Bone Mass and Markers of Bone and Calcium Metabolism in Postmenopausal Women Treated with 1,25-Dihydroxyvitamin D (Calcitriol) for Four Years

To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 μg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P= 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P= 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0.001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P= 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels. Received: 8 January 1999 / Accepted: 29 February 2000     

The Decrease in Serum Bone-Specific Alkaline Phosphatase Predicts Bone Mineral Density Response to Hormone Replacement Therapy in Early Postmenopausal Women

Hormone replacement therapy (HRT) prevents bone loss in postmenopausal women. Up to 20% of women demonstrate no increase in bone mineral density (BMD) on HRT. We examined whether early changes in serum bone alkaline phosphatase (B-ALP) predict long-term BMD changes in postmenopausal women on HRT. Ninety women within 1 year of menopause were randomly assigned to continuous or sequential estrogen/progestin (beta estradiol/norethisterone acetate) if naturally postmenopausal, or beta estradiol if within 1 month of surgical menopause. Spine, femoral neck BMD (DXA), and B-ALP were determined over 2 years. The mean percent BMD changes were 3.8%, 2.9%, 1.6% in the spine and 2.4%, 4.0%, 1.1% in the femoral neck in sequential, continuous, and estrogen alone treatment groups, respectively, significantly different from zero except for femoral neck BMD change in the estrogen alone group. HRT was associated with spine and femoral neck BMD loss in 17.4% and 25.3% of women, respectively. In estrogen/progestin-treated women, baseline B-ALP correlated with spine BMD change (r = 0.42, P < 0.01). At 3 months, B-ALP dropped significantly in the estrogen/progestin-groups with a maximal decrease at 12 months, but no change from baseline in the estrogen alone group. Using quartile analysis, women with the greatest drop in B-ALP (≥50%) at 6 months demonstrated the greatest gain in spine BMD at 2 years. A 40% decrease at 6 months in B-ALP had a 56% sensitivity, 83% specificity, 95% positive predictive value for spine BMD gain at 2 years. The decrease in B-ALP can be used to monitor BMD response to HRT. Received: 6 January 1999 / Accepted: 13 August 1999     

Radial and Metacarpal Bone Mineral Density and Calcaneal Quantitative Ultrasound Bone Mass in Normal Japanese Women

The purpose of this study was to examine the effect of lifetime physical activity of farmers on skeletal status. Seventy-one healthy, postmenopausal women (mean age 52.3 ± 5.9 years, range 42–61 years) who worked professionally on farms were compared with 78 matched controls (mean age 51.8 ± 5.5 years, range 42–61 years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the os calcis were measured using an ultrasound transmission imaging system. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DXA). Differences in BUA, SOS, and BMD between farmers and controls were expressed relative to standard deviation (SD) of the farmers. Farmers had significantly higher density values than controls (difference = 1.3 SD in the spine and 1.5 SD in the femoral neck, P < 0.0001 for both comparisons). Ultrasound values were significantly higher in the farmers compared with the controls in calcaneus (difference = 1.1 SD for BUA and 0.7 SD for SOS, P < 0.0001 for both comparisons). The difference of spine BMD, femoral neck BMD, BUA, and SOS between farmers and controls, as judged by comparison of the slopes of the regression lines, was unchanged with age and years since menopause. These results suggest that lifetime physical activity has a positive effect on bone status of postmenopausal farmers. Received: 19 March 1998 / Accepted: 7 August 1998     

A Comparative Study of Computed Digital Absorptiometry and Conventional Dual-Energy X-ray Absorptiometry in Postmenopausal Women

