Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause.

We made longitudinal measurements of bone mineral density (BMD) in 139 normal women (ages 20-88 yr) at midradius (99% cortical bone) and lumbar spine (approximately 70% trabecular bone) by single- and dual-photon absorptiometry. BMD was measured 2-6 (median, 3) times over an interval of 0.8-3.4 yr (median, 2.1 yr). For midradius, BMD did not change (+0.48%/yr, NS) before menopause but decreased (-1.01%/yr, P less than 0.001) after menopause. For lumbar spine, there was significant bone loss both before (-1.32%/yr, P less than 0.001) and after (-0.97%/yr, P = 0.006) menopause; these rates did not differ significantly from each other. Our data show that before menopause little, if any, bone is lost from the appendicular skeleton but substantial amounts are lost from the axial skeleton. Thus, factors in addition to estrogen deficiency must contribute to pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally.

Bone mineral density in Australia compared with the United States.

Bone density measurements are currently being performed throughout the world in the diagnosis and management of osteoporosis as well as in research into this major health problem. However, it is not clear to what extent bone mineral density (BMD) values determined by dual-photon absorptiometry at one center can be applied to another. This is particularly relevant for the quantitative comparison of results from studies carried out in different laboratories. Furthermore, many centers now acquiring densitometers may not have the resources to determine their own normal range, relying instead on a "normal" range provided by the manufacturer. The question of the comparability of BMD data obtained in different centers was examined by comparing the normal range for the lumbar spine and proximal femur in 203 normal white Australian women and 892 normal white U.S. women, obtained using the same model densitometer. The two populations were compared according to decade. From superimposition of the Australian individual values on the North American normal ranges, only minor differences between the two populations were seen at any of the sites measured at any decade. None of these minor differences were statistically significant. This study shows a close similarity between BMD values in both the proximal femur and lumbar spine in normal white women in Australia and North America, provided the same model densitometer is used. Thus data obtained from different centers in populations with similar ethnic composition may be compared directly. These findings provide for the first time a sound basis for the quantitative comparison of the at times conflicting studies carried out in widely differing settings around the world.

Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

Quantitative digital radiography versus dual photon absorptiometry of the lumbar spine.

Lumbar spine bone mineral density (BMD) was measured by quantitative digital radiography, a new dual energy x-ray technique, and by 153Gd dual photon absorptiometry (DPA) in 85 patients. Each patient was measured twice by the new method and once by DPA on the same day, with repositioning between measurements. Serial measurements were made on an hydroxyapatite spine phantom embedded in tissue-equivalent plastic to evaluate the long term reproducibility of each instrument. The spinal BMD measurements with the 2 techniques were linearly related and highly correlated (r = 0.98) over a range from severely osteopenic to high normal. This correlation was not affected by the age, weight, or BMD of the patient measured. Quantitative digital radiography's long-term reproducibility using the spine phantom was stable for 180 days (coefficient of variation, 0.23%); DPA values were 3 times as variable for 170 days (coefficient of variation 0.73%) and increased 1.0% (P less than 0.0001) after a software change. The short term reproducibility of quantitative digital radiography, estimated from paired patient measurements, was 2-fold better than reported values for DPA and was independent of the patient's age, weight, or BMD. Measurement time by quantitative digital radiography was 5-8 min, with a maximum radiation exposure of 3 mrem, significantly lower than the corresponding DPA values. Quantitative digital radiography's image resolution was superior to that of DPA, enabling it to measure more bones. These advantages along with the elimination of 153Gd source changes and Nuclear Regulatory Commission licensing requirements indicate that quantitative digital radiography is the superior method for spinal BMD measurements.

Lack of seasonal variation in bone mass and biochemical estimates of bone turnover.

