To test the hypotheses that baseline concentrations of sex steroids, sex hormone binding globulin (SHBG), and calciotropic hormones predict rates of bone loss in elderly women, sera were stored at ؊190°C, and calcaneal bone mineral density (BMD) was measured in 9704 community-dwelling white women aged 65 and over (1986 -1988). Hip BMD was measured 2 years later (1990). Repeat measurements of calcaneal and hip BMD were obtained in 1993-1994, after 5.7 and 3.5 years of follow-up, respectively. In 1994, sera were assayed for circulating hormone levels in random subcohorts of 231 and 218 women who did not report current use of hormone replacement therapy at baseline. Lower levels of endogenous estrogens and higher SHBG concentrations were associated with more rapid subsequent bone loss from both the calcaneus and hip. After adjusting for age and weight, women with high SHBG levels (highest quartile > 2.3 g/dl) experienced an average of 2.2% (95% confidence interval ‫؍‬ 1.6%, 2.9%) calcaneal bone loss per year compared with 1.2% (0.7%, 1.2%) among women with low SHBG concentrations (lowest quartile < 1.1 g/dl; p < 0.01). This association was independent of concentrations of other sex hormones. Women with estradiol levels > 10 pg/ml averaged only 0.1% (؊0.7%, 0.5%) annual hip bone loss while women with levels below 5 pg/ml averaged 0.8% (

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in

To evaluate the skeletal effects of endogenous serum estradiol, we measured bone mineral density (BMD) at the calcaneus and radius (single photon absorptiometry) and at the hip and spine (dual x-ray absorptiometry) in 274 women aged 65 yr or more who participated in the Study of Osteoporotic Fractures. Lateral radiographs of the thoracic and lumbar spine were also taken, and serum was assayed for estradiol. Those who had estradiol levels from 10-25 pg/mL had 4.9%, 9.6%, 7.3%, and 6.8% greater BMD at total hip, calcaneus, proximal radius, and spine than those with levels below 5 pg/mL. After multiple adjustments, BMD differences remained statistically significant and corresponded to about 0.4 SD. Vertebral deformities were less prevalent among women whose estradiol level exceeded 5 pg/mL; the multiple adjusted odds ratio was 0.4 (95% confidence interval, 0.2-0.8). We conclude that physiologically low estradiol has a salutary effect on the skeleton in elderly women, possibly by reducing skeletal remodeling.

An immunoblotting technique allows direct visualization of Chido and Rodgers antigenic determinants on intact C4 proteins. C4 molecules separated by electrophoresis are selectively transferred to nitrocellulose membranes saturated with goat antiserum to human C4. The membranes are then incubated in alloanti-Chido or anti-Rodgers followed by enzyme-conjugated goat antihuman IgG. Molecules with Chido or Rodgers reactivity are visualized by incubation with an indicator substrate for the bound enzyme.

An immunoblotting technique allows direct visualization of Chido and Rodgers antigenic determinants on intact C4 proteins. C4 molecules separated by electrophoresis are selectively transferred to nitrocellulose membranes saturated with goat antiserum to human C4. The membranes are then incubated in alloanti-Chido or anti-Rodgers followed by enzyme-conjugated goat antihuman IgG. Molecules with Chido or Rodgers reactivity are visualized by incubation with an indicator substrate for the bound enzyme.