BACKGROUNDSerum osteoprotegerin (OPG) and matrix metalloproteinase-2 (MMP-2) have been shown to play a role in bone metabolism by degrading the bone matrix. The present study was undertaken to compare OPG and MMP-2 with bone mineral density and three markers (alkaline phosphatase (AKP), calcium and phosphorus) in postmenopausal women in Wuhan.

METHODSSerum OPG, MMP-2, and AKP of 78 Chinese postmenopausal women aged 48 to 65 were measured using enzyme-linked immunosorbent assay (ELISA). Bone mineral density was measured with dual energy X-ray absorptiometry (DEXA), and serum calcium and phosphorus were measured by auto biochemical analysis.

RESULTSSerum OPG and MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis ((127.6 +/- 6.3) ng/L; (1388 +/- 121) microg/L)) than those in age-matched normal controls ((72.3 +/- 2.4) ng/L; (1126 +/- 141) microg/L, P < 0.01). Negative relationships were found between serum OPG, MMP-2 levels and bone mineral density in osteoporotic women. Adjusted by age and body mass index (BMI), the correlation of MMP-2 with bone mineral density of the neck of the femur disappeared. In osteoporotic women, negative correlations between OPG, MMP-2 levels and serum calcium were found (r = -0.216; r = -0.269, P < 0.05), but positive correlations between OPG and serum AKP, serum phosphorus (r = 0.235; r = 0.124, P < 0.05).

CONCLUSIONSSignificant correlations exist between serum OPG, MMP-2 levels and bone metabolism in high bone turnover of postmenopausal osteoporotic women. The concentrations of serum OPG and MMP-2 increase possibly as a concomitant event in the high bone turnover state, such as postmenopausal osteoporosis. Therefore serum OPG and MMP-2 could be used as indicators for the bone metabolism in postmenopausal osteoporotic women.

Aged ; Bone Density ; Bone and Bones ; metabolism ; Calcium ; blood ; Female ; Humans ; Matrix Metalloproteinase 2 ; blood ; Middle Aged ; Osteoprotegerin ; blood ; Postmenopause ; metabolism

Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-gamma, which is an important transcriptional factor in adipocyte differentiation, also plays an important role in the bone microenvironment. The objective of the study was to clarify whether Pro12Ala polymorphism was related to the serum OPG levels and bone mineral metabolism in healthy Korean women. In 239 Korean women (mean age 51 years), who participated in medical check-up program in a health promotion center, anthropometric measurements, lumbar spine and femoral neck bone mineral density (BMD), bone turnover markers, such as serum total alkaline phosphatase (ALP) levels, urine deoxypyridinoline levels, and 24-h urine calcium excretion were measured. Serum levels of OPG were measured with ELISA method. DNAs were extracted from the samples and the genotyping of the Pro12Ala polymorphism (rs1801282) in the PPAR-gamma gene was performed via an allelic discrimination assay using a TaqMan probe. In addition, we examined the haplotype analysis between two polymorphisms of PPAR-gamma gene, Pro12Ala in exon B and C161T in exon 6 (rs3856806). Allelic frequencies were 0.950 for Pro allele and 0.050 for Ala allele, which was in compliance with Hardy- Weinberg equilibrium, and there was no Ala12Ala genotype among the genotyped subjects. Mean serum OPG level was significantly lower (P=0.035), and serum total ALP was significantly higher (P=0.014) in the Pro12Ala genotype group compared with the Pro12Pro genotype group, which were consistently significant even after adjustment for weight, height, and serum follicle stimulating hormone (FSH). In multiple regression analysis with serum OPG as the dependent variable and age, weight, ALP, femoral neck BMD and Pro12Ala genotype included in the model, only Pro12Ala genotype was significant determinant of serum OPG level (beta=-0.136, P=0.035). The haplotype analysis with C161T polymorphism revealed that subjects with Ala and T alleles showed significantly lower serum OPG levels compared with those with Pro12Pro/CC genotype, which were consistently significant even after adjustment for age, weight, height and FSH (P=0.010). This result suggests statistically significant association of Pro12Ala polymorphisms with serum OPG levels in Korean females.
Alanine/genetics ; *Amino Acid Substitution ; Asian Continental Ancestry Group ; Bone Density/physiology ; Bone and Bones/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Frequency ; Humans ; Korea ; Middle Aged ; *Mutation ; Osteoprotegerin/*blood/metabolism ; PPAR gamma/*genetics/metabolism ; Polymorphism, Genetic ; Proline/genetics

