Studies look at ways to sequence, cycle osteoporosis drugs
■ Researchers seek new approaches to maximize the potential of treatments to build up bones or slow bone loss.
By Victoria Stagg Elliott — Posted Sept. 19, 2005
The two classes of osteoporosis drugs currently on the market -- one that builds bone and one that slows bone breakdown -- don't always work well together. But two papers published last month in the New England Journal of Medicine say this circumstance could be just a matter of timing.
Several studies have suggested that taking bisphosphonates and parathyroid hormone together might dull both treatments' efficacy, but these new studies showed that cycling or taking the drugs in sequence could lead to more satisfactory results.
"They're both good studies," said Robert Recker, MD, who wrote an accompanying editorial and is the director of the Osteoporosis Research Center at Creighton University in Omaha, Neb. "We need to figure out the best way to manage patients to get the best out of both medications."
One study involved 126 women already taking the bisphosphonate alendronate long term to reduce bone turnover. Participants were randomized into three groups. The first continued on this drug alone. The second group took alendronate and also received daily injections of teriparatide, a form of parathyroid hormone, continuously for 15 months. The third also took both drugs daily but injected the parathyroid hormone on a three-month on-again, off-again cycle.
Both groups receiving the hormone built more bone than the group that was only on alendronate. The group that cycled, however, did not re-absorb bone as much as the group that received non-stop hormone injections.
Teriparatide was approved by the Food and Drug Administration in November 2002 to be used no longer than two years because of concerns that longer use would increase the risk of bone cancer.
Authors of this paper suggest that their findings indicate that cycling the drug over a longer period but not exceeding the two-year limit in actual time a patient takes it may lead to better outcomes.
"The biggest effect is when we give the medication for a short period of time," said Felicia Cosman, MD, lead author and medical director of clinical research at Helen Hayes Hospital in West Haverstraw, N.Y. "We think we'll do even better if we give the drug over four years but for three-month cycles."
The second study involved women who had taken another version of parathyroid hormone, not yet approved by the FDA, for a year and then discontinued it.
Participants were randomized to receive either alendronate or placebo for a year. Women in the placebo arm lost the bone they had gained while taking the hormone. Those who took alendronate, however, maintained their bone density.
"[The] results are very exciting, because they have the potential to change how physicians currently treat women with osteoporosis," said Dennis M. Black, PhD, lead author and professor of epidemiology and biostatistics at the University of California, San Francisco.
Experts praised both studies for attempting to answer several open questions about osteoporosis treatment, including how to use the two strategies together, the effectiveness of parathyroid hormone in patients who already have been treated with biophosphonates such as alendronate, and what to do with patients after they've taken this hormone for the two years now allowed by the FDA.
"These are very exciting studies," said Kathryn Ryder, MD, associate professor of internal and preventive medicine at the University of Tennessee Health Science Center, Memphis. "They're going to have a direct impact on my practice."
But while these studies do take steps toward addressing some open questions, doctors who treat osteoporosis patients say the conclusions would have been stronger if the endpoint used was fracture incidence rather than biomarkers of bone formation. Experts note, though, that such an endpoint would have required the studies to be too large to be practical.
"Fracture reduction is hard to see, and that kind of study would be extremely expensive," said Jeffrey P. Levine, MD, MPH, assistant professor of family medicine at Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey in New Brunswick.