Insights into the bisphosphonate holiday: a preliminary FTIRI study

Area of Science:

• Bone biology and pharmacology
• Post-menopausal health
• Drug efficacy and safety

Background:

• Bisphosphonates (BP) are crucial for preventing fragility fractures but prolonged use raises safety concerns.
• Recent guidelines suggest BP holidays for long-term users not at high fracture risk.
• Limited data exist on bone quality changes after BP discontinuation.

Purpose of the Study:

• To evaluate the impact of a 5-year bisphosphonate holiday on bone composition.
• To test the hypothesis that a 5-year BP holiday causes no major bone compositional changes.
• To provide data supporting or refuting BP holiday recommendations based on bone quality.

Main Methods:

• Analysis of iliac crest bone biopsies from post-menopausal women using Fourier transform infrared imaging (FTIRI).
• Comparison between a group on continuous alendronate for 10 years and a group with 5 years of alendronate followed by a 5-year drug holiday.
• Assessment of key FTIRI parameters including mineral-to-matrix ratio, carbonate-to-phosphate ratio, acid phosphate substitution, and collagen cross-link ratio, along with their heterogeneity.

Main Results:

• No significant differences in key FTIRI parameters between continuous and discontinued alendronate groups in age-adjusted models.
• The discontinued group showed a 2% increase in cortical crystallinity (p=0.01).
• The discontinued group exhibited 31% greater cortical acid phosphate heterogeneity (p=0.02) and 24% lower trabecular crystallinity heterogeneity (p=0.02).

Conclusions:

• Discontinuation of alendronate for 5 years did not substantially alter bone composition.
• Observed modest differences in specific parameters are unlikely to impact bone mechanical properties.
• Preliminary findings suggest a 5-year bisphosphonate holiday is not detrimental to bone composition.