Three previous studies have indicated a seasonal variation in bone mineral content, with values during the summer being 1.7% to 7.5% higher than during the winter. We have examined the seasonal influence on both bone mass, biochemical estimates of bone turnover and vitamin D metabolites in 86 healthy women, aged 29-53 years. All participants were followed up for 2 years with examinations every 6 weeks or 3 months. Bone mineral content in the proximal and distal part of the forearm (single photon absorptiometry) did not reveal any significant seasonal variation, whereas bone mineral density of the lumbar spine (dual photon absorptiometry) indicated that the highest values occurred in winter. None of the biochemical parameters showed any statistically significant cyclical changes. Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D3 showed a highly significant seasonal variation, whereas the serum 1,25-dihydroxyvitamin D concentration was virtually unchanged. We conclude that seasonal variation in bone mineral content and bone turnover should not be taken into account when interpreting data from longitudinal studies of healthy pre- and postmenopausal women on a sufficient vitamin D nutriture.

Genetic determinants of bone mineral content at the spine and radius: a twin study.

The possible role of genetic and/or environmental factors in determining bone mass has been investigated in 30 pairs of twins (16 monozygotic and 14 dizygotic) divided in two age groups (below and above 25 years of age). Bone mineral content was evaluated by single- and dual photon absorptiometry at the distol third of the radius for peripheral cortical bone and in the lumbar spine for the axial bone. The "within pair" variance has been used as an index of genetic influence. A significant (p less than 0.01) genetic determinant was found for the bone mass of the radius in adults and for the spinal bone mass in the age group younger than 25 years. The heritability index h2 was 0.75 for cortical BMC and 0.88 for axial BMC. Such a genetic determinant could not conclusively be demonstrated in adult twins for the spine and in youngsters for the cortical bone, suggesting that environmental factors may play a more dominant role in growth of cortical bone during adolescence and diminution of axial bone during adult life.

Accuracy of lumbar spine bone mineral content by dual photon absorptiometry.

The accuracy of measurement of the bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2) of the lumbar spine by dual photon absorptiometry (DPA) was estimated by means of two different spine scanners (a Nuclear Data 2100 and a Lunar Radiation DP3). The lumbar spines of 13 cadavers were used. BMC and BMD were measured in situ and on the excised vertebrae in a solution of water/ethanol; and covered with ox muscle/porcine muscle/lard. The actual mineral weight and areal density were determined after chemical maceration, fat extraction, drying to a constant weight, ashing for 24 hr at 600 degrees C, and correction for the transverse processes. The true are was measured by parallax free X rays and planimetry. All measurements of BMC or BMD were highly interrelated (r = 0.94-0.99). The standard error of estimate (s.e.e.) of BMC in situ versus BMC in water/ethanol was 5.2%. The agreement between the BMD values of the two scanners was very good (s.e.e. = 2.9%). BMC in situ predicted the actual vertebral mineral mass with an s.e.e. of 8.1%. BMD in situ and BMD in water/ethanol predicted the actual area density with s.e.e.s of 10.3% and 5.0%, respectively. This study discloses the correlation and accuracy error of spinal DPA measurements in situ in whole cadavers versus the actual BMC and BMD. The error, which is underestimated in in vitro studies, amounts to 10%.

Age-, sex-, and menopause-related changes of vertebral and peripheral bone: population study using dual and single photon absorptiometry and radiogrammetry.

Vertebral and peripheral bone mass have been measured with single and dual photon absorptiometry and radiogrammetry in 146 male and 220 female volunteers ranging in age from 20 to 85 yr. One hundred four subjects with interfering diseases, treatment, or x-ray manifestations of lumbar osteoarthritis were excluded for purposes of this study. Patterns of age-related bone gain and diminution differed between sexes and measuring sites. The effect of menopause on the peripheral and vertebral skeleton also differed. Men, at all measured sites, have more bone than women. In the fifth decade, however, women's lumbar bone mineral content was almost equal to the value found in men. Bone loss associated with aging was more marked in women than in men and started, for the lumbar spine, at about the age of 25 yr in both women and men and, for the peripheral bones, at the age of 55 in women and 65 in men. Bone loss in the spine in women was not linear. Women in the fifth and sixth decade, who still had menstruation, differed significantly from those who had not menstruated for at least the last 6 mo. Bone diminution at menopause was twice as great in the lumbar spine than elsewhere in the peripheral skeleton, 15% versus 7%. Of the 25% total bone loss of the spine during adult life in women, 60% was lost within 10 yr after menopause. Estrogen deficiency, not aging, is the predominant cause of bone loss in the spine. For the peripheral skeleton, there is a two-component decrease, a rapid loss induced by the menopause superimposed on a slower age-related loss. Although there was a significant correlation between peripheral and vertebral bone mass indices, it was clear that observations made at one site will not necessarily reflect changes observed at another site.

