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A B S T R A C T Longitudinal studies have shown that individuals lose bone mineral at unequal rates with aging. It has been postulated that individuals with the more rapid rates of loss constitute a separate population having an increased risk for developing fractures, i.e., osteoporosis. To examine this postulate, we made a search for a separate population of elderly women using a precise and objective measurement technique of bone mineral, photon absorptiometry.Bone mineral content (BMC) was measured in the radius of 571 Caucasian females who were age 50 or older. It was found that BMC values adjusted for width had a normal distribution in all decades and the variation in BMC values did not increase with age. Subjects with vertebral fractures (n = 108) were estimated to be losing bone mineral at the same rate as those without vertebral fractures (n = 161). Thus evidence for a separate population of rapid losers of bone mineral was not found.Reconciliation of longitudinal studies which show unequal rates of loss with the present population survey, in which evidence for unequal rates was not found, would require that (a) the rate of loss of bone mineral for an individual is not constant and/or (b) the rate of mineral loss is proportional to the amount of mineral present at maturity.The incidence of vertebral fractures was inversely proportional to BMC values. In a group of 278 women followed for 470 subject-yr, the incidence of all fractures during the study (n = 31) was also inversely proportional to BMC. These data suggest that the BMC values of osteoporotics would be at the lower end of normally distributed values for the population.

Subjects (109) with symptomatic Paget's disease of bone were treated with 5, 10, or 20 mg of sodium etidronate (EHDP)/kg body weight - day for 6 to 24 months. Significant decreases in serum alkaline phosphatase and urinary hydroxyproline were noted after 6 months of therapy; no significant further improvement resulted after prolonged therapy. Some patients maintained biochemical remission after withdrawal of EHDP but others showed a relapse, related primarily to the pretreatment severity. Clinical improvement was noted in 61% of the patients. Similar findings were seen after a second course of EHDP. No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day. In patients treated with 10 or 20 mg of EHDP/kg body weight - day, severe diarrhea, bone pain, and nontraumatic fractures were noted in 3, 13, and 12 patients respectively. Quantitative histomorphometry showed mineralization delay in patients receiving 10 or 20 mg of EHDP/kg body weight - day but not in those receiving 5 mg/kg body weight - day. Five milligrams of EHDP/kg body weight - day was effective and appears to be safer than the higher doses.

A B S T R A C T It has been postulated that the rate of mineral loss in postmenopausal women remains constant with aging and that the decreased activities of daily living associated with aging contribute to mineral loss. These hypotheses were examined by measuring the bone mineral content at the midshaft of the radius with the photon absorption technique. The estimated rate of loss was calculated in a cross-sectional study as the regression coefficient of bone mineral content vs. age and in a longitudinal study as the regression coefficient of bone mineral content vs. time.In the cross-sectional study, Group A, which consisted of 264 women aged 50-72 yr, had an estimated rate of loss of -0.0114±0.0014 (SE) g/cm per yr.Group B, which consisted of 266 women aged 73-96 yr, had an estimated rate of loss of -0.0055+0.0017 g/cm per yr.In the longitudinal study, Group C consisted of 33 women aged 51-65 yr who were followed for an average of 4.5 yr with a mean number of 16 visits per subject; they were found to have a mean rate of loss of -0.00990 ±0.00107 g/cm per yr. Group D consisted of 38 women aged 70-91 yr who were followed for an average of 3.8 yr with a mean number of 31 visits per subjects; they were found to have a mean rate of loss of -0.00020± 0.00236 g/cm per yr.The estimated and directly measured rates of loss were more rapid in the younger groups than in the older groups (A vs. B, P < 0.001; C vs. D, P < 0.001). jects it is significantly slower than that of the earlier postmenopausal years. Since the elderly women were the less active, these findings suggest that factors other than decreased physical activity are more important in determining the rates of mineral loss. INTRODUCTIONThe study of the pathogenesis of postmenopausal osteoporosis has been hampered until recently by the lack of a sufficiently precise method of bone mineral measurement to detect the low rate of mineral loss which ultimately leads to the disease state. Consequently, clinical investigations have been approached primarily by means of cross-sectional (population survey) studies of subjects over a wide age range. These studies have suggested that mineral loss from the skeleton is widespread within the population, if not a universal phenomenon (1)(2)(3)(4)(5). Furthermore, they have demonstrated that a primary consequence of the reduction of bone mineral is an increase in the incidence of fractures (1, 3-5).The inability to directly measure rates of mineral loss has largely prevented further studies such as the relationship of rates of loss to the development of osteoporosis, i.e., to determine if osteoporotics are rapid or slow losers of mineral, and the variables which affect rates of mineral loss. Recently, the value of the photon absorption technique to measure rates of loss of mineral has been demonstrated (6). The precision of the photon absorption method and ability to make multiple measurements on the same individual has made the direct measurement of rates feasible in longitudinal studies (6). Although this measurement is made...

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