Reproducibility and safety of the incremental shuttle walking test for cardiac rehabilitation

The objective of this study was to evaluate the relationship between coronary disease and osteoporosis and determine the effect of osteoprotegerin (OPG) on bone remodeling and bone mineral density (BMD) in a group of patients with acute coronary syndrome. Eighty-three patients (52 males and 31 women) with acute coronary syndrome (75 patients with acute myocardial infarction and 8 with unstable angina) with an average age of 61 ± 10 years were studied. Levels of osteocalcin, urinarydeoxypyridinoline, OPG and the receptor activator of nuclear factor-κB ligand (RANKL) were determined during the hospital stay. Femoral neck, trochanter and lumbar spine densitometry was carried out using a DXA densitometer. Thirty percent of patients presented osteoporosis (39% of females and 26% of males). Osteoporotic patients were older and had a lower weight and height and elevated serum levels of osteocalcin (3.6 ± 2.25 2.63 versus ± 1.55, p = 0.05). Levels of OPG and RANKL were similar in both groups and showed no relationship with BMD. In conclusion, no relationship was observed between the OPG/RANKL system and BMD in these patients.     

Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males

OBJECTIVE: Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-kappaB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG-RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in males. PATIENTS AND MEASUREMENTS: Serum concentrations of OPG, RANKL, oestradiol, total testosterone and IGF-I and bone mineral density (BMD) were measured in 80 Korean males aged 42-70 (mean age, 54.5 year). Enzyme-linked immunosorbent assays were used to determine the serum concentrations of OPG and RANKL. Serum concentrations of oestradiol, total testosterone, IGF-I and bone turnover markers were determined using standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. RESULTS: We observed a significant negative correlation between the serum OPG levels and lumbar spine BMD (r =-0.259, P < 0.05) in Spearman correlation analysis. Serum OPG levels and RANKL/OPG ratios were found to be significantly correlated to the serum osteocalcin levels (r =- 0.254, P < 0.05; r = 0.264, P < 0.05) in Spearman correlation analysis. Serum OPG levels were found to be negatively correlated with serum oestradiol levels (r =-0.319, P < 0.01) in Spearman correlation analysis. In addition, a significant positive correlation was found between serum RANKL/OPG ratios and oestradiol levels (r = 0.374, P < 0.001) in Spearman correlation analysis. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG levels or RANKL to OPG ratios in Spearman correlation analysis. In a multiple regression analysis, age, body mass index (BMI), and serum OPG levels were identified as a significant predictor for lumbar spine BMD, and age, BMI, serum OPG and RANKL levels for femoral neck BMD. In another multiple regression analysis, only serum oestradiol level was identified as a significant predictor for serum OPG or RANKL levels. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG or RANKL levels in multiple regression analysis. CONCLUSIONS: Our data show that the circulating OPG-RANKL system is associated with bone metabolism in the male populations. Also, our data suggest that OPG and RANKL may be mediators of the effects of oestradiol in male bone metabolism.     

Bone metabolism in patients more than five years after bone marrow transplantation

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.     

Relationship between RANKL and neuroendocrine activation in elderly males with heart failure

The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.     

Impaired skeletal health in patients with chronic atrophic gastritis

Objective: In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls.

Material and methods: We performed a cross-sectional study on 17 CAG patients aged 54?±?13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed.

Results: We found lower lumbar BMD Z-score (?0.324?±?1.096 versus 0.456?±?1.262, p?=?0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p?=?0.046) and osteopenia at total hip (p?=?0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p?=?0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups.

Conclusions: We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls.     

Regulatory Effect of Parathyroid Hormone on sRANKL-Osteoprotegerin in Hemodialysis Patients With Renal Bone Disease

Abstract: Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin are newly identified molecules that contribute to the modulation of bone remodeling. RANKL activates osteoclast function by binding to RANK in either a soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in cohorts of hemodialysis patients and the establishment of possible correlations between their serum levels and those of other biochemical markers. We measured intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis patients. The patients were studied as a whole and in two subgroups according to their bone turnover state. In patients with low serum levels of bone turnover markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4U/L; 33 patients), the following correlations were found: (i) positive correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r = 0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = −0.365, P = 0.037). The subgroup of patients with normal or high serum levels of bone turnover markers (iPTH ≥ 150 pg/mL, ALP ≥ 100U/L, OC ≥ 40 ng/mL; 19 patients) exhibited the following significant correlations: (i) a positive correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a negative correlation between RANKL/OPG ratio and iPTH (r = −0.464, P = 0.045). In conclusion, the observation that PTH favors RANKL and inhibits OPG production was only demonstrated in the serum of hemodialysis patients in a low turnover state. The positive correlation between serum OPG and iPTH in normal or high turnover rates implies a homeostatic mechanism to limit bone resorption, probably associated with skeletal resistance to PTH.     

Vitamin D deficiency,serum leptin and osteoprotegerin levels in older diabetic patients: an input to new research avenues

The aim of this study was to assess the effects of single oral bolus of 300,000 IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic patients. This study is a Phase IV, randomized, double-blind, placebo-controlled, monocenter clinical trial. Thirty patients, 60 years or older, with type 2 diabetes mellitus, and diabetic foot complications, were enrolled and monitored for 24 weeks: 14 were treated with Vitamin D3 and 16 with placebo. Parameters including glucose, adiponectin, leptin, osteoprotegerin (OPG), 25-hydroxyvitamin D [25(OH)D], beta-CrossLaps, osteocalcin, bone-specific isoenzyme of alkaline phosphatase, tumor necrosis factor-α and parathyroid hormone were measured at screening and baseline and 12 and 24 weeks after treatment. Analysis of covariance was used to compare treatment groups. Analysis of the data detected a significant increase in 25(OH)D serum levels both at 12 and 24 weeks with respect to baseline values only in the treated patients. Significant variations with respect to baseline values were noted in OPG (P = 0.0085) and in leptin (P = 0.0442) levels: these were lower in the placebo group at week 24 but higher in the treated group. Vitamin D3 supplementation significantly increased serum leptin and OPG levels. Further, large-scale clinical trials are warranted to confirm these results.     

Relationship between serum adiponectin and bone mineral density in male patients with obstructive sleep apnea syndrome

Purpose

Obstructive sleep apnea syndrome (OSAS) is reported to have an association with bone mineral density (BMD). However, the underlying mechanism is far from clear. The aim of this study was to investigate the relationship between OSAS, bone turnover markers, and BMD and to evaluate the effect of adiponectin on BMD in patients with OSAS.

Methods

Seventy-one male patients with OSAS and 13 male control subjects were enrolled in this study. Serum adiponectin, calcium, phosphorus, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin, and procollagen type 1 N-propeptide were measured in all subjects, and BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) in the lumbar spine (L1–L4), the femoral neck, and the hip total.

Results

No statistically significant differences were found between the studied groups in terms of demographic data and bone turnover markers. Serum adiponectin significantly decreased with the aggravation of OSAS. Compared with subjects without OSAS, those with OSAS had a higher hip total BMD and t scores (p = 0.027 and p = 0.028). The significant negative association was found between serum adiponectin levels and hip total BMD. After adjusting for confounders, adiponectin as well as oxygen desaturation index (ODI) significantly predicted the hip total BMD (β = ?0.232, p = 0.005 and β = 0.226, p = 0.037).

Conclusions

In male subjects, the presence of obstructive sleep apnea syndrome is associated with higher bone mineral density of the hip. These findings suggest that serum adiponectin may be an underlying mediator for BMD in OSAS.

     

The foot in type 2 diabetes: Is there a link between vascular calcification and bone mineral density?

