Amgen’s experimental bone drug, called denosumab, was found to reduce the risk of spinal fractures in women with osteoporosis by 68 percent in a clinical trial which involved 7,868 patients with osteoporosis. The drug targets a protein involved with bone-destroying cells called osteoclasts, which are cells that remove bone tissue by removing its mineralized matrix. Osteoclasts formation requires the presence of RANK ligand (receptor activator of nuclear factor κβ). Osteoclasts and osteoblasts play a major role in controlling the amount of bone tissue: osteoclasts resorb bone, osteoblasts are bone builders.

The idea behind the new osteoporosis drugs, denosumab and odanacatib, 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,” Susan Bukata, MD, an orthopaedic surgeon and associate professor who directs the University of Rochester's Center for Bone Health tells WebMD. Denosumab targets a chemical called RANK ligand, which osteoclasts, the so-called bone builders, need to complete their work.

Data from two studies of Amgen Inc.’s denosumab were presented at the American Society of Bone and Mineral Research meeting in Montreal.

The results from the company’s latest clinical trials were presented his week in Montreal at the annual meeting of the American Society for Bone and Mineral Research.

In the latest clinical trials, 2.3 percent of the postmenopausal women getting denosomab experienced a vertebral fracture over a period of three years, compared with 7.2 percent of the participants taking a placebo. Overall, the drug has achieved a 68 percent reduction in spinal fractures compared with the percentage of 40 to 50 of the placebo group. The drug also reduced hip fractures by 40% and nonvertebral fractures by 20%.

Denosumab’s side effects in the trial were comparable to a placebo’s. About 4.3 percent of patients on denosumab developed serious infections compared to 3.4 percent of those receiving a placebo.

Another study, involving 504 postmenopausal women with osteoporosis, found that those who were given denosumab as an injection every six months increased bone density by about 2 percent compared with a 1 percent increase in women taking Fosamax. The researchers compared Amgen’s osteoporosis drug candidate with Merck & Co.’s Fosamax.

Another advantage is that denosumab is given once every six months by an injection. Amgen said that about three-quarters of the patients in one of its clinical trials preferred an injection of denosumab every six months to a bisphosphonate pill taken weekly.

Preliminary results of the study supported by Amgen showed that its experimental drug denosumab reduced the risk of osteoporosis and fracture in men with prostate cancer who were treated with drugs which cause bone loss.

About 200 million people are affected by low bone density or osteoporosis world-wide. Osteporosis is a bone disease in which the bone mineral density is reduced and is common for women after the menopause. The patients with osteoporosis present high risk of fractures, mostly involving the lumbar vertebrae, hip, and wrist.

The company should have all of data for its first denosumab filing with US regulators by the end of 2008 or early 2009. The drug could reach the market by 2010, Amgen said. Amgen is also testing the drug as a treatment for bone complications from cancer.