associated with greater reductions in fracture risk, and the association was more striking for bone-formation markers – bone-specific alkaline phosphatase (bone ALP) and pro-collagen I N-propeptide (PINP) – than for bone-resorption markers (N-terminal and C-terminal telopeptide of type I collagen).
A 12% net reduction in bone ALP predicted a 33% reduction in vertebral fracture risk, and a 30% net reduction in bone ALP predicted a 65% reduction in fracture risk, the researchers report in the Journal of Bone and Mineral Research, online January 10.
Similarly, for PINP, a 22% net reduction predicted a 30% reduction in vertebral fracture risk, and a 50% net reduction predicted a 62% reduction in fracture risk.
In meta-regression analyses, changes in bone ALP and PINP significantly predicted vertebral-fracture risk, but none of the BTMs significantly predicted the risk of nonvertebral or hip fractures.
“Fracture-endpoint trials for osteoporosis treatments are large and expensive, so relatively few new agents are expected in the near future,” Dr. Bauer said. “Our data suggest short-term changes in several bone turnover markers predict subsequent vertebral fractures.”
“Pooling individual-level data from multiple trials sponsored by pharmaceutical companies is feasible and may help expedite the testing of effective osteoporosis treatments,” he added.
Senior author Dr. Richard Eastell from the University of Sheffield, UK, told Reuters Health by email, “Our hope is that when drugs are developed for use in osteoporosis the changes in the markers will help to identify the optimal dose and regimen. For clinical use, the results support the use of bone-turnover markers for monitoring osteoporosis therapy. The greater the change in bone-turnover marker, the greater the therapeutic benefit.”
“This is the first of several reports based on the FNIH bone-quality initiative,” he said. “We hope to be publishing soon on bone-mineral density and later on the combination of bone-turnover markers and bone mineral density.”
One of the 10 authors is employed by Merck & Co.; another is employed by Amgen, Inc.
Reference
- Bauer DC, Black DM, Bouxsein ML, et al. Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Anti-Resorptive Drugs: A Meta-Regression. Journal of Bone Mineral Research. 2018 Jan 10. [Epub ahead of print]