The aim of the study was to evaluate whether computed digital absorptiometry (CDA) of the hand might be a useful screening technique for identifying patients with postmenopausal osteoporosis and to compare the results of CDA with those of dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. We studied 230 postmenopausal women (mean age 58.4 ± 7.9 years). For CDA, bone mineral density (BMD) was measured with an AccuDEXA Schick densitometer in the third middle phalanx of the nondominant hand. For DXA, BMD of the lumbar spine and upper femur was assessed using a DXA Hologic QDR-1000 densitometer. We did a comparative analysis (ANOVA) and linear correlation tests. Sensitivity and specificity of CDA and receiver operating characteristic (ROC) curves for the diagnosis of osteoporosis were calculated. The mean BMD with CDA was 0.445 ± 0.084 (T-score: −1.27 ± 1.29). The mean BMD (g/cm²) with DXA at the lumbar spine was 0.877 ± 0.166 (T-score: −1.52 ± 1.59) and 0.708 ± 0.127 at the femoral neck (T-score: −1.12 ± 1.25). BMD at the lumbar spine and femoral neck correlated positively with CDA of the hand (r= 0.66 and r= 0.65 respectively, p<0.001). When using as cut-off a T-score of −2.5, according to WHO criteria, 76 women (33%) had osteoporosis of the lumbar spine and/or femoral neck with DXA and 42 (18%) with CDA (p<0.001). The kappa score for osteoporosis was 0.33 for CDA versus spinal DXA and 0.35 for CDA versus femoral DXA. With the cut-off level used, sensitivity and specificity of CDA in detecting osteoporosis at the lumbar spine were 0.39 and 0.90, respectively; sensitivity and specificity of CDA in identifying osteoporosis at the femoral neck were 0.58 and 0.87, respectively. The positive predictive value of CDA for osteoporosis was 69% and the negative predictive value was 75%. The area under the ROC curve for osteoporosis was 0.822 ± 0.028. We conclude that: (a) CDA assessment has a moderate correlation with BMD measured by DXA at the lumbar spine and femoral neck; (b) CDA has a low sensitivity for the diagnosis of osteoporosis compared with spinal and femoral DXA; and (c) predictive values for osteoporosis at both the lumbar spine and femoral neck are acceptable. Received: September 2000 / Accepted: January 2001     

Ultrasound Velocity Through the Phalanges in Normal and Osteoporotic Patients

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200? (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles? LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment. Received: 23 September 1996 / Accepted: 25 November 1997     

Loss of Bone Mineral Density in Women Athletes During Aging

Total and regional bone mineral density (BMD) by dual-energy-X-ray absorptiometry (DXA) and bone turnover were tested in 50 highly trained women athletes and 21 sedentary control women (18–69 years; BMI < 25 kg/m²). VO_2max (ml · kg⁻¹· min⁻¹) and lean tissue mass (DXA) were significantly higher in the athletes versus controls (both P < 0.0001). Total body BMD did not decline significantly with age in the athletes whereas lumbar spine (L₂–L₄) BMD approached statistical significance (r =−0.26; P= 0.07). Significant losses of the femoral neck (r =− 0.42), Ward's triangle (r =−0.53), and greater trochanter BMD (r =−0.33; all P < 0.05) occurred with age in the athletes. In the athletes, total body BMD, L₂–L₄ BMD, and BMD of all sites of the femur were associated with lean tissue mass (r = 0.32 to r = 0.57, all P < 0.05) and VO_2max (r = 0.29 to r = 0.48, all P < 0.05). Femoral neck and greater trochanter BMD were higher in the athletes than in controls (both P < 0.05) and lumbar spine and Ward's triangle BMD approached statistical significance (both P= 0.07). Bone turnover was assessed by serum bone-specific alkaline phosphatase (B-ALP), urinary deoxypyridinoline cross-links (Dpd), and urinary aminoterminal cross-linked telopeptides (NTX). There were no relationships between B-ALP or Dpd with age whereas NTX increased with age (r = 0.46, P < 0.05) in the entire group. Levels of B-ALP and NTX were negatively associated with total body, L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (P < 0.05). B-ALP and Dpd were not significantly different between athletes and controls whereas NTX was lower in the athletes than in controls (P < 0.001). The high levels of physical activity observed in women athletes increase aerobic capacity and improve muscle mass but are not sufficient to prevent the loss of bone with aging. Received: 28 November 1997 / Accepted: 8 April 1998     

