Osteoporosis patients who remain at high risk for fracture despite a course of parathyroid hormone (PTH) therapy may benefit from a second discrete course of PTH, thus potentially enhancing their quality of life, according to new research presented at the 27th Annual Meeting of the American Society for Bone and Mineral Research in Nashville, Tennessee.

Patients on long-term ongoing alendronate therapy, rechallenged with PTH after a 12-month period without the hormone, showed increases in bone formation, resorption, and BMD that were similar to those seen during the first course of PTH administration.¹

"Many women were still at risk for future fracture, even if they responded well to the first course of PTH therapy," lead researcher Felicia Cosman, MD, medical director of the Clinical Research Center at Helen Hayes Hospital in West Haverstraw, New York, and clinical director of the National Osteoporosis Foundation in Washington, DC, tells CIAOMed. "A second discrete course given at a 1-year interval gives us the best chance of seeing a similar effect," she explains.

Extension study protocol

The new research is an extension of a randomized clinical trial of 126 women with osteoporosis who were treated with alendronate for at least 1 year and then assigned to remain on the therapy and receive daily PTH (1-34) at 25 µg/day, cyclic PTH (1-34) at 25 µg/day administered in 3-month-on/3-month-off cycles, or alendronate alone.² While these 3-month cycles were as effective as daily injections at building bone at the spine, with less cost and effort for patients, the combination of the two agents did not produce as significant a gain in bone mineral density (BMD) as PTH alone.

After 15 months of therapy, patients continued taking alendronate for an additional 12 months and then were invited to participate in this observational extension protocol, where they were offered daily PTH (1-34) therapy for an additional 15 months. Of the 108 subjects who completed the original 15-month trial, 82 patients completed the 12-month follow-up. Of these, 43 agreed to participate in the extension study.

Data reported from first 24 patients in extension trial

Among the first 24 patients analyzed, results showed that biochemical indices returned to pre-PTH treatment baseline levels, with no significant decline in peak BMD during the 12-month interval between the PTH challenge and the rechallenge. Since all subjects in both the original daily and cyclic PTH groups received the same PTH dose for the first 3 months, data from the PTH groups were combined for the 3-month biochemical bone turnover analyses, Dr. Cosman and colleagues report.

Effects of the PTH rechallenge on BMD of the lumbar spine at 15 months were comparable to those seen at the same time during the first PTH challenge. Serum osteocalcin increased by 77.9 +10% during the initial PTH challenge and by 75.6 +23% at 3 months during the rechallenge. Urine N-telopeptide increased by 102 +52% during the initial PTH challenge and then by 124 +55% during the PTH rechallenge at 3 months. In addition, spine BMD increased by 5.3 +1.2% during the first PTH challenge and by 4.3 +0.7% during the PTH rechallenge at 15 months.

"You can use PTH to induce stepwise, but progressive increases in bone density occur particularly when you have an intervening drug such as alendronate," Dr. Cosman tells CIAOMed, qualifying that this is only one small study. "I think we need to consider it ‘proof of concept' at this point. I would like to see further investigation before it becomes routine standard of care," she says, adding that follow-up studies are already planned by her research team.

Sequential therapy may be the key according to previous study

A related study showed that bone-mineral density gains seen after PTH treatment were rapidly lost when treatment was stopped. However, these gains were maintained and increased when PTH was followed by alendronate.³

According to the study researchers, led by Dennis Black, PhD, professor of epidemiology and biostatistics at the University of California in San Francisco, "increases in BMD during 1 year of treatment with PTH appear to be rapidly lost after therapy is discontinued." However, the study showed that "treatment with the bisphosphonate alendronate immediately after the discontinuation of PTH either maintains or further increases BMD in year 2." Specifically, results showed a 31% increase in spine BMD among women taking PTH followed by alendronate, compared with only a 14% increase in those taking PTH followed by placebo.

References

Cosman F, Nieves JW, Zion M, Barbuto N, Lindsay R. Effects of PTH rechallenge 1 year after the first PTH course in patients on long-term alendronate. Presented at: 27th Annual Meeting of the American Society for Bone and Mineral Research; September 23–27, 2005; Nashville, Tenn. Presentation 1079.