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Toxicological Sciences 55, 171-188 (2000)
Copyright © 2000 by the Society of Toxicology

Safety Evaluation

Modeling Normal Aging Bone Loss, with Consideration of Bone Loss in Osteoporosis

Ellen J. O'Flaherty

Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, Ohio 45267-0056

A physiologically based model of normal bone loss in human aging is presented. The model is a modification of an existing physiologically based model of body and bone growth from birth to maturity. To account for loss of bone after peak bone mass is reached between ages 25 and 30 years, a slow first-order loss of bone is incorporated into the existing model. The rate constants for this first-order loss are the same for men and women but differ with the type of bone, being 3%/decade for cortical bone and 7–11%/decade for trabecular bone. In women, a 10-year period of more rapid loss of both cortical and trabecular bone is superimposed on the slow loss, beginning at the time of menopause. The superimposed loss occurs at the same relative rate in cortical and trabecular bone. Alterations in parameter values allow simulation of bone mass in osteoporotic men and women. The model is calibrated to quantitative estimates of cortical and trabecular bone mass as functions of age; in particular, to data sets of fractional vertebral bone volume as functions of age, and it is compared to the International Commission on Radiological Protection trend curves for skeletal mass in men and women to age 60. It is also applied to the question of whether loss of bone in women after menopause could create a hazard related to the return to blood of lead previously stored in bone. In agreement with observations made during 1976–1980, the model simulates an increase due to bone resorption of approximately 1 µg/dl in blood lead concentration in a postmenopausal (60-year-old) woman compared with a premenopausal (50-year-old) woman with typical lifetime ambient lead exposure.

Key Words: osteoporosis; bone lead; blood lead; aging.


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