Osteoclasts prefer aged bone

Summary We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones. Introduction Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption. Methods To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized βCTX fragment and the non-isomerized αCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones. Results We found that the αCTX / βCTX ratio is 3:1 in young compared to aged bones, and we found that both α and βCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology. Conclusions These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones. Kim Henriksen and Diana J. Leeming contributed equally. Financial disclosure: Morten A. Karsdal, Per Qvist and Claus Christiansen own stock options in Nordic Bioscience A/S