Bauer DC, et al. - Experts examined the effects of antiresorptive (AR) treatment in terms of short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction. The vertebral fracture treatment efficacy was strongly speculated via the short-term AR treatment-related changes in bone alkaline phosphatase (ALP) and pro-collagen I N-propeptide (PINP). However, this was not true for nonvertebral or hip fracture treatment efficacy. It was deduced that the change in bone formation markers could assist in predicting the anti-vertebral fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs.

Methods

• In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, individual-level data were assessed from 28,000 participants.
• Subjects were enrolled in 11 bisphosphonate (BP) and three selective estrogen receptor modulator (SERM) placebo-controlled fracture endpoint trials.
• During this study, experts used BTM results for two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and pro-collagen I N-propeptide [PINP]) and two bone resorption markers (N-terminal and C-terminal telopeptide of type I collagen) and incident fracture outcome data.
• A meta-regression was performed associating the mean net effect of treatment on change in bone turnover (active minus placebo % difference after 3 to 12 months) to the log of study-wide fracture risk reduction.
• Linear regression was used to plot the best fitting line.
• Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 4 years of follow-up.
• Change in bone ALP and PINP were available for over 16,000 and 10,000 participants, respectively.

Results

• A strong link was illustrated for vertebral fracture between treatment-related bone ALP or PINP changes and vertebral fracture risk reduction (r² = 0.82 [p < 0.001] and r² = 0.75 [p=0.011], respectively).
• It was discovered that the correlations were weaker and no longer statistically prominent for nonvertebral (r ² = 0.33 [p=0.053] and r² = 0.53 [p=0.065], respectively) and hip fracture (r² = 0.17 [p=0.24] and r² = 0.43 [p=0.11], respectively) outcomes.
• Similar results were yielded via analyses limited to BP trials.
• Findings disclosed that relationships were weaker and nonsignificant for bone resorption markers for all fracture types.