Accretion of Bone Mass and Strength with Parathyroid Hormone Prior to the Onset of Estrogen Deficiency Can Provide Temporary Beneficial Effects in Skeletally Mature Rats

Authors

  • V. Shen,

    Corresponding author
    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
    2. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A.
    • Address reprint requests to: Victor Shen, Ph.D., Regional Bone Center, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993 U.S.A.
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  • R. Birchman,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
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  • X. G. Liang,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
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  • D. D. Wu,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
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  • D. W. Dempster,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
    2. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A.
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  • R. Lindsay

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, U.S.A.
    2. Departments of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A.
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Abstract

Intermittent administration of parathyroid hormone (PTH) has been shown to be an anabolic agent for animal and human skeletons. In previous studies, PTH has been used concurrent with, or subsequent to, the onset of bone loss. However, it is entirely possible that PTH may be used as an anabolic agent in a situation where there is stable skeletal remodeling. Increasing bone mass at this time might confer long-lasting beneficial effects when bone loss begins, for example, subsequent to the loss of ovarian function. To test this hypothesis, we evaluated the effects of administering rat PTH(1–34) (80 μg/kg/day, subucutaneously [sc]) to 6-month-old rats for a 2-week period prior to ovariectomy, and followed the natural occurrence of bone loss over a 14-week period. To determine the effects of estrogen intervention on bone gained by PTH treatment, one group was repleted with 17β-estradiol (10 μg/kg/day via sc implant). Serial measurements of bone mass in vivo at the distal femur were obtained at 2-week intervals using dual-energy X-ray absorptiometry, while histologic and mechanical strength data were obtained from excised proximal tibiae and distal femurs after sacrifice. Two weeks of PTH treatment resulted in an increase of bone mineral density (BMD), mechanical strength, and cancellous bone volume (CnBV/TV). Four weeks after PTH withdrawal, significant residual beneficial effects on BMD and strength, irrespective of ovarian status, were observed. However, 14 weeks after PTH withdrawal, although there were still residual effects on CnBV/TV in ovariectomized animals pretreated with PTH, the PTH effects on BMD and mechanical strength had been lost. Estradiol repletion during the rapid bone loss phase following ovariectomy prevented the reduction in BMD associated with either ovariectomy or PTH withdrawal. Our results suggest that: treatment of rats with PTH prior to ovariectomy produces an increase in BMD and strength, these beneficial effects extend for a period of at least three times the treatment duration, the BMD that is lost when PTH is discontinued equates to the amount accrued during the PTH treatment, estrogen replacement can be used to maintain the bone gained as a result of PTH treatment.

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