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From the Clinical Research Centers |
Bone and Mineral Metabolism Laboratory, Departments of Physical Medicine, Medicine, and Nutrition, Davis Medical Research Center (V.M., J.Z.I., M.S., N.E.B., A.C., D.K., J.D.L.); and the Department of Statistics (P.G., R.W.N.), Ohio State University, Columbus, Ohio 43210
Address all correspondence and requests for reprints to: V. Matkovic, M.D., Ph.D., Bone and Mineral Metabolism Laboratory, Davis Medical Research Center, Ohio State University, 480 West 9th Avenue, Columbus, Ohio 43210.
Over the last century there has been a trend toward an earlier onset of menarche attributed to better nutrition and body fatness. With the discovery of the obesity gene and its product, leptin, we reexamined this hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the relation between leptin and bone mass. Body composition and serum leptin levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-ray absorptiometry, and leptin by a new RIA. All participants were premenarcheal at baseline (aged 8.3–13.1 yr). Leptin was strongly associated with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0.58; P < 0.0001). The rise in serum leptin concentration up to the level of 12.2 ng/mL (95% confidence interval, 7.2–16.7) was associated with the decline in age at menarche. An increase of 1 ng/mL in serum leptin lowered the age at menarche by 1 month. A serum leptin level of 12.2 ng/mL corresponded to a relative percent body fat of 29.7%, a body mass index of 22.3, and body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively related to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001).
A critical blood leptin level is necessary to trigger reproductive ability in women, suggesting a threshold effect. Leptin is a mediator between adipose tissue and the gonads. Leptin may also mediate the effect of obesity on bone mass by influencing the periosteal envelope. This may have implications for the development of osteoporosis and osteoarthritis.
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B. Kriström, B. Carlsson, S. Rosberg, L. M. S. Carlsson, and K. Albertsson-Wikland Short-Term Changes in Serum Leptin Levels Provide a Strong Metabolic Marker for the Growth Response to Growth Hormone Treatment in Children J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2735 - 2741. [Abstract] [Full Text]
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