title: Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series.
abstract: Recent reports of long-term bisphosphonate-treated patients developing cortical fractures have raised concerns that such fractures may relate to excessive suppression of bone turnover after prolonged use of these drugs. To evaluate the bone histology of patients presenting with cortical fractures after bisphosphonate therapy, we conducted a retrospective analysis of patients treated at Washington University Bone Health Program presenting with a history of low-energy cortical fractures (femoral shaft, pelvis, rib, metatarsal, and ankle), who had received bisphosphonates for at least two consecutive years and had undergone bone biopsy. Fifteen of 54 patients who underwent bone biopsy between November 2004 and March 2007 met the criteria. Of these, 10 patients had findings of suppressed trabecular bone remodeling, as demonstrated by lack of double tetracycline labels. There were no significant differences in bone density, clinical features, and biochemical features between those with suppressed turnover and the other five subjects with normal remodeling. However, the low-turnover group had received bisphosphonates (primarily alendronate) for a significantly longer duration (6.5 +/- 0.6 vs. 3.9 +/- 0.8 years, P = 0.02). Thus, about two-thirds of patients presenting with cortical fractures while on long-term treatment with bisphosphonates had suppressed turnover. Since the prevalence of such histological findings in nonfracture patients remains unknown, the impact of suppressed bone turnover on the development of cortical fractures cannot be determined. Considering the widespread use of bisphosphonates, it appears that the overall risk of cortical fractures is low. However, there may be a subset of as yet unidentified patients who could be predisposed to this complication.
authors: Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, Campus Box 8301, 660 South Euclid Avenue, St. Louis, MO 63110, USA. rvillare@im.wustl.edu
authors: Reina
authors: R
authors: Armamento-Villareal
authors: Nicola
authors: N
authors: Napoli
authors: Kathryn
authors: K
authors: Diemer
authors: Marcus
authors: M
authors: Watkins
authors: Roberto
authors: R
authors: Civitelli
authors: Steven
authors: S
authors: Teitelbaum
authors: Deborah
authors: D
authors: Novack
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates