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.     

Effects of insulin-like growth factor I (IGF-I) therapy on body composition and insulin resistance in IGF-I gene deletion

We have recently reported a patient with a homozygous partial deletion of the insulin-like growth factor-I (IGF-I) gene, resulting in IGF-I deficiency, insulin resistance, and short stature. Recombinant human IGF-I (rhIGF-I) therapy has been shown to improve insulin sensitivity (Si) and growth in other causes of IGF-I deficiency. We now report results of 1 yr of rhIGF-I therapy on body composition, bone mineral density (BMD), insulin sensitivity, and linear growth in this patient. rhIGF-I therapy was initiated at age 16.07 yr (bone age, 14.2 yr), at a starting dose of 40 microg/kg daily, increasing after 3 months to 80 microg/kg daily. Body composition, BMD, markers of bone mineralization, and auxological parameters (height, weight) were measured at 0, 6, and 12 months after start of therapy. Si, acute insulin response to glucose, and glucose effectiveness were determined at baseline, 3 months, and 12 months into therapy. On IGF-I therapy, body mass index increased from 17 kg/m2 to 18.6 kg/m2. Body composition studies (dual-energy x-ray absorbtiometry) revealed an initial decrease in total body fat, from 19.9% at baseline to 15.1% at 6 months; but by 12 months of therapy, this had reversed, with an increase to 21.8%. Si, calculated using Bergman's minimal model, was substantially reduced at baseline at 1.45 x 10-4 min-1 (microU/mL) [normal value, 5.1 x 10-4 min 1 (lean adult male)]. rhIGF-I therapy resulted in a dose-related improvement of Si into the normal range (NR) (rhIGF-I dose: 40 microg/kg x day, Si = 2.06 x 10-4 min-l; rhIGF-I dose: 80 microg/kg x day, Si = 4.39 x 10-4 min-1). Baseline reduction in Si was accompanied by elevated acute insulin response to glucose, which also fell in a dose-dependent manner. Baseline BMD was severely reduced when compared with age-matched controls (-4.88 SD); however, calculation of bone mineral apparent density indicated that the true reduction in BMD was minimal. rhIGF-I therapy increased BMD by 17% and bone mineral apparent density by 7%, indicating that IGF-I has a greater effect on bone growth than bone mineralization. Bone turnover markers also increased on rhIGF-I; mean serum osteocalcin: 8.3 ng/mL pretreatment, 21.7 ng/mL after 6 months of rhIGF-I (NR for adult male, 3.4-9.1 ng/mL); mean bone specific alkaline phosphatase: 36.5 U/L pretreatment, 82.2 U/L after 6 months of therapy (NR for adult male, 15-41). Height velocity increased from 3.8 cm/yr pretreatment to 7.3 cm/yr on 80 microg/kg.day of rhIGF-I. In this patient with severe insulin resistance, therapy with rhIGF-I resulted in beneficial effects on Si, body composition, bone size, and linear growth. These results have implications for IGF-I therapy in a variety insulin resistant states.     

Body composition and osteoporosis in elderly women

OBJECTIVES: To study body composition in elderly osteoporotic women to determine the relationship of body weight, body fat mass and lean mass to bone mineral density (BMD), and to investigate the association between one-leg balance, osteoporosis and sarcopenia. Design and Setting: A cross-sectional study of a community-based population in Toulouse, France. METHODS: For each participant, whole body composition and BMD were estimated using a dual-energy x-ray absorptiometry scanner. We investigated balance using a one-leg balance test. Participants: 129 healthy women aged 75-89 years, volunteers, ambulatory and living at home. RESULTS: Total fat mass and appendicular skeletal muscle mass (ASM) were significantly lower in osteoporotic women than in the age- and sex-matched non-osteoporotic controls [18.7 +/- 4.6 vs. 22.2 +/- 6.6 for total fat mass (p < 0.01); 13.1 +/- 1.6 vs. 13.8 +/- 2.2 for ASM (p < 0. 05)]. We did not find a positive association between osteoporosis and sarcopenia (OR = 0.75, CI 0.3-1.84), osteoporosis and one-leg balance (OR = 1.27, CI 0.51-3.17), or sarcopenia and one-leg balance (OR = 1.31, CI 0.52-3.36). There were significant positive correlations between BMD in all areas and body measurements (weight, fat mass, lean tissue mass), but fat mass accounted for more of the variance in total body and femoral BMD than lean tissue mass. Total fat mass alone, in a multivariate model, was correlated with whole body BMD, whereas femoral BMD was associated with both fat mass and lean tissue mass. CONCLUSION: Higher values of fat mass and lean tissue mass may have a protective effect on femoral bone density. Sarcopenia and osteoporosis are not necessarily linked with balance.     

Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with spondyloarthropathy (SpA) treated with infliximab. PATIENTS AND METHODS: 29 patients (six women; 23 men) aged 22-68 years, with persistently active SpA despite a high dose of non-steroidal anti-inflammatory drug and/or treatment with methotrexate or sulfasalazine, were studied. Median duration of disease was 13 years (range 3-30). Twenty five patients were treated with 5 mg/kg and four with 3 mg/kg of infliximab at weeks 0, 2, 6 and then received either no infusion (n=3), or additional infusion of infliximab every other month (n=6), and the remainder received one infusion only in the case of a relapse. Lumbar and femoral BMD was measured by dual energy x ray absorptiometry at baseline and six months later. Serum osteocalcin and urinary deoxypyridinoline were measured in 19 patients at weeks 0, 2, 24, and in 13 patients at all visits. RESULTS: In six months there was a significant increase in BMD at the spine (3.6%, p=0.001), total hip (2.2%, p=0.0012), and trochanter (2.3%, p=0.0012). A trend for increase (1.1%) was observed at the femoral neck. There was an increase in osteocalcin between baseline and week 6 (third infusion)-median 1.45 micro g/l (p=0.013). No change in marker of bone resorption was observed at the same time. There was no change in biochemical markers between baseline and final visits. There was a trend for a correlation between the decrease at six months in erythrocyte sedimentation rate, and lumbar spine BMD change (r(s)=-0.35, p=0.06). CONCLUSION: These data suggest that a benefit of anti-tumour necrosis factor alpha therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells.     

The relation between bone mineral density, insulin-like growth factor I, lipoprotein (a), body composition, and muscle strength in adolescent males.

Osteoporosis is the most common metabolic bone disease. A low peak bone mass is regarded a risk factor for osteoporosis. Heredity, physical activity, and nutrition are regarded important measures for the observed variance in peak bone mass. Lp(a) lipoprotein is a well-known risk factor for atherosclerosis. Serum insulin-like growth factor I (IGF-I) has been found to be increased in males with early cardiovascular disease. In this study, we evaluated the association between bone mass, body constitution, muscle strength, Lp(a), and IGF-I in 47 Caucasian male adolescents (mean age, 16.9 yr). Bone mineral density (BMD) and body composition were measured by dual x-ray absorptiometry, muscle strength of thigh using an isokinetic dynamometer, IGF-I by RIA, and Lp(a) by enzyme-linked immunosorbent assay. IGF-I was only associated with Lp(a) (r = 0.38, P < 0.01). Lp(a) was related to total body (r = 0.40, P < 0.01), skull (r = 0.45, P < 0.01), and femoral neck BMD (r = 0.44, P < 0.01). Lp(a) was also related to fat mass (r = 0.34, P < 0.05) and muscle strength (r = 0.30-0.42, P < 0.05). After multiple regression and principal component (PC) analysis, the so-called PC body size (weight, fat mass, lean body mass, and muscle strength) was the most significant predictor of BMD (beta = 0.28-0.51, P < 0.05-0.01), followed by the so-called PC physical activity (beta = 0.28-0.38, P < 0.05-0.01, weight-bearing locations). However, the PC analysis confirmed that Lp(a) was an independent predictor of total body, skull, and femoral neck BMD (beta = 0.33-0.36, P < 0.01). The present investigation confirms that BMD, body size, and muscle strength are closely related and that the level of physical activity is a major determinant of BMD. However, the positive relation of Lp(a), a major risk factor for cardiovascular disease, to BMD has not previously been described. The importance of this observation has to be further investigated.     

