New antiresorptive agents may be better tolerated.(Clinical Rounds)

DESTIN, FLA. -- Investigational antiresorptive agents with novel methods of action and dosing regimens may improve patient compliance and persistence, but will not reduce the risk of fracture associated with osteoporosis beyond that seen with current agents.

"The objective of all these drugs is to normalize bone turnover, which we already do extraordinarily well and easily with bisphosphonates," Dr. Michael McClung said at a rheumatology meeting sponsored by the Virginia Commonwealth University.

However, some of the investigational antiresorptives are just as good at increasing bone mineral density as are the bisphosphonates, and may be easier for patients to take, he added.

Denosumab, currently in phase III studies, has shown some promising effects. The agent inhibits the binding of the RANK protein to its ligand. The binding increases the population of osteoclasts and allows them to live longer, inhibiting the binding blocks that process, thus reducing bone turnover.

A phase II study compared different denosumab doses with placebo and with alendronate. It found that denosumab increased bone density as well or better than alendronate, especially at sites greater in cortical bone. Denosumab reduced serum C-telopeptide levels more than did alendronate. Within 3 days of initiating therapy, the levels dropped 80% with all doses of denosumab, compared with 25% with alendronate (N. Engl. J. Med. 2006;354:821-31).

The drug was well tolerated, said Dr. McClung, director of the Oregon Osteoporosis Center, Portland, and principal investigator of the study. There were no injection site reactions or adverse events that increased with dosage, and no observed immune response problems. "Two patients did develop transient nonneutralizing antibodies, but in neither case was response to therapy affected," he said at the meeting, also sponsored by the International Society for Clinical Densitometry and the Alabama Chapter of the ...