Long-Term Vegetarian Diet and Bone Mineral Density in Postmenopausal Taiwanese Women

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subject characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03–5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21–12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians. Received: 10 May 1996 / Accepted: 9 August 1996     

Estimation of the Prevalence of Low Bone Density in Canadian Women and Men Using a Population-Specific DXA Reference Standard: The Canadian Multicentre Osteoporosis Study (CaMos)

The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm² for women and 1.058 ± 0.127 g/cm² for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm² for women and 0.910 ± 0.125 g/cm² for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%. Received: 23 April 1999 / Accepted: 14 April 2000     

Ultrasound and X-ray-Based Bone Densitometry in Patients with Anorexia Nervosa

In 20 patients (mean age 23 ± 5 years) with anorexia nervosa (AN), bone mass was evaluated by broadband ultrasound attenuation (BUA) of the calcaneus, peripheral quantitative computed tomography (pQCT) of the distal radius, and dual X-ray absorptiometry (DXA) of the lumbar spine and the hip. Compared with 20 age- and sex- matched healthy controls, patients with AN showed marked osteopenia at all measuring sites. Values of BUA (33.0 ± 9dB/MHz vs. 51.0 ± 5.7 dB/MHz; P < 0.0001) and of BMD of all regions of the hip (e.g., femoral neck: 0.71 ± 0.13 g/cm² versus 0.89 ± 0.07 g/cm²; P < 0.001), lumbar spine (0.82 ± 0.15 g/cm² versus 1.24 ± 0.06 g/cm²; P < 0.003) and total BMD of the peripheral radius (303.2 ± 75 g/cm³ versus 369.4 ± 53.2 g/cm³, P < 0.001) were significantly reduced. Calculating a Z-score we found the most prominent differences between AN and controls by BUA of the calcaneus (−3.2 ± 1.6), followed by DXA at the lumbar spine (−2.9 ± 2.2) and the hip (femoral neck −2.1 ± 1.7) and by pQCT at the distal radius (total BMD −1.2 ± 2.0). There were highly significant correlations between BUA of the calcaneus and BMD of the femoral neck (r = 0.78, P < 0.0001) and lumbar spine (r = 0.75, P < 0.0001) as well as between BMD values of the femoral neck and lumbar spine (r = 0.95; P < 0.0001). In addition, there were significant correlations (P < 0.001) between body mass index (BMI) and the three different measuring sites and between the duration of the disease and BUA (r = 0.5, P < 0.05). Our data suggest that BUA of the calcaneus is a valuable tool in the management of osteoporosis. Being a fast, radiation-free investigation method of good acceptance, it may be well suited for an assessment of the skeletal status in patients with AN. Received: 14 October 1998 / Accepted: 10 December 1999     

The Relation of Dietary Vitamin C Intake to Bone Mineral Density: Results from the PEPI Study

Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0.017 g/cm² increment in BMD (P= 0.002 femoral neck; P= 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P= 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and ≤500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm² in BMD per 100 mg vitamin C (P= 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the β coefficient in the higher calcium stratum was similar to that for the total sample (β= 0.0172, P= 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (β= 0.0199, P= 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg. Received: 12 September 1997 / Accepted: 27 January 1998     

Calcaneal Ultrasonometry: Response to Treatment in Comparison with Dual X-ray Absorptiometry Measurements of the Lumbar Spine and Femur

