New Osteoporosis Drugs in the Works

Sept. 18, 2008 -- Two experimental osteoporosis drugs are getting attention from bone experts -- and may become the first biologic drugs to treat osteoporosis.

The drugs are called denosumab and odancatib. Results from their latest clinical trials, presented this week in Montreal at the annual meeting of the American Society for Bone and Mineral Research, show that the drugs boosted bone mineral density in postemenopausal women with osteoporosis.

Denosumab and odanacatib are "totally, completely new" ways of approaching osteoporosis, says Susan Bukata, MD, an orthopaedic surgeon and associate professor who directs the University of Rochester's Center for Bone Health.

"This is the new frontier in osteoporosis. This is the step into biologics for osteoporosis treatment," Bukata tells WebMD. She predicts that denosumab or odanacatib probably won't be the first osteoporosis treatments that doctors prescribe for most patients, and she says cost may be a factor in how widely the new drugs get used, if approved by the FDA.

How the New Drugs Work

Denosumab and odanacatib are both biologic drugs that target osteoclasts, which are cells that tear down bone to make way for new bone.

Your bones don't just sit there; they're constantly being remodeled. Osteoclasts are the wrecking crew; other cells, called osteoblasts, are the bone builders.

After you reach peak bone mass at about age 30, the balance between the bone breakdown and bone buildup shifts, favoring bone loss. Age -- and, for women, menopause -- tilts the balance further toward bone loss. In osteoporosis, the bones have become dangerously weak.

"As you age, things slow down," Bukata explains. "Unfortunately, for a lot of people, bone-building capacity slows down a little bit more than their bone-loss capacity."

The basic idea behind the new osteoporosis drugs is to rebalance bone loss and bone building so that those two processes "either stay in balance or, in fact, allow the osteoblasts to catch up a little bit," says Bukata. "By adding these agents, we are able to push things the way a younger person manages bone."

Denosumab's Clinical Trial

Denosumab is a monoclonal antibody given by injection twice a year. It targets a protein called RANK ligand, which osteoclasts need to do their job.

Denosumab has finished its phase lll clinical trials, the last set of trials needed before submitting a drug to the FDA for approval.

In those trials, postmenopausal women with low bone mineral density either got a shot of denosumab every six months or took alendronate (the active ingredient in Fosamax) every week.

A year later, bone mineral density in the lumbar spine and in the hip had improved more for the denosumab group than for the alendronate group.

Bukata notes that because biologic drugs affect the immune system, researchers keep a close eye on infection rates for biologic drugs, but infections weren't more common with denosumab in the trial.