Microcrack Frequency and Bone Remodeling in Postmenopausal Osteoporotic Women on Long-Term Bisphosphonates: A Bone Biopsy Study
- 1 October 2007
- journal article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 22 (10), 1502-1509
- https://doi.org/10.1359/jbmr.070609
Abstract
We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover. 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. 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-microm-thick sections using optic microscopy and were confirmed by laser confocal microscopy. Microcrack frequency (number of microcracks/mm2 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. Among treated women, cancellous bone microcrack frequency was low (mean, 0.13 microcracks/mm2) and did not differ significantly from that observed in controls (0.05 microcracks/mm2; 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/mm2 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. Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.Keywords
This publication has 41 references indexed in Scilit:
- Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosisBone, 2007
- Osteonal crack barriers in ovine compact boneJournal of Anatomy, 2006
- Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal OsteoporosisJournal of Bone and Mineral Research, 2004
- Long-Term Treatment of Incadronate Disodium Accumulates Microdamage but Improves the Trabecular Bone Microarchitecture in Dog VertebraJournal of Bone and Mineral Research, 2003
- Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral DensityNew England Journal of Medicine, 2002
- Sequential labelling of microdamage in bone using chelating agentsJournal of Orthopaedic Research, 2000
- In vivo trabecular microcracks in human vertebral boneBone, 1996
- Risedronate treatment does not increase microdamage in the canine femoral neckBone, 1995
- Increased intracortical remodeling following fatigue damageBone, 1993
- Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: Comparison with normal postmenopausal womenOsteoporosis International, 1990