Prepubertal girls with premature adrenarche have greater bone mineral content and density than controls.

Body composition in premature adrenarche (PA) has not been described. We hypothesized that the increased adrenal androgens in PA would have a trophic effect on lean body components. We studied 14 PA subjects and 16 controls, all prepubertal Hispanic girls. The body composition parameters tested included height, weight, bone mineral density (BMD), bone mineral content (BMC), nonbone fat-free mass, total body potassium, total body water, and extracellular water. Bone age was determined in all PA subjects. Compared with controls, PA subjects had significantly higher BMC (P = 0.02) and BMD (P = 0.03) when adjusted for age, weight, height, and fat mass, but were not different in the following lean body components: fat-free mass, total body potassium, total body water, and extracellular water. There was no difference in BMD or BMC between the PA subjects with and without advanced bone age. These data suggest a specific effect of PA on bone mineral, but not on other lean body components. The absence of a correlation between bone age and bone mineral in this small group leads us to propose there are separate promoters of bone age advancement and bone mineral accrual. Candidate hormones for these processes include adrenal androgens, E, and IGF-I. The findings of this study suggest that hormonal alterations associated with PA affect bone mineral accrual and may elucidate the mechanisms involved in this process.     

Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover

BACKGROUND: Loop diuretics (LD) are widely used in the treatment of cardiovascular diseases and disorders with fluid accumulation. LD are known to increase renal calcium losses and may thereby affect calcium homeostasis and bone metabolism. OBJECTIVE: We studied to what extent long-term treatment with LD affects calcium homeostasis and bone metabolism. DESIGN AND SUBJECTS: In a cross-sectional design we compared 140 postmenopausal women treated with a LD for more than 2 years with 140 age-matched women not in diuretic therapy. RESULTS: Treatment with LD was associated with significantly increased urinary calcium, plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels. Per 40 mg day(-1) of furosemide, urinary calcium was increased by 17% (P < 0.05) and plasma PTH levels were increased by 28% (P = 0.04). Users of LD had a 17% higher body weight (P < 0.001) compared with nonusers. This was due to a 32% higher fat mass (P < 0.001) and a 6% higher lean tissue mass (P < 0.001). Moreover, users of LD had a higher bone mineral density (BMD) at the spine (+7.5%, P < 0.001), hip (+4.8%, P = 0.004), forearm (+3.7%, P = 0.01) and whole body (+2.5%, P = 0.06). However, after adjustment for body weight differences, BMD did not differ between groups. Nevertheless, duration of LD treatment was positively associated with BMD at the spine (P = 0.03) and whole body (P < 0.05). BMD at the spine increases by 0.3% per 1 year of treatment. CONCLUSIONS: The increased renal calcium losses in users of LD are compensated for by a PTH-dependent increase in 1,25(OH)(2)D levels. Thereby calcium balance remains neutral without major effects on bone metabolism.     

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.     

