The influence of serum ghrelin,IGF axis and testosterone on bone mineral density in boys at different stages of sexual maturity

The aim of our study was to examine the relationship between bone mineral density (BMD) and serum ghrelin, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), and testosterone levels in boys at different stages of puberty. The study included 60 healthy nonobese Estonian schoolboys at the age of 10–18 years. Subjects were divided in three groups (20 boys in each) based on the results of self-assessment using illustrated questionnaire of pubertal stage (G1, I; G2–G3, II; G3–G4, III). Morning fasting blood samples were collected for analysis of ghrelin, testosterone, IGF-1, and IGFBP-3. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD), and bone mineral content (BMC) were measured by DXA. Serum testosterone concentration was the most important biochemical predictor of BMD in the total group, explaining 48.8% of variability in total body BMD, 51.4% in lumbar BMD, and 36.8% in lumbar BMAD. Body mass and height were both related to BMD and BMC throughout puberty. The serum IGF-1/IGFBP-3 ratio was correlated with serum testosterone (r = 0.69) and ghrelin (r = −0.58) levels, but also with total BMD (r = 0.39), lumbar BMD (r = 0.42; P < 0.001 in all cases), BMAD (r = 0.29; P < 0.01), and total BMC (r = 0.48; P < 0.001). We conclude that serum testosterone concentration and serum IGF-1/IGFBP-3 molar ratio are the major determinants of bone mineral density in boys at different pubertal stages. Serum ghrelin concentration did not appear to have a direct independent effect on BMD. If present, the association may be mediated through sex hormones and the GH-IGF-I axis.     

The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone.     

Plasma Leptin Values in Relation to Bone Mass and Density and to Dynamic Biochemical Markers of Bone Resorption and Formation in Postmenopausal Women

After the menopause it has been noted that heavier women conserve bone better than those with lower body weight. The protective effect of obesity on bone mass has been ascribed to a high body fat content. The present study of 54 postmenopausal women was undertaken to determine whether circulating plasma levels of leptin, the newly described hormone produced in adipocytes, were correlated with age-adjusted total body bone mineral content (BMC) or bone mineral density (BMD), or with dynamic biochemical markers of bone resorption or of bone formation. Leptin values were strongly correlated with all measures of adiposity (P < 0.001). Age-adjusted values for BMC and BMD, respectively, were also positively correlated (P < 0.001) with body weight (r = 0.643, r = 0.502), total fat mass (r = 0.557, r = 0.510) and with plasma leptin concentrations (r = 0.480, r = 0.551), confirming a positive relationship between fat mass and bone mass. By contrast, no significant correlations were observed between plasma leptin and dynamic markers of bone resorption (urinary deoxypyridinoline/creatinine r =−0.105, hydroxyproline/creatinine r =−0.193) or formation (plasma osteocalcin r = 0.103). Because there was no evidence for an association between ciculating plasma levels of leptin and biochemical markers of either osteoclastic or osteoblastic activity we conclude it is unlikely that circulating leptin plays any significant direct role in controlling bone cell activity. Our results do not support the hypothesis that leptin mediates the bone-sparing effects of obesity. Received: 23 September 1997 / Accepted: 11 May 1998     

Circulating β2 Microglobulin in Relation to Bone Metabolism: Implications for Bone Loss with Aging

The aim of this cross-sectional study was to evaluate the relationships between circulating β₂ microglobulin (β₂ m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic β₂ m correlated with BMD (g/cm²) levels for total hip and Ward's triangle (r =−0.298, P < 0.0001; and r =−0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r =−0.145, P= 0.0604). Serum β₂ microglobulin markedly correlated with age (r = 0.512, P= 0.0001). β₂ m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD₃, 1,25(OH)₂D₃, PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD₃ was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, β₂ m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic β₂ m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss. Received: 21 July 1998 / Accepted: 10 June 1999     

Plasma adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts

The aim of the present study was to investigate possible differences in plasma adipocytokine and ghrelin levels and body composition parameters in prepubertal rhythmic gymnasts (RG) and untrained controls (UC), and to examine the relationships of bone mineral density (BMD) with hormonal status in prepubertal children with different physical activity patterns. Eighty-nine 7- to 9-year-old girls participated in the study (RG, n = 46; UC, n = 43). Body composition and BMD were measured by dual-energy X-ray absorptiometry. Bone maturity was estimated by using a radiograph of the nondominant hand. The measured whole-body, lumbar spine (LS), and femoral neck (FN) BMD values were significantly higher (P < 0.05) in gymnasts than in controls. In addition, RG presented significantly lower and higher values (P < 0.05) for leptin and ghrelin concentrations, respectively, in comparison with UC. No differences were observed for adiponectin levels between the studied groups. No relationships between measured BMD values with leptin and ghrelin were observed even after adjustment for age and fat mass (FM) in RG. Whole-body and LS BMD values were significantly correlated with leptin after controlling for age and FM (r = 0.32, P < 0.05) in UC. Femoral neck BMD remained significantly correlated with ghrelin after adjusting for age and FM (r = −0.4, P < 0.05) in UC. No relationships were found between measured BMD values and adiponectin even after controlling for age and FM values in both groups. In conclusion, although all measured BMD values were significantly higher in RG, plasma adipocytokine and ghrelin concentrations were not directly related to bone mineralization in prepubertal RG in contrast to UC.     

