In vitro effects of growth hormone on osteoclastic activity: clinical applications

Purpose of the study This study was designed to investigate the in vitro effects of human growth hormone (hGH) on osteoclastic resorption in a nonfractionated rabbit bone cell model. Material and methods Rabbit bone cells were cultured on dentine slices in the presence of parath yroid hormone and vitamin D3. The percentage of dentine slice surface resor bed, number of lacunae per surface unit and mean area of lacunae were compa red between cell cultures grown in the presence of graded concentrations of hGH and human insulin-like growth factor-1 (hIGF-1) and controls. Results After 4 days of culture, rabbit bone cells cultured on dentine slices in th e presence of hGH and hIGF-1 showed significantly stimulated osteoclastic r esorption activity. When neutralizing anti-hIGF-1 anti-serum (4 mu g/l) was added to the starting culture, the stimulatory effects of hIGF-1 and hGH o n osteoclastic resorption activity were totally abolished. Discussion These findings indicate that the effects of hGH stimulation on osteoclastic resorption in vitro are mediated via local hIGF-1 secretion by stromal cel ls such as osteoblasts. Proteases appear to play a role In the degradation of the organic matrix. Our experiments show that hIGF-1 and hGH stimulate t he production of matrix metalloproteinases MMP-9 and MMP-2. Similar to the resorption activity, hGH stimulates protease activity via stromal cell prod uction of hIGF-1. Conclusion This study suggests that natural or synthetic MMP inhibitor modu lation of protease activity could reduce the degradation of the organic mat rix and then prevent, for example, inflammatory reactions subsequent to pro sthetic loosening.