A comparison of single and multi-site BMC measurements for assessment of spine fracture probability.

In a prospective study of 699 women, 39 new spine fracture cases were observed during a mean follow-up of 3.6 yr. Spine fracture incidence was compared to initial bone mineral content (BMC) of the calcaneus, distal radius, proximal radius, and the lumbar spine. BMC at all four sites was significantly related to spine fracture incidence. Women at -1 s.d. for calcaneal BMC had a sevenfold greater probability of spine fracture than women at +1 s.d.; women at -2 s.d. had a 50-fold greater probability than women at +2 s.d., even after adjustment for the effects of age. Combinations of BMC at two sites further strengthened the relationship to spine fracture; the best two-site combination is calcaneus and distal radius BMC. Thus women can be categorized and stratified according to future fracture risk, and the selection of postmenopausal women for preventive treatments can be guided by measurements of BMC.

Comparison of bone density measurements from different skeletal sites.

Absorptiometric measurements from multiple sites in 212 consecutive patients were examined to determine the interrelationships among bone mineral content values obtained from the lumbar spine, hip, and forearm. Dual photon absorptiometry was used to examine the spine, femoral neck, Ward's triangle, and greater trochanter while the radius and ulna were studied with single photon absorptiometry. All studies were performed on the same day. Concurrent measurements were available for the spine and hip in 197 patients, for the spine and forearm in 151 patients, and at all three sites for 146 patients. Variable degrees of correlation were found among the mineral content values from the six sites, with r values ranging from 0.40 to 0.93. The femoral neck and Ward's triangle showed the highest degree of correlation (r = 0.93); the ulna and lumbar spine demonstrated the poorest correlation (r = 0.40). Relationships between distant anatomic sites exhibited a large amount of variability (large standard error of the estimate) even when highly correlated. Useful predictions of bone mineral content could be obtained only for sites in close proximity. These results suggest that bone mineral content determinations in the upper extremities by single photon absorptiometry may not be useful for predicting mineralization in clinically more significant areas such as the lumbar spine and hip.

Relationship between bone mineral density of spine and strength of back extensors in healthy postmenopausal women.

We determined the bone mineral density of the lumbar spine and the strength of back extensors in 68 healthy postmenopausal Caucasian women. Bone mineral density of the second to fourth lumbar vertebrae was measured by dual-photon absorptiometry, and back extensor strength was determined with use of a strain-gauge dynamometer. The bone mineral density percentile ranged from 2 to 99%, and back extensor strength ranged from 37 to 145 lb. Statistical analysis demonstrated a significant positive correlation (P = 0.004) between bone mineral density and back extensor strength, even when bone mineral density was corrected for age. Bone mineral density was also significantly positively correlated with body weight (P = 0.003), height (P = 0.001), and arm span (P = 0.008). These data suggest that the strength of back muscles may contribute to the bone mineral density of vertebral bodies.

Efficacy of nonloading exercises in prevention of vertebral bone loss in postmenopausal women: a controlled trial.