High plasma leptin is not associated with higher bone mineral density in insulin-resistant premenopausal obese women

Obesity's protective effect on bone density may be mediated through increased muscle mass, fat mass, increased estrogen, and possibly insulin and leptin levels. To determine the impact of leptin and insulin on bone metabolism, we studied 48 obese normally cycling premenopausal women (age, 31 +/- 10 yr; body mass index, 35.7 +/- 5 kg/m2): 28 insulin resistant (IR) and 20 insulin sensitive (IS) by McAuley index. Anthropometric, body composition, and bone mineral density (BMD) measurements were made, and serum leptin, insulin, free testosterone, IGF-I, bone remodeling markers, and calciotropic hormones were measured. Anthropometric, lifestyle, and biochemical markers were similar in the two groups. Despite higher circulating insulin and leptin levels, IR subjects had similar mean values of serum osteocalcin but higher C-telopeptide (P = 0.052). They had similar BMD at all skeletal sites compared with IS subjects. In the IR group, fat mass but not lean mass, serum leptin, insulin, testosterone, and IGF-I levels correlated positively with hip and/or total-body bone density with R varying between 0.38 and 0.65; no correlations were observed at the spine. Conversely, in the IS group, lean mass, but not fat mass, and only IGF-I correlated with hip BMD/total-body bone mineral content. In conclusion, there is a dichotomy in the impact of body composition parameters and insulin and leptin levels on bone parameters in obese individuals. The interaction between the fat-related endocrine system and bone seems to be complex and may be modulated by local resistance to the putative protective effect of insulin and leptin on bone.     

Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa

BACKGROUND: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Adipokines and insulin play an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown. OBJECTIVE: The aim of the study was to determine whether adipokines and insulin are independently associated with measures of BMD in adolescents with AN and controls. DESIGN/METHODS: Levels of adiponectin and insulin, fasting and after oral glucose, were evaluated in 17 AN patients and 19 controls (age, 12-18 yr), in whom hormonal parameters [GH, IGF-I, cortisol, estradiol, leptin, ghrelin, and peptide YY (PYY)] had been previously determined. Body composition, bone mineral content, and BMD at the lumbar spine, hip, femoral neck, and total body were assessed by dual energy x-ray absorptiometry. Two bone formation and bone resorption markers were examined. SETTING: The study was conducted at a General Clinical Research Center. RESULTS: Adiponectin differed between AN subjects and controls after controlling for fat mass and decreased in both after oral glucose (P = 0.02 and 0.07). On regression modeling, independent associations were observed of: 1) body mass index and adiponectin with lumbar spine bone mineral apparent density Z-scores (r(2) = 0.45); 2) lean mass, PYY, and ghrelin with hip Z-scores (r(2) = 0.55); 3) adiponectin and lean mass with femoral neck-bone mineral apparent density Z-scores (r(2) = 0.34); and 4) lean mass, PYY, GH, and ghrelin with total body-bone mineral content/height Z-scores (r(2) = 0.64), for the combined group. Adiponectin was also independently associated with BMD, and insulin was associated with bone turnover markers in the groups considered separately. CONCLUSIONS: Adiponectin contributes significantly to the variability of bone density, and insulin contributes to bone turnover markers in adolescent girls.     

