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Background Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. Methods Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, − 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. Results Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (− 3.27% [95% CI, − 5.86 to − 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P P P Conclusions Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247

Plastin 3 (PLS3) has been identified as a candidate gene for bone fragility in the Rotterdam study (RS) population. So far, however, whether PLS3 polymorphisms are genetic risk factors for osteoporosis in Asian population remains unclear. In order to investigate the association between genetic variants in PLS3 and the risk of fragility fracture and/or bone mineral density (BMD) in postmenopausal Chinese women, we conducted a case-control association study. A total of 1083 postmenopausal patients with osteoporotic fractures and 2578 unrelated non-fracture controls in Shanghai were enrolled. Seven SNPs, including six tagSNPs in PLS3 and one identified genetic risk factor (rs140121121) for osteoporosis in the RS population, were genotyped in all the participants. BMD at lumbar spine and hip sites were measured in 2578 controls. Association between SNPs and the risk of osteoporotic fractures and/or BMD were analyzed. The GC genotype of rs757124 and AC genotype of rs10521693 were associated with lumbar vertebral fracture (P = 0.020 and 0.046, respectively). The association between tagSNPs and BMD were analyzed only in 2546 controls to avoid biased conclusion. rs757124 was significantly associated with BMD at lumbar spine and hip sites. GG genotype had the highest BMD at lumbar spine (L1-4), while CC genotype had the highest BMD at hip sites. Our results suggest that polymorphisms in PLS3 are genetic loci for osteoporosis in postmenopausal Chinese women.

Purposes: In order to investigate the association between serum periostin levels and the variation of its encoding gene POSTN and the prevalence of vertebral fractures and bone mineral density (BMD) in Chinese postmenopausal women, an association study was performed. Materials and Methods: 385 postmenopausal women were recruited. For participants without a history of vertebral fracture, lateral X-rays of the spine covering the fourth thoracic spine to the fifth lumbar spine were performed to detect any asymptomatic vertebral fractures. Ten tag-single nucleotide polymorphisms (SNP) of POSTN were genotyped. Serum periostin levels, biochemical parameters, and BMD were measured individually. Results: rs9603226 was significantly associated with vertebral fractures. Compared to allele G, the minor allele A carriers of rs9603226 had a 1.722-fold higher prevalence of vertebral fracture (p = 0.037). rs3923854 was significantly associated with the serum periostin level. G/G genotype of rs3923854 had a higher serum periostin level than C/C and C/G (67.26 ± 19.90 ng/mL vs. 54.57 ± 21.44 ng/mL and 54.34 ± 18.23 ng/mL). Furthermore, there was a negative correlation between the serum level of periostin and BMD at trochanter and total hip. Conclusion: Our study suggested that genetic variation of POSTN could be a predicting factor for the risk of vertebral fractures. The serum level of periostin could be a potential biochemical parameter for osteoporosis in Chinese postmenopausal women.

Purpose. GWAS has successfully located and analyzed the pathogenic genes of osteoporosis. Genetic studies have found that heritability of BMD is 50%–85% while the other half is caused by hip geometric parameters and tissue horizontal characteristics. This study was designed to study the GWAS of osteoporosis in Shanghai Han population. Methods. We collected 1224 unrelated healthy young men (20–40 years old), young women (20–40 years old), and postmenopausal women (over 50 years old) who lived in Shanghai. BMD and hip geometric parameters were measured by dual-energy X-ray absorptiometry. The genomic DNA of peripheral blood was extracted and analyzed by using Illumina Human Asian Screening Array-24 + v 1.0 (ASA) gene chip. Statistical analysis was carried out to evaluate the relationship between these SNPs and BMD and hip geometric parameters. Results. A total of 1155 subjects were included. We found that one SNP rs35282355 located in the human immunodeficiency virus type 1 enhancer-binding protein 3 gene (HIVEP3) and another 25 SNPs located in LINC RNA were significantly correlated with bone mineral content (BMC) in the femoral neck ( P = 2.30 × 10−9, P P = 5.95 × 10−8). Conclusions. Through this study, we found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. These results provide important information for us to further understand the etiology and genetic pathogenesis of osteoporosis. In the future, we will expand the sample size to verify these loci and carry out molecular research.

Sclerostin is an important regulator of bone mass involving Wnt/β-catenin signaling pathway. We aimed to obtain the profile of serum sclerostin level and explore its associations with bone metabolism markers and sex hormones in healthy community-dwelling Chinese elderly individuals and adolescents. A cross-sectional study was performed in three communities in Shanghai. In all, 861 participants, including 574 healthy elderly individuals, and 287 healthy adolescents, were recruited. The levels of serum sclerostin, procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX), parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], estradiol (E2), testosterone (T), and sex hormone-binding globulin (SHBG) were measured in blood samples from all participants. Median sclerostin level was higher in males than in females and in elderly individuals than in adolescents (elderly males: 54.89 pmol/L, elderly females: 39.95 pmol/L, adolescent males: 36.58 pmol/L, adolescent females: 27.06 pmol/L; both P < 0.05). In elderly individuals, serum sclerostin was positively correlated with age (β = 0.176, P < 0.001) and T (β = 0.248, P = 0.001), but negatively associated to P1NP (β = −0.140, P = 0.001). In adolescents, circulating sclerostin was significantly and positively associated with P1NP (β = 0.192, P = 0.003). The directions of the association between sclerostin and P1NP were opposite in Chinese elderly individuals and adolescents, which may reflect that sclerostin plays distinct roles in different functional states of the skeleton. Our findings revealed the rough profile of circulating sclerostin level in general healthy Chinese population and its associations with bone metabolism markers and sex hormones, which may provide a clue to further elucidate the cross action of sclerostin in bone metabolism and sexual development.

Primary hyperparathyroidism is commonly caused by excess production of parathyroid hormone from sporadic parathyroid adenomas. However, the genetic architecture of sporadic primary hyperparathyroidism remains largely uncharacterized, especially in the Chinese population. To identify genetic abnormalities that may be involved in the etiology of sporadic parathyroid adenomas and to determine the mutation frequency of previously identified genes in the Chinese population, we performed whole-exome sequencing of 22 blood-tumor pairs from sporadic parathyroid adenomas. The most important finding is the recurrently mutated gene, ASXL3, which has never been reported in parathyroid tumors before. Moreover, we identified two different somatic mutations in the CDC73 gene and one somatic mutation in the EZH2 gene. The Y54X mutation in the CDC73 gene was previously identified in parathyroid carcinomas, which proved that parathyroid adenomas and carcinomas might possess similar molecular signatures. No mutations in the MEN1 or CCND1 genes were observed in our study. Thus, our data provide insights into the genetic pathogenesis of sporadic parathyroid adenomas and are valuable for the development of diagnostic and therapeutic approaches for sporadic primary hyperparathyroidism.

Introduction Collagen cross-linking, which is regulated by lysyl oxidase (LOX), plays critical roles in bone mechanical strength. LOX can influence bone remodeling by modulating osteoblast and osteoclast activity. This study aimed to explore the effect of LOX gene polymorphisms on osteoporotic fractures susceptibility in postmenopausal Chinese women. Methods This was a prospective study of postmenopausal women who visited the outpatient and community clinics of the local Hospital. Five tagging single nucleotide polymorphisms (SNPs) in the LOX gene were determined. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and hip using dual-energy X-ray absorptiometry. Fractures were confirmed by X-ray and divided into: vertebral compression fracture (OVCF) and non-OVCF (all other fractures). Results This study included 602 patients with non-traumatic fractures and 1343 healthy volunteers. The rs1800449 was significantly associated with vertebral compression fracture (OVCF) after adjusting for age and BMI (P = 0.012). Compared with subjects with the GG genotype, the risk of having OVCF was 1.28 and 1.74, respectively for subjects with the GA and AA genotypes (P = 0.043 and P = 0.018). A recessive genetic model showed that carriers of the AA genotype had higher fracture risk compared to G carriers (GA and GG genotypes) (P = 0.015). The rs2288393 SNP exhibited marginally significant association with OVCF (P = 0.051). Haplotype analyses corroborated our single SNP results: both haplotype CGA and CCG contained rs10519694, rs2288393, and rs1800449, and were significant associated with OVCF (P = 0.048 and P = 0.032, respectively). On the other hand, we found no evidence of an association of LOX gene allelic variants with either BMD or non-OVCF (all P > 0.05). Conclusion The results suggest that genetic polymorphisms in LOX may contribute to susceptibility to OVCF in Chinese postmenopausal women.

Background Chondrosarcomas is a rare tumour that has a variable biological characteristic. Also, their treatment clinically and surgically is controversial. We performed a comparison review of different regional institutions series with the aim of assessing the clinical outcome of patients. Purposes We, therefore, compare different institutions from different regions patients with grade 1 to 3 chondrosarcomas to (1)determine difference in survival rate, (2) local recurrence results, (3) determine successful outcome after surgery, (4) differences among surgical procedures. (5) Determine any association of clinical and demographic behaviour with gender, follow-up, treatment and chondrosarcoma affected body locations. Methods A retrospective review of 33 chondrosarcoma(all grades) patient’s data since 2013, compared with 15 author’s total 868 patients research literature to find more about clinical and statistical advantages and similarities with our study. Here is mentioning of clinical information’s, surgery type categorised, adjuvants types, genders, follow-up years, recurrence, affected areas, death rates, successful outcome and survival rates by using statistical methods. Results The overall survival rate was 94%, successful outcome 85% in 4.3 + 1.2 years follow-up. Observed wide resection, distilled water as adjuvant, chemo & radiotherapy significantly shows excellent result over our compared chondrosarcoma literature datas. We have also marked that females and humerus bone are more affected by chondrosarcoma among those literatures data. Conclusions Low-grade chondrosarcoma of the skeleton can be treated with wide resection and by the use of distilled water, which give good oncological outcome and a very low rate of post-surgical complications, as well as chondrosarcoma all grades recurrence.

Background Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with equal sex incidence that is characterized by neurofibromas, café‐au‐lait macules, axillary freckling, optic pathway tumor, distinctive osseous lesion, and iris Lisch nodules. Inactivating variants in the NF1 gene have been identified to be correlated with NF1. This tumor suppressor gene is located at 17q11.2. Methods Ten affected NF1 probands and their available relatives from 10 unrelated Chinese families with neurofibromatosis type 1 were clinically studied. All of these probands mainly complained of osseous lesions. PCR was used to analyze and sequence the variants. We collected both laboratory and radiological information. Results We detected five novel pathogenic variants including two de novo variants in these 10 families: one missense variant, p.Cys709Arg(c.2125T>C), in exon 18 and four frameshift variants: p.Leu1459Profs*2(c.4436dupT) in exon 34; p.Lys99Argfs*4(c.296delA) in exon 4; p.Leu762Cysfs*2(c.2283delA) in exon 19; and p.Leu1522Ilefs*53(c.4562_4563dupAT) in exon 34. Conclusion Novel pathogenic variants in the NF1 gene in these families correlated with the phenotype and genotype and explained the clinical manifestations of these patients. The results help us to understand the genetic basis of patients with neurofibromatosis type 1 in China. Our study expands the pathogenic variant spectrum of the NF1 gene and may be helpful in genetic counseling and prenatal genetic diagnosis.

Background: The aims of this study were: (1) to evaluate the association of serum osteocalcin with bone mineral density (BMD) and markers of bone metabolism in postmenopausal and elderly Chinese women, and (2) to observe the relationships of single-nucleotide polymorphisms (SNPs) in and around the osteocalcin gene with osteocalcin and BMD. Methods: A cross-sectional study was conducted with 725 postmenopausal Chinese women. Five SNPs (rs1543294, rs1800247, rs759330, rs2842880, and rs933489) of the osteocalcin gene were genotyped. Serum osteocalcin and intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], and type I collagen containing cross-linked C-telopeptide (β-CTX) were measured. The BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry. Results: Osteocalcin was positively correlated with serum phosphorus (p = 0.001), alkaline phosphatase (ALP; p < 0.001), PTH (p = 0.002) and β-CTX (p < 0.001), and negatively correlated with BMD at the lumbar spine (p < 0.001) and total hip (p = 0.002). No significant association was obtained between the SNPs, haplotypes of the osteocalcin gene, and BMD or osteocalcin. Conclusion: Our results suggest that osteocalcin was positively correlated with serum phosphorus, ALP, PTH, and β-CTX, but negatively correlated with BMD at the lumbar spine and total hip. Common genetic variants of the osteocalcin gene may not be a major contributor to variations in serum osteocalcin or BMD in postmenopausal and elderly Chinese women.

The aim of the present study was to characterize the clinical manifestations and identify the mutations of Serpin family F member 1 (SERPINF1) and FK506 binding protein 10 (FKBP10) genes in Chinese patients with osteogenesis imperfecta (OI). Using whole‑exome sequencing in the first and third probands, a novel mutation was identified in SERPINF1 and a novel compound heterozygous mutation was revealed in FKBP10. Using Sanger sequencing, an additional novel mutation in SERPINF1 was identified in a proband of family 2. In family 1, the proband presented with a novel homozygous missense mutation of the SERPINF1 gene, c.1067T>A (V356E). In family 2, the proband had a novel homozygous deletion mutation of the SERPINF1 gene, c.283+473_643+104del (p.Ala96_Gly215del). Serum pigment‑epithelium‑derived factor concentration was not detected in probands with OI type VI. For both families, the proband's father was demonstrated to have a heterozygous mutation of SERPINF1, whereas no mutations was detected in the probands' mothers. An assessment of allelic copy numbers revealed a deletion of SERPINF1 in the mother of family 1. The results of the present study demonstrate that patients may have mild symptoms of OI with a large fragment deletion in the SERPINF1 gene. Thus, the phenotype of Chinese patients with type VI OI is milder than that of Caucasian and Korean patients. In family 3, the proband displayed a novel compound heterozygous mutation in FKBP10, c.813_814delGA (p.Glu271AspfsX101) and c.831delC (p.Gly278AlafsX20), and did not have Bruck syndrome. Codon 831 of the FKBP10 gene may represent a mutation hotspot for human OI. These results extend both the phenotypic and the genotypic contents of OI patients with SERPINF1 or FKBP10 mutations.

Hypophosphatemic rickets/osteomalacia is characterized by defective renal phosphate reabsorption and abnormal bone mineralization. Hypophosphatemic rickets/osteomalacia consists of inherited and acquired forms, many of which have unknown aetiology. In the present study, next‑generation sequencing‑based resequencing was used on samples from Chinese subjects with hypophosphatemic rickets/osteomalacia, aiming to detect the spectrum of pathogenic genes in these patients. A total of 86 hypophosphatemic rickets/osteomalacia patients (ranging from 3 to 70 years old) were recruited. Patients with tumour‑induced osteomalacia (TIO), renal tubular acidosis, renal osteodystrophy, and adefovir‑induced Fanconi syndrome were excluded. Targeted massively parallel resequencing of 196 candidate genes for hypophosphatemic rickets/osteomalacia was performed in the 86 affected unrelated individuals (cases) and in 100 unrelated healthy controls to identify new genes and mutations in known genes that cause hypophosphatemic rickets/osteomalacia. The results identified seven phosphate‑regulating gene with homologies to endopeptidases on the X chromosome (PHEX) mutations (of which two were novel) and one novel dentin matrix protein 1 (DMP1) mutation in eight patients. Following targeted exome sequencing data analysis, 14 candidate disease‑related gene loci were selected, two of which were of most concern regarding disease severity. Further validation of the present results is warranted, with additional sequencing projects and functional tests. To our knowledge, the present study is the largest cohort of cases with hypophosphatemic rickets/osteomalacia to undergo targeted resequencing. The diagnosis and understanding of the molecular aetiologies of these disorders will be improved by this fast and efficient approach.

Human autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, is a rare genetic bone disorder that often causes death. Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO. Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO. In order to expand the mutation spectrum and clinical diversity for a better understanding of the ARO phenotype and to further investigate the clinical characteristics of benign subjects with ARO, we here report five individuals with ARO from four unrelated Chinese families. X-ray examination was conducted and bone turnover markers were assayed. The gene of T-cell immune regulator 1 (TCIRG1) was screened and analyzed. Monocyte-induced osteoclasts were prepared and their resorption ability was studied in vitro. We identified five novel mutations (c.66delC, c.1020+1_1020+5dup, c.2181C>A, c.2236+6T>G, c.692delA) in these patients. Four patients displayed a malignant phenotype, three of them died, and one who received bone marrow transplantation survived. The remaining one, a 24-year-old male from a consanguineous family, was diagnosed based on radiological findings but presented no neurological or hematological defects. He was homozygous for c.2236+6T>G in intron 18; this mutation influenced the splicing process. An in vitro functional study of this novel splicing defect showed no resorption pits on dentine slices. TCIRG1-dependent osteopetrosis with a mild clinical course was observed for the first time in Chinese population. The present findings add to the wide range of phenotypes of Chinese patients with TCIRG1-dependent ARO and enrich the database of TCIRG1 mutations.

Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.

The aims of this study were as follows: 1) to evaluate the association of serum sclerostin with bone mineral density (BMD) and markers of bone metabolism in postmenopausal Chinese women and 2) to observe the relationships of single-nucleotide polymorphisms (SNPs) within the sclerostin (SOST) gene with serum sclerostin, BMD, and markers of bone metabolism.A cross-sectional study was conducted with 703 postmenopausal Chinese women. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. Serum sclerostin and markers of bone metabolism were measured, including serum intact PTH, 25-hydroxyvitamin D [25(OH)D], procollagen type 1 N-terminal propeptide, and β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX). The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry.Serum sclerostin was positively correlated with BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D (all P.01) but negatively correlated with β-CTX (P.01). The significant relationships between serum sclerostin and BMD and with serum β-CTX persisted, even after adjustments for age, body mass index, and serum 25(OH)D (all P.01). However, there was no correlation between serum sclerostin and age or serum procollagen type 1 N-terminal propeptide. We failed to identify a significant association between the SNP, haplotypes of SOST and BMD, or serum sclerostin.Our results suggested that serum sclerostin was positively correlated with the BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D but was negatively correlated with serum β-CTX. Genetic polymorphisms of SOST may not be a major contributor to variations in the serum sclerostin or BMD in postmenopausal Chinese women.

Vitamin D deficiency has been recognized as a major public health issue worldwide. Recent studies have indicated that genetic factors might play an important role in determining serum 25-hydroxyvitamin D [25(OH)D] levels in Caucasians and African Americans. However, the genes that contribute to the variation in serum 25(OH)D levels in Chinese are unknown. In this study, we screened 15 key genes within the vitamin D metabolic pathway using 96 single-nucleotide polymorphism (SNP) markers in a group of 2897 unrelated healthy Chinese subjects. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. An association test for quantitative traits was performed to evaluate the association between candidate genes and serum 25(OH)D levels. In the present study, variants and/or haplotypes in GC, CYP2R1, and DHCR7/NADSYN1 were identified as being associated with 25(OH)D levels. Participants with three or four risk alleles of the two variants (GC-rs4588 and CYP2R1-rs10766197) had an increased chance of presenting with a 25(OH)D concentration lower than 20 ng/mL (odds ratio 2.121, 95% confidence interval 1.586–2.836, p = 6.1 × 10−8) compared with those lacking the risk alleles. Each additional copy of a risk allele was significantly associated with a 0.12-fold decrease in the log-25(OH)D concentration (p = 3.7 × 10−12). Haplotype TGA of GC rs705117-rs2282679-rs1491710, haplotype GAGTAC of GC rs842999-rs705120-rs222040-rs4588-rs7041-rs10488854, haplotype CA of GC rs1155563-rs222029, and haplotype AAGA of CYP2R1 rs7936142-rs12794714-rs2060793-rs16930609 were genetic risk factors toward a lower 25(OH)D concentration. In contrast, haplotype TGGGCCC of DHCR7/NADSYN1 rs1790349-rs7122671-rs1790329-rs11606033-rs2276360-rs1629220-rs2282618 were genetic protective factors. The results suggest that the GC, CYP2R1, and DHCR7/NADSYN1 genes might contribute to variability in the serum 25(OH)D levels in a healthy Chinese population in Shanghai. These markers could be used as tools in Mendelian randomization analyses of vitamin D, and they could potentially be drug targets in the Chinese population in Shanghai.

To assess associations of the serum level of 25-hydroxyvitamin D with insulin resistance and β-cell function in a healthy Chinese female population. This cross-sectional study included 1382 female participants free of type 2 diabetes who were recruited in Shanghai. Blood samples were collected within a winter season and the serum levels of 25-hydroxyvitamin D, fasting plasma glucose and insulin, and other biochemical parameters were determined. Insulin resistance and β-cell function were assessed using the homeostasis model assessments of insulin resistance (HOMA-IR) and β-cell function (HOMA-B), respectively. Multiple linear regression analyses adjusted for age, parathyroid hormone, Ca2+ and BMI revealed that independent inverse associations existed between the serum level of 25-hydroxyvitamin D and HOMA-IR (P

Spondyloperipheral dysplasia (SPD; OMIM 271700) is an autosomal dominant connective tissue disorder characterized by vertebral body abnormalities (platyspondyly, end-plate indentations), hip dysplasia and brachydactyly type E. Here, we identified a novel truncating mutation (p.Lys1444AsnfsX27) in the C-propeptide of type II collagen in an affected Chinese individual with SPD. Our findings will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis of SPD but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.

Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease that closely mimics hypertrophic osteoarthropathy secondary to pulmonary or other pathology. The study of PHO provides an opportunity to understand both the pathogenesis of hypertrophic osteoarthropathy and the functions of the underlying genes. PHO is characterized by digital clubbing, periostosis and pachydermia. Two genes are known to be related to PHO: SLCO2A1 and HPGD. Here, we identified a recurrent heterozygous guanine-to-adenine transition at the invariant +1 position of the donor site of intron 7 (c.940+1GA) and a novel heterozygous missense mutation p.Asn534Lys (c.1602CA) in exon 11 of SLCO2A1 in a Chinese young man with PHO. Identification of a novel genotype in PHO will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis of PHO but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.

Background Pyknodysostosis (OMIM 265800 ) is a rare, autosomal recessive sclerosing skeletal dysplasia as a consequence of the diminished capacity of osteoclasts to degrade organic bone matrix. Pyknodysostosis is caused by mutation in the cathepsin K (CTSK) gene. Up to date, 34 different CTSK mutations have been identified in patients with Pyknodysostosis; however, only one mutation was previously identified in a Chinese patient. The objective of this study was to characterize the clinical manifestations and features of Pyknodysostosis and identify the mutation of the causative gene in a Chinese family with Pyknodysostosis. Methods We investigated a non-consanguineous Chinese family in which an 11-year-old child was affected with Pyknodysostosis. Altogether, 203 persons, including the affected individual, his parents and 200 healthy donors, were recruited and genomic DNA was extracted. All 8 exons of the CTSK gene, including the exon–intron boundaries, were amplified and sequenced directly. Results The proband displayed a novel homozygous missense mutation c.365G>A in exon 4 of the CTSK gene. This mutation leads to the substitution of the arginine at position 122 by glutamine (R122Q) in cathepsin K. The parents were heterozygous for this gene mutation, and the mutation was not found in the 200 unrelated controls. Conclusion Our study suggests that the novel missense mutation c.365G>A (R122Q) in exon 4 of CTSK gene was responsible for Pyknodysostosis in the Chinese family.

We previously demonstrated that deficiency of the prostaglandin transporter (SLCO2A1) is a cause of primary hypertrophic osteoarthropathy (PHO). However, its clinical and metabolic characteristics have not been well defined.The objective of the study was to expand this mutational spectrum to better delineate the SLCO2A1 deficiency phenotype and investigate the clinical and metabolic characteristics of a cohort of subjects with PHO.Eleven affected individuals and their available healthy family members from 9 unrelated Chinese families with PHO (7 of which were previously undescribed) were clinically studied. The SLCO2A1 gene was screened and analyzed. Urinary levels of prostaglandin E₂ (PGE₂) and prostaglandin E metabolite (PGE-M) were measured using competitive ELISAs. The serum levels of total T, estradiol, sex hormone-binding protein, LH, FSH, and fasting gastrin were detected.Nine different SLCO2A1 mutations were identified in affected individuals in the 7 previously undescribed families, 7 of which (Glu165X, Ala286GlnfsX35, Gln356AlafsX77, Gly369Asp, Gly379Glu, Glu465Lys, and c.861+2TC) were novel. The urinary levels of PGE₂ and PGE-M were much higher in the SLCO2A1-deficient individuals and decreased with age. There was no relationship between sex hormones and PGE₂ or PGE-M. There was no significant difference in the levels of fasting serum gastrin between PHO patients with watery diarrhea and their relatives.The present findings broaden the allelic spectrum of SLCO2A1 mutations. The urinary levels of PGE₂ and PGE-M in the SLCO2A1-deficient individuals decreased with age. The measurement of the excreted PGE₂ and PGE-M may have implications in the differential diagnosis, treatment, and follow-up of PHO.

PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16) is a cell-autonomous transcriptional component that stimulates the development of brown fat cells. The aim of this study was to investigate the contribution of genetic variants of PRDM16 to obesity-related phenotype variations in Chinese.A total of 3204 subjects (consisting of 400 male-offspring nuclear families, 401 female-offspring nuclear families, and 729 unrelated older males) were recruited. Ten tag single nucleotide polymorphisms (SNPs) within the PRDM16 gene were genotyped using multiplex quantitative real-time PCR by Taqman assay. Body compositions were measured by dual-energy X-ray absorptiometry (DXA). The associations of the SNPs with the obesity-related phenotypes were analyzed using the quantitative transmission disequilibrium test (QTDT), GLM-ANOVA and PLINK statistical methods.Rs2236518 was the only SNP that was associated with BMI in young (aged 20-40 years) males (P=0.011) using QTDT, and in the older men (aged 50-80 years) (P=0.003) using GLM-ANOVA. No significant associations were detected in the females. Nor was a relationship found between any haplotype and obesity-related phenotypes. When PLINK was used, no significant relationship was detected between 10 SNPs and obesity-related phenotypes in any of the studied cohorts.Rs2236518 is associated with BMI in the young males (using QTDT), and the older males (using GLM-ANOVA).However, the result is not confirmed using PLINK. The discrepancy needs to be further addressed.

To analyze the relationship between the reference values of fibrinogen (FIB) in healthy Chinese adults and geographical factors to provide scientific evidences for establishing the uniform standard.The reference values of FIB of 10701 Chinese healthy adults from 103 cities were collected to investigate their relationship with 18 geographical factors including spatial index, terrain index, climate index, and soil index. Geographical factors that significantly correlated with the reference values were selected for constructing the BP neural network model. The spatial distribution map of the reference value of FIB of healthy Chinese adults was fitted by disjunctive kriging interpolation. We used the 5-layer neural network and selected 2000 times of training covering 11 hidden layers to build the simulation rule for simulating the relationship between FIB and geographical environmental factors using the MATLAB software.s The reference value of FIB in healthy Chinese adults was significantly correlated with the latitude, sunshine duration, annual average temperature, annual average relative humidity, annual precipitation, annual range of air temperature, average annual soil gravel content, and soil cation exchange capacity (silt). The artificial neural networks were created to analyze the simulation of the selected indicators of geographical factors. The spatial distribution map of the reference values of FIB in healthy Chinese adults showed a distribution pattern that FIB levels were higher in the South and lower in the North, and higher in the East and lower in the West.When the geographical factors of a certain area are known, the reference values of FIB in healthy Chinese adults can be obtained by establishing the neural network mode or plotting the spatial distribution map.