The object of this study was to determine the effectiveness of calcaneal ultrasonometry in the prediction of bone mineral changes in the lumbar spine and femoral neck in response to treatment of osteoporosis. There were 673 women in the study who had one or more follow-up measurements between 1 and 4 years after the initial baseline determination for a total of 881 same-day measurements of the calcaneus, spine, and femur. The LUNAR Achilles and LUNAR DPX (LUNAR Corporation, Madison, WI) were used. Patients were divided into three treatment time groups: Group 1, 1–<2 years, n = 461; Group 2, 2–<3 years, n = 278; Group 3, 3–<4 years, n = 142. There were significant increases in the bone mineral density (BMD) of the lumbar spine, femoral neck, and in the broadband ultrasonic attenuation (BUA) of the calcaneus for the three groups. In contrast, a significant decrease in speed of sound (SOS) was obtained in these time frames and the stiffness index remained unchanged. Spearmen correlations showed an inverse relationship between the percent changes in SOS and BUA, the reasons for which are speculative. Correlations between the percent changes in calcaneal parameters and the BMDs of the lumbar spine and femoral neck were weak, whether significant or not, rho varying from −0.12 to 0.20. There was a subset of 371 patient measurements that registered BMD increases in both the lumbar spine and femoral neck. This was considered to be an objective indication of adequate compliance with prescribed treatment. Analysis of this subset yielded parameter correlations similar to those of the entire group. It is concluded that changes in the calcaneal ultrasound parameters in response to treatment of osteoporosis are not a reflection of mineral changes occurring in the lumbar spine and femoral neck in a given individual, and in this regard, calcaneal ultrasonometry is not a substitute for direct-site dual X-ray absorptiometry (DXA) measurement of the lumbar spine and femur. Received: 19 February 1998 / Accepted: 24 June 1998     

Cytokine Production and Bone Mineral Density at the Lumbar Spine and Femoral Neck in Premenopausal Women

Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss were observed in women with ``high' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high' =−1.56% ± 0.70 versus ``low' (<75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites. Received: 5 February 1997 / Accepted: 11 May 1998     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

The Effect of Weight Change on DXA Scans in a 2-Year Trial of Etidronate Therapy

Variation in soft tissue composition is a potential cause of error in dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD). We investigated the effect of patients' change of weight on DXA scans in 152 women enrolled in a 2-year trial of cyclical etidronate therapy. Scans of the spine, hip, and total body were performed at baseline, 1 and 2 years on a Hologic QDR-2000. The study was completed by 135 subjects (64 on etidronate, 71 on placebo). Results were expressed as the percentage change in BMD (spine, femoral neck, total body) or bone mineral content (BMC) (total body only) at 2 years. Total body scans were analyzed using the manufacturer's `standard' and `enhanced' algorithms. Analysis was performed using multivariate regression with percentage change in BMD or BMC as the dependent variable, and treatment group and percentage change in weight as the independent variables. Weight change varied between −14.4% and +16.7%. All DXA variables showed a statistically significant treatment effect. Standard total body BMD and BMC and enhanced total body BMC all showed a significant dependence on weight change (P < 0.01, P < 0.001 and P < 0.01, respectively). No effect of weight change was seen on spine, femoral neck, or enhanced total body BMD. In order to investigate the effects of weight on long-term precision, patients were allocated to two groups according to baseline body mass index (BMI <25 and >25 kg/m², respectively). For femoral neck BMD the root mean square (RMS) residual percentage change was statistically significantly larger in the high BMI group (P < 0.05) but all other bone density variables showed no significant difference. With patients allocated to two groups according to their absolute percentage change in weight (<5% and >5%, respectively) the RMS residual percentage changes in the bone density variables were statistically significantly larger in the large weight change group for femoral neck BMD (P < 0.05) and for standard and enhanced total body BMC (P < 0.01 and P < 0.05, respectively). With the exception of the standard total body algorithm, weight change in a longitudinal study of postmenopausal women was not found to cause systematic errors in the results of DXA studies but may adversely affect precision. Received: 22 November 1996 / Accepted: 30 April 1997     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

Bone Mineral Density and Androgen Levels in Elderly Males

To clarify the relationship of sex male hormones and bone in men, we studied in 140 healthy elderly men (aged 55–90 years) the relation between serum levels of androgens and related sex hormones, bone mineral density (BMD) at different sites, and other parameters related to bone metabolism. Our results show a slight decrease of serum-free testosterone with age, with an increase of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a third of the elderly subjects studied. BMD decreased significantly with age in all regions studied, except in the lumbar spine. We found a positive correlation between body mass index (BMI) and BMD at the lumbar spine and femoral neck (P < 0.001). No relationship was found (uni- and multivariate regression analysis) between serum androgens or sex hormone-binding globulin (SHBG) and BMD. We found a positive correlation of vitamin D binding protein (DBP) and osteocalcin with lumbar spine BMD and with BMI, DBP, IGF-1, and PTH with femoral neck BMD. In conclusion, there is a slight decline in free testosterone and BMD in the healthy elderly males. However, sex male hormones are not correlated to the decrease in hip BMD. Other age-related factors must be associated with bone loss in elderly males. Received: 29 April 1997 / Accepted: 9 November 1997     

