title: Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study.
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.
  
  
  BACKGROUND
  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.
  
  
  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-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Among postmenopausal osteoporotic women on long-term BPs, microcrack frequency in the iliac bone is low, despite a marked reduction of bone turnover.
authors.affiliation: INSERM Research Unit 831 and Université de Lyon, Lyon, France. chapurlat@lyon.inserm.fr
authors.forename: Roland D
authors.initials: RD
authors.lastname: Chapurlat
authors.forename: Monique
authors.initials: M
authors.lastname: Arlot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Burt-Pichat
authors.forename: Pascale
authors.initials: P
authors.lastname: Chavassieux
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Roux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Portero-Muzy
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016723:Bone Remodeling / Q000187:drug effects*; D002102:Cadaver; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D013997:Time Factors