The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

OBJECTIVE: Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults. PATIENTS AND MEASUREMENTS: For 80 male adults (average age 54.5 +/- 6.4 years; average body mass index (BMI) 24.4 +/- 2.5 kg/m2), the correlations between serum resistin, leptin, adiponectin and ghrelin levels with BMD were investigated. RESULTS: Among the adipocytokines, serum resistin levels were negatively correlated with lumbar spine BMD (r = -0.237, P = 0.05). After adjustment was made for age and BMI, log-transformed serum leptin showed a significant negative correlation with lumbar spine BMD, which was not seen on bivariate analysis (r = -0.237, P = 0.039). Femoral neck BMD was marginally associated only with serum adiponectin levels (r = -0.226, P = 0.062). In multiple regression analyses, among the adipokines, only resistin was a significant determinant of lumbar spine BMD, although the variance was small (R2 = 0.256). Serum ghrelin levels were not correlated with the BMD of either body site. CONCLUSIONS: Serum resistin level showed a significant negative correlation with lumbar spine BMD, although the variance was small. Further studies are needed to elucidate the role of adipocytokines in bone metabolism.     

Fitness,fatness and activity as predictors of bone mineral density in older persons

OBJECTIVES: To determine relationships of bone mineral density (BMD) with fitness, physical activity, and body composition and fat distribution. DESIGN: Cross-sectional. SETTING: General Clinical Research Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. SUBJECTS: Men (n = 38) and women (n = 46), aged 55-75 years with high normal blood pressure or mild hypertension but otherwise healthy. METHODS: Aerobic fitness (oxygen uptake) on a treadmill, muscle strength by one-repetition maximum, activity by questionnaire, abdominal obesity by magnetic resonance imaging; anthropometrics, and body composition by dual energy X-ray absorptiometry (DXA) which measured total fat and lean mass, and BMD for the total skeleton, lumbar spine (L1-L4) and total hip. RESULTS: Aerobic fitness did not correlate with BMD. Using multivariate analysis to ascertain independent contributions to the variance in BMD, in women, with adjustment for hormone replacement therapy (HRT), total skeleton BMD was independently related to muscle strength and abdominal total fat; total hip BMD to body weight; lumbar spine BMD to abdominal total fat. HRT also influenced BMD in the lumbar spine. In men, lumbar spine BMD was independently related to abdominal total fat physical activity and total hip BMD related to lower body strength. P < 0.05 for all of these correlations. CONCLUSIONS: Abdominal obesity and muscle strength emerge as predominant correlates of BMD in older persons with stronger relationships seen in women. Body weight and HRT also explained portions of the variance in BMD in women. Whether abdominal obesity is simply a marker for general obesity or has independent protective effects on bone is yet to be determined.     

Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial

BACKGROUND: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss. METHODS: Forty-eight adults (30 women; 18 men; mean +/- SD age, 57 +/- 3 years; and mean +/- SD body mass index, 27 +/- 2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n = 19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones. RESULTS: Body weight decreased similarly in the CR and EX groups (10.7% +/- 6.3% [-8.2 +/- 4.8 kg] vs 8.4% +/- 6.3% [-6.7 +/- 5.6 kg]; P = .21), whereas weight did not change in the HL group (-1.2% +/- 2.5% [-0.9 +/- 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (-2.2% +/- 3.1% vs 1.2% +/- 2.1%; P = .02) and intertrochanter (-2.1% +/- 3.4% vs 1.7 +/- 2.8%; P = .03). The CR group had a decrease in spine BMD (-2.2% +/- 3.3%; P = .009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R = 0.61; P = .007) but not in the EX group. Bone turnover increased in both CR and EX groups. CONCLUSIONS: CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.     

Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome

Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.     

Influence of muscle strength and body weight and composition on regional bone mineral density in healthy women aged 60 years and over.