Effects of sodium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 ± 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer−NaB−). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB−), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to anova with the Tukey–Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB− groups than in the two other groups (P < 0.005–0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB− group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects. Received: May 1, 2000 / Accepted: August 11, 2000     

Bone Mineral Density of the Spine and Femur in Healthy Saudi Females: Relation to Vitamin D Status, Pregnancy, and Lactation

Bone mineral density (BMD) measurements of the anterio-posterior lumbar spine and the proximal femur using dual-energy x-ray absorptiometry, as well as relevant clinical and biochemical parameters, were determined in 321 healthy Saudi females in order to establish reference values and to study the effects of physical and lifestyle factors on BMD. Mean ± SD of age, body mass index (BMI), number of pregnancies, and total duration of lactation were 35.4 ± 11.3 years, 26.5 ± 5.2 kg/m², 3.1 ± 3.1, and 23.7 ± 42.4 months, respectively. Mean ± SD of serum calcium, 25-hydroxyvitamin D (25OHD), and PTH levels were 2.37 ± 0.09 mmol/liter, 24.5 ± 17.2 nmol/liter, and 52.0 ± 30.8 pg/ml, respectively. Peak BMD values were observed around age 35 years at the spine and earlier at the femur. Compared with USA females, Saudi females had lower weight-matched Z scores at the spine (−0.126 ± 1.078, P= 0.04), femoral neck (−0.234 ± 0.846, P < 0.0001), and Ward's triangle (−0.269 ± 1.015, P < 0.0001). Further, the prevalence of osteopenia and osteoporosis in subjects ≥31 years old were 18–41% and 0–7%, respectively, depending on the site examined. Severe hypovitaminosis D (25OHD level ≤20 nmol/liter) was present in 52% of the subjects. However, there was no correlation between 25OHD level and BMD at any site. Parathyroid hormone (PTH) levels correlated significantly with 25OHD levels (r =−0.28, P < 0.0001) and with weight-matched BMD Z scores at the spine (r =−0.17, P= 0.005), femoral neck (r =−0.16, P= 0.007), and Ward's triangle (r =−0.2, P= 0.0008), suggesting that the distribution of 25OHD levels in the cohort is below the threshold needed for maintaining normal BMD. On the other hand, number of pregnancies and total duration of lactation correlated with weight-matched BMD Z scores at the spine (r =−0.17, P= 0.003; r =−0.1, P= 0.08, respectively). We conclude that BMD in healthy Saudi females is significantly lower than in their USA counterparts. This may be due in part to increased number of pregnancies and longer duration of lactation together with prevalent vitamin D deficiency. Received: 21 July 1998 / Accepted: 1 November 1998     

Relationships of acylated and des-acyl ghrelin levels to bone mineralization in obese children and adolescents

AimsBodyweight is a significant predictor of bone mass. Hormonal factors are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. Very recently, the orexigenic hormone ghrelin has also been implicated in bone metabolism. In this study we examined the associations of circulating acylated and des-acyl ghrelin concentrations with measures of bone in a group of obese children and adolescents as well as in a group of healthy control children. We also determined whether the associations were independent of body composition, chronological age, gender, Tanner stage, and leptin, glucose, insulin and insulin-like growth factor (IGF)-1 levels.MethodsWe performed a prospective cross-sectional study of 100 obese children [age, 8.9 (8.3 to 9.4); BMI-Standard Deviation Score (SDS), 2.2 (2.0 to 2.3)], and 100 age-matched lean healthy subjects. Fasting insulin, leptin, IGF-1, acylated and total ghrelin were measured by radioimmunoassay. Des-acyl ghrelin values were calculated as total ghrelin minus acylated ghrelin. Whole body (WB) and lumbar spine (LS) BMD, and BMC as well as body composition were assessed by DXA (Hologic QDR-4500W). LS volumetric BMD (BMAD) was estimated using the formula of Katzman (BMC/area^1.5), while WB BMC data were expressed as BMC/height.ResultsBackward linear regression analysis was performed for individual groups, with age, gender, Tanner stage, weight, height, body composition (lean and fat mass), acylated ghrelin, des-acyl ghrelin, leptin, glucose, insulin, and IGF-1, entered into the model. In healthy children, acylated ghrelin was a significant and independent negative predictor of WB BMD, and WB BMC/height, while lean mass was positively associated significantly with these bone measures. In contrast, in obese children, a positive significant association was observed between des-acyl ghrelin and WB BMD as well as WB BMC/height, along with lean mass, and to a lesser degree, with fat mass. Acylated as well as des-acyl ghrelin were not significant predictors of LS BMD and LS BMAD in obese as well as control children.ConclusionsThe results of this investigation indicate that the influence of the two distinct isoforms of ghrelin on BMD is mediated by specific body composition parameters in obese and control healthy children.     

