Activation, development, and attenuation of modeling- and remodeling-based bone formation in adult rats.

Activation of modeling-based bone formation (MBF - bone formation without prior activation of bone resorption), has been identified as an important mechanism by which anabolic agents, such as intermittent parathyroid hormone (PTH), rapidly elicit new bone formation. Using a novel cryohistology imaging platform, coupled with sequential multicolor fluorochrome injections, we demonstrated that MBF and remodeling-based bone formation (RBF) in the adult rat tibia model have similar contributions to trabecular bone homeostasis. PTH treatment resulted in a 2.4-4.9 fold greater bone formation rate over bone surface (BFR/BS) by RBF and a 4.3-8.5 fold greater BFR/BS by MBF in male, intact female, and ovariectomized female rats. Moreover, regardless of bone formation type, once a formation site is activated by PTH, mineral deposition continues throughout the entire treatment duration. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we discovered that MBF, a highly efficient but often overlooked regenerative mechanism, is activated more rapidly but attenuated faster than RBF in response to PTH. This suggests that MBF and RBF contribute differently to PTH's anabolic effect in rats: MBF has a greater contribution to the acute elevation in bone mass at the early stage of treatment while RBF contributes to the sustained treatment effect.