Androgens and bone density in women with hypopituitarism

Hypopituitarism is associated with osteopenia and a reduction in lean body mass. We have recently demonstrated markedly reduced serum androgen levels in women with hypopituitarism. We hypothesized that serum androgen levels and lean body mass are important determinants of bone mineral density (BMD) in women with hypopituitarism. In addition, because IGF-I may stimulate androgen secretion in women, we investigated whether GH administration results in an increase in serum androgen levels. Sixteen women with a history of pituitary disease of adult-onset and serum GH levels less than 5 ng/ml on stimulation testing underwent BMD and body composition testing by dual-energy x-ray absorptiometry. Univariate regression analysis revealed strong correlations between androgen levels and BMD [lateral spine BMD and dehydroepiandrosterone sulfate (DHEAS) (r = 0.68, P = 0.03), total hip BMD and free T (r = 0.60, P = 0.01), Ward's triangle BMD and DHEAS (r = 0.68, P = 0.004), Ward's triangle BMD and free T (r = 0.54, P = 0.03), femoral neck BMD and free T (r = 0.52, P = 0.04), and femoral neck BMD and DHEAS (r = 0.51, P = 0.04)]. When adjusted for age using Z scores, correlations at the femoral neck no longer reach significance. Correlations between androgens and BMD at other sites, including anterior-posterior spine and total body, were not significant, and neither total T nor androstenedione correlated with BMD at any site. Lean body mass strongly correlated with BMD [total hip (r = 0.80, P = 0.0002), total body (r = 0.78, P = 0.0003), trochanter (r = 0.74, P = 0.001), Ward's triangle (r = 0.56, P = 0.02), femoral neck (r = 0.53, P = 0.04), and anterior-posterior spine (r = 0.52, P = 0.04)]. In stepwise regression models, DHEAS determined 47% of the variation in Ward's triangle BMD (R(2) = 0.47, P = 0.004) and 46% of lateral spine BMD (R(2) = 0.46, P = 0.03). Lean body mass determined 64% of the variation in total hip BMD (R(2) = 0.64, P = 0.0002), 62% of total body (R(2) = 0.62, P = 0.0003), and 55% of trochanter BMD (R(2) = 0.55, P = 0.001). Subjects were then randomized to receive GH at a dose of 12.5 microg/kg per day or placebo for 12 months in a double-blind protocol. Serum androgen levels were obtained at baseline, 1, 3, 6, 9, and 12 months after initiation of GH. Androgen levels did not increase in the women receiving GH for 12 months, compared with those receiving placebo. Stimulation of androgen secretion is therefore unlikely to be a mechanism underlying the improvement in BMD, body composition, or quality of life observed with GH administration. In conclusion, androgen levels and lean body mass may be important determinants of BMD in women with hypopituitarism. It remains to be determined whether androgen replacement therapy itself or an increase in lean body mass achieved as a result of androgen administration will result in an improvement in BMD in this population.     

Bone mineral density and bone remodelling in Tunisian patients with ankylosing spondylitis: A cross-sectional study

Aim of the workTo assess the bone turnover markers and bone mineral density (BMD) in ankylosing spondylitis (AS) patients and to evaluate their association with clinical variables.Patients and methodsForty-seven AS patients were compared with 47 matched control. Clinical features and inflammatory parameters were assessed. C-terminal telopeptide fragments of type I collagen (CTX), alkaline phosphatases (ALP), N-terminal propeptide of type I procollagen (PINP) serum levels, and BMD of the lumbar spine and femoral neck were evaluated. The Bath AS disease activity and functional indices (BASDAI and BASFI) were assessed.ResultsMean serum levels of C-reactive protein, ALP and CTX were higher in AS patients than control (p = 0.001, p = 0.001 and p = 0.027 respectively). Osteopenia and osteoporosis were significantly more frequent in AS patients (57.4%) than control (21.3%) (p < 0.001). The PINP and ALP significantly correlated with disease duration (r = 0.33, p = 0.02 and r = 0.3, p = 0.04 respectively). BMD of the femoral neck was significantly lower in AS patients with history of coxitis than AS patients without (p = 0.02). Patients on anti-tumour necrosis factor (TNFα) therapy had higher T score (lumbar spine) compared to those not. Multivariate regression showed that CRP levels and disease activity were independently associated with low BMD and T score (lumbar) was significantly associated with anti-TNF use (p = 0.007).ConclusionsAn increase in bone turnover markers and decrease of BMD were observed in AS patients. Inflammatory activity of AS was associated to hyper bone remodelling and decrease of BMD. Anti-TNF use seems to be beneficial on AS inflammation and therefore on the BMD.     

Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men

OBJECTIVES It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free-living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin-like growth factor I (IGF-I), serum testosterone, habitual physical activity and mobility.
SUBJECTS Forty-nine independent, community-dwelling older men, and 49 men of similar age residing in two Veterans Administration extended care facilities. The age range was 58–95 years.
MEASUREMENTS Serum IGF-I and testosterone were measured by radioimmunoassay. Habitual physical activity in the independent men and mobility in the institutionalized men were estimated by standard instruments. LBM and bone status at nine skeletal sites were determined by dual X-ray absorptiometry.
RESULTS The BMD and TBBMC values of the free living men were 4–20% higher than those of the institutionalized men. In the independent old men, serum testosterone was the strongest predictor of BMD and TBBMC, while age was the only predictor of LBM. In the chronically institutionalized men, age, body weight and immobility were the strongest predictors of body composition, and testosterone was correlated only with femoral neck BMD.
CONCLUSIONS In aging independent men, low levels of testosterone are associated with demineralization of the skeleton. Immobility and under-weight are associated with the osteopenia of old men residing in nursing homes. In this cross-sectional study of elderly men, there was no evidence of a relation of the somatotrophic axis to bone status or LBM, or of the gonadotrophic axis to LBM.     

Body composition,bone mineral density,and circulating leptin levels in postmenopausal Turkish women

OBJECTIVE: We analyzed the relationship between serum leptin levels and bone mineral density (BMD) values as well as the relationship between serum leptin levels and whole body composition, whether or not they were associated. In addition, we also investigated whether lean mass or fat mass is a better predictor of BMD in postmenopausal Turkish women. DESIGN AND MEASUREMENTS: One hundred consecutive postmenopausal women with a mean age of 55.1 +/- 6.3 years who visited our outpatient clinic for the evaluation of osteoporosis were recruited. Skin fold thickness at four sites and waist:hip ratio were measured. Body mass index (BMI) was calculated in kg/m(2). Serum concentrations of leptin, insulin, and estradiol were evaluated. Bone formation and resorption markers were also determined. The BMD values were measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Whole body composition (lean mass, fat mass, and percentage of fat), total bone mineral content (BMC) in g, and total BMD were also measured by DEXA. RESULTS: Serum leptin levels did not correlate with BMD values at all skeleton sites measured. Leptin correlated positively with fat mass, percentage of fat, and BMI (r = 0.738 and P = 0.00, r = 0.536 and P = 0.00, r = 0.356 and P = 0.00, respectively). Lean mass correlated with BMD at all sites measured (r = 0.339 and P = 0.00, r = 0.312 and P = 0.01, r = 0.523 and P = 0.00, r = 0.636 and P = 0.00). Lean mass correlated with BMI (r = 0.636, P = 0.00) but not with serum leptin (r = -0.021, P = 0.881), and it was an independent determinant of BMD at all skeleton sites measured. CONCLUSION: Our study showed that lean mass is a better predictor than fat mass of bone mineral density and that serum leptin levels are not associated with BMD.     

Relationship between growth hormone-IGF-I-IGFBP-3 axis and serum leptin levels with bone mass and body composition in patients with rheumatoid arthritis

OBJECTIVES: Hormonal factors playing a role in bone mass and body composition have been rarely assessed in rheumatoid arthritis (RA). In this study, we aimed to evaluate the growth hormone (GH)-insulin-like growth factor-I (IGF-I)-insulin-like growth factor binding protein-3 (IGFPB-3) axis and serum leptin levels in patients with RA and to determine whether these hormonal/growth factors may influence bone mass and body composition in RA. METHODS: Serum GH, IGF-I, IGFPB-3 and leptin were evaluated in 38 corticosteroid-treated RA patients, 14 non-RA patients under corticosteroids (corticosteroid controls, CC) and 32 healthy controls (HC). Bone density was evaluated using dual X-ray absorptiometry (DEXA), and expressed as bone mineral density (BMD), and quantitative ultrasound (QUS). Body composition was assessed by DEXA. RESULTS: The three groups differed regarding femoral neck, total body BMD, lean mass and QUS parameters with lower values in the RA group (all P < or = 0.05). Growth hormone was higher in RA patients (P=0.0001) while IGF-I and IGFBP-3 did not differ between the three groups. In RA patients there was a tendency to high serum leptin levels and leptin strongly correlated with fat mass (r=0.83, P<0.0001), but not with bone mass measurements or inflammatory parameters. There were no differences for lean mass, GH and leptin between CC and HC. CONCLUSION: Our results suggest that these GH and leptin modifications could have an influence on both bone mass and body composition in RA.     

Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density.

BACKGROUND: Patients with coeliac disease have low bone mineral density (BMD), but the underlying mechanisms are unclear. Our aim was to study circulating insulin-like growth factor I (IGF-I) and its possible relationship to BMD in adults with untreated coeliac disease and after 1 year on a gluten-free diet. METHODS: In 29 consecutive adult coeliac patients fasting IGF-I and BMD (n = 28) were examined before and 1 year after starting a gluten-free diet. Intact parathyroid hormone (PTH) was measured (n = 20) before the gluten-free diet was started. RESULTS: Untreated coeliac patients had lower IGF-I values than controls matched for age and sex, and their BMD was low. A relationship was observed between BMD and IGF-I but not independent of age and body mass index. During the 1st year on a gluten-free diet BMD increased (P < 0.001), as did the circulating IGF-I levels in 21 of the 29 patients (P = 0.078). In the subgroup of 14 patients with normal initial PTH the increase in IGF-I correlated positively with the increase in BMD (femoral trochanter, r = 0.62, P < 0.05, and lumbar spine, r = 0.70, P < 0.02). CONCLUSIONS: BMD and circulating IGF-I levels are low in adults with untreated coeliac disease. In patients with normal initial PTH level there is an association between the change in BMD and circulating IGF-I, although this parallel increase may not be causally connected.     

Systemic insulin-like growth factor-I, insulin and vitamin D status in relation to age-associated bone loss in women.

This cross-sectional study, performed on 146 healthy (n = 64) or osteoporotic but otherwise normal (n = 82) pre- (n = 38) or post-menopausal (n = 108) female subjects, analyzed the relationships between bone mineral density (BMD) (measured by dual-energy X-ray absorptiometry), parameters of bone remodelling, indices of calcium homeostasis and systemic IGF-I or insulin levels against a background of natural aging. BMD (g/cm(2)) at the hip correlated to serum IGF-I concentration (r = 0.207, p < 0.05), as well as to insulin levels (r = 0.241, p < 0.01), while BMD at the spine correlated only to IGF-I levels (r = 0.173, p < 0.05). After adjustment for age, body mass index, serum PTH, vitamin D status and calcitonin levels, neither IGF-I nor insulin levels could be significantly related to BMD at the spine or hip. On the other hand, 25-OH vitamin D(3) was found to be an important predictor of BMD at the hip (beta = 0.1686, p = 0.0437). In conclusion, this study failed to demonstrate a predictive importance of insulin-IGF-I axis to the development of bone mass. Instead, a significant predictive value to BMD at the hip was documented for serum 25-OH vitamin D(3).     

Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender

GH deficiency (GHD) in adults is accompanied by reduced bone mass that may revert only after 2 yr of GH replacement. However, it is unclear whether the gender may modify bone responsiveness to GH replacement in adults. In this study we have evaluated whether bone mineral density (BMD) and turnover improve after GH replacement according to patients' gender. BMD at lumbar spine (LS) and femoral neck (FN), serum osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) were assessed in 64 hypopituitaric patients (35 men, 30-50 yr) before and 2 yr after the beginning of GH replacement. Values of IGF-I and BMD at LS and at FN were expressed as Zscores. At study entry, IGF-I and BMD resulted similar among men and women with GHD. During GH replacement, IGF-I levels increased in both men and women without any difference in the percentage of IGF-I increase between the genders (p=0.47). In women receiving estrogen replacement, however, the percentage of IGF-I increase (p<0.05), and the Z IGF-I score (p<0.001) were significant lower than estrogen untreated women, although IGF-I levels were similar in the 2 groups (p=0.53). The GH dose adjusted for body weight required to restore normal age- and sex- matched IGF-I levels was lower in men than in women (p<0.001), and was higher in women receiving than in those not receiving estrogen replacement (p<0.05). In contrast, hypogonadal men treated with testosterone and eugonadal men received a similar GH dose (p=0.97). Also OC, Ntx levels, lumbar and femoral BMD improved (p<0.001) in all patients. Nevertheless, a greater increase in lumbar BMD increase was observed in men than in women (8.0+/-2.1 vs 2.6+/-0.4%; p<0.05). No significant difference was revealed in bone parameters in women treated or untreated with estrogen replacement and in men treated or not with testosterone replacement for concomitant hypogonadism. At the multiple correlation analysis, gender was a stronger predictor for the required GH dose than the age (p<0.001 and p=0.02, respectively). In conclusion, a 2-yr GH replacement normalizes IGF-I levels, increases bone mass and improves bone turnover both in men and in women with GHD without any difference between the 2 groups, provided that the dose of GH was modulated on the basis of IGF-I levels. Women receiving oral estrogens should receive a GH dose approximately doubled, as compared to men and women not receiving oral estrogens, to achieve similar effects on bone density and turnover. In particular, GH replacement dose, to be successful on bone mass and turnover, depends on gender in hypopituitary patients aged below 50 yr.     

Fat mass is an important determinant of whole body bone density in premenopausal women but not in men.

We recently reported that total body fat mass is the principal determinant of bone density in normal postmenopausal women. We have now reexamined the relationships among these variables and lean mass in 68 healthy premenopausal women and 51 men. Areal bone density (BMD), fat mass, and lean mass were measured in total body scans by dual-energy, x-ray absorptiometry. In women, BMD was correlated with weight (r = 0.69), fat mass (r = 0.60), and lean mass (r = 0.55). In men, the respective correlations were 0.56, 0.26 (NS), and 0.51. Multiple regression analysis confirmed a codependence of female BMD on fat and lean masses, whereas male BMD was related only to lean mass. Because BMD is an areal not volumetric density, it is dependent on body size. The analysis was therefore repeated using BMD/height as an index of "true" density. Correlations with fat mass were little changed but those with lean mass were reduced (women) or eliminated (men). By multiple regression, female BMD/height was related to fat mass alone, and in men there was a borderline effect of fat (P = 0.05) but none of lean mass. As a second method to exclude a scale artifact, fat mass was expressed as percent body weight. It was related to BMD (r = 0.48) only in women. It is concluded that bone density is closely related to fat mass in premenopausal women, but less so in men. In both sexes, apparent relationships between BMD and lean mass are artifacts attributable to the use of areal density (which is dependent on body size) as a surrogate for volumetric density. The mechanism of this fat-bone density relationship is an important question to be addressed in bone biology.     

Leptin and bone mineral density: a cross-sectional study in obese and nonobese men

Leptin has been suggested to decrease bone mineral density (BMD). This observational analysis explored the relationship between serum leptin and BMD in 327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/- 6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg/m(2), age 47.5 +/- 5.1 yr). Whole-body dual-energy x-ray absorptiometry scan measured BMD, fat mass, and lean mass. Fasting serum leptin (nanograms per milliliter) was strongly associated with fat mass (kilograms) in both controls (r = 0.876; P < 0.01) and juvenile obese (r = 0.838; P < 0.001). An inverse relation between BMD adjusted for body weight and serum leptin emerged in both the control group (r = -0.186; P < 0.01) and the juvenile obese group (r = -0.135; P < 0.05). In a multiple linear regression, fat mass, lean body mass, and occupational physical activity were positively associated with BMD in the control group, whereas in the juvenile obese, only lean body mass was positively associated with BMD and smoking negatively associated with BMD. Our study supports that leptin is inversely associated with BMD and may play a direct role in the bone metabolism in nonobese and obese Danish males, but it also stresses the fact that the strong covariation between the examined variables is a shortcoming of the cross-sectional design.