AimsTo examine the relationship between vascular calcification in the foot (FVC) and bone mineral density (BMD) in the heel of type 2 diabetes mellitus (DM) subjects.Methods65 subjects with type 2 DM and serum creatinine < 125 μmol/l underwent CT scanning of the foot to assess FVC and dual energy X ray absorptiometry (DEXA) scan to assess heel BMD. Routine biochemistry including osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-B ligand (RANKL) was also carried out.ResultsThe proportion of subjects with FVC was 43%, whilst 40% had low BMD (T score < −1.0). Age, neuropathy and 25 hydroxyvitamin D were independent predictors of FVC. Body-weight, eGFR, 25 hydroxyvitamin D, OPG, and total cholesterol were independent predictors of low heel BMD. There was no correlation between albuminuria and BMD or FVC. There was no difference in heel BMD between those with FVC and those without, but those with frank osteoporosis were significantly more likely to have FVC than those with higher BMD.ConclusionsThere is no clear-cut association between FVC and low BMD in type 2 DM with relatively well-preserved renal function. Age, neuropathy, eGFR, hyperlipidemia, body-weight, 25 hydroxyvitamin D and OPG play a complex role in their pathogenesis.     

Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects

OBJECTIVES: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha) levels, a reliable marker of in vivo oxidative stress and lipid peroxidation, with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in hypercholesterolaemia. DESIGN: Cross-sectional study. SETTING: University hospital centre. METHODS: Serum 8-iso-PGF(2alpha) levels were measured in 173 hypercholesterolaemic subjects and in 152 age- and sex-matched normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I), were also assessed. RESULTS: Hypercholesterolaemic subjects showed higher (P < 0.0001) serum 8-iso-PGF(2alpha) levels than controls. They also had decreased (P < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and OC levels. No significant differences between hypercholesterolaemic and control subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL levels. In multivariate linear regression analysis, serum 8-iso-PGF(2alpha) was the only negative predictor for femoral neck BMD and serum BAP and OC levels in hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was present between serum 8-iso-PGF(2alpha) levels and urinary CTX-I levels, or serum OPG and RANKL levels, in hypercholesterolaemic subjects. CONCLUSIONS: We found an association between increased serum 8-iso-PGF(2alpha) levels and lower bone mass and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects. These results would suggest a possible role for oxidative stress in the development of lower bone mass in hypercholesterolaemia.     

Bone turnover markers and bone mineral density in children with haemophilia

Summary. During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross‐sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X‐ray absorptiometry and Z‐scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C‐telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm^?2) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL^?1 in the low BMD group (P = 0.012). C‐telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL^?1 in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z‐score.     

Serum osteoprotegerin and its ligand in cirrhotic patients referred for orthotopic liver transplantation: relationship with metabolic bone disease.

AIMS: A prospective study was carried out in 22 cirrhotic patients referred for orthotopic liver transplantation, in order to analyze serum osteoprotegerin (OPG) and RANKL levels and their relationship with metabolic bone disease. METHODS: Serum levels of OPG and RANKL were measured in all patients as well as bone markers, serum parathyroid hormone and 25-hydroxyvitamin D levels. OPG and RANKL values were compared with those obtained in 29 healthy controls. Bone mineral density (BMD) of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry and spinal X-rays were obtained to assess vertebral fractures. RESULTS: Serum OPG levels were higher in cirrhotic patients than in controls (6.4+/-2 vs 2.7+/-0.7 pmol/l; P=0.001) and RANKL serum levels were lower in cirrhotic patients (0.215+/-0.6 vs 1.012+/-1.2 pmol/l; P=0.002), with an increased OPG:RANKL ratio when compared with the control group (280.3+/-334.5 vs 113+/-137.6; P=0.04). Ten patients had osteoporosis (45%) and up to 45% skeletal fractures. No differences were found in OPG levels between patients with and without osteoporosis by densitometric criteria or fractures. Negative correlations were found between OPG levels and femoral neck (R-0.46; P=0.03) and total hip BMD (R-0.48; P=0.025). By contrast, OPG values were not related to markers of bone turnover. CONCLUSIONS: OPG values are elevated in cirrhotic patients before liver transplantation, particularly in those with low bone mass at the proximal femur.     

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.     

