An in vivo model for the rapid assessment of the local effects of parathyroid hormone on bone histomorphometry

The process of bone remodelling is likely to be controlled to a large extent by factors acting locally in a paracrine or autocrine manner, along with some systemic control. In our laboratory we routinely use an in vivo model in which the local effects of factors on bone histomorphometry can be determined. The factor under investigation is injected just above the periosteum of the right hemicalvaria in the adult male mouse. These subcutaneous injections are given daily over a 1-week period and the animals sacrificed at intervals after the last injection. With appropriate staining techniques it is possible to determine the effects of a particular agent on osteoblast and osteoclast numbers; the area of total bone, mineralized bone, osteoid and periosteum; osteoblast, osteoclast and eroded surfaces, and thus to infer the rate of bone formation and bone resorption in the right hemicalvaria compared to the uninjected left hemicalvaria and to vehicle-injected control animals. All these parameters are measured using a bone-dedicated image analyzer. Utilizing this in vivo model, we and others have studied a number of bone-active factors. We report the effects of parathyroid hormone, as well as reviewing results of our studies of leukemia inhibitory factor, amylin, calcitonin and calcitonin gene-related peptide in the model. The results obtained are similar to those found in most other animal models and in man. In conclusion, we describe an in vivo model whereby bone-active factors, injected locally, can be rapidly assessed.