Bone Abstracts (2013) 1 PP437 | DOI: 10.1530/boneabs.1.PP437

The spatial relationship between bone formation and bone resorption in healthy and ovariectomized mice treated with PTH, bisphosphonate or mechanical loading

Davide Ruffoni, Claudia Weigt, Elisa Fattorini, Alina Levchuk, Friederike Schulte, Gisela Kuhn & Ralph Müller

Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.

Bone is continuously remodeled to remove damage, to adapt to changes in mechanical demands and to regulate calcium homeostasis. The first aim is accomplished by coupled bone formation and resorption whereas adaptation requires sites of formation to differ from those of resorption. The regulation of circulating ions is achieved by a stochastic exchange of bone packets. Here, we investigated these different aspects of remodeling in healthy and ovariectomized (OVX) mice treated with PTH, bisphosphonate or mechanical loading. 15-week old C57BL/6J female mice were divided into the following groups: untreated OVX (OVX, n=17); treated daily with PTH (PTH, n=9); treated once with zolendronate (BIS, n=9); treated with cyclic mechanical loading (8 N, 10 Hz, 3000 cycles) at the 6th caudal vertebra (CML, n=17); and sham operated mice (SHM, n=8). Treatment started 11 weeks after ovariectomy and micro-CT measurements were performed at start of the treatment and after 2 and 4 weeks. Registration of three consecutive scans allowed estimating the amount of coupled bone formation (i.e., bone formed at the locations where it was previously resorbed) and coupled bone resorption (i.e., bone resorbed at the locations where it was previously formed). Considering that it is biologically irrational that newly formed bone gets immediately removed, coupled resorption could be interpreted as stochastic untargeted remodeling. OVX significantly increased the amount of coupled resorption by 44% when compared to SHM (P<0.001) whereas PTH, BIS and CML decreased it by 61, 22 and 39% when compared to OVX (P<0.001). Coupled formation was significantly decreased following OVX (−35%, P<0.001) while it increased following the three treatments by 126% (PTH), 90% (BIS) and 46% (CML) (P<0.001). The proposed analysis allowed measuring the coexisting types of remodeling in living bone and indicated that PTH caused the strongest increase in coupled bone formation and the highest reduction of untargeted remodeling.