While in other chronic diseases combined treatment regimens are the rule, there is a lack of reported experience or study data on combining different specific drugs to treat osteoporosis. Significant differences in the mode of action (MOA) of the substances to be combined may be important for achieving optimal therapeutic results.
Recognising that today bisphosphonates are the leading therapy for osteoporosis, researchers at the Leverkusen Clinic in Germany suggested that the active D-hormone analogue alfacalcidol, with its completely different mechanisms of action, could be an interesting combination to improve the therapeutic outcome of the pure antiresoptive action of bisphosphonates. Alfacalcidol is activated by the enzyme 25-hydroxylase in the liver for systemic actions, and in osteoblasts for local D-hormone actions. It possesses a unique pattern of pleiotropic effects on, for example, the gut, bone, pararthyroids, muscle and brain. Alfacalcidol is superior to plain vitamin D (cholecalciferol) because the final kidney activation of the latter is regulated by a negative feedback mechanism. In vitamin D replete patients, or patients with impaired kidney function, no increased D-hormone action at the target tissues can be achieved. Animal studies and several trials in humans with alendronate plus calcitriol or alfacalcidol proved that the combination induced significantly higher increases of bone mineral density (BMD) than the respective mono-therapies. The results of the 2-year AAC-trial from the Leverkusen Clinic indicate that the combination alendronate and alfacalcidol is also superior in terms of falls, fractures and back pain. From the review of the literature and their own new results, the researchers concluded that this combined therapeutic regimen is a very promising option for treating established osteoporosis. They propose a differentiated use of alfacalcidol alone or the combination with alendronate in different stages and clinical situations of osteoporosis.(Source: Ringe JD, Schacht E. Improving the outcome of established therapies for osteoporosis by adding the active D-hormone analog alfacalcidol. Rheumatol Int. 2007 Aug 1; [Epub ahead of print]. : August 2007)