Two New Osteoporosis Drugs Increase BMD More Than Alendronate

Barbara Boughton

October 30, 2008

October 30, 2008 (San Francisco, California) — Teriparatide prevents bone loss and increases bone mineral density (BMD) over the long term in patients taking glucocorticoids, such as prednisone, compared with alendronate, according to a new study. In a second study, denosumab increased bone mass in postmenopausal women. Both papers were presented here at the American College of Rheumatology 2008 Annual Scientific Meeting.

The double-blind randomized controlled trial that compared the effects of teriparatide (Forteo) and alendronate (Fosamax) in patients taking glucorticoids was the first to extend teriparatide use to 36 months. The researchers randomized 214 patients to either teriparatide 20 μg per day or alendronate 10 mg per day.

Although both groups experienced increases in bone mass, the researchers found that the mean percent increase in BMD was significantly greater in patients taking teriparatide than in those taking alendronate at the lumbar spine (11% vs 5.3%) and femoral neck (6.3% vs 3.4%), both frequent fracture sites for patients taking glucocorticoids. They also noted that fewer patients taking teriparatide than taking alendronate experienced vertebral fractures (1.7% vs 7.7%).

“Teriparatide stimulates osteoblastic activity and inhibits osteblast apoptosis, so there’s a rationale for its use in this condition. It’s a therapeutic strategy that could be considered for glucocorticoid-induced osteoporosis, particularly those at high risk for fracture,” said Kenneth Saag, MD, professor of medicine and epidemiology at the University of Alabama, in Birmingham, and lead investigator in the study.

However, the number of nonvertebral fractures was similar in both groups, although both drugs were well tolerated. One patient exhibited symptomatic hypercalcemia in the teriparatide group, but no patient in the alendronate group experienced this adverse event.

Like many patients taking glucorticoids, the population in the study was at significantly increased risk for fracture. All had been taking at least 5 mg of prednisone for at least 3 months. Most had bone mass within the osteopenic range, and some had been diagnosed with osteoporosis. More than 40% had experienced a previous nonvertebral fracture.

“This was an at-risk population,” Dr. Saag said. “The results show that teriparatide can be another alternative for these patients. Many such patients have an estimated rate of fractures approaching 50% with chronic glucocorticoid use,” he told the attendees.

In the second double-blind randomized controlled trial, the researchers compared the effects of denosumab and alendronate on bone mass in postmenopausal women. Denosumab is a fully humanized monoclonal antibody against RANKL, a ligand that is critical for osteoclast survival and development.

The researchers followed 1189 postmenopausal women with low bone mass who were randomly assigned to receive either a 60-mg injection of denosumab every 6 months and a weekly oral placebo, or an injection of placebo every 6 months and a weekly 70-mg dose of alendronate. The subjects had a mean lumbar spine T-score of –2.6.

Results showed that a greater number of patients in the denosumab group gained more than 3% of BMD than those in the alendronate group at the total hip (62% vs 39%) and at the lumbar spine (77% vs 65%) after 12 months. Denosumab also caused superior gains in BMD at all 5 skeletal sites evaluated: the total hip, lumbar spine, femoral neck, trochanter, and distal third of the radius.

Denosumab also suppressed serum markers of bone turnover, such as serum type 1 C-telopeptide and procollagen type 1 N-propeptide within 1 month of treatment, and this effect was sustained over 12 months. Adverse events were similar in both groups.

Another significant difference between the drugs is their half-lives. “Fosamax has a long residual effect on bone, particularly for patients who take it for 5 years or more. But denosumab has both a quicker onset and a quicker offset,” said lead investigator Chad Deal, MD, head of the Center for Osteoporosis and Metabolic Bone Disease at the Cleveland Clinic, in Ohio, at a press conference.

In a trial of 7868 women with osteoporosis, reported by the same researchers at the American Society for Bone and Mineral Research meeting in September, denosumab also significantly decreased the risk for nonvertebral and hip fractures.

“The results show that both these medications are effective for glucocorticoid-induced osteoporosis, a very serious problem, and for postmenopausal women with osteoporosis,” said Willem Lems, MD, professor of rheumatology at Free University Hospital in Amsterdam, the Netherlands. “Together, they are very attractive data,” said Dr. Lems, who attended both presentations.

Dr. Lems noted that denosumab has the potential to increase patient compliance in those with osteoporosis. “The research we’re hearing now shows us that many patients prefer to take an injection every 6 months than weekly oral medications,” he said.

The teriparatide study was funded by Eli Lilly. Dr. Saag has reported consulting fees from Amgen, Eli Lilly, Merck, Novartis, Roche Savient, and Tap Pharmaceuticals. The denosumab study was funded by Amgen. Dr. Deal has reported receiving consulting fees from Amgen, Eli Lily, GlaxoSmithKline, Merck Human Health, Merck, Novartis, Proctor & Gamble, and Roche Pharmaceuticals. Dr. Lems has disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2008 Annual Scientific Meeting: Abstracts 2101 and 2102. Presented October 29, 2008.

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