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OBJECTIVE: The objectives of this study were to develop a software program that calculates bone cross-sectional area (CSA) and moments of inertia from digital images, test the computations for accuracy, and implement the software in a study of longitudinal changes in bone properties in a large group of postmenopausal women. MATERIALS AND METHODS: A program called SLICE was adapted to use computed tomography (CT) bone images as input. The main outcome variables of the resulting program, SLICE_CT, were bone CSA, areal moments of inertia, and mass-weighted moments of inertia. SLICE_CT was tested for accuracy using representative arrays of CT numbers that approximate cross-sections of cortical bone. Then the technique was applied to images from a 3 year longitudinal study of the radius in 86 postmenopausal women who underwent quantitative CT of the dominant radius at 30% the distance from the wrist to the elbow. The mean age of the subjects at entry into the study was 57 years. Images at baseline and at 3 years were analyzed, and the null hypothesis of no change in cross-sectional geometry was tested by a paired difference two-tailed t test. RESULTS: The error of SLICE_CT was < 1% with proper segmentation, using half-maximal height as the threshold. In the longitudinal study of postmenopausal women, the mean change of CSA of the radius was -1.4% (SD = 3.0%; p < 0.001). However, there was a compensatory 2.4% increase in the cross-sectional second polar moment of inertia (SD = 3.7%; p < 0.001). CONCLUSION: SLICE_CT is an accurate method with which to determine cross-sectional geometry of digital images and can be used to detect changes in cross-sectional geometry of the radius with age in postmenopausal women. The results indicate that the radius remodels to compensate for bone loss and decreasing material properties of bone associated with aging.

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This study focused on age and physical activity as determinants of muscle strength. The study involved 620 women 25-73 yr of age. The five muscle groups assessed were: grip, plantarflexors, hip abductors, trunk flexors, and trunk extensors. Pearson correlations yielded significant negative correlations of muscle strength with age and positive correlations with height as well as physical activity. The greatest decremental differences in muscle strength were registered in the perimenopausal years between the age decades of 45-54 yr and 55-64 yr. In stepwise regression analyses age was the strongest predictor of the strength of all muscle groups, with smaller contributions to the variance by physical activity and anthropometric variables. When the sample population, divided by decades of age, was further subdivided by tertiles of physical activity, the results of factorial analysis indicated that the main effects due to age and physical activity were significant. It was concluded that 1) moderate levels of physical activity tend to improve muscle strength even in older women, and 2) normative values of muscle strength could serve as an indicator of the adequacy of the habitual levels of physical activity.

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This communication explores the correlation in 255 postmenopausal women of grip strength to bone tissue density (BTD) and cross-sectional area (CSArea) of the radius. While grip strength correlated cross-sectionally with the baseline measures of both BTD and CSArea, grip strength affected differentially the changes that transpired in the two bone parameters over the 3 years of the study. Thus, the increases in the CSArea of the radius were significantly enhanced by higher grip strength, while BTD losses were not. Since the power of muscle contraction is a factor in the mechanical loading of a bone, it is argued that the differential effects of grip strength on the two bone parameters of the radius suggest that moderate loading can effect favorable changes in the geometry of the bone, without necessarily affecting changes in BTD.

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To examine the interactions between hormone levels and calcium with cortical bone, we have attempted to combine risk factors for the development of peak skeletal mass with factors that may be related to the maintenance of bone integrity after menopause. A total of 174 postmenopausal women participated in our study. There was little relationship found between androgen hormones and radial bone density. Estrone levels were independently related to radial bone density. Examination of the relationship of calcium intake to bone revealed a protective effect solely in women who reported high "lifetime" calcium intakes. Taking calcium and estrone together revealed an additive relationship between the two factors, in that women with high estrone and high calcium levels had significantly greater bone density than women with less calcium and/or estrone. The results suggest that a lifetime of adequate calcium intake coupled with adequate levels of serum estrogens could maximize bone density after menopause.

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The aim of the present research was to determine the association between historical physical activity and baseline bone measurements in a group of 223 postmenopausal women participating in a clinical trial in Pittsburgh, Pennsylvania, from 1981 to 1986 by evaluating the effect of moderate physical activity on bone loss. Historical physical activity was assessed by a survey which divided the life span into four time periods (14-21, 22-34, 35-50, and 50+ years) and inquired about participation in leisure time physical activities for each period. From the responses, kilocalories of energy expenditure were calculated. Cortical bone density and area were measured in the radius with a computerized tomography scanner. The historical physical activity survey was administered a second time two to three months after the initial test to a 10% random sample of the women in order to determine the test-retest reliability of the instrument. Since the measurements of historical physical activity proved to be reliable, estimates of kilocalories determined for the entire population of women were correlated with bone area and density. A significant relation was found to exist between historical physical activity and dimensions of adult bone, particularly bone area. This association remained significant after adjustment for potential confounding variables and seemed to be strongest in the earlier age periods. To the authors' knowledge, this is the first report of a significant association between historical physical activity and bone.