Inappropriate Reference Range for Peak Bone Mineral Density in Dual-energy X-ray Absorptiometry: Implications for the Interpretation of T-scores

An inappropriate reference range for peak bone mineral density (BMD) may result in identification of an incorrect proportion of subjects with osteopenia and osteoporosis at dual-energy X-ray absorptiometry (DXA). In this study, we assessed the prevalence of low BMD in Turkish young adults with respect to local population reference range T-scores and the US reference range T-scores. The BMD values of lumbar spine (L1–L4) and proximal femur (femoral neck, intertrochanter, trochanter, Ward”s triangle and total) were measured by DXA in 323 healthy young adults (171 women, 152 men) aged 19–25 years. The World Health Organization criteria for the diagnosis of osteopenia (−2.5 <T-score <−1) and osteoporosis (T-score ≤−2.5) were applied. In women, the means of the US reference range T-scores were significantly lower than zero at the spine and proximal femoral sites (p<0.0001). In men, the means of the US reference range T-scores were significantly lower than zero at the spine, femoral neck, intertrochanter, total femur (p<0.0001) and trochanter (p<0.05), but not at Ward”s triangle (p=0.92). When the diagnoses were based on local population reference range T-scores instead of the US reference range T-scores, the prevalence of low BMD (T-score <−1) in women fell from 50.3% to 14.0% at the lumbar spine and from 60.8% to 14.6% at the femoral neck, and in men from 42.8% to 15.8% at the lumbar spine and from 30.9% to 17.1% at the femoral neck. Our data suggest that individual populations should use their own reference range T-scores to avoid misdiagnoses of osteopenia and osteoporosis by DXA. Received: 4 November 1999 / Accepted: 29 March 2000     

Early Postmenopausal Bone Loss is Prevented by Estrogen and Partially by 1α-OH-vitamin D3: Therapeutic Effects of Estrogen and/or 1α-OH-vitamin D3

A total of 79 Japanese women who were within 5 years of menopause were randomly assigned 1α-hydroxyvitamin D₃ [1α(OH)D₃] 1.0 μg/day, conjugated estrogens 0.625 mg/day, a combination of both, or control (no treatment). Lumbar spine and proximal femur bone mineral density (BMD) and biochemical indices were monitored over 2 years. In the 1α(OH)D₃-treated group, there was a nonsignificant decrease in lumbar spine BMD compared with controls, and no significant loss in the femoral neck compared with controls. In the estrogen-treated group, there was a nonsignificant increase in spine BMD (+2.17% in the first year and +1.71% in the second year), and no loss in femoral neck BMD. The combination of conjugated estrogens +1α(OH)D₃ was more effective in increasing BMD in the spine (+3.68% in the first year and +3.63% in the second year) and femur (+2.56% in the first year and +4.44% in the second year) BMD. There was a significant difference in lumbar spine BMD in both the first and second years between the combination-treated group and the 1α(OH)D₃-treated and control groups (P < 0.01). Serum osteocalcin (OC) significantly decreased in the combination-treated group (−23.8% in the first year) and the estrogen-treated group (−37.6% and −41.2% at 6 and 18 months, respectively), and serum alkaline phosphatase (Alp) decreased significantly in the first year in the combination-treated (−31.5%), estrogen-treated (−27.3%), and 1α(OH)D₃-treated (−7.9%) groups, whereas serum OC increased (+45.4% in the first year) in women without treatment. The results of this study indicate that early postmenopausal bone loss in the femoral neck is prevented by conjugated estrogens, 1α(OH)D₃, or both, whereas bone loss in the spine is not prevented by 1α(OH)D₃. Estrogen proves effective in preventing early postmenopausal bone loss by markedly inhibiting bone turnover. Moreover, a synergistic bone-sparing effect can be expected when estrogen is administered concomitantly with 1α(OH)D₃ rather than when used alone. Received: 28 April 1998 / Accepted: 23 December 1998     

