Rationale for treatment of involutional osteoporosis in women and for prevention and treatment of corticosteroid-induced osteoporosis with alfacalcidol.
Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines. Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodeling induced by sex hormone deficits and by a so-called somatopause (insulin-like growth factor [IGF]-deficit), but also by lack of vitamin D and, very importantly, by reduced synthesis of D-hormone (Calcitriol) in kidneys and bone as well as by a lack of receptors or receptor affinity for D-hormone in the target organs. As a consequence of these facts, a rise in parathormone (PTH) frequently occurs. The lack of D-hormone and IGF-1 evidently causes a reduction in muscle strength as well and reinforces the risk of falling and, thus, the risk of a fracture. Alfacalcidol, a prodrug of D-hormone, is a specific antiosteoporotic therapy. In alfacalcidol therapy, D-hormone is provided to the body in circumvention of its own regulation, by means of which much higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. Chances have been significantly improved of reducing and frequently preventing the real osteoporosis complication for older male and female patients, i. e., bone fractures, by alfacalcidol. A clear distinction should be made between supplementation with low-dosed plain vitamin D and calcium as base supply in elderly housebound subjects or as adjuvant to antiosteoporotic drugs and the specific antiosteoporotic therapy with alfacalcidol in patients with osteoporosis. The expanded understanding of the pathogenesis of corticosteroid-induced osteoporosis with its disturbed Ca homeostasis and the pharmacological effects of alfacalcidol, counteracting such iatrogenic bone loss, explain the particularly good clinical efficacy in this most frequent form of secondary osteoporosis. Normalizing de-coupled bone remodeling due to cytokine modulation and the potential influence on deteriorated bone quality in patients with rheumatoid arthritis and Crohn's disease predestine this form of therapy for prevention and treatment of osteoporosis as a result of chronic inflammatory diseases as well as of transplantation osteoporosis cases in particular.
Schacht
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Strategic Business Unit Bone, Byk Gulden, Byk-Gulden-Str. 2, 78467 Konstanz, Germany.
D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000818:Animals; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control
D000305:Adrenal Cortex Hormones; D006887:Hydroxycholecalciferols; C008088:alfacalcidol