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Most of the research on the level of high density lipoprotein cholesterol (HDL-C) and physical activity (PA) has been cross-sectional and thus self-selection of the exercisers may occur. In the current research, 229 white postmenopausal women, mean age 57.7 years, were randomized into either a walking or a control group. Of these 229 women, 204 women had blood samples available for lipid determinations. PA was measured subjectively by the Paffenbarger Survey and objectively with activity monitors. At baseline, there were no differences in PA, total HDL-C (HDL-TC), HDL-2C or HDL-3C between the two randomized groups. After two years, the PA of the walking group was significantly higher than the PA of the control group. This increase in PA was not accompanied by changes in any of the lipids or lipoproteins. Examination of the lipid changes in the walking group by compliance status and actual activity changes revealed little difference between groups. These results suggest that it is possible to increase physical activity in older women. However, the long-term effects of the increased activity on HDL-C were not apparent despite an observed strong cross-sectional relationship between PA and HDL-C.

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This report deals with the analysis of data from a 3-year clinical trial on the effect of walking on postmenopausal bone loss. Two hundred fifty-five women, with an average age of 57 at entry, were randomized into two groups, a walking and a control group. Bone measures in the shaft of the radius were carried out with a CT scanner in search of generalized skeletal effects rather than effects localized to the bones of the leg. Although bone density losses were comparable in the two randomized groups, changes in the cross-sectional area of the radius were significantly greater in the walkers with high grip strength (greater than 25 Kg) than in the controls with comparable high grip strength which corresponded to the upper half range of the grip-strength distribution. It is concluded that the moderate activity of walking exerted systemically positive effects on the radius which, within the protocol of the study, could be substantiated only when synergized with inherent muscle strength.

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The focus of this study was the relationship of grip strength to age, physical activity and anthropometric factors, in a population of 255 post-menopausal women not on estrogen therapy (mean age = 57.6) and 55 women currently on estrogen replacement therapy (mean age = 56.9). Grip strength was measured as an indicator of muscular strength in the upper limbs. The grip strength of the estrogen users was significantly higher than that of the estrogen abstainers. Grip strength was related to age (r = -0.25, p less than 0.01), and the body habitus parameters of height (r = 0.36, p less than 0.01) and weight (r = 0.18, p less than 0.01). Although estrogen use was univariately correlated with strength (r = 0.16, p less than 0.05), multiple regression analyses revealed that only the height, age and physical activity were independent determinants of grip strength. These data suggest: height is the major determinant of upper body strength in older women; the reduction in physical activity with advancing age may contribute to strength decline, and modest increase in physical activity may retard the loss of strength that accompanies aging; the loss of ovarian estrogen in menopause may be related to the loss of strength in postmenopausal women.

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Five methods for assessing physical activity were evaluated in a population of 255 white, postmenopausal women participating in a randomized trial on the effects of walking on bone loss. Methods were the Paffenbarger survey, a modified Paffenbarger, the large-scale integrated activity monitor (LSI), caloric intake, and the Baecke survey. Significant increase in physical activity was observed in the intervention group. Activity measures were weakly related to each other. Results of factor analyses suggest that factor I reflected voluntary leisure-time pursuits (such as walking) and factor II, activities of daily living. Participation in sports was not a significant contributor to overall activity of the women. Research on physical activity must define the particular dimension of activity measured. Several types of instruments should be used because different instruments reflect different activity patterns which, in turn, may be differentially related to disease.

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The relationship of endogenous concentrations of estrogen, in particular estrone, to the dominant radial bone density and bone area was examined in 78 normal postmenopausal women (mean age 57 years). The women were a subset of a population participating in a clinical trial designed to determine the effects of walking on bone loss. The data reported here were collected at baseline prior to randomization. Radial cortical bone density and bone area were measured at 30 per cent of the distance between the wrist and the elbow in the dominant arm. Estrone levels obtained by extraction and column chromatography were measured by radioimmunoassay. Estrone concentrations were cross-sectionally related to both radial bone density (r = 0.39, p less than 0.001) and bone area (r = 0.39, p less than 0.001). This relationship was independent of age, number of years since onset of menopause, and degree of obesity. In multiple regression analysis, estrone levels accounted for 15 per cent of the variance in bone density and bone area in this population. These results suggest that measurement of estrone in normal postmenopausal women may assist in the identification of women who are at high risk for osteoporosis and, thus, possible candidates for estrogen replacement therapy.

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The health effects of increased physical activity in the prevention or treatment of any disease can only be meaningfully assessed if compliance to the exercise regimen is maintained. The current research examined compliance in a clinical trial investigating the effect of walking on bone loss in 229 postmenopausal women, randomized into either a walking or a control group. Although at baseline there was no difference in physical activity between the two groups, after a period of 2 yr, the walking group reported significantly greater physical activity as measured by reported mean blocks walked daily and objective activity monitor day readings. Closer examination of the walking group revealed that compliers (average 7+ miles walked/wk over the 2 yr), when compared to non-compliers, tended at baseline to be more active, lighter weight, and non-smokers. However, the variable that best differentiated between the two compliance groups was the frequency of reported illness over the 2-yr period, with compliers claiming significantly less illness.