Although weight, lean mass, fat mass and muscular strength are often found to be intercorrelated, the respective role of each parameter in bone mineral density (BMD) remains unknown in older women. The aim of the present study was to investigate the relationship between body weight and composition and quadriceps strength on femoral neck and lumbar spine BMD in healthy postmenopausal women. The relationship between isokinetic quadriceps strength measured by Biodex and BMD measured by dual energy X-ray absorptiometry was studied in 56 women aged 60-81 (70.5 +/- 6.2) years in multiple regression models adjusted for age, body composition and menopausal treatment. Weight and age were associated with femoral neck BMD (33 and 10% of variance accounted for, respectively) and lumbar spine BMD (23 and 8% of its variance). When body weight and quadriceps strength were excluded from the model, lean mass and age were associated with femoral neck BMD (29 and 14% of variance explained, respectively) and lumbar spine BMD (28 and 11% of variance explained, respectively). When quadriceps strength was entered into the model, it was strongly associated with femoral neck BMD (30% of variance accounted for), in addition to lean mass (9%) and age (7%), whereas it was not associated with lumbar spine BMD. In conclusion, lean mass explains a great part of the strong association between body weight and femoral neck and lumbar spine BMD. Quadriceps strength explains a great part of the association between lean mass and BMD at the femoral neck site but not at the lumbar spine site. These results suggest a site-specific effect of muscular strength on bone and a potential role of the age-related decline of muscle strength in age-related bone loss in postmenopausal women.     

Bone mineral density remains stable in HAART-treated HIV-infected men over 2 years

OBJECTIVE: Recently we reported that human immunodeficiency virus (HIV)-infected Caucasian men treated with highly active antiretroviral therapy (HAART) have normal weight-adjusted bone mineral density (BMD), in contrast to most other cross-sectional analyses, which have reported low BMD in HIV-infected patients. We have now addressed the question of whether there is accelerated BMD loss over time in HIV-infected men. DESIGN: A 2-year, prospective, longitudinal study. SUBJECTS: Twenty-three HAART-treated, HIV-infected men and 26 healthy controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters at baseline, and a repeat measurement of BMD at 2 years. RESULTS: In the HIV-infected men the mean age was 47 years, the mean duration of infection was 8.2 years, and the mean duration of HAART was 54 months. Over 2 years of follow-up, BMD increased from baseline in the HIV-infected men by 2.6% at the lumbar spine (P = 0.05 vs. baseline), and remained stable at the total hip (mean change 0.1%, P > 0.99) and total body (mean change 0.6%, P = 0.39). Mean changes in BMD in the control group were 1.4% at the lumbar spine, -0.1% at the total hip, and -0.8% at the total body. The HIV-infected men lost less total body BMD than the control group (P = 0.01). In the HIV-infected men, body weight remained stable over 2 years while fat mass decreased and lean mass tended to increase, whereas in the controls, body weight and fat mass increased while lean mass remained stable. CONCLUSIONS: Accelerated bone loss does not occur in HIV-infected men treated with HAART. Monitoring of BMD in HIV-infected men may not be necessary.     

Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures

BACKGROUND: Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown. METHODS: We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures. RESULTS: Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results. CONCLUSION: In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures.     

Radiographic features of lumbar disc degeneration and bone mineral density in men and women

OBJECTIVES: To determine the association between individual radiographic features of lumbar disc degeneration and bone mineral density (BMD) at the spine and hip. METHODS: SUBJECTS: were recruited from a population register for a screening survey of vertebral osteoporosis. BMD was assessed at the spine and hip using dual energy x ray absorptiometry. Lateral spinal radiographs were evaluated for features of lumbar disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes, end plate sclerosis, and disc space narrowing. Linear regression was used to determine the association between each of these features and BMD at the spine and hip, with adjustments for age, body mass index, and levels of physical activity. Analyses were done separately in men and women. RESULTS: 250 women and 256 men (mean age around 65 years) were studied. At the lumbar spine, after age adjustment there was an increase in BMD with increasing grade for all radiographic features of disc degeneration in both men and women. At the femoral neck, after age adjustment there was an increase in BMD with increasing osteophyte and end plate sclerosis grade though not disc space narrowing. Adjusting for body mass index and physical activity did not influence the strength of the associations. CONCLUSIONS: Radiographic features of lumbar disc degeneration are associated with an increase in BMD at the spine. Osteophytes and end plate sclerosis, but not disc space narrowing, are associated with an increase in BMD at the hip.     

X-ray absorptiometry of bone in obese and eutrophic children from Valparaiso, Chile

OBJECTIVE: To assess and compare bone mineral content (BMC) and bone mineral density (BMD) by dual X-ray absorptiometry (DEXA) measurement in obese and eutrophic children. METHODS: In a cross sectional, case control study 16 obese children (8 male, 8 female) aged 5 to 13 years were recruited from the outpatient nutrition clinic of Carlos van Buren Hospital, Valparaiso, Chile, during 1997. Sixteen healthy eutrophic children matched for sex, chronological age, height, and pubertal stage were enrolled as controls. The mean dietary calcium intake was 580 +/- 100 mg/day. All obese patients had more than 2 standard deviation (SD) of height/weight ratio. Lumbar spine (L2-L4) BMD, femoral neck BMD, total body BMD, and total body BMC were measured by posteroanterior dual photon DEXA. The results were expressed as mean +/- SD. Comparison of the data was determined by Wilcoxon and Student t test. RESULTS: Mean BMC was 1684.1 +/- 492.38 g in obese children and 1418.2 +/- 483.48 g in controls (p < 0.001, Student t test; p = 0.001, Wilcoxon test). Mean total BMD was 817.5 +/- 99.37 g/cm2 in obese children and 771.62 +/- 105.62 g/cm2 in controls. (p = 0.041 by Wilcoxon). Mean hip BMD was 784.4 +/- 117.05 g/cm2 in obese children and 801.67 +/- 150.34 g/cm2 in controls. Mean spine BMD was 724.87 +/- 171.75 g/cm2 in obese children and 686 +/- 137.08 g/cm2 in controls (not significant). CONCLUSION: Obese children have more total body BMC than eutrophic children. There was no significant difference in regional hip BMD and lumbar spine BMD among obese and normal children. Obese children may have larger bones.     

Bone mineral metabolism in adults with beta-thalassaemia major and intermedia

Bone disease is an important cause of morbidity in older patients with beta-thalassaemia major and intermedia. We studied 27 women and 23 men with beta-thalassaemia major (37) and intermedia (13) whose mean age was 32.3 +/- 9.7 years. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius was determined by dual-energy X-ray absorbiometry (DXA). The longitudinal change in BMD over a mean of 5.6 years was determined in 19 patients. Serum 25-hydroxyvitamin D, insulin growth factor-1 (IGF-1), bone formation markers bone-alkaline phosphatase, osteocalcin and the resorption marker urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined. The BsmI vitamin D receptor (VDR) gene polymorphism was analysed. Reduced BMD (Z-score < -2) was present in 89%, 62% and 73% of patients in the spine, hip and radius respectively. Vitamin D deficiency was found in 62%, decreased IGF-1 in 72% and increased urinary NTx in 84% of patients. Serum IGF-1 correlated with spine and hip BMD (r = 0.4, r = 0.39, P < 0.01 respectively), and NTx correlated with the hip BMD Z-score (r = 0.35 P < 0.05). The mean annual percentage change in spine BMD was -1.36%. Patients with the VDR BB genotype had lower spine BMD than patients with the bb genotype. In conclusion, bone loss continues in adult thalassaemia patients and is associated with increased bone resorption and decreased IGF-1. The BsmI VDR gene polymorphism is associated with osteopenia in thalassaemia.     

Bone mineral density in adults with Marfan syndrome

OBJECTIVES:Reduced bone mineral density (BMD) has been reported in pre-menopausal women and children with Marfan syndrome (MFS). The bone mineral status of adult men with MFS is unknown. The objective of this study was to determine the BMD of adult men and women with MFS. METHODS:BMD (g/cm(2)) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4), femoral neck and total hip in 25 adults (12 male) who fulfilled the 1996 MFS diagnostic criteria. The results were compared with age- and sex-matched controls and expressed as S.D. from the population mean (z score). RESULTS:Overall, BMD was significantly reduced in the lumbar spine (z = -0.42 +/- 0.97, P < 0.05), total hip (z = -0.57 +/- 0.88, P < 0.005) and femoral neck (z = -0.51 +/- 0.88, P < 0. 005). In women alone, BMD was reduced at the femoral neck (z = -0.53 +/- 0.95, P < 0.05) and at the hip (z = -0.64 +/- 0.77, P < 0.005). In men, BMD was reduced at the femoral neck (z = -0.48 +/- 0.84, P < 0.05) with a non-significant trend to lower BMD at the hip (z = -0. 49 +/- 1.01, P = 0.054) and lumbar spine (z = -0.59 +/- 1.02, P = 0. 09). CONCLUSION:Axial BMD is lower than normal in Marfan adults. This reduction may contribute to fractures seen in the Marfan population.     

HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients

Recently, it was reported that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors increased bone mineral density (BMD) in mice. We studied the effect of HMG-CoA reductase inhibitors on BMD of type 2 diabetes mellitus by a retrospective review of medical records. Sixty-nine type 2 diabetic patients were included. The control group (n = 33) did not take HMG-CoA reductase inhibitors. The treatment group (n = 36) was administered either lovastatin, pravastatin, or simvastatin. BMD of the spine, femoral neck, femoral trochanter, and total hip were measured by dual-energy X-ray absorptiometry. There were no significant differences between control and treatment groups in age, sex, body mass index, glycemic control, and serum insulin levels. In the control group, BMD of the spine significantly decreased (from 1.116 +/- 0.165 to 1.081 +/- 0.178 g/cm2) after 14 months. In the treatment group, BMD of the femoral neck significantly increased (from 0.853 +/- 0.139 to 0.878 +/- 0.147 g/cm2) after 15 months. In male subjects treated with HMG-CoA reductase inhibitors, there was a significant increase in BMD of the femoral neck and femoral trochanter (from 0.899 +/- 0.139 to 0.934 +/- 0.139 and from 0.801 +/- 0.145 to 0.833 +/- 0.167 g/cm2, respectively), but in female subjects, only BMD of the femoral neck increased (from 0.819 +/- 0.132 to 0.834 +/- 0.143 g/cm2). Percentage increments of BMD of the femoral neck, femoral wards triangle, femoral trochanter, and total hip in the treatment group were significantly higher than in the control group (2.32% vs. -0.99, 1.77% vs. -1.25%, 1.40% vs. -1.21%, 0.88% vs. -1.03%, respectively). The proportion of subjects who had an increase in BMD of the spine and total hip more than two percentages was significantly larger in the treatment group than in the control group (30.6% vs. 15.2% and 30.6% vs. 9.1%, respectively). The increased increment in BMD of the treatment group was significantly greater than those in the control group after adjustment for age and body mass index (P < 0.05). These results suggest that HMG-CoA reductase inhibitors may increase BMD of the femur in male patients with type 2 diabetes mellitus.     

Bone mineral density and clinical hand osteoarthritis in elderly men and women: the Rancho Bernardo study

OBJECTIVE: Many studies have found increased bone mineral density (BMD) in patients with osteoarthritis (OA). As a result, clinicians may not consider osteoporosis in patients with OA. We examined the relation between hand OA and BMD levels among 1779 community-dwelling, ambulatory white adults aged 50-96 years. METHODS: BMD was measured by dual energy x-ray absorptiometry at the hip, lateral and anteroposterior (AP) lumbar spine, and total body. Both hands of each subject were systematically examined for bony enlargement, swelling, and deformity. RESULTS: Using the American College of Rheumatology criteria for epidemiologic studies, the clinical diagnosis of hand OA was made in 6.6% of men and 14.5% of women. In women, BMD measurements adjusted for age, body mass index, smoking, alcohol, exercise, and current estrogen use were significantly lower only at the hip in those with versus those without hand OA. In contrast, men with hand OA had higher multiply-adjusted mean BMD levels at all sites compared to those without hand OA. These differences were statistically significant only at the AP spine; the absent difference for lateral spine BMD suggests that degenerative changes may explain the higher AP spine BMD levels. Patterns in both men and women were similar in those with isolated hand OA or hand OA in the presence of knee or hip OA. CONCLUSION: OA was not associated with increased BMD levels in men or women. Contrary to expectations the only significant difference was that women with hand OA had lower hip BMD. Thus evaluation for osteoporosis should not be overlooked in women with hand OA.     

Whole body and regional bone mineral density in ankylosing spondylitis

OBJECTIVE: To study the regional distribution of bone mass and look for factors leading to bone loss in ankylosing spondylitis (AS). METHODS: Thirty-nine patients, all men, aged 20 to 55 years and presenting with AS were studied. Four hundred sixteen gendarmes, all men aged 20 to 55 years, formed an age matched control population used to define standard values for bone mineral density (BMD) in men. The patients with AS and the controls underwent measurement of whole body BMD and regional BMD by dual-energy x-ray absorptiometry. RESULTS: AS was associated with spinal bone loss, with lumbar spine BMD (LSBMD) 1.085 +/- 0.178 g/cm2 in the AS group compared with 1.232 +/- 0.136 g/cm2 in the control group (p < 0.01). Whole body BMD and regional BMD of head, whole spine, pelvis, and legs were reduced, although this was not statistically significant. Using standard values for LSBMD from the controls, we found that 46% (18/39) of patients with AS had Z score < -1.5 SD. Biological markers of disease activity were higher in the subgroup of patients with low LSBMD than in the subgroup with normal LSBMD, with an erythrocyte sedimentation rate of 29.4 +/- 23.4 mm/h versus 12.1 +/- 10.8 mm/h (p < 0.05) and C-reactive protein at 24.8 +/- 18 mg/l versus 12.7 +/- 14.2 mg/l (p < 0.05). CONCLUSION: AS is associated with bone loss, mainly concerning the lumbar spine, in patients whose disease is biologically most active.     

