A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women.

Background. The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes. Methods. We undertook a double-blind, placebo-controlled, randomized trial to determine the effect of calcium on bone loss from the spine, femoral neck, and radius in 301 healthy postmenopausal women, half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day. The women received placebo or either calcium carbonate or calcium citrate malate (500 mg of calcium per day) for two years. Results. In women who had undergone menopause five or fewer years earlier, bone loss from the spine was rapid and was not affected by supplementation with calcium. Among the women who had been postmenopausal for six years or more and who were given placebo, bone loss was less rapid in the group with the higher dietary calcium intake. In those with the lower calcium intake, calcium citrate malate prevented bone loss during the two years of the study; its effect was significantly different from that of placebo (P less than 0.05) at the femoral neck (mean change in bone density [+/- SE], 0.87 +/- 1.01 percent vs. -2.11 +/- 0.93 percent), radius (1.05 +/- 0.75 percent vs. -2.33 +/- 0.72 percent), and spine (-0.38 +/- 0.82 percent vs. -2.85 +/- 0.77 percent). Calcium carbonate maintained bone density at the femoral neck (mean change in bone density, 0.08 +/- 0.98 percent) and radius (0.24 +/- 0.70 percent) but not the spine (-2.54 +/- 0.85 percent). Among the women who had been postmenopausal for six years or more and who had the higher calcium intake, those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine. Conclusions. Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day. At the dose we tested, supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate.

[Bone mineral content and quantitative computerized tomography]. / Contenuto minerale osseo e tomografia computerizzata quantitativa.

Many methods are used to determine bone mineral content (BMC). Quantitative computed tomography (QCT) appears to be the most reliable method also because it allows the trabecular and the cortical bone to be measured separately. QCT is usually performed on the first four lumbar vertebral bodies. BMC is expressed in mg/ml and a mean value is calculated. Three hundred and fifteen subjects were studied (281 women and 34 men). The patients affected with Paget's disease or malignancies, with or without bone metastases, were not included in this study. The measurements were performed by means of a General Electric 9800 tomograph with software and calibration phantom (QCT-Bone program by Image Analysis). Fractured vertebrae were not included when calculating the mean value since an increased density is caused by fracture. The BMC of any studied vertebral body is considered in comparison with the BMC of the other lumbar vertebrae of the same subject. When the BMC of a given vertebral body exceeds the others by 25 mg/ml or more, nodules and/or stripes are observed during multiple-slice scanning of the bone. Lytic areas or angiomas are observed when the BMC of a given vertebral body is -25 mg/ml or higher. In calculating the mean vertebral BMC, vertebrae with both +25 and -25 must be excluded. In this way the method reliability increases.

[Postmenopausal osteoporosis: early detection of subjects at risk using spinal dual photon absorptiometry]. / Ostéoporose post-ménopausique: dépistage précoce des sujets à risque par absorptiométrie biphotonique rachidienne.

With quantification techniques of the spinal bone condition, especially with spinal biphotonic absorptiometry, early screening of patients risking subsequent development of osteoporosis complicated with vertebral compression is possible. An investigation was conducted in Lower Normandy, in 386 women who had undergone menopause or an ovariectomy, with ages ranging between 40 and 56 years; 274 were in a peri-menopausal state. We had previously established a curve of the bone mineral content according to age. From this curve, in semilogarhythmic representation, we assessed each patient's risk. This risk is considered as high in 30 p. cent of the patients, non existent in 52 p. cent and 18 p. cent are borderline. The percentage of high risk patients increases with the number of years since menopause. It is hoped that the incidence of osteoporosis will decrease with early screening and preventive therapeutic measures.

Assessment of osteoporotic spine deformity. A new method.

For the objective assessment of the severity and progression of osteoporotic deformities of the spine, a mathematical model has been developed which permits evaluation of a single set of radiographs of the spine without reference to absolute values of vertebral height. The model was based on measurements of anterior, central and posterior heights of the vertebrae Th4 to L5 of 50 subjects, aged 20 to 50 years, without a history or radiologic signs of osteoporosis or other metabolic bone disease and without traumatic deformities. The model follows a simple sinusoidal function which describes the general form of the spine, adapted to the individual's height and build. A spine fracture index (SFI) is produced and the method allows calculation of the total number of vertebral deforming events (VDE), manner. The method has been used prospectively in 178 spine radiographs of 109 subjects (60 healthy early postmenopausal women and 49 with osteoporosis). Sensitivity and specificity of SFI in identifying osteoporotic patients were 94 and 88% respectively. In all 109 persons, densitometry of the spine was performed by dual photon absorptiometry at the same time. In the osteoporotic patients the examination was repeated once or twice during fluoride therapy for osteoporosis. The SFI and the total score of VDE and VDS correlated significantly with lumbar bone mineral content (r = -0.38 P less than 0.001). The method offers the advantage of being objective, not dependent on projection errors, and adaptable to the shape of the individual spine.