Evaluation of bone mineral density, bone turnover markers, the OPG/RANKL system and sTNF-RI in Crohn's disease

Introduction

Patients with Crohn's disease are at risk of developing osteoporosis, a disease in which the inflammatory process seems to be gaining importance. We performed a cross-sectional study to evaluate bone metabolism, osteoclastogenic factors [receptor activator of NF-kB ligand (RANK-L) and osteoprotegerin (OPG)] and soluble tumor necrosis factor-α receptor I (sTNF-RI) in patients with Crohn's disease and to correlate the findings with the degree of disease activity.

Method

Sixty-four patients with Crohn's disease from the province of Granada (Spain) were included in this study. Bone mineral density (BMD) was studied through dual X-ray absorptiometry. Immunoassay was used to assess markers of bone formation [bone alkaline phosphatase (bALP) and osteocalcin (OC)] and bone resorption [tartrate resistant acid phosphatase (TRAP) and carboxyterminal telopeptide of type I procollagen (CTX)] as well as RANKL, OPG and sTNF-RI.

Results

The percentage of patients with a Z-score ≤-2 in the femoral neck or lumbar spine was 20.3% and was higher in patients with active disease, although this difference was not significant. This percentage was only higher in patients receiving corticosteroids (11.1 vs. 9.1%; P = .001). Patients with the highest disease activity had higher TRAP levels. No significant differences were found in BMD but significant differences were found in TRAP levels with respect to C-reactive protein concentrations. No association was found between levels of OPG, RANKL and sTNF-RI and BMD or disease activity.

Conclusions

A substantial proportion of our patients had low BMD. Levels of bone turnover markers suggested higher bone resorption, possibly in relation to disease activity, without a compensatory increase in bone formation.     

Bone Mineral Density Patterns in Vitamin D Deficient African American Men With Sickle Cell Disease

ObjectiveTo describe bone mineral density (BMD) patterns by densitometry in adult African American (AA) men with sickle cell disease (SCD) who are vitamin D deficient (Vit DD). Inclusion/Exclusion Criteria: All SCD phenotypes were eligible. Those with chronic renal failure or hyperparathyroidism were excluded.Inclusion/Exclusion CriteriaAll SCD phenotypes were eligible. Those with chronic renal failure or hyperparathyroidism were excluded.Data CollectionDemographics, body mass index and SCD genotype.LaboratoryAlbumin, ferritin, calcium, phosphorus, 25-hydroxy vitamin D and intact–parathyroid hormone were obtained. BMD, T and Z scores: T scores at the lumbar spine were used to categorize normal, osteopenia and osteoporosis based on World Health organization criteria.Statistical AnalysesMean ± standard deviation was used to describe continuous data, whereas categorical data were described by counts and percentages. The χ² test was used to analyze categorical variables; Student's t test or one-way analysis of variance, when appropriate, was used to compare continuous variables. Rates of osteopenia-osteoporosis were determined, and the parameter with 95% confidence interval (CI) of a proportion was constructed. All tests were 2-sided, and a P ≤ 0.05 was considered statistically significant. We used StatView Version 5.01 (SAS institute Inc, Cary, NC) for the statistical analysis.ResultsSeventy-eight AA men with SCD disease and Vit DD were enrolled in this study. We found that 42% of the men studied had low-BMD (osteopenia or osteoporosis) using T scores at the lumbar spine to establish densitometry strata. The prevalence of osteoporosis was 14%.ConclusionsA large proportion of adult AA men with SCD and Vit DD showed low BMD.     

RANKL:osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

OBJECTIVE: To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease. METHODS: Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects. RESULTS: At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003). CONCLUSION: Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.     

Association of adiponectin with peripheral muscle status in elderly patients with heart failure

BackgroundReduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.MethodsWe measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.ResultsSerum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.ConclusionsOur findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.     

