Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification.

摘要

Bone-resorbing osteoclasts normally resorb ectopic mineral in their innate immune role. Therefore, we hypothesize that: blockade of osteoclastic bone resorption is required for heterotopic bone formation and that lifting repression will allow resorption of ectopic bone in heterotopic ossification. Purpose: to test methods to enhance osteoclast activity to reduce HO. Scope: This work will use a mouse model of HO to test mechanisms to enhance osteoclast formation and function. Osteoclast blockade is released by antibody inhibition of OPG, the natural antagonist of RANKL. OPG knockout (ko) mice were tested for the ability to form HO. Major findings: We have characterized a mouse model of HO by histological and histochemical analysis, X-ray, and micro-CT imaging. We show few osteoclast cells in HO bone relative to adjacent skeletal elements. We show that anti-OPG antibody treatment reduces bone formation (by micro-CT analysis), increases osteoclast numbers and serum resorption products and improves range-of-motion in the HO model (by passive ROM assay). We show that the OPG ko mouse makes little mineralized HO yet produces cartilage. Our results support our hypothesis and show that enhanced resorption may be a novel approach to treat HO.