Lead concentrations in human bones from the Canadian population.

Stable lead was determined in post-mortem samples of human bones from three Canadian cities. All age groups and both sexes were represented. The cities selected for investigation were Winnipeg, Montreal and Charlottetown. No significant difference was found between the locations, although levels tended to be higher for Montreal. Mean lead concentrations (micrograms Pb/g ash) were 8.98 +/- 1.17, 11.11 +/- 1.74 and 8.47 +/- 1.06 for Winnipeg, Montreal and Charlottetown, respectively. Corresponding geometric means were 6.21, 7.88 and 6.71, respectively. Individual values ranged from 0.45 to 240.07 micrograms Pb/g ash. Concentrations were highest in the greater than 20-year age group, indicating increased body burden with age. An increase in lead concentration was observed for the ages 1-11 years with a decrease for the 12-19-year age group. Differences in concentrations between the sexes were not significant. Higher than average concentrations were observed in samples obtained from Winnipeg for the period 1976-1980, particularly in the 1-4-year age group. A similar pattern was observed in the air lead concentrations, suggesting a possible correlation between the concentrations of lead in the air and in bones at Winnipeg.

Calibration and standardization of bone mineral densitometers.

Measurements of bone mineral density (BMD) by four 153Gd and two x-ray bone densitometers were compared utilizing spine phantoms that simulated the human lumbar spine. The six instruments provided BMD values that differed by as much as 16%, due to differences as large as 8% in bone mineral content and as large as 7% in bone area. Instrument calibration curves, determined by measuring thin, medium, and thick hydroxyapatite blocks, were linear (r = 0.99) but had different (p less than 0.0001) slopes and intercepts. Serial measurements of spine and total body phantoms were employed to evaluate the long-term stability of 153Gd bone densitometry. These measurements of spine phantom BMD increased 1.0-2.6% (p less than 0.0001) following a software change, and measurements of total body bone density increased 4-6% after 153Gd source replacement. The changes occurred at a time when serial measurements of cylindrical calibration standards were stable, indicating that such simple standards are unable to detect and correct for changes in instrumental response. We conclude that investigators, manufacturers, and government regulatory agencies must develop and implement the following: (1) effective calibration procedures that would assure comparability among instruments, and (2) appropriate quality control phantoms that would allow the confident interpretation of serial patient measurements.

Measurement of bone in the os calcis: a clinical evaluation.

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.

Age and bone mass in premenopausal women.

It is important to determine the bone mass in normal premenopausal women because increasing numbers of conditions have been identified that result in premenopausal osteoporosis. The relationship between age and bone density was evaluated in 57 carefully characterized normal, premenopausal women using both single energy quantitative computed tomography (SEQCT) and dual energy (DEQCT). The mean bone density measurements were 172 mg/ml K2HPO4 SEQCT and 185 DEQCT. Bone density showed no statistically significant decline between age 18 and age 44. Single- and dual-energy data were highly correlated with each other (r = 0.89), and dual energy appeared to confer no advantage. There was an inverse relation between density and age of menarche. Bone density did not correlate with ideal body weight, percentage fat, or subcutaneous fat area.

The effects of muscle-building exercise on bone mineral density of the radius, spine, and hip in young men.

We previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19-40 years) were studied. The body weights of the two groups were not different from each other (78 +/- 2 vs. 74 +/- 1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35 +/- 0.03 vs. 1.22 +/- 0.02 g/cm2, P less than 0.01), trochanter (0.99 +/- 0.04 vs. 0.86 +/- 0.02 g/cm2, P less than 0.01), and femoral neck (1.18 +/- 0.03 vs. 1.02 +/- 0.02 g/cm2, P less than 0.001) but not at the midradius (0.77 +/- 0.02 vs. 0.77 +/- 0.01 g/cm2, NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.

Local differences in mineral content in vertebral trabecular bone measured by dual-energy computed tomography.

Twelve lumbar vertebral bodies from cadavers were examined with dual-energy CT, to measure the calcium content in a big central region of interest (ROI). In each of five vertebrae the calcium content was also measured in six small ROI. After completed scanning, six small cylinders were drilled out from each vertebra, and the ash-density of each cylinder was measured. The dual-energy CT measurements correlated well with the ash-density. Both ash-density and dual-energy CT showed a significantly higher mineral content in the posterior part of the vertebrae than in the anterior part, and this difference might be responsible for problems encountered with the reproducibility of dual-energy CT.