The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study

OBJECTIVE: The role of osteoprotegerin (OPG) and its receptor activator of nuclear factor kappaB legend (RANKL) in the regulation of bone in humans remain unclear. We examined the sex-specific associations of serum OPG, RANKL, and their ratio with bone mineral density (BMD) in older adults. DESIGN: Participants were 681 community-dwelling adults, ages 45-90 years, who had serum OPG and RANKL measured and bone density scans in 1988-1991, with follow-up scans 5 and/or 10 years later. METHODS: Analyses were sex-specific; women using and not using estrogen were evaluated separately. Cross-sectional analyses used multivariable regression models; longitudinal analyses used repeated measures mixed effects models. RESULTS: In cross-sectional analyses, age- and weight-adjusted serum OPG levels were significantly positively associated with BMD at the lumbar spine in men, and at the femoral neck, total hip, and lumbar spine in women using estrogen, but not in non-users of estrogen. RANKL concentrations were significantly and inversely associated with BMD in men only, and at the total hip. Neither OPG nor RANKL was significantly associated with bone loss. Results for the RANKL/OPG ratio were the same as those for RANKL alone. CONCLUSIONS: These results suggest a modulatory effect of both endogenous and exogenous sex hormones on the biologic interaction of OPG, RANKL, and bone.     

Baseline serum total adiponectin level is positively associated with changes in bone mineral density after 1-year treatment of type 2 diabetes mellitus

Although recent clinical studies have shown that serum adiponectin level was negatively associated with bone mineral density (BMD), serum adiponectin action on bone metabolism in humans is still unclear. We investigated the relationships between serum levels of total and high-molecular weight (HMW) adiponectin and its ratio (HMW-total ratio) vs chronological changes in BMD at the lumbar spine, femoral neck (FN), and one third of the radius after 1-year treatment of type 2 diabetes mellitus in 32 Japanese patients. Serum total adiponectin, but not HMW adiponectin or HMW-total ratio, was significantly and positively correlated with percentage change in FN-BMD (r = 0.35, P < .05). Multiple regression analysis adjusted for age, duration of diabetes, sex, body height, body weight, waist circumference, serum creatinine, and hemoglobin A_1c showed that serum total adiponectin was still significantly and positively correlated with percentage change in FN-BMD (r = 0.65, P < .01). On the other hand, no significant relationships were found between serum levels of hemoglobin A_1c, pentosidine, bone formation markers (bone-specific alkaline phosphatase and osteocalcin), or a bone resorption marker (urinary N-terminal cross-linked telopeptide of type-I collagen) vs percentage change in BMD at any site. These findings suggest that serum total adiponectin could be clinically useful for predicting BMD change during treatment of type 2 diabetes mellitus. Adiponectin might protect against BMD reduction in patients with type 2 diabetes mellitus.     

Does osteoprotegerin or receptor activator of nuclear factor-kappaB ligand mediate the association between bone and coronary artery calcification?

CONTEXT: Accumulating evidence indicates that vascular and bone mineralization may be related, although the exact mechanism remains unknown. OBJECTIVE: Our objective was to investigate whether an observed inverse association between bone mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal women currently taking estrogen therapy is mediated by osteoprotegerin (OPG) or receptor activator of nuclear factor-kappaB ligand (RANKL). DESIGN: Participants were 92 postmenopausal women (aged 58-81 yr) taking estrogen therapy who had hip and spine BMD assessed by dual-energy x-ray absorptiometry and CAC measured by electron-beam computed tomography in 1998-2002 and serum RANKL and OPG levels measured in samples collected in 1997-1999. Total CAC score was dichotomized as none/minimal (10). RESULTS: OPG serum levels were higher in women who had some CAC compared with those who had none/minimal (126.8 +/- 1.08 vs. 102.9 +/- 1.07 pg/ml, respectively, P = 0.03); these differences became nonsignificant after adjustment for age and other risk factors (P = 0.51). A 1 sd increase in hip BMD was associated with significantly lower odds of having CAC > 10 (odds ratio = 0.52; 95% confidence interval = 0.29-0.93) independent of age, fat-free mass, high-density lipoprotein cholesterol, current smoking, and use of cholesterol-lowering medications. Other skeletal sites demonstrated a similar pattern. Addition of RANKL and/or OPG to the model had minimal effect on the magnitude or statistical significance of the BMD-CAC association. Additionally, a test of interaction indicated that RANKL and OPG are not significant effect modifiers. CONCLUSIONS: Serum OPG and RANKL do not account for the observed association between bone and coronary artery calcification among postmenopausal women using hormone therapy.