An estimated 10 million Americans over the age of 50 years old suffer from osteoporosis and a further 32.9 million have low bone mass, placing them at an increased risk for developing this condition. Associated with an increased risk of fractures, which are both clinically problematic and costly to healthcare systems, the development of new osteoporosis treatments offers immense opportunities to the pharmaceutical industry. The global osteoporosis therapies market, including estrogen replacement therapy drugs was estimated at $5.5 billion in 2001 and projected to double by 2008 in the face of population aging, decreased bone quality and increased awareness of osteoporosis.

Once dominated by hormone replacement therapies (HRTs), the field of osteoporosis has undergone three major changes since the mid-1990's. First, the bisphosphonate Fosamax was launched in 1995. Since this launch the bisphosphonates have become the most effective means of limiting bone loss. Then, in January 1998 Eli Lilly launched Evista (raloxifene), the first selective estrogen receptor modulator and as a result the concept of combining the beneficial effects of estrogen antagonism (ie anti-cancer activity) and agonism (ie bone health) became a real therapeutic possibility. Most recently the FDA has approved the use of the parathyroid hormone Forteo (teriparatide), the first treatment for osteoporosis with anabolic activity. In a recent DiscoveryDossier we analyze therapeutic and pharmaceutical opportunities in the field of osteoporosis (click here for access).

Bone remodeling represents a balance between the activities of osteoclasts that remove bone and osteoblasts that synthesize bone matrices and mineralize them. These two cell types are coupled through the expression of osteoclastogenic factors such as RANKL and monocyte macrophage colony-stimulating factor (M-CSF) by osteoblasts and their progenitors (stromal cells) which regulate osteoclast differentiation. It remains likely that other osteoblast factors exist to ensure coordinated remodeling.

Japanese researchers have recently conducted a study in which rat antibodies to an osteoclastogenic mouse stromal cell line, TSB13, were raised. One such monoclonal antibody, A15-1, bound to a surface antigen on TSB13 cells, termed osteoclastogenesis-related antigen (OCRA) and prevented the ability of these cells or primary stromal cells to drive the differentiation of osteoclast precursors. The inhibitory effect of A15-1 on osteoclastogenesis was found to be rather specific for the cell-cell functional interaction between stromal cells and osteoclast progenitors and was also observed in vivo. The mechanism of action remains unclear however it appears unrelated to downregulation of RANKL expression or upregulation of OPG expression, two molecules that have been closely related to bone remodeling. The authors speculate that OCRA behaves as a functional co-factor for RANKL-mediated osteoclastogenesis. Pharmexa are currently developing a blocker of RANKL for the treatment of osteoporosis. The current study suggests that the development of strategies that block OCRA may be similarly useful.

Entry date Wednesday, April 23, 2003

Adapted from Arai et al, J Bone Miner Res 2003 Apr;18(4):686-95 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk