[Relationship between polymorphism of parathyroid hormone and bone mineral density and relevant biochemical indicators in women].

OBJECTIVE: To investigate the distribution of parathyroid hormone (PTH) gene polymorphisms and the relationships of PTH gene polymorphisms with bone mass and serum bone relative biochemical markers. METHODS: Blood samples of 314 normal female volunteers, aged 20 - 80, were collected. Serum PTH, bone alkaline phosphatase (sBAP), cross-linked N-telopeptide of collagen type I (sNTX), cross-linked C-telopeptide of collagen type I (sCTX), osteoprotegerin (OPG) and leptin were determined by ELISA. Polymorphisms of PTH gene were detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme BstBI. BMD (QDR4500A) of the anteroposterior spine (AP), supine lateral spine (Lat), and femoral neck (FN) were measured. RESULTS: (1) The genotype frequency of BB, Bb, and bb were 75.8%, 23.3% and 0.9% respectively in normal females volunteers. The frequencies of RFLP alleles B and b were 87.5% and 12.5% respectively. There was no difference in the polymorphism frequency of PTH gene between the post- and pre menopausal women. (2) There were no significant differences in the BMD of the AP, Lat, and FN and the serum biochemical markers between the BB and Bb genotypes. (3) Multiple stepwise regression analysis showed that PTH did not influence the BMD values. CONCLUSION: PTH gene polymorphism has no relationship with bone mass and serum bone biochemical markers in normal females.

Age-related changes of serum bone alkaline phosphatase and cross-linked C-telopeptides of type I collagen and the relationship with bone mineral density in Chinese women.

BACKGROUND: Previous studies have shown that bone turnover rate changes with age. At the same time, there is no definitive research regarding age-related changes of bone turnover level and its association with bone mineral density (BMD) in Chinese mainland women. METHODS: In a cohort of 663 Chinese mainland women aged 20-70 years, serum bone alkaline phosphatase (BAP) and serum cross-linked C-telopeptides of type I collagen (sCTX) were measured to evaluate the state of bone formation and resorption, respectively. BMD was measured in the posteroanterior spine, supine lateral spine, hip and forearm using a dual-energy X-ray absorptiometry. RESULTS: The cubic polynomial regression model best fit age-related changes in serum BAP (R2=0.398, p<0.001) and sCTX concentrations (R2=0.148, p<0.001) with largest R2 from comparison 8 different regression models. Their values reached a minimal level in the 30-39 years age group, and increased dramatically in the 40-59 years groups. There was a decreasing trend of BAP in women >60 years. The levels of BAP and sCTX were inversely correlated to BMD in various skeletal regions over the entire population (r=-0.096 to -0.357, p<0.05). sCTX was a significant predictor of a T-score< or =-2.5 of BMD in postmenopausal women with sCTX levels above mean+2 SD of women aged 30-39 years compared with other postmenopausal women, which indicated by odds ratios 1.9-3.7 (p<0.05) for various skeletal regions, especially for the lateral lumbar spine (2.2, p<0.01), Ward's triangle (3.7, p<0.01), and ultradistal end of radius + ulna (2.8, p<0.001). CONCLUSIONS: Age-dependent serum BAP and sCTX were inversely correlated to BMD, and sCTX was a useful parameter for the prediction of a low T-score of BMD at skeletal sites with abundant cancellous bone in postmenopausal women.

[Serum osteoprotegrin and serum bone gamma-carboxyglutamine acid-containing protein are correlated with bone mineral density in normal women].