A considerable increase in muscle strength and bone mass can be achieved in young adults through athletic exercise programs. We studied a less demanding nonloading exercise program for the back extensor muscles in postmenopausal women who were not on estrogen therapy. We randomly assigned 65 healthy Caucasian women without evidence of or risk factors for osteoporosis into an exercise group and a control group. The strength of the back extensor muscles and bone mineral density of the lumbar spine were measured at baseline and every 6 months for 2 years. In addition, a physical activity score was determined. Compliance was assessed by regular interviews and review of diaries. During the 2-year study, the mean rates of bone loss in the two groups were not statistically different. The strength of the back extensor muscles increased in both groups but significantly more (P = 0.002) in the exercise group. We conclude that postmenopausal bone loss is unaffected by a modest exercise program despite an increase in muscle strength. Nonloading muscle exercise may be ineffective in retarding vertebral bone loss in ambulatory, healthy postmenopausal women.

Bone mineral density and skeletal fractures in familial benign hypercalcemia (hypocalciuric hypercalcemia).

To determine whether familial benign hypercalcemia, or familial hypocalciuric hypercalcemia (FHH), has adverse effects on the skeleton, we measured bone mineral density (BMD) in 31 affected persons from 14 families (16 women and 15 men), ranging in age from 19 to 68 years. Forearm BMD was measured by single-photon absorptiometry, and spinal BMD was measured by dual-photon absorptiometry. In addition, we systematically queried 82 hypercalcemic and 52 normocalcemic family members about skeletal fractures. Both men and women with FHH had normal BMD (expressed as grams per square centimeter) in the lumbar spine, distal radius, and midradius. Osteoporotic-type fractures (vertebrae, hip, and distal radius) were virtually absent in both affected and unaffected family members. Detailed evaluation of larger numbers of of older affected persons may be necessary to resolve this issue definitively, but we conclude provisionally that FHH has no important adverse effects on skeletal health.

Dichromatic absorptiometry of vertebral bone mineral content.

A dichromatic photon absorptiometric technique for the in vivo measurement of the bone mineral of the spine is discussed. A high purity, high activity 153Gd source which has photons of predominantly 44 and 100 keV was used as the transmission source. The transmission scans were performed on a modified Ohio Nuclear whole body rectillinear scanner. The precision of four measurements on three individuals and three measurements on one individual over a one month period was 2.3% (coefficient of variation). The accuracy determined by measurements of phantoms with known concentrations of dipotassium hydrogen phosphate solutions was 1.2% (standard error of estimate). This technique can be applied in most well equipped nuclear medicine departments.

Vertebral and peripheral bone mineral content by photon absorptiometry.

Dual photon absorptiometry with 153Gd was used to determine the bone mineral content of the lumbar spine of 46 subjects. The bone mineral content of the radius and ulna were measured on these same subjects using single photon absorptiometry. The bone mineral content at the peripheral sites was not a very accurate indicator of absolute bone mineral content in the spine. However, the rate of bone loss with age was greater in the peripheral bones than in the spine. Measurement sites on the appendicular skeleton may provide a more sensitive indication of age changes in bone mineral content throughout the skeleton than would sites on the axial skeleton.

Mechanical behavior of the human lumbar spine. II. Fatigue strength during dynamic compressive loading.

Seventeen cadaveric human lumbar motion segments from eight spines were cyclically loaded in vitro under axial compression. Loading frequency and magnitude were chosen to simulate rigorous activity within an in vivo physiological level. The load magnitude was determined as a percentage of the ultimate compressive load, the latter estimated from the bone mineral content (BMC) of lumbar vertebrae determined by dual-photon absorptiometry. Following testing, the degree of macroscopic disc degeneration was assessed and the type of fracture in each specimen was determined from serial sagittal sections. Fractures were found in all but one specimen. Three types of fractures were formed: the node of Schmorl and Junghanns (type I), central endplate fracture (type II), and a crush or burst fracture (type III). The results suggested that type I fractures were predominantly associated with segments with normal discs, type II fractures were found primarily in segments with moderately degenerated discs, and type III fractures were associated with segments that failed on the first cycle. Segment stiffness and fatigue strength (cycles to failure) were correlated with disc degeneration, age, and segment BMC, the latter an in vivo measure of bone density. Fatigue strength also decreased in proportion to a power coefficient with increasing relative stress (cyclic stress range/ultimate stress).

