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Studies on the Potential Mediators of Skeletal Changes Occurring during Puberty in Girls¹

Departments of Medicine, Pediatrics, Biochemistry and Physiology, Loma Linda University and Musculoskeletal Disease Center, J. L. P. Memorial Veterans Administration Medical Center (C.L., D.J.B., S.M.); and the Department of Pediatrics, Loma Linda University (E.L.-W.), Loma Linda, California 92357; and the Department of Endocrinology, University of Madras (N.S.), Taramani, Madras 600 113, India

Address all correspondence and requests for reprints to: Dr. Subburaman Mohan, Research Service (151), J. L. P. Memorial Veterans Administration Medical Center, 11201 Benton Street, Loma Linda, California 92357. E-mail: hyperlink mailto:mohans{at}llvamc.va.gov

In this study we evaluated the role of cytokines and insulin-like growth factor (IGF) system in mediating the skeletal changes that occur during puberty by determining the relationship between serum levels of cytokines and IGF system components vs. 1) bone formation and resorption parameters in serum and urine, 2) bone density, and 3) metacarpal bone indexes in 65 pubertal girls. Lumbar bone mineral density and metacarpal width increased significantly both between Tanner stages (TS) II and III and between TS III and IV, whereas metacarpal length and serum levels of stimulatory IGF system components increased significantly only between TS II and III. Biochemical markers of bone turnover were significantly less in TS IV girls than in TS II and III girls. In general, serum levels of IGF system components showed a significant positive correlation to bone density in TS II and III girls, whereas bone resorption markers corrected for creatinine showed a significant negative correlation to bone density in TS III and IV girls. Serum levels of IGF system components showed a significant positive correlation to serum osteocalcin levels as well as metacarpal width in TS II girls, whereas urinary levels of bone resorption markers showed a significant negative correlation to metacarpal width in TS IV girls. Serum levels of interleukin-6 were decreased during late puberty and were negatively correlated with bone density in TS III and IV girls. Our data are consistent with a model in which the sex steroid hormone-induced increase in the IGF system leads to an increase in longitudinal growth and periosteal bone expansion, whereas the sex steroid hormone-induced reduction in bone turnover (possibly via cytokines) leads to an increase in cortical thickness via endosteal regulation.

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