David G Little1, Harry K W Kim. 1. Department of Orthopaedics, Orthopaedic Research and Biotechnology, The Children's Hospital at Westmead, Westmead NSW, Australia. DavidL3@chw.edu.au
Abstract
BACKGROUND: The observation that the pathogenesis of femoral head deformity in Legg-Calve-Perthes disease (LCPD) relates to bone resorption without subsequent coupled bone formation leads quickly to the hypothesis that antiresorptive agents may provide a useful adjunctive avenue for therapy. Robust bone catabolism in the absence of anabolism can only lead to femoral head deformity. METHODS: The published data on bisphosphonate use in models of LCPD was reviewed. RESULTS: Multiple animal studies support the further investigation of bisphosphonates and other anticatabolic agents in LCPD. Clinical data is only now starting to be gathered on the basis of animal and safety data.Rodent studies of traumatic and spontaneous osteonecrosis confirm that femoral head shape can be preserved by systemic bisphosphonate administration. Large animal piglet studies also show better preservation of the femoral head shape with systemic and local bisphosphonate administration, and also illustrate that systemic therapy requires initial revascularization of the necrotic head before its distribution within the head-a potential drawback of systemic therapy. Timing of effective dosing is likely to be very important. If the goal of treatment is to prevent deformity, then the window of therapy may be limited to an early stage of the disease before the significant collapse of the head.Although limiting bone resorption and preserving femoral head shape with bisphosphonates or other anticatabolic drugs may be of use, anabolic stimulation to speed up healing and new bone formation may also be desirable. Physical factors such as weight relief and activity modification may be important as the mechanical properties of the necrotic femoral head are significantly compromised during healing. The inflammatory nature of early LCPD is likely to also play a role in pathogenesis. These factors cannot be addressed by the use of antiosteoclastic therapy alone. CLINICAL RELEVANCE: Further basic science and clinical studies are required to clarify the role of bisphosphonates as adjunctive therapy in LCPD.
BACKGROUND: The observation that the pathogenesis of femoral head deformity in Legg-Calve-Perthes disease (LCPD) relates to bone resorption without subsequent coupled bone formation leads quickly to the hypothesis that antiresorptive agents may provide a useful adjunctive avenue for therapy. Robust bone catabolism in the absence of anabolism can only lead to femoral head deformity. METHODS: The published data on bisphosphonate use in models of LCPD was reviewed. RESULTS: Multiple animal studies support the further investigation of bisphosphonates and other anticatabolic agents in LCPD. Clinical data is only now starting to be gathered on the basis of animal and safety data.Rodent studies of traumatic and spontaneous osteonecrosis confirm that femoral head shape can be preserved by systemic bisphosphonate administration. Large animal piglet studies also show better preservation of the femoral head shape with systemic and local bisphosphonate administration, and also illustrate that systemic therapy requires initial revascularization of the necrotic head before its distribution within the head-a potential drawback of systemic therapy. Timing of effective dosing is likely to be very important. If the goal of treatment is to prevent deformity, then the window of therapy may be limited to an early stage of the disease before the significant collapse of the head.Although limiting bone resorption and preserving femoral head shape with bisphosphonates or other anticatabolic drugs may be of use, anabolic stimulation to speed up healing and new bone formation may also be desirable. Physical factors such as weight relief and activity modification may be important as the mechanical properties of the necrotic femoral head are significantly compromised during healing. The inflammatory nature of early LCPD is likely to also play a role in pathogenesis. These factors cannot be addressed by the use of antiosteoclastic therapy alone. CLINICAL RELEVANCE: Further basic science and clinical studies are required to clarify the role of bisphosphonates as adjunctive therapy in LCPD.
Authors: Tegan L Cheng; Ciara M Murphy; Laurence C Cantrill; Kathy Mikulec; Clare Carpenter; Aaron Schindeler; David G Little Journal: Int Orthop Date: 2014-01-04 Impact factor: 3.075