Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: A bone biopsy study

Introduction: Animal studies suggest that bisphosphonates (BPS) could increase microdamage frequency in a dose-dependent manner, caused by excessively suppressed bone turnover. However, there is limited data in humans receiving BP therapeutic doses for >3 yr. Materials and Methods: We measured microcrack frequency and histomorphometry parameters on transiliac bone biopsies in 50 postmenopausal osteoporotic women (mean age = 68 yr) who had received BP therapy (3 on intravenous pamidronate, 37 on oral alendronate, and 10 on oral risedronate) for at least 3 yr (mean treatment duration = 6.5 yr). We compared these results with transiliac bone biopsies obtained from 12 cadavers. We used bulk staining with green calcein as a fluorochrome. The microcracks were quantified in three 100-mu m-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm(2) of bone tissue) was compared between treated women and controls using nonparametric tests. We also explored predictors of microcrack frequency, including age, duration of BP therapy, and activation frequency. Results: Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm(2)) and did not differ significantly from that observed in controls (0.05 microcracks/mm(2); P = 0.59). Of note, 54% of the treated women and 58% of the controls had no observable Microcracks. There was no association between microcrack frequency and the duration of BP therapy (for microcrackS/mm(2) and duration, Spearman r = 0.04, p = 0.80) and between patients' ages and the number of microcracks (Spearman r = -0.09, p = 0.61). Although bone remodeling parameters were suppressed in treated women, we found no relationship between microcrack density and activation frequency (Spearman r = -0.003, p = 0.99). Also, microcrack frequency was not increased in women with prevalent vertebral fracture compared with those without fractures. Conclusions: Among postmenopausal osteoporotic women on long-term BPS, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.