Effect of physical activity on lumbar spine and femoral neck bone densities.

The lumbar spine and femoral neck densities of 123 and 141 normal adult women (50 +/- 10 years), respectively, measured by dual photon absorptiometry, were correlated with the number of hours of walking per day associated with their regular daily activities. This measure of exercise, obtained by detailed questionnaire and interview, was analyzed because it is regular, seasonally stable, and quantifiable. Both lumbar spine and femoral neck densities were significantly correlated with walking, with 0.8% and 1.9% increases in average bone density per hour of daily walking, respectively. This increase in density is substantial, considering that the age-related rate of bone loss in the same population is 0.7% and 0.5% per year of lumbar spine and femoral neck, respectively. This means that, on the average, a woman walking one additional hour per day has a femoral neck bone density comparable to that of a women 4 years younger who does not pursue this additional activity. This physical activity-associated enhancement of bone density may be critical at old age when osteoporosis is clinically manifested.

Quantification of bone mineral content using dual-photon absorptiometry in a normal Japanese population.

The bone mineral content of lumbar spine and/or total body were quantified in 217 healthy Japanese (86 males and 131 females) using a Dichromatic Bone Densitometer (Norland Corp., Model 2600). The bone mineral density of the third lumbar vertebra (L3 BMD) decreased significantly after age 20 in males (r = -0.417, p less than 0.0002), with acceleration of the decrease after age 50 (r = -0.621, p less than 0.00002). A significant correlation was found between L3 BMD and age after age 40 (r = -0.747, p less than 0.0001) in females. L3 BMD correlated with both the body height (r = 0.335, p less than 0.0001) and the body weight (r = 0.340, p less than 0.0001). Total bone mineral content from the second to fourth lumbar vertebrae correlated significantly with total body bone mineral (r = 0.880, p less than 0.00001) in these normal subjects. Lumbar spine bone mineral as measured by dual-photon absorptiometry is lower in Japan than the bone mass in the United States, although not lower than in other parts of the world.

Some factors which influence the evaluation of a dual photon measurement of lumbar spine bone mineral mass.

The accuracy of a commercial dual photon densitometer was found to be within 3.0% of true values when measured using a cadaver spine. The precision, the ratio of standard deviation to mean derived from repeated measurements of a tissue-equivalent phantom spine, was 1.6%. Patient size and the age of the radioisotope source had no discernable effect upon bone mineral mass measurements. The intervention of the technologist during data analysis can influence the determination of bone mineral mass in approximately 40% of measurements. When a lumbar spine phantom was measured on six different densitometers manufactured by three different companies, within-manufacturer variations of between 4% and 7% were found. Bone mineral densities differed by up to 30% between manufacturers. Values of lumbar spine mineral mass were measured for 206 apparently normal women. The resultant normal range was similar to others documented by the manufacturer. The differences between these studies and a published study of 892 normal women can best be explained on the basis of intermanufacturer differences.

Utilization of femoral head for estimating the skeletal burden of U and Pu in humans.

Uranium and Pu were determined in vertebrae, ribs and femoral head samples obtained from the same population. Vertebrae and rib samples were obtained at autopsy and femoral head samples were obtained from persons undergoing hip surgery. The results indicate that there was no statistically (p less than or equal to 0.05) significant difference between the mean concentration of 239,240Pu in vertebrae and ribs. Also, there was no significant difference between the mean concentration of 239,240 Pu in ribs and femoral head. Also, statistical tests were performed to see whether the mean concentrations of 238U and 234U in three different bones differ from each other. The results suggest that there was no statistically significant difference between vertebrae and ribs, vertebrae and head of the femur nor between ribs and femoral head. These results indicate that femoral head may be an appropriate substitute for vertebrae or ribs, the most commonly used bone for inferring the skeletal burden of U and Pu in human. Femoral head samples can be obtained from living persons undergoing hip surgery, while vertebrae and ribs are obtained only at autopsy.

The error due to fat inhomogeneity in lumbar spine bone mineral measurements.

Bone mineral mass measurements using dual photon absorptiometry rely on the assumption that fat thickness is constant within the region scanned by the photon beam. This assumption has been tested using both single and multiple slices from archived CT scans. In 26 patients, the difference in fat content between the bone and baseline measurement sites, the fat deviation, was found to vary from -2.7 to 18.7%. The median fat deviation was 4.4% which can lead to errors in measured lumbar spine bone mineral of 6 to 11%. Approximately one third of patients will have errors greater than 10%.

Effects of age and sex on bone density in the rhesus monkey.