One-Year Changes in Energy Expenditure and Serum Leptin Following Adjustable Gastric Banding in Obese Women

Background: Weight loss is associated with a decrease in both energy expenditure and circulating leptin levels. Whether this holds true when the influence of body composition on energy expenditure and leptin is taken into account remains controversial. The aim of the study was to assess changes in resting metabolic rate (RMR) and serum leptin adjusted for body composition during surgically induced weight loss. Methods: In 36 women (age 42.7±8.7 years; BMI 47.2±8.5 kg/m²; mean±SD) undergoing laparoscopic adjustable gastric banding (LAGB) for morbid obesity, we measured RMR (by indirect calorimetry), body composition (by dual-energy X-ray absorptiometry) and serum leptin (by immunoradiometry), immediately before and 1 year after surgery. Results: 1 year after LAGB, there were significant decreases in body weight (−23.7±11.6 kg, P<0.001), fat mass (FM: −20.9±11.3 kg, P<0.0001), lean body mass (LBM: −3±5.3 kg, P=0.005), RMR (−298±309 kcal/day, P<0.0001), serum leptin (−24.0±18.4 ng/ml, P<0.0001), RMR/LBM ratio (−3.9±5.8 kcal/kg LBM/day, P<0.01) and leptin/FM ratio (−0.21±0.29 ng/kg FM/ml, P<0.001). RMR values after surgery were correctly predicted by the regression equation relating RMR to LBM and FM at baseline, whereas this was not the case for serum leptin (in relation to FM). Conclusions: Changes in RMR 1 year after LAGB were explained by changes in body composition whereas changes in serum leptin were not. The data provide no evidence for a metabolic adaptation of RMR with weight loss, but suggest that serum leptin is decreased beyond expected values based on body composition, a factor that may favor weight regain after surgically induced weight loss.     

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of β-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than −1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3–15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5–12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5–12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7–6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in β-thalassaemia-associated osteopenia.     

Relationship Between Visceral Adiposity and Bone Mineral Density in Korean Adults

The objective of the study was to investigate the relationship between visceral and subcutaneous adiposity measured by computed tomography and bone mineral density (BMD) and to identify the metabolic factors associated with BMD. We studied 461 subjects recruited from the health-care center at Severance Hospital, Yonsei University College of Medicine. Multivariate regression analyses were conducted to examine the cross-sectional associations between body composition-related or metabolic parameters and BMD. After adjusting for body weight and other confounders, visceral fat area had an inverse association with BMD in men (β = −0.133, P = 0.049 for lumbar spine; β = −0.135, P = 0.037 for femoral neck; β = −0.179, P = 0.005 for total hip) and women (β = −0.424, P < 0.001 for lumbar spine; β = −0.302, P = 0.005 for femoral neck; β = −0.274, P = 0.014 for total hip). However, the subcutaneous fat area showed no statistically significant relationship with BMD at most sites. Among the metabolic parameters, HDL cholesterol was positively associated with BMD, while LDL cholesterol was negatively associated with BMD in men. In women, total and LDL cholesterol were negatively associated with BMD at the lumbar spine. We conclude that visceral adiposity is inversely associated with BMD after adjusting for confounders and that metabolic factors may partly contribute to this inverse relation.     

Racial Differences in the Association of Subcutaneous and Visceral Fat on Bone Mineral Content in Prepubertal Children

Total fat mass plays a significant role in determining bone mass, but the specific role of central adiposity independent of total fat mass has not been widely studied. Prepubertal (Tanner 1) children (n = 181; 65 boys, 116 girls, 7.8 ± 1.5 years), including 99 Caucasians and 82 African Americans from Birmingham, Alabama, participated in this study. Body composition, including total body and trunk fat mass, and bone mineral content (BMC) were measured using dual-energy X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAAT) and intra-abdominal adipose tissue (IAAT) were determined by single-slice computed tomography (CT). After adjusting for gender, age, height, total fat, and lean mass, trunk weight was inversely correlated with BMC in Caucasians (r = −0.56, P < 0.0001) and in African Americans (r = −0.37, P < 0.05). In Caucasians, independent of gender, age, height, total fat, and lean mass, there was an inverse correlation between SAAT and BMC (r = −0.58, P < 0.0001) but no significant correlation between IAAT and BMC; in addition, SAAT explained 6% of the variance in BMC. In contrast, in African Americans, SAAT and BMC were not significantly correlated. However, while adjusting for gender, age, height, SAAT, total fat, and lean mass, an inverse association between IAAT and BMC was observed in African Americans (r = −0.50, P < 0.01); IAAT also explained 3% of the variance in BMC. These findings suggest that, in general, total abdominal weight is negatively associated with bone mass, but there appear to be racial differences with regard to the contributions of subcutaneous and visceral fat to BMC in prepubertal children.     

Association between bone mineral density,lean mass,and fat mass among healthy middle-aged premenopausal women: a cross-sectional study in southern Sri Lanka

Associations between lean mass, fat mass, and bone mass have been reported earlier; however, most of those studies have been done in Caucasian populations, and data from Asian countries, especially those in South Asia, are limited. We examined the associations between lean mass, fat mass, bone mineral density (BMD), and bone mineral content (BMC), determined by dual-energy X-ray absorptiometry technology, in a group of healthy, middle-aged, premenopausal female volunteers. The mean (SD) age of the women (n = 106) was 42.1 (6.1) years and the mean (SD) body mass index was 24.3 (3.6) kg/m². Total body BMD, total body BMC, and BMD in total spine, total hip, and femoral neck showed statistically significant partial correlations (adjusted for age) with total fat mass (r = 0.19–0.43, P < 0.05) and lean body mass (r = 0.28–0.54, P < 0.05). Truncal fat mass correlated positively with total body BMC and BMD at total hip and femoral neck (r = 0.33–0.40, P < 0.001). When a stepwise regression model was fitted, lean mass remained the strongest predictor of total body BMD, total body BMC, and total spine BMD (regression coefficients = 0.004–0.008 g/cm² per 1-kg change in lean mass, P < 0.001). Similarly, crude BMD and BMC increased across the tertiles of lean mass (P trend < 0.05). We show that lean mass is the strongest predictor of total body BMC and BMD at different sites, although positive correlations with fat mass also exist.     

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     

Interactions of interleukin-6 gene polymorphisms with calcium intake and physical activity on bone mass in pre-menarche Chinese girls

Summary  This study assessed independent associations and interactions of IL-6 promoter alleles (−174G/C and −634C/G), calcium intake and physical activity with bone mass among pre-menarche Chinese girls. The −634 CC carriers, greater calcium intake and physical activity were associated with better bone mass. The gene-bone association was more pronounced among girls with high physical activity or with low calcium intake. Introduction  The association between interleukin (IL)-6 promoter polymorphisms and bone mass remains in debate. This cross-sectional study examined the association between the IL-6 promoter alleles (−174G/C and −634C/G) and bone mass, and assessed if the association could be modified by calcium intake or physical activity in pre-menarche Chinese girls. Methods  Two-hundred and twenty-eight healthy pre-menarche girls aged 9–11 years were recruited from primary schools in Guangzhou, China by sending letters to parents. None of them had diseases or medications known to affect bone metabolism. The IL-6 promoter genotypes were determined by PCR-RFLP, and BMD and BMC at the total body, lumbar spine, total hip and femoral neck were measured by DXA. Calcium intake and physical activity were assessed by face-to-face questionnaire interview. Results  One hundred and seventy-six subjects completed the entire study. We did not detect gene polymorphism at the IL-6 −174G/C locus, all were GG homozygotes. The IL-6 −634C/G polymorphism was significantly associated with both BMD and BMC even after adjusting for age and weight. Girls with CC genotype had higher levels of BMC and BMD than G allele carriers (+8.3% for the total body BMC, and +2.9%, +5.8%, and +5.7% for BMDs at the total body, total hip, and femoral neck, respectively; P < 0.05). The favorable effect of physical activity on BMDs at the total hip and femoral neck was much more pronounced in CC carriers than in G allele carriers, and the CC genotype associated higher BMDs at the total hip and femoral neck were observed only in girls with high level physical activity (P for interactions = 0.036 and 0.021, adjusted for age and weight). Calcium had a more benefit to the total body BMC in G allele carriers than in CC carriers, and the G allele-associated lower total body BMC was found only in subjects with low calcium intake. Conclusion  The IL-6 −634C/G polymorphism was significantly associated with BMD and the association might be modified by calcium intake or physical activity in pre-menarche Chinese girls.     

