Concerns have been raised about infections among trial subjects. There were 11 instances of cellulitis in the denosumab group and one in the placebo group, he said. There were also more reports of endocarditis in the denosumab group.
But the problems have not grown worse in the three-year extension of manufacturer Amgen’s study of the drug, and two of the three endocarditis reports were fleeting cases, Dr. Watts said.
“I think that the cellulitis and endocarditis are simply random events that are likely to be different in low numbers of patients when you have a large clinical trial,” Dr. Watts said.
As far as more novel agents, Dr. Watts pointed to the cathepsin-K inhibitor odanacatib, which is in a phase III trial. Its hallmark, he said, is that it doesn’t appear to interfere with the “crosstalk” between the cells that can lead to bone resorption. Trials have shown good results with regard to bone density and a bone resorption pattern that varies over time, according to data supplied to Dr. Watts by manufacturer Merck.
Antisclerostin antibody, a blocker of sclerostin that is produced by osteocytes and has a key role in the cessation of bone formation, has also shown promising early results.4
“The inhibition of cathepsin-K and sclerostin offer the potential for novel effects” that are “more truly antiresorptive and anabolic,” Dr. Watts said.
Dr. Watts was an investigator on denosumab’s trials by manufacturer Amgen and on odanacatib’s trials by Merck.
Kenneth Saag, MD, MSc, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, examined several traditional topics—like the role of calcium and Vitamin D and measuring fracture risk—in the context of the latest information.
Calcium and vitamin D have their benefits in maintaining and improving bone density, but they also have drawbacks. One meta-analysis found a 30% increase in risk of myocardial infarction related to calcium.5 But, Dr. Saag cautioned that no meta-analysis looking at this link had cardiovascular events as a primary outcome.
Another meta-analysis found that calcium does not increase atherosclerosis, hospitalizations, or death outcomes.6
For vitamin D intake, doses that won’t be adequate and doses that are too high, should be avoided, Dr. Saag said. Generally, 800 to 2,000 IU/d is a good range for those at risk for fractures or falls, he said. “Overuse of calcium and vitamin D supplements may be deleterious.”
