Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates
- 123 Downloads
Osteogenesis imperfecta (OI) has been treated with bisphosphonates for many years, with some clear clinical benefits. In adults, there are reports of a new pattern of atraumatic subtrochanteric fractures with bisphosphonate treatment. This study assesses if bisphosphonate treatment leads to an altered pattern of femoral fractures.
Retrospective review of imaging for a cohort of 176 bisphosphonate-treated OI patients to identify the locations of femoral fractures over a two-year period, as compared to a historical control group managed pre-bisphosphonates.
Sixteen femoral fractures were identified in this time period in the bisphosphonate-treated group. All but two were within the subtrochanteric region. In comparison, the historical group—composed of 26 femoral fractures—had a more widespread fracture pattern, with the most frequent location being the mid-diaphysis. Many of the subtrochanteric fractures in the treatment group occurred with minimal trauma.
It appears that concerns over the treatment of the adult osteoporotic population with bisphosphonates are amplified and mirrored in OI. It is possible that the high bending moments in the proximal femur together with altered mechanical properties of cortical bone secondary to the use of this group of drugs increase the risk of this type of injury, which warrants further modification of surgical management of the femur.
KeywordsOsteogenesis imperfecta Bisphosphonates
- 2.Roughley PJ, Rauch F, Glorieux FH (2003) Osteogenesis imperfecta—clinical and molecular diversity. Eur Cell Mater 5:41–47; discussion 47Google Scholar
- 3.King JD, Bobechko WP (1971) Osteogenesis imperfecta—an orthopaedic description and surgical review. J Bone Joint Surg Br 53-B:72–89Google Scholar
- 10.Roelofs AJ, Coxon FP, Ebetino FH, Lundy MW, Henneman ZJ, Nancollas GH, Sun S, Blazewska KM, Bala JL, Kashemirov BA, Khalid AB, McKenna CE, Rogers MJ (2010) Fluorescent risendronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J Bone Miner Res 25(3):606–616PubMedPubMedCentralCrossRefGoogle Scholar
- 11.Reinholz GG, Getz B, Pederson L, Sanders ES, Subramaniam M, Ingle JN, Spelsberg TC (2002) Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts. Cancer Res 60:6001–6007Google Scholar
- 15.Giuliani N, Pedrazzoni M, Negri G, Passeri G, Impicciatore M, Girasole G (1998) Bisphosphonates stimulate formation of osteoblast precursors and mineralized nodules in murine and human bone marrow cultures in vitro and promote early osteoblastogenesis in young and aged mice in vivo. Bone 22:455–461PubMedCrossRefGoogle Scholar
- 16.Poyrazoglu S, Gunoz H, Darendeliler F, Bas F, Tutunculer F, Eryilmaz SK, Bundak R, Saka N (2008) Successful results of pamidronate treatment in children with osteogenesis imperfecta with emphasis on the interpretation of bone mineral density for local standards. J Pediatr Orthop 28(4):483–487PubMedCrossRefGoogle Scholar
- 20.Letocha AD, Cintas HL, Troendle JF, Reynolds JC, Cann CE, Chernoff EJ, Hill SC, Gerber LH, Marini JC (2005) Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement. J Bone Miner Res 20(6):977–986PubMedCrossRefGoogle Scholar
- 28.Phillipi CA, Remmington T, Steiner RD (2008) Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 4:CD005088Google Scholar
- 46.Bishop N, Harrison R, Ahmed F, Shaw N, Eastell R, Campbell M, Knowles E, Hill C, Hall C, Chapman S, Sprigg A, Rigby A (2010) A randomized, controlled dose-ranging study of risendronate in children with moderate and severe osteogenesis imperfecta. J Bone Miner Res 25(1):32–40PubMedCrossRefGoogle Scholar
- 47.Evans KD, Lau ST, Oberbauer AM, Martin RB (2003) Alendronate affects long bone length and growth plate morphology in the oim mouse model for osteogenesis imperfecta. Bone 32(3):268–274Google Scholar
- 54.Uveges TE, Kozloff KM, Ty JM, Ledgard F, Raggio CL, Gronowicz G, Goldstein SA, Marini JC (2009) Alendronate treatment of the brtl osteogenesis imperfecta mouse improves femoral geometry and load response before fracture but decreases predicted material properties and has detrimental effects on osteoblasts and bone formation. J Bone Miner Res 24(5):849–859PubMedPubMedCentralCrossRefGoogle Scholar
- 55.Shahnazari M, Yao W, Dai W, Bob Wang B, Ionova-Martin SS, Ritchie RO, Heeren D, Burghardt AJ, Nicolella DP, Kimiecik MG, Lane NE (2010) Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone 46(5):1267–1274PubMedPubMedCentralCrossRefGoogle Scholar