Age-Related Changes in Serum Undercarboxylated Osteocalcin and its Relationships with Bone Density, Bone Quality, and Hip Fracture

The effect of the degree of carboxylation of osteocalcin (OC) on the properties of bone is unclear. The aim of this study was to relate serum concentrations of total OC (tOC) and undercarboxylated OC (ucOC), measured with a two-site immunoassay, to bone mineral density (BMD) at the femoral neck and ultrasonic transmitted velocity (UTV) at the os calcis in 257 women aged 60–99 years, 22 of whom had sustained a hip fracture. There was an increase in tOC (r = 0.19, P= 0.003) and ucOC (r = 0.20, P= 0.002) with age. No significant difference in tOC or ucOC between subjects with and without hip fracture was found. Serum tOC was negatively correlated with femoral neck BMD (r =−0.23, P= 0.0001) and os calcis UTV (r =−0.29, P= 0.0001) and partial correlations indicated that these relationships were independent of age. Serum ucOC also correlated negatively with os calcis UTV (r =−0.21, P= 0.001) and less strongly with femoral neck BMD (r =−0.13, P= 0.052). After adjusting for age, only the relationship between ucOC and os calcis UTV remained significant (r =−0.16, P= 0.017). It is concluded that in women over 60 years, the increase in tOC reflects an age-related rise in bone remodeling, whereas the increase in ucOC reflects an age-related fall in vitamin K status. The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content. Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed. Received: 8 January 1997 / Accepted: 29 September 1997     

Correlations between bone mineral density and demographic, lifestyle, and biochemical variables in community-dwelling Japanese women 69 years of age and over

Introduction A few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over.Methods The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.3 (SD 4.4) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 osteometer.Results Simple linear regression analyses showed that BMD was significantly positively associated with body height, weight, body mass index, grip strength, serum albumin concentration, and “housework,” and negatively associated with age, years since menopause, age at menarche, number of children, serum 1,25(OH)₂D concentration, serum OC concentration, and ucOC concentration. The stepwise multiple regression analysis showed that weight (β=0.00316, SE=0.00028, R²=0.180), age (β=−0.00321, SE=0.00050, R²=0.108), log-transformed serum OC (β=−0.0445, SE=0.0064, R²=0.053), log-transformed serum 1,25(OH)₂D (β=−0.0401, SE=0.0074, R²=0.050), “farmwork” (β=0.00904, SE=0.00426, R²=0.005), and serum 25(OH)D concentration (β=0.000281, SE=0.000120, R²=0.003) were significantly associated with BMD.Conclusion It was concluded that body weight is a major predictor of forearm BMD among the factors measured in this study in independent Japanese women 69 years of age and over and that serum 1,25(OH)₂D concentration may be associated with cortical BMD. Maintenance of body weight is very important for maintaining BMD in this population, unless a large weight aggravates obesity-related diseases. A follow-up study is needed to confirm these findings.     

PIXImus Bone Densitometer and Associated Technical Measurement Issues of Skeletal Growth in the Young Rat

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.     

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     

Influence of Grip Strength on Metacarpal Bone Mineral Density in Postmenopausal Japanese Women: A Cross-Sectional Study

Most published studies on the role of muscle strength in the maintenance of bone mineral density (BMD) focused on the relationship between specific muscle groups and adjacent bones, mostly in young and premenopausal women. This study examined the influence of grip strength on BMD of the metacarpal index in postmenopausal Japanese women. Subjects included 1168 postmenopausal women aged 40–70 years. BMD measurement was done with computed X-ray densitometry (CXD) by analyzing X-ray films of the right second metacarpal index. Grip strength was measured in both the dominant and nondominant hands using a squeeze dynamometer. Grip strength (r = 0.2474; P= 0.0001) and age (r =−0.5443; P= 0.0001) significantly correlated positively and negatively, respectively, with BMD. Physical activity (r = 0.1318; P= 0.0001) also correlated positively with BMD. Breastfeeding (r =−0.1658; P= 0.0001), however, correlated negatively with BMD. Subjects with a history of regular physical activity had higher grip strengths and BMD, than those with no physical activity. Adjustment for age, physical activity, calcium intake, BMI, breastfeeding, testing site, and menopausal type indicated a significant (P for trend = 0.0013) positive association of grip strength with BMD. Subjects with stronger grip strengths had a decreased risk for low BMD. Received: 24 February 1998 / Accepted: 7 August 1998