Impairment of bone mass development in children with chronic cholestatic liver disease

OBJECTIVE: To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF-1 levels in children with chronic cholestatic disease (CCLD). PATIENTS AND MEASUREMENTS: A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7.2 +/- 4.8 years) and 22 control subjects (mean age 7.6 +/- 4.5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25-hydroxyvitamin D, PTH and IGF-1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient. RESULTS: Z-score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0.107 +/- 0.02 vs. CCLD = 0.092 +/- 0.02 g/cm(3), P < 0.05) and after conversion for bone age. All participants showed normal 25-hydroxyvitamin D levels, with no significant differences in serum levels of 25-hydroxyvitamin D and PTH between groups. IGF-1 levels were significantly lower in the CCLD group (control = 19.6 +/- 16.8 vs. CCLD = 6.4 +/- 7.6 nmol/l, P < 0.05) and a positive correlation was observed between whole body BMD and IGF-1 in this group. CONCLUSIONS: These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF-1 production might be responsible, at least in part, for the low bone mass of these patients.     

Calcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls

OBJECTIVE: Bone mineral density (BMD) in adolescence is under strong genetic control. The calcium sensing receptor (CASR) is involved in the regulation of calcium homeostasis and bone resorption. The A986S polymorphism of the CASR has recently been associated with serum calcium levels, in one hitherto unconfirmed report. We investigated whether this polymorphism was related to BMD, circulating calcium and parathyroid hormone (PTH) concentrations in girls. DESIGN: BMD, plasma calcium and serum PTH were measured in adolescent girls and compared with regard to CASR genotype. METHODS: In 97 healthy Caucasian girls (mean age 16.9+/-1.2 years (mean+/-s.d.)), the A and S alleles were determined using PCR with a mismatched primer and the restriction enzyme BsaHI. BMD (g/cm) of the total body, humerus, femoral neck and lumbar spine was measured using dual energy X-ray absorptiometry. RESULTS: The genotype frequencies were 71% AA, 26% AS and 3% SS. The genotypes were divided into presence (29%) or absence of S allele (71%). Subjects with the S allele had higher levels of plasma calcium, corrected for albumin (2.17+/-0.06>2.14+/-0.06; P < 0.05, using independent samples t-test), lower BMD at the lumbar spine (P=0.02) and total body (P=0.04), and were significantly less physically active (2.9+/-2.6 vs 4.3+/-2.6 h/week; P=0.01) than the subjects lacking the S allele. PTH levels were not significantly different between the two allelic groups. A multiple regression analysis, including age, height, weight and physical activity, revealed that the CASR allelic variants were not independent predictors of BMD at any site measured (beta=-0.03-0.09; P>0.05). Physical activity was an independent predictor of BMD, was significantly different between the CASR genotypes, and could therefore have a role in explaining the difference in BMD between the CASR genotypes. CONCLUSIONS: The CASR alleles are related to BMD, but it cannot be definitely concluded whether the CASR polymorphism has a direct influence on BMD, or whether the differences in BMD were mediated via an influence of the amount of physical activity.     

Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects

OBJECTIVE: The genetic factors determining peak bone mineral density (BMD) in men are not well characterized. Recent studies have investigated the relationship between the start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene and BMD in different populations. We have now examined the relationship between SCP of the VDR gene and BMD in a group of healthy Caucasian men from the north-east of England. SUBJECTS: Ninety-six healthy men (median age 50, range 40.0-77.0 years). MEASUREMENTS: Analysis of the FokI genotypes of SCP of the VDR and measurements of BMD at the femoral neck and lumbar spine were performed. RESULTS: FF, Ff and ff VDR FokI genotypes were found to have the highest, intermediate and the lowest lumbar spine BMD, respectively (Mean +/- SD, for FF 1.07 +/- 0.14, Ff 1.05 +/- 0.16 and ff 0.95 +/- 0.10 g/cm2). There was a significant difference in spine BMD between FF and ff genotypes (P < 0.05, analysis of variance [ANOVA]), but no such difference was apparent between Ff and ff (P > 0.05, ANOVA). Interestingly, there was no association between FokI polymorphism and femoral neck BMD (Mean +/- SD, for FF 0.85 +/- 0.12, Ff 0.87 +/- 0.15 and ff 0.83 +/- 0.15 g/cm2). The distribution of FokI VDR genotypes approached Hardy-Weinberg equilibrium and was similar to that reported for women from different ethnic groups, as the prevalence of FF and ff genotypes was 44% and 16%, respectively. CONCLUSION: The study shows that in this population of healthy men there is a weak association between lumbar spine bone mineral density and FokI restriction fragment length polymorphism at the translation initiation site of the vitamin D receptor gene.     

Prospective assessment of body weight, body composition, and bone density changes in patients with spondyloarthropathy receiving anti-tumor necrosis factor-alpha treatment

OBJECTIVE: To determine the changes in body weight, body composition, and bone density in patients with spondyloarthropathy (SpA) receiving anti-tumor necrosis factor-alpha (TNF-alpha) treatment. METHODS: One hundred six patients with SpA (80 men, 26 women) aged 20-71 years were included in a 2-year prospective open study. Fifty-nine patients received infliximab (3 or 5 mg/kg/infusion each 6 or 8 weeks); and 47 patients received etanercept (25 mg twice a week) because of persistent active disease despite an optimal treatment, according to ASsessments in Ankylosing Spondylitis Working Group criteria. Body weight, total body composition (lean mass, fat mass), and spine and femoral bone mineral density (BMD; dual-energy x-ray absorptiometry) were measured at baseline and at 1 and 2 years. RESULTS: There was a significant increase in body weight after 1 year (2.2 +/- 3.9 kg, i.e., 3.4%; p < 0.0001) and 2 years (2.2 +/- 4.7 kg, 3.5%; p < 0.0001), mostly due to a significant gain in fat mass at 1 year (1.4 +/- 2.6 kg, 12.1%; p < 0.0001) and 2 years (1.5 +/- 3.1 kg, 14.5%, p < 0.0001). Gain in lean mass was also significant at 1 year (0.8 +/- 2.2 kg, 1.9%; p < 0.0001) and 2 years (0.9 +/- 2.5 kg, 2%; p < 0.0001). At 2 years, lumbar spine and femur BMD increased: +5.8 +/- 13% (p < 0.0001) and +2.26 +/- 4.5% (p = 0.001), respectively. CONCLUSION: This 2-year prospective study showed a significant increase in body weight at 1 year and 2 years, mostly due to a gain in fat mass and a significant increase in BMD, in patients with SpA receiving anti-TNF-alpha treatment.     

Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross-sectional and longitudinal study

The purpose of the present study was to investigate the influence of estrogen receptor alpha gene polymorphism and estradiol on height and bone density during and after puberty in males. Using the restriction enzymes XbaI and PvuII, the allelic variants XX, Xx, xx, PP, Pp, and pp were identified in 90 Caucasian boys 16.9+/-0.3 yr of age (mean +/- SD). Bone mineral density (BMD; g/cm2) of the total body, head, femoral neck, and lumbar spine was measured using dual-energy x-ray absorptiometry. Volumetric BMD (vBMD; mg/cm3) was estimated for the spine. The XbaI or PvuII genotypes were not related to the levels of estradiol, and the levels of estradiol were not related to BMD (P > 0.05). The xx allelic variant was associated with a higher spine vBMD than the Xx allelic variant (361 vs. 340 mg/cm3, P = 0.04). In a multivariate analysis including pubertal development, physical activity, and body weight, the XbaI genotype independently predicted total body BMD, head BMD, and spine vBMD (P < 0.05). The PvuII genotype independently predicted spine vBMD (pp > PP, P = 0.01). The 20 boys with the PP allelic variant were found to have a greater body height than the other 70 boys (182 cm vs. 179 cm, P = 0.03). At a 2-yr follow-up the XbaI genotype was still independently related to total body BMD, head BMD, and spine vBMD. In conclusion, estrogen receptor gene polymorphism is related to bone density and height during late puberty and at attainment of peak bone density in young men.