Plain vitamin D or active vitamin D in the treatment of osteoporosis: where do we stand today?

Osteoporosis is a major cause of morbidity and mortality worldwide and its prevention in order to avert fractures was considered of great importance in maintaining well-being and independence among the elderly. Strategies for osteoporosis prevention are well delineated, but research shows that the treatment options offered today could still be improved. The role of plain vitamin D (cholecalciferol) in bone health and the prevention of osteoporosis are well documented; however, as a treatment for osteoporosis, either with or without calcium, it has been shown to be ineffective. This is due in part to the strong negative feedback mechanisms in place in vitamin D-replete patients. However, other factors linked directly to ageing such as oestrogen depletion, reduced kidney or liver function may also be involved in reducing the body's capability to activate plain vitamin efficiently. This is why active vitamin D analogues such as alfacalcidol, 1-alpha-(OH)D3, are of clinical interest. Alfacalcidol requires only one hydroxylation reaction to become active 1,25-(OH)2-vitamin D3, and the 25-hydroxylase catalyzing this reaction is found in the liver and also interestingly in osteoblasts suggesting a local effect. Registered for use in postmenopausal osteoporosis, in most countries worldwide, alfacalcidol has also shown efficacy in glucocorticoid-induced and male osteoporosis. The present review provides compelling evidence for the efficacy of this compound in the treatment of osteoporosis and prevention of fractures both in monotherapy and when combined with other osteoporotic drugs where additive effects are clear. The safety profile of alfacalcidol is shown to be highly acceptable and it is considered less likely to induce hypercalcaemia than another more widely used analogue, calcitriol. Therefore, it remains unclear as to why alfacalcidol is not more widely used in clinical practice.