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Combined Therapy Superior for Osteoporosis

For post-menopausal women with osteoporosis, a recent study suggests that combined therapy with Fosamax (alendronate) and parathyroid hormone (PTH) improves bone-mineral density better than either drug taken alone, according to a report on MedPage Today published 10 August.

The study by Dennis Black et al. at the University of California, San Francisco, published in the New England Journal of Medicine (NEJM), included 119 women with osteoporosis.

Previously, Dr. Black and colleagues from the Parathyroid Hormone and Alendronate (PaTH) study reported results from the study’s first year. These results compared the effects on bone of treatment with PTH alone, Fosamax alone and combined therapy with PTH and Fosamax. Results of this study showed no advantage for combination therapy.

The current study included four study groups:

  • 59 women who had received PTH alone were randomly assigned to receive Fosamax (alendronate) for one year;
  • 60 women who had received PTH alone were randomized to receive placebo for one year;
  • 60 women who had already received Fosamax for one year were continued on Fosamax for a second year;
  • 59 women who had received one year of combination therapy were then randomized to receive Fosamax for one year.

At two years, bone mineral density (measured at the lumbar spine) increased significantly in all four groups. Women who received PTH alone, followed by Fosamax, had the largest increase (12.1%); this increase was significantly higher than those in the other three groups.

Women who received combination therapy followed by Fosamax had significantly greater increases than women who received PTH followed by placebo, who had the smallest increase (4.2%).

Based on their results, Black et al. concluded that "treatment with parathyroid hormone should be followed by antiresorptive therapy to consolidate the gains made in trabecular and cortical bone density during treatment with parathyroid hormone alone."

A Second Study

In the same issue of the NEJM, results of a second trial by Felicia Cosman, MD, and colleagues at Helen Hayes Hospital, West Haverstraw, NY, similarly showed combined therapy with PTH and Fosamax (alendronate) (taken concurrently or sequentially) resulted in significant improvements in bone-mineral density of the spine.

This study included 126 post-menopausal women with osteoporosis who had received Fosamax for one year or more. These women then randomly received either Fosamax plus Forteo (human PTH 1-34) subcutaneously daily; Fosamax plus Forteo in cyclic doses (3 months on, 3 months off); or a continuation of Fosamax alone for 15 months.

Women in both Forteo/Fosamax groups showed rapid rises in bone-formation indices. Among women receiving cyclic Forteo dosing, bone formation decreased during the off-Forteo cycles. Spinal bone-mineral density rose 6.1% in women receiving Forteo daily, and 5.4% in women receiving cyclic treatment.

Forteo therapy may be an effective, yet less costly, treatment option, according to Dr. Cosman and colleagues, because "early direct stimulation of bone function by parathyroid hormone might be more important to the ultimate accrual of bone mineral density than later activation of bone remodeling by parathyroid hormone."

Based on their findings, Dr. Cosman and colleagues concluded that "a second course of parathyroid hormone can stimulate bone formation with a magnitude similar to that induced by the first course of parathyroid hormone after a short interval without therapy."

Editorial Comments

In the same issue of the NEJM, an editorial by Robert P. Heaney, MD, and Robert R. Recker, MD, of the Osteoporosis Research Center at Creighton University in Omaha commented that the two studies showed that monotherapy with either PTH or alendronate is effective, but that combining the two drugs increases central bone-mass, "but to a lesser extent than parathyroid hormone alone."

Heaney and Recker also noted these studies confirmed "in the months and years after treatment with parathyroid hormone, some of all the bone gained during treatment appears to be lost if no further therapy is implemented," and that Fosamax preserves bone-mineral density gains achieved with PTH, and "adds a further quantum of bone in its own right, roughly similar in magnitude to the short-term effect of [Fosamax] given to previously untreated patients. Finally, parathyroid hormone appears to retain its anabolic effect in patients previously treated with [Fosamax]."

One Year of Alendronate after One Year of Parathyroid Hormone (1–84) for Osteoporosis, Dennis M. Black, et al. New England Journal of Medicine, volume 353, pages 555-565, 2005.
Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate, Felicia Cosman et al. New England Journal of Medicine, volume 353, pages 566-575, 2005.
Combination and Sequential Therapy for Osteoporosis, Heaney RP and Recker RR. New England Journal of Medicine, volume 353, pages 624-625, 2005.

Posted: August 2005