Interferon-alpha, unlike interferon-gamma, does not cause bone loss in therat

Interferons (IFN) are a group of related glycoproteins, IFN-gamma, in vitro , has been shown to inhibit resorption; however, an in vivo experiment show ed that it had the opposite effect, resulting in bone loss that was compara ble to that caused by cyclosporine A. IFN-alpha has numerous clinical appli cations but is used most extensively in the treatment of chronic hepatitis B and chronic hepatitis C, Research into the effects of IFN-alpha on bone m ineral metabolism has been very sparse, and the majority of studies reflect in vitro models, Like IFN-gamma, there exists discordance between in vitro and in vivo studies on IFN-alpha. Both in vivo and in vitro studies demons trate that IFN-alpha decreases bone resorption, whereas osteoblasts may or may not be affected in vivo. This study was designed to provide information on the in vivo effects of IFN-alpha in the rat model, because we feel that , given its widespread clinical use, this is an extremely important issue. Rats were given low dose IFN-alpha (1.6 x 10(6) IU/m(2)), intermediate dose IFN-alpha (5.35 x 10(6) IU/m(2)), and high dose IFN-alpha (30 x 106 IU/m(2 )) three times per week for 28 days. Serum osteocalcin (bone gla protein, o r BGP) and parathyroid hormone (PTH) were measured serially and, after doub le labeling, the bones were examined histomorphometrically. IFN-alpha did n ot alter any of the histomorphometric parameters measured and did not affec t PTH, However, it produced a disparate BGP response, Low dose IFN-alpha re sulted in a statistically significant increase in serum BGP on days 14 and 28, whereas intermediate and high doses of IFN-alpha did not. Overall, thes e results provide no evidence of a deleterious effect of IFN-alpha on bone metabolism and confirm the limited clinical study. (C) 1999 by Elsevier Sci ence Inc. All rights reserved.