Schacht E, Richy F, Reginster J-Y
Department of Rheumatology and Rehabilitation, University Clinic Balgrist, Zurich/Switzerland.
J Musculoskelet Neuronal Interact. 2005 Jul-Sep;5(3):273-84.
Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by sex hormone deficits and by somatopause, but also by lack of vitamin D and reduced synthesis of the D-Hormone (calcitriol; 1.25 (OH)2D) in the kidneys and bone, as well as from lack of receptors and/or receptor affinity for D-Hormone in the target organs. Parallel to the decreased bone strength a loss of muscle power occurs, together with an increase in balance disorders and an increasing risk of "intrinsic", nonsyncopal locomotoric falls. In alfacalcidol therapy, D-Hormone is provided to the body in circumvention of its own regulation, by means of which higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. In vitro and in vivo experiments have provided growing evidence that D-Hormone analogs tend to normalize PTH, lead to an increase in the number and activity of osteoblasts, reduce the activity of osteoclasts, and might thus normalize the "high bone turnover" in elderly osteoporotic patients ("supercoupling"). In addition, it has been shown that D-Hormone analogs are able to increase muscle power and walking distance in elderly D-Hormone deficient patients. Besides the known effect on the vertebral fracture rate, new clinical data confirm that D-Hormone analogs might reduce peripheral fractures by reducing falls. The expanded understanding of the pathogenesis of glucocorticoid- induced osteoporosis with its disturbed calcium homeostasis and the pharmacological effects of alfacalcidol, which counteract such iatrogenic bone loss, contribute to the understanding of its clinical efficacy in this most frequent form of secondary osteoporosis. Due to its recently discovered immunomodulating properties, alfacalcidol might find a slot in the management of bone loss caused by chronic inflammatory diseases or by organ transplantations. Alfacalcidol has multifactorial effects, among which the best known are its anti-bone loss and anti-fracture efficacies in postmenopausal osteoporosis. This demonstrated efficacy is related to its involvement in bone remodelling, leading to an improved bone strength. Its mode of action on muscle power, which reduces falls, is unique, differentiating this form of therapy from all other anti-osteoporotic drugs, none having demonstrated any influence on falls.
老年男性和女性的已确诊骨质疏松症的特征在于,由性激素缺乏和生长停滞引起的骨重塑解耦联,同时还表现为维生素D缺乏、肾脏和骨骼中D激素(骨化三醇;1,25-(OH)₂D)合成减少,以及靶器官中D激素受体缺乏和/或受体亲和力降低。与骨强度下降同时出现的是肌肉力量丧失,平衡障碍增加,以及“内在性”、非晕厥性运动性跌倒风险增加。在阿法骨化醇治疗中,绕过机体自身调节向体内提供D激素,通过这种方式,与单纯补充维生素D相比,靶组织中可实现更高的激素浓度。体外和体内实验越来越多地证明,D激素类似物倾向于使甲状旁腺激素正常化,导致成骨细胞数量和活性增加,破骨细胞活性降低,从而可能使老年骨质疏松患者的“高骨转换”(“超级耦联”)正常化。此外,已表明D激素类似物能够增加老年D激素缺乏患者的肌肉力量和行走距离。除了对椎体骨折率的已知影响外,新的临床数据证实,D激素类似物可能通过减少跌倒来降低外周骨折风险。对糖皮质激素诱导的骨质疏松症发病机制的深入理解,以及其钙稳态紊乱,和阿法骨化醇的药理作用,后者可抵消这种医源性骨质流失,有助于理解其在这种最常见的继发性骨质疏松症中的临床疗效。由于其最近发现的免疫调节特性,阿法骨化醇可能在治疗慢性炎症性疾病或器官移植引起的骨质流失方面发挥作用。阿法骨化醇具有多方面的作用,其中最广为人知的是其在绝经后骨质疏松症中的抗骨质流失和抗骨折疗效。这种已证实的疗效与其参与骨重塑有关,从而提高骨强度。其对肌肉力量的作用方式,即减少跌倒,是独特的,这使这种治疗方式与所有其他抗骨质疏松药物区分开来,其他抗骨质疏松药物均未显示对跌倒有任何影响。
J Musculoskelet Neuronal Interact. 2005
J Rheumatol Suppl. 2005-9
J Rheumatol Suppl. 2005-9
J Rheumatol Suppl. 2005-9
Rheumatol Int. 2009-8
J Musculoskelet Neuronal Interact. 2007
Clin Pharmacol Ther. 2025-6-6
J Musculoskelet Neuronal Interact. 2020-6-1
Clin Cases Miner Bone Metab. 2010-9