Increased Bone Mineral Density after Prolonged Electrically Induced Cycle Training of Paralyzed Limbs in Spinal Cord Injured Man

Spinal cord injured (SCI) individuals have a substantial loss of bone mass in the lower limbs, equaling approximately 50% of normal values in the proximal tibia, and this has been associated with a high incidence of low impact fractures. To evaluate if this inactivity-associated condition in the SCI population can be reversed with prolonged physical training, ten SCI individuals [ages 35.3 ± 2.3 years (mean ± standard error [SE]); post injury time: 12.5 ± 2.7 years, range 2–24 years; level of lesion: C6–Th4; weight: 78 ± 3.8 kg] performed 12 months of Functional Electrical Stimulated (FES) upright cycling for 30 min per day, 3 days per week, followed by six months with only one weekly training session. Bone mineral density (BMD) was determined before training and 12 and 18 months later. BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by dual energy absorptiometry (DEXA, Nordland XR 26 MK1). Before training, BMD was in the proximal tibia (52%), as well as in the femoral neck, lower in SCI subjects than in controls of same age (P < 0.05). BMD of the lumbar spine did not differ between groups (P > 0.05). After 12 months of training, the BMD of the proximal tibia had increased 10%, from 0.49 ± 0.04 to 0.54 ± 0.04 g/cm² (P < 0.05). After a further 6 months with reduced training, the BMD in the proximal tibia no longer differed from the BMD before training (P > 0.05). No changes were observed in the lumbar spine or in the femoral neck in response to FES cycle training. It is concluded that in SCI, the loss of bone mass in the proximal tibia can be partially reversed by regular long-term FES cycle exercise. However, one exercise session per week is insufficient to maintain this increase. Received: 30 July 1996 / Accepted: 31 December 1996     

Bone Density in an Immigrant Population from Southeast Asia

The epidemiology of bone loss in populations of Asian heritage is still poorly known. This study compared the skeletal status of a convenience sample of 396 Southeast Asian immigrants (172 Vietnamese, 171 Cambodians and 53 Laotians) residing in Rochester, Minnesota in 1997 with 684 white subjects previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 instrument for the white population and the QDR 4500 for Southeast Asian subjects; the machines were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 7% higher in white than Southeast Asian women ( p < 0.001), and similar results were observed for the femoral neck; lumbar spine BMD was 12% higher in white than nonwhite men ( p < 0.001). Race-specific discrepancies were reduced by calculating BMAD: for premenopausal women, lumbar spine and femoral neck differences between whites and Southeast Asians were eliminated; for postmenopausal women the lumbar spine differences persisted ( p < 0.0001), while femoral neck BMAD was actually higher for Southeast Asians. There were no race-specific differences in femoral neck BMAD among men of any age ( p= 0.312), but lumbar spine BMAD was less for younger ( p= 0.042) but not older ( p= 0.693) Southeast Asian men. There were differences among the Southeast Asian subgroups, but no clear pattern emerged. Predictors of lumbar spine BMAD in Southeast Asian women were age ( p < 0.001), weight ( p= 0.015) and gravidity ( p= 0.037). Even after adjusting for bone size using BMAD, 32% and 9% of Southeast Asian women and men, respectively, would be considered to have osteoporosis at the femoral neck and 25% and 4%, respectively, at the lumbar spine. These findings indicate a need for culturally sensitive educational interventions for Southeast Asians and for physicians to pursue diagnosis and treatment to prevent osteoporosis-related disabilities in this population. Received: 12 October 2000 / Accepted: 15 February 2001