A previous study shows that bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with bone mineral density (BMD) in 920 European Americans. To determine the association of BMP7 polymorphisms and BMD and osteoporotic fracture susceptibility, we performed a case-control association study in postmenopausal Chinese women with or without osteoporotic fracture.A total of 3815 unrelated postmenopausal Chinese women (1238 with osteoporotic fracture and 2577 healthy controls) were recruited. BMDs of the lumbar spine 1-4 (L1-4) and proximal femur (including total hip and femoral neck) were measured using dual-energy X-ray absorptiometry. Eight tagging single nucleotide polymorphisms (SNPs) in BMP7 gene, including rs11086598, rs4811822, rs12481628, rs6025447, rs230205, rs17404303, rs162316 and rs6127980, were genotyped.Among the 8 SNPs, rs6025447 and rs230205 were associated with total hip BMD (P=0.013 and 0.045, respectively). However, the associations became statistically insignificant after adjusting for age, height and weight. The TGTG haplotype of BMP7 gene was associated with total hip BMD (P=0.032), even after adjusting for age, height and weight (P=0.048); but the association was insignificant after performing the Bonferroni multiple-significance-test correction. Moreover, the 8 SNPs and 9 haplotypes of BMP7 gene were not associated with L1-4 or femoral neck BMD or osteoporotic fracture.This large-sample case-control association study suggests that the common genetic polymorphisms of BMP7 gene are not major contributors to variations in BMD or osteoporotic fracture in postmenopausal Chinese women.

By using whole-exome sequencing, we identified a homozygous guanine-to-adenine transition at the invariant -1 position of the acceptor site of intron 1 (c.97-1GA) in solute carrier organic anion transporter family member 2A1 (SLCO2A1), which encodes a prostaglandin transporter protein, as the causative mutation in a single individual with primary hypertrophic osteoarthropathy (PHO) from a consanguineous family. In two other affected individuals with PHO from two unrelated nonconsanguineous families, we identified two different compound heterozygous mutations by using Sanger sequencing. These findings confirm that SLCO2A1 mutations inactivate prostaglandin E(2) (PGE(2)) transport, and they indicate that mutations in SLCO2A1 are the pathogenic cause of PHO. Moreover, this study might also help to explain the cause of secondary hypertrophic osteoarthropathy.

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by brittle bone fractures. The aim of the present study was to investigate the pathogenic gene mutation spectrum and clinical manifestations of mutations in collagen type I, alpha 1 (COL1A1) and collagen type I, alpha 2 (COL1A2) genes in Chinese patients with OI. A total of 61 unrelated Chinese OI patients with COL1A1 and COL1A2 mutations were recruited. All the exons and the exon-intron boundaries of the COL1A1 and COL1A2 genes were amplified and directly sequenced and lumbar spine bone mineral density was measured by dual‑energy X‑ray absorptiometry. The mutations of the 61 probands included 33 missense mutations, 8 nonsense mutations, 7 splicing variants and 13 frameshift mutations in COL1A1 and COL1A2 genes. A total of 25 novel mutations were identified, including 18 in COL1A1 and 7 in COL1A2. The mutations p.Gly257Arg, p.Gly767Ser and p.Gly821Ser in COL1A1 and p.Gly337Ser in COL1A2 may be located at a mutation hotspot for human OI due to the high repetition rate in OI patients. Family history was positive for OI in 33 probands (54%). All probands had suffered fractures and the most common fracture site was the femur. A total of 49 probands presented with blue sclerae (80.3%), 20 probands suffered from dentinogenesis imperfecta (32.8%) and 1 patient had hearing loss (1.6%). These findings may improve understanding of the pathogenic gene mutation spectrum and the clinical manifestations of mutations of COL1A1 and COL1A2 genes in Chinese patients with OI.

Objective: Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase superfamily, which catalyzes the incorporation of molecular oxygen into polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARG). The activation of the PPARG pathway in marrow-derived mesenchymal progenitors stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to determine whether polymorphisms in the ALOX12 gene were associated with variations in peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. Methods: All six tagging single-nucleotide polymorphisms (SNPs) in the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese nuclear families by allele-specific polymerase chain reaction. The BMD at the lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were measured using dual-energy X-ray absorptiometry. The pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both the individual SNP markers and the haplotypes were tested for an association with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using the quantitative transmission disequilibrium test (QTDT). Results: Using the QTDT, significant within-family association was found between the rs2073438 polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012, respectively). Haplotype analyses were combined with our individual SNP results and remained significant even after correction for multiple testing. However, we failed to find significant within-family associations between ALOX12 SNPs and the BMD at any bone site in young Chinese men. Conclusions: Our present results suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of obesity phenotypes in young Chinese men, although we failed to replicate the association with the peak BMD variation in this sample. Further independent studies are needed to confirm our findings.