Normative data for bone density of cortical and trabecular bone in the rhesus monkeys is described in the present study. Changes of bone density (g/cm2) for the humerus, the third lumbar vertebra, and the eighth caudal vertebra of the rhesus monkey show differences due to age and sex of the subjects (males n = 57; females n = 49). In general, bone density increased with age and then reached a plateau at approximately 3 to 4 years in all bones measured. In the humerus, older females (greater than 30 years) had a significantly lower bone density than females of 4 to 24 years, while bone density in older males did not decrease. In the vertebrae, some evidence of advanced age-related decreases in bone density was found in both sexes. These results indicate that the rhesus monkey shows a natural pattern of change in bone mineralization which parallels that seen in humans. The physiological similarity between the rhesus monkey and human further suggests a potential role for this species in the future investigation of osteoporosis.

Effects of nandrolone decanoate and antiresorptive therapy on vertebral density in osteoporotic postmenopausal women.

Conventional antiresorptive therapy for osteoporosis can delay bone loss, but secondary inhibition of bone formation appears to prevent an increase in bone density. Recently, anabolic steroid therapy has been shown to increase total body calcium and forearm density in osteoporotic patients, perhaps by causing an increase in bone formation. It is not known if these agents affect vertebral density. We have measured vertebral mineral density in 71 postmenopausal osteoporotic women before and after treatment with either the anabolic steroid nandrolone decanoate or antiresorptive therapy. After a mean treatment period of 14 months, there was a mean increase of 20% in vertebral mineral density in the former group, and no significant change in the latter group. The difference in the time-weighted mean rates of change between the two groups was significant. The results suggest that nandrolone decanoate therapy increases bone formation.

Bone mineral density of the spine and proximal femur in normal and osteoporotic subjects in Japan.

Bone mineral density (BMD) of the spine and proximal femur in Japanese men and women was investigated with dual photon absorptiometry, using gadolinium-153. Peak bone mass of the spine (L2-4) was 1.20 g/cm2 in women which was lower than that of men by 4.7%, whereas BMD of the femoral neck was 0.91 g/cm2 in women and lower than in men by 13.3%. Bone loss was faster in postmenopausal women than in men of the corresponding age, and the regressions of BMD on age were 6.7-times higher at L2-4 and 5.1-times higher at the femoral neck than in men. Such rates of loss became slower both in the lumbar spine and proximal femur in women after 70 years of age, but the density at the proximal femur kept decreasing in men after 70 years of age. Fracture thresholds of each region were evaluated at the 90th percentile for BMD of L2-4 in patients with vertebral crush fractures and for BMD of the proximal femur in patients with hip fractures. The fracture threshold was 0.97 g/cm2 at the spine and 0.67 g/cm2 at the femoral neck in women. BMD values at the spine and proximal femur in normal Japanese men and women appear to be lower than those in white American control population.

Bone mass is low in relatives of osteoporotic patients.

STUDY OBJECTIVE: To determine whether the failure to attain normal bone mass in young adulthood contributes to the later development of osteoporotic fractures. DESIGN: Case-control study. SETTING: Referral-based bone clinic at a large teaching hospital. PATIENTS: Sequential sample of 35 asymptomatic relatives, aged 19 to 59 years, of patients with osteoporotic fractures, and 24 patients with osteoporotic fractures. MEASUREMENTS AND MAIN RESULTS: Bone mineral density in the spine was measured by quantitative computed tomographic scanning. Bone mineral content in the os calcis was measured in 19 of the relatives of osteoporotic patients by single-photon absorptiometry. The values for bone mineral density in the spine were corrected to age 50 years with the regression equation derived from the normal values in the controls. The values were lower in relatives of osteoporotic patients than in controls. In men, the mean values (+/- standard deviation [SD]) for relatives were 91 +/- 16 mg/cm3, and for controls, 129 +/- 21 mg/cm3 (P less than 0.001). In women, the mean values for relatives were 96 +/- 17 mg/cm3 and for controls, 126 +/- 19 mg/cm3 (P less than 0.001). In the osteoporotic patients, the corrected mean value for men was 53 +/- 12 mg/cm3, and for women, 77 +/- 20 mg/cm3. The os calcis values did not correlate with the spine values and were mostly well within the normal range. CONCLUSIONS: Mean bone mass is lower in apparently healthy young and middle-aged adult relatives of osteoporotic patients than in normal persons with no family history of osteoporosis. Our findings suggest that the failure to attain an adequate peak bone mass may play an important role in the later development of osteoporotic fractures. Relatives of osteoporotic patients should be advised to have measurements of bone mass taken. This measurement should be taken at the spine, because peripheral sites do not appear to provide adequate information about early osteoporosis.