BACKGROUND: Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastogenesis through binding to receptor activator of nuclear factor-kappaB ligand (RANKL). OPG-knockout mice develop early-onset osteoporosis and arterial calcification. Recent studies report that serum OPG levels are elevated in diabetic patients with cardiovascular disease and are associated with the presence and severity of coronary artery disease. We examined the relationships between serum OPG levels and insulin resistance, bone metabolism and cardiovascular risk factors in diabetic patients. METHODS: In 84 diabetic patients (33 men, 51 women, mean age 56.7 years old) were studied. Blood pressure, body mass index (BMI), fasting blood glucose, postprandial 2-hour blood glucose, fasting insulin and lipid profiles were measured. Serum OPG levels were measured with sandwich ELISA method. Bone mineral density (BMD)s were checked and serum osteocalcin and urine deoxypyridinoline levels were checked as bone turnover markers. 24-hour urine microalbumin were checked and left ventricular mass index (LVMI) were evaluated with echocardiography. From simple chest X-ray, the presence of aortic calcification were confirmed by a trained radiologist. Homeostatic model assessment (HOMA)-insulin resistance (IR), quantitative insulin sensitivity check index (QUICKI) were calculated as insulin resistance indices. RESULTS: Serum OPG levels were positively correlated with age, LVMI, HOMA and negatively correlated with lumbar spine BMD and QUICKI. After adjustment for age, only LVMI showed persistent correlation with serum OPG levels and when multiple regression analysis was performed with LVMI as the dependent variable, BMI and OPG were the significant predictors of LVMI (R2=0.054, p=0.012). Dividing the subjects into 3 groups according to 24-hour urine microalbumin levels, mean values for serum OPG levels increased as 24-hours urine microalbumin levels increased, but without statistical significance. Mean serum OPG levels were higher in patients with aortic calcification, without statistical significance. CONCLUSION: Serum OPG levels were positively correlated with insulin resistance indices and negatively correlated with lumbar spine BMD in diabetic patients, suggesting a compensatory mechanism to counteract bone loss progression. Serum OPG levels were independent predictor for LVMI in diabetic patients, warranting further research on OPG as the marker for future cardiovascular mortality in diabetic patients.
Animals ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Bone Density ; Cardiovascular Diseases ; Coronary Artery Disease ; Diabetes Mellitus ; Echocardiography ; Enzyme-Linked Immunosorbent Assay ; Fasting ; Female ; Glycoproteins ; Humans ; Hypertrophy, Left Ventricular ; Insulin Resistance* ; Insulin* ; Male ; Metabolism* ; Mice ; Mortality ; Osteocalcin ; Osteoporosis ; Osteoprotegerin* ; RANK Ligand ; Risk Factors* ; Spine ; Thorax

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p<0.05) than those with the CC genotypes. There were no differences in the bone turnover markers between the different genotypes (p>0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (p<0.05). When the subjects were divided into 3 groups, i.e., normal, osteopenic and osteoporotic groups, according to the lumbar spine BMD, the group with the T allele had a significantly higher prevalence of osteopenia and smaller numbers with normal BMD than those with the CC genotype (p=0.032). CONCLUSION: The frequencies of the C161-->T substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis
Adipocytes ; Alkaline Phosphatase ; Alleles ; Blood Pressure ; Bone Density ; Bone Diseases, Metabolic ; Calcium ; Collagen Type I ; Continental Population Groups ; DNA ; Enzyme-Linked Immunosorbent Assay ; Estradiol ; Exons* ; Femur Neck ; Gene Frequency ; Genotype ; Humans ; Insulin-Like Growth Factor I ; Male ; Metabolism* ; Osteocalcin ; Osteoporosis ; Osteoprotegerin* ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes* ; Phosphorus ; Prevalence ; Spine ; Testosterone