Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years

Abstract

This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1-16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy.

Keywords: bisphosphonates; bone biopsy; bone quality; microcracks; osteoporosis therapy.

Figure 1

Representative examples of fuchsin stained human bone samples showing microcracks.

Figure 2

Microcrack density (# cracks/mm² trabecular bone area) versus bisphosphonate treatment duration (years). Solid circles represent mean number of microcracks averaged over 50 optical fields for each sample. Dotted line represents best-fit linear relationship obtained from polynomial regression.

Figure 3

Mean microcrack length (microns) versus bisphosphonate treatment duration (years). Solid circles represent mean microcrack length per bone sample averaged over 50 optical fields. Dotted line represents best-fit linear relationship obtained from polynomial regression.