Accumulated data describing the time course of bone loss in postmenopausal women were combined with metabolic data on estrogen-calcium interactions to produce a comprehensive, quantitative model of involutional bone loss. The model was shown to be able to mimic results of published intervention studies with considerable fidelity. Implicit in existing understanding, and made explicit by the model, are such relationships as: (1) calcium deficiency, if present in a woman, is masked during the early years of estrogen withdrawal bone loss; (2) accordingly, except in severe deficiency states, it is unlikely that calcium supplementation can confer much benefit in the immediate postmenopause; (3) however, by 5-8 years postmenopause, an underlying calcium deficiency, if present, becomes manifest, and if uncorrected will greatly augment the bone loss produced by estrogen withdrawal; (4) estrogen replacement therapy, if stopped, does not produce a sustained difference in bone mass in calcium-replete women; however, (5) estrogen, by effectively reducing the level of any calcium deficiency that may be present, does produce a permanent benefit in women with such deficiency. These relationships suggest that late fracture protection from earlier estrogen therapy is either confined to women with calcium deficiency, or has a non-mass basis (or both).
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