OBJECTIVE: To study the relationships of serum osteoprotegrin (sOPG), serum bone gamma-carboxyglutamine acid-containing protein (sBGP), and urine deoxypyridinoline (uDPD)/creatinine (Cr) with age and bone mineral density (BMD) in women. METHODS: ELISA was used to examine the sOPG, sBGP, and uDPD/Cr of 672 female volunteers aged 20-80. The BMD (QDR4500A) value of the anteroposterior lumbar spine and femoral neck were measured by DXA. RESULTS: (1) The levels of sOPG, sBGP, and uDPD/Cr in the age group of 30-39 were 2.8 pmol/L +/- 1.4 pmol/L, 5 microg/L +/- 3 microg/L, and 4.9 nmol/mmol +/- 2.5 nmol/mmol respectively, all significantly lower than those in the age groups 40-49, 50-59, and 60-69 (all P < 0.05). (2) In the age group 40-49, the values of sOPG, sBGP, and uDPD in menopausal subjects were significantly higher than those of the non-menopausal subjects (5.7 pmol/L +/- 3.1 pmol/L vs 3.4 pmol/L +/- 2.0 pmol/L, 11 microg/L +/- 5 microg/L vs 6 microg/L +/- 3 microg/L, and 6.9 nmol/mmol +/- 3.3 nmol/mmol vs 5.2 nmol/mmol +/- 3.9 nmol/mmol, all P < 0.001). (3) Age was positively correlated with sOPG, sBGP, uDPD/Cr, and BMD of anteroposterior lumbar spine and femoral neck (r = 0.130, 0.355, 0.106, -0.600, -0.545; P < 0.01). sOPG and sBGP were negatively correlated to anteroposterior lumbar spine BMD (r = -0.183, -0.108, P < 0.01; and r = -0.541, -0.441, P < 0.001). sOPG was positively correlated with sBGP and uDPD/Cr (r = 0.216 and 0.083; both P < 0.05). CONCLUSION: sOPG, sBGP, and uDPD/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age, and menopausal status in women, and predict the bone lose prior to BMD determination by DXA.

[Pathology and molecular pathogenesis of spondyloepiphyseal dysplasia tarda with progressive arthropathy caused by compound CCN6 heterogeneous gene mutations].

OBJECTIVE: To characterize the clinical manifestations, features of roentgenography and MR imaging, and the pathology of articular cartilage and matrix of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA), to screen the mutations of the disease-causing CCN6 gene, and try to elucidate the molecular pathogenesis of SEDT-PA. METHODS: A questionnaire survey on the clinical manifestations and history was conducted among a pedigree of SEDT-PA with 57 persons (53 living members) in tolal, including 2 probands, a 19-year old female and a 9-year old male. Physical examination and roentgenography and MR imaging were used on the 2 probands to characterize the features of their joints and articular cartilage. The femoral head extracted during replacement of hip of the proband 1 underwent hematoxylin-eosin staining and toludine blue (TB) staining to observe the pathological changes and ultra-microstructure of the articular chondrocytes and cartilage matrix using electron microscopy. Peripheral blood samples were collected from these 53 living members and 100 healthy controls. PCR was used to examine and sequence the exons of CCN6. 3D-conformational illustration of mutant CCN6 proteins were predicted using the Prospect Software. RESULTS: The clinical manifestations, radiology, and MR imaging established the diagnosis of SEDT-PA. Pathologic examination demonstrated that the articular cartilage chondrocytes became hyper-proliferative and immature, while the density and diameter of matrix collagens were dramatically decreased. Mutation studies showed the two probands carried a deletion (840delT) mutation in maternal allele, that caused the truncated CCN6 protein to miss 43 residues in C-terminus; and a substitution mutation (1000T-->C, Ser334Pro) in paternal allele, which was also inherited down to other 4 members in the SEDT-PA kindred. The predicted 3D-conformational changes of the truncated mutant and the Ser334Pro mutant CCN6 proteins demonstrated that in comparison with the wild CCN6 protein, the single long peptide loop in the region from signal peptide to the beginning 24 amino acid residues in the first domain (IGFBP) was subjected to folding into two smaller cross-loops accompanied with a much shorter C-terminus in 840 delT truncated mutant CCN6 protein, and no substantial 3D-conformational change of Ser334Pro mutant CCN6 protein was detected except for the C-terminal peptide towards the opposite direction. CONCLUSION: Novel 840delT mutation of CCN6 gene is the leading cause of SEDT-PA though coexistence of T1000C substitution is necessary for the clinical onset of SEDT-PA, in which marked abnormalities of cartilage chondrocytes and matrix are morphologically and functionally presented.