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Original Article
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Volume 353:566-575 August 11, 2005 Number 6
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Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate
Felicia Cosman, M.D., Jeri Nieves, Ph.D., Marsha Zion, M.S., Lillian Woelfert, R.N., Marjorie Luckey, M.D., and Robert Lindsay, M.D.

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ABSTRACT

Background We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to parathyroid hormone treatment and whether short, three-month cycles of parathyroid hormone therapy could be as effective as daily administration.

Methods We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus parathyroid hormone (1–34) subcutaneously daily, continued alendronate plus parathyroid hormone (1–34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without parathyroid hormone, or alendronate alone for 15 months.

Results In both parathyroid hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic parathyroid hormone, bone formation declined during cycles without parathyroid hormone and increased again during cycles with parathyroid hormone. Bone resorption increased in both parathyroid hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each parathyroid hormone group as compared with the alendronate group and no significant difference between parathyroid hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities.

Conclusions This study suggests that a regimen of three-month cycles of parathyroid hormone alternating with three-month cycles without parathyroid hormone causes the early phase of action of parathyroid hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with parathyroid hormone increase spinal bone mineral density.


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From the Clinical Research Center, Helen Hayes Hospital, West Haverstraw, N.Y. (F.C., J.N., M.Z., L.W., R.L.); the Department of Medicine, College of Physicians and Surgeons (F.C., R.L.), and the Department of Epidemiology, Mailman School of Public Health (J.N.), Columbia University, New York; Saint Barnabas Osteoporosis and Metabolic Bone Disease Center, Livingston, N.J. (M.L.); and the Department of Medicine, Mount Sinai Medical Center, New York (M.L.).

Address reprint requests to Dr. Cosman at the Regional Bone Center, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993, or at cosmanf{at}helenhayeshosp.org.

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Related Letters:

Alendronate and Parathyroid Hormone
Muldowney F. P., Black D. M., Sellmeyer D., Rosen C. J., Cosman F., Nieves J., Lindsay R.
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N Engl J Med 2005; 353:2618-2619, Dec 15, 2005. Correspondence

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