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N Engl J Med. 2005 Aug 11;353(6):566-75.

Daily and cyclic parathyroid hormone in women receiving alendronate.

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  • 1Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY 10993, USA.



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.


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.


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.


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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