Feasibility study: in vivo neutron activation for regional measurement of calcium using californium 252.

The feasibility of using a collimated 252Cf neutron source to measure regional changes in skeletal calcium was tested because in vivo regional activation of diseased bone should offer advantages over the more widely reported total-body calcium measuring techniques. Regional activation allows examination of discrete regions where the greatest changes in calcium content occur. Additionally, a simpler radiation facility is required for regional studies. Using a 5.5-mug 252Cf source, thermal neutron flux and absorbed dose were measured in a tissue-equivalent phantom. Detection efficiency of 49Ca gamma rays for conditions simulating regional activation were measured using a 29-cm-diameter X 10-cm-thickness sodium iodide detector. These in vitro measurements indicate that a collimated 252Cf source can be used for regional neutron activation of the lower spine and legs. Preliminary calculations indicate that a 1-3-mg source provides adequate count rates for statistical accuracy with a bone marrow dosage acceptable for human patients and normal subjects.

Lower vertebral bone density in male long distance runners.

Bone density in 13 male long distance runners (28.7 +/- 1.2 yr, 67.6 +/- 2.0 kg) and 11 male nonrunners (26.8 +/- 1.3 yr, 71.0 +/- 2.2 kg) was compared. Bone was measured at the lumbar spine and mid-tibia using dual photon absorptiometry and at the mid-radius using single photon absorptiometry. Runners (mean weekly training 92.2 +/- 6.3 km) had significantly lower (P less than 0.05) vertebral bone mineral density (1.12 +/- 0.03 g.cm-2) than nonrunners (1.24 +/- 0.04 g.cm-2). Tibial and radial bone mineral density did not differ between the groups. Daily calcium intake for runners (1,373 +/- 486 mg) and nonrunners (1,267 +/- 236 mg) exceeded the RDA. The results of this study suggest that long distance running may lead to decreased vertebral bone mineral density. The hormonal changes that occur with endurance training may contribute to this decrease.

Correlation of mechanical properties of vertebral trabecular bone with equivalent mineral density as measured by computed tomography.

We tried to determine whether mineral-equivalent measurements that were obtained using computed tomography could be used to predict the mechanical properties of vertebral trabecular bone. Vertebral bodies that had been obtained during routine autopsy were evaluated by computed tomography. The mechanical properties of the vertebral trabecular bone were determined by subjecting cylindrical specimens to simple compression until failure occurred. The ultimate strength and elastic modulus were determined from load time curves, using constant displacement rate loading. Atomic absorption spectrophotometry was used to determine the weight per cent calcium of each specimen, and quantitative light microscopy was used to determine area fraction bone. Significant positive correlations were found between the observed mechanical properties of the trabecular bone and the equivalent mineral density as measured by computed tomography. Compressive strength (r = 0.720), elastic modulus (r = 0.574), trabecular calcium density (r = 0.780), and area fraction bone (r = 0.579) were all correlated with the equivalent mineral density.

Dual photon absorptiometry of the spine with a low activity source of gadolinium 153.

Apparatus and data-processing techniques were developed to measure the bone mineral content (BMC) of the lumbar spine. 153Gd was used as the dual photon source with an activity down to 7 GBq, lower than that adopted by other workers. The compromise between resolution and sensitivity was optimised. A reproducibility in normal subjects of 1.5% (coefficient of variation) was obtained. Normalisation procedures using parameters of the scan image and other indicators of body size such as span were developed, and reduced the coefficient of variation between normal subjects to 10% for men and 8% for pre-menopausal women. The absolute values of BMC are similar to those reported by others. Cross-sectional studies in women demonstrated an accelerated loss of BMC after the menopause.