Osteroporosis affects an estimated 10 million Americans over the age of 50 years old and a further 32.9 million have low bone mass, placing them at an increased risk for developing this condition. Osteoporosis is blamed for more than 1.5 million fractures in the US each year. One in two women and one in eight men over 50 years of age will suffer an osteoporosis-related fracture during their lifetime. The direct medical cost for treating such fractures was estimated at $16.8 billion in 2001, up from around $13.8 billion in 1995. The US osteoporosis therapies market, including estrogen replacement therapy drugs, generated approximately $3.9 billion in 2001; the global market was estimated at $5.5 billion and projected to double by 2008. LeadDiscovery have recently published an analysis of therapeutic and pharmaceutical opportunities surrounding osteoporosis (Click here for access).

Vitamin K and vitamin D analogs have both been investigated for their ability to prevent the development of osteoporosis or even increase bone mass in patients with this disease (click here for further details). However, therapeutic use of the natural form of vitamin D, 1,25-dihydroxyvitamin D(3) has been precluded in most cases because of its potent calcemic activity. Vitamin D analogs such as calcitriol and alfacalcidol have also been investigated, however these analogs are likewise limited by their calcemic activity. More recently Chugai (now Hoffman-La-Roche) have been developing 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71). In preclinical studies, ED-71 increased bone mass in the ovariectomized rat model for osteoporosis to a greater extent than alfacalcidol, while having an effect on calcium absorption and parathyroid hormone levels comparable with that of alfacalcidol. Since this preclinical data suggested selective effects on the bone an early phase II clinical trial was conducted with 109 primary osteoporotic patients. The results, which have recently been published, support these early findings indicating that oral daily administration of ED-71 for 6 months increased lumbar bone mineral density in a dose-dependent manner without causing hypercalcemia and hypercalciuria. These results demonstrate that ED-71 has preferential effects on bone with diminished effects on intestinal calcium absorption. ED-71 offers a new modality of therapy for osteoporosis with selective effects on bone. Chugai announced in 2000 that ED-71 represented a licensing option, however since then Roche's acquisition of Chugai has been reported and the status of ED-71 remains to be clarified.

Entry date January, 2003

Adapted from Kubodera et al, J Cell Biochem 2003 Feb 1;88(2):286-289 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.