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The cross sectional relationship between blood pressure and current calcium intake was examined in 199 white women aged 46-66 yr with no history of hypertension. Calcium intake was assessed from 3-day food logs and from elemental calcium composition of the reported calcium supplement. No significant correlation between calcium intake and blood pressure was detected even after controlling for other known risk factors for hypertension. In logistic regression analysis, the relative risk of having a systolic blood pressure greater than or equal to 130 mmHg, or a diastolic blood pressure greater than or equal to 90 mmHg according to calcium intake, was not significantly different from 1.0. These data suggest that dietary manipulation of calcium intake may not be beneficial in the prevention or treatment of hypertension in older women.

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The relationships of physical activity to total HDL, HDL-2 and HDL-3 cholesterol were examined in 255 white postmenopausal women, mean age, 57.6 years. Physical activity was measured by the Paffenbarger Index (a composite index of walking, stair climbing and sports in the past week); by a modified Paffenbarger which included only sport activities; and by an objective activity monitor (LSI). Depending on which activity measure was used, different univariate relationships between physical activity and the HDL-cholesterol subfractions were noted. Physical activity, as measured by sport kcal/week or by objective monitors was related to HDL-2 cholesterol [r = 0.22 (p less than 0.01)] and [r = 0.19 (p less than 0.01)], respectively, but not to HDL-3 cholesterol. Physical activity, as measured by the Paffenbarger kcal/week was only related to HDL-3 [r = 0.15 (p less than 0.05)]. Multiple regression analyses revealed that sport activity was significantly related to total HDL and HDL-2 cholesterol. Activity as measured by objective monitors was not independently related to either HDL-total or HDL-2. Activity as measured by the Paffenbarger kcal/week was an independent determinant of HDL-3, after controlling for body fatness. Insulin, caloric intake and liver function were analyzed as possible underlying mechanisms, but we could not demonstrate any mediating or interacting effect on any of these mechanisms for the association of HDL-cholesterol to physical activity.

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Skeletal mass is a major determinant of susceptibility to osteoporotic fracture in menopause. At menopause, the skeletal mass is the resultant of the Peak Skeletal Mass (PSM) reached early adulthood minus the bone mass lost through the process of Adult Bone Loss (ABL). Current interventions for the maintenance of skeletal resilience in advanced age address the ABL peri- or postmenopausally. This study indicates that the effects of milk consumption in childhood and adolescence on bone density may manifest as higher bone density decades later in menopause. The assumed mechanism of the reported effect is through augmentation of the PSM, and acquisition of favorable nutritional habits which may influence the extent of ABL.

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Forty-eight menopausal women taking exogenous estrogen were compared with 246 postmenopausal women not on estrogen. The estrogen users had significantly higher total high density lipoprotein (HDL) (76.0 vs 61.4 mg/dl) and HDL2 (36.7 vs 23.0 mg/dl) cholesterol than the controls. There was a similar concentration of HDL3 cholesterol for the two groups (39.2 for the estrogen users and 38.4 for the controls). A dose-response was evident between the amount of daily estrogen and HDL-total and HDL2 cholesterol. The significant differences between the two groups remained after adjusting for body composition, alcohol intake, cigarette smoking and physical activity. There was a significant difference between the two groups in liver function as measured by the liver enzymes, SGOT, SGPT, with liver enzyme concentrations lower in the estrogen users. The results indicate that the increase in the total HDL cholesterol as a result of menopausal estrogen is primarily the result of increased HDL2. The increase could not be explained by alterations in hepatic microsomal activity as measured by liver enzymes since estrogen users had lower concentrations of liver enzymes than non-estrogen users.

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Estrogen and calcium are two well described determinants of postmenopausal skeletal mass. In protecting the organism against bone erosion, the two factors interact in a reciprocally sparing fashion. This manifests in the fact, that correction of the deficiency of one of the factors, as in the case of estrogen replacement therapy, prevents further bone loss despite the persistence of unaltered calcium intakes. The obverse is also true. Large dietary calcium intakes lead to calcium balance, despite the unrelieved estrogen deficiency of the menopause. It is hypothesized that physical activity which functions as another bone mass determinant, may also exert a sparing effect, and thus lower the requirements for calcium intake and perhaps bypass the need for estrogen replacement in the menopause. Confirmation of this hypothesis could provide a method for a nonpharmacologic approach to the prevention of osteoporosis and perhaps even an effective therapy for the repletion of bone tissue in the depleted osteoporotic skeleton.

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Although, with the newer and more sophisticated radiologic methods the precision of bone mass measurement has been greatly improved, it is still impossible to predict the imminence of osteoporotic fractures, for two main reasons. First, current radiologic methods measure bone mass accurately only in appendiceal bone (largely cortical and regularly shaped) and not in axial bone (largely trabecular and irregularly shaped). However, most clinically significant fractures occur in the axial skeleton and involve trabecular bone, which is more prone than cortical bone to resorptive losses. Second, because of large differences in body habitus, the normal range of bone densities varies widely in any cohort of the same sex and race. Thus, although bone density measurements cannot be used to predict osteoporotic fractures, they have an important application in monitoring changes in skeletal mass for therapeutic and prophylactic purposes.

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