Rationale for active vitamin D and analogs in the treatment of osteoporosis

In 1981, Chugai Pharmaceutical succeeded in marketing alfacalcidol, a prodrug of calcitriol, as a therapeutic agent for renal osteodystrophy. In 1983, Chugai succeeded in extending the application of alfacalcidol to the treatment of osteoporosis as well. Clinicians in Japan have accepted alfacalcidol as a remedy for osteoporosis. However, the use of calcitriol and its analogs for the treatment of osteoporosis is still controversial. Some misunderstandings exist internationally about the efficacy of the active form of vitamin D for the treatment of osteoporosis. It is important to emphasize that patients with osteoporosis have intestinal calcium malabsorption and dysfunction in renal activation of vitamin D. When massive doses of parent vitamin D were administered to OVX rats, bone mass increased, but surprisingly, many porotic area were observed in the cortical bone. On the other hand, administration of alfacalcidol increased physiological bone without porotic observation. It is necessary to give the active form of vitamin D, D‐hormone, with an RDA‐equivalent supply of calcium. Alfacalcidol forms physiological strong bones that are hardly fractured by regulating calcium and bone metabolism. We proposed a new vitamin D analog, 2β (3‐hydroxypropoxy)calcitriol [ED‐71] as a therapeutic drug for osteoporosis, which is more potent than calcitriol. ED‐71 is now being investigated in phase 2 clinical studies in Japan. ED‐71 will appear as more improved drugs for osteoporosis until 2010. J. Cell. Biochem. 88: 381–386, 2003. © 2002 Wiley‐Liss, Inc.