Alfacalcidol Versus Plain Vitamin D in Inflammation Induced Bone Loss
STEPHAN H. SCHARLA, ERICH SCHACHT, and UTA G. LEMPERT
ABSTRACT.
Inflammatory diseases lead to systemic osteoporosis. Causal factors include increased circulating concentrations of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-a (TNF-a), glucocorticoid medication, and reduced physical activity. In addition, disturbances of vitamin D metabolism play an important role for the development of inflammation induced osteoporosis. Therefore, D-hormone analogs offer an important treatment option. 1,25-dihydroxyvitamin D (D-hormone) prevented bone loss in the rat model of inflammation mediated osteopenia and in an arthritis model. One explanation is that animals and humans with inflammatory diseases exhibit markedly reduced circulating concentrations of D-hormone, partly the result of inhibition of renal 1-alpha-hydroxylase by TNF-a. In addition, the number of vitamin D receptors is reduced by glucocorticoids. Moreover, D-hormone has pleiotropic effects not only on calcium homoeostasis but also on muscle (improving power), the nervous system, and the immune system. D-hormone inhibits the release of cytokines (IL-1, IL-6, TNF-a) from macrophages and stimulates osteoprotegerin secretion in vitro and improves arthritis in animal models. This article reviews the interaction between inflammatory disease and vitamin D metabolism, summarizes the rationale for the therapeutic use of alfacalcidol, and provides recent data from controlled clinical trials comparing the effect of alfacalcidol versus plain vitamin D in secondary osteoporosis. Alfacalcidol, but not plain vitamin D, has pleiotropic effects improving bone and muscle metabolism and clinical symptoms in patients with rheumatoid arthritis. (J Rheumatol 2005;32 Suppl 76:26-32)
Key Indexing Terms:
ALFACALCIDOL
RHEUMATOID ARTHRITIS
INFLAMMATION
BONE DENSITY
INTERLEUKIN
TUMOR NECROSIS FACTOR
From the Praxis für Innere Medizin und Endokrinologie, Bad Reichenhall; Medizinische Fakultät, Ludwig-Maximilians-University, Munich, Germany; and the Department of Rheumatology and Rehabilitation, University Clinic Balgrist, Zurich, Switzerland.
S.H. Scharla, MD, Praxis für Innere Medizin und Endokrinologie and Medizinische Fakultät, Ludwig-Maximilians-University; E. Schacht, Department of Rheumatology and Rehabilitation, University Clinic Balgrist; U.G. Lempert, Praxis für Innere Medizin und Endokrinologie.
Address reprint requests to Dr. S. Scharla, Medizinische Fakultät, Ludwig-Maximilians-Universität München & Praxis für Innere Medizin und Endokrinologie, Salinenstrasse 8, D-83435 Bad Reichenhall, Germany. E-mail: Dr.Scharla@t-online.de