To determine the associations between HOXD4 gene polymorphisms with peak bone mineral density (BMD) throughing measuring three tagging single nucleotide polymorphisms (tagSNPs), including rs1867863, rs13418078, and rs4972504, in HOXD4. Four hundred Chinese nuclear families with male offspring (1215 subjects) and 401 Chinese nuclear families with female offspring (1260 subjects) were recruited. BMD of the lumbar spine 1-4 (L1-4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. The quantitative transmission disequilibrium test (QTDT) was performed to investigate the association among the tagging SNPs, haplotypes and peak BMD. Only the CC genotype was identified in rs13418078 in the Chinese population, unlike other populations. We failed to find significant within-family association among these SNPs, haplotypes and peak BMD at any bone site in either male- or female-offspring nuclear families. The results suggest that genetic polymorphisms in HOXD4 may not be a major contributor to the observed variability in peak BMD in the lumbar spine and the hip in Chinese men and women.

Osteoclastic activity is mainly assessed by measurement of urinary markers (eg C-terminal cross-linked telopeptides of type I collagen, N-terminal cross-linked telopeptides of type I collagen etc), the levels of which could often be affected by renal clearance. Recently, serum tartrate-resistant acid phosphatase 5b (TRACP5b) has been used as an alternative serum marker to evaluate osteoclastic activity. We investigated the age-related changes of TRACP5b level and its association with bone mineral density (BMD) in Chinese women. Seven-hundred and twenty-two Chinese mainland women aged 20–79 years were recruited in the study. Serum TRACP5b level was measured using immunoassay to evaluate the state of bone resorption. Bone mineral density (BMD) (g/cm2) at lumbar spine 1–4 and proximal femur were measured by duel-energy X-ray absorptiometry. The serum TRACP5b level reached a bottom value in premenopausal women aged 30–39, gradually increased in women aged 40–49, rapidly rose in women aged 50–59, and culminated with a maximum value in women aged 60–69 before a slow drop in women aged 70–79. The average level of TRACP5b was significantly higher in postmenopausal women [(3.29±1.07) U/L] than in premenopausal women ([1.70±0.59] U/L). The levels of TRACP5b were inversely correlated with BMD at all measured sites (P

Inactivating mutations in phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) have been identified as a cause of X-linked hypophosphatemic rickets (XLH; OMIM 307800). In the present study, we enrolled 43 patients from 18 unrelated families clinically diagnosed with hypophosphatemic rickets and 250 healthy controls. For each available individual, all 22 exons with their exon-intron boundaries of the PHEX gene were directly sequenced. The levels of serum fibroblast growth factor 23 (FGF23) were measured as well. Sequencing analysis detected 17 different PHEX gene mutations, and 7 of these were identified as novel: 3 missense mutations, including c.304G>A (p.Gly102Arg) in exon 3, c.229T>C (p.Cys77Arg) in exon 3 and c.824T>C (p.Leu275Pro) in exon 7; 2 deletion mutations, including c.528delT (p.Glu177LysfsX44) in exon 5 and c.1234delA (p.Ser412ValfsX12) in exon 11; and 2 alternative splicing mutations, including c.436_436+1delAG in intron 4 at splicing donor sites and c.1483-1G>C in intron 13 at splicing acceptor sites. Moreover, 6 mutations were proven to be de novo in 6 sporadic cases and the probands were all females. No mutations were found in the 250 healthy controls. The serum levels of FGF23 varied widely among the patients with XLH, and no significant difference was found when compared with those of the healthy controls. On the whole, the findings of this study provide new insight into the spectrum of PHEX mutations and provide potential evidence of a critical domain in PHEX protein. In addition, the finding of an overlap of the serum FGF23 levels between the patients with XLH and the healthy controls indicates its limited diagnostic value in XLH.

Pseudoachondroplasia (PSACH; MIM no. 177170) is an autosomal dominant osteochondrodysplasia characterized by short‑limb short stature, brachydactyly and early‑onset osteoarthropathy. Typically, at approximately two years of age, the rate of growth falls below the standard growth curve, causing a moderately severe form of disproportionate short‑limb short stature. The current study described the clinical and radiographic observations of six Chinese patients with PSACH, and identified two de novo novel missense mutations [p.Asp326Asn (c.976G>A) and c.1585A>G (p.Thr529Ala)] in cartilage oligomeric matrix protein (COMP) in the patients. The current study expanded the mutation spectrum of the COMP gene, and contributes to the understanding of phenotype/genotype of COMP‑associated diseases.

Oral risedronate is effective in the treatment of postmenopausal osteoporosis when administered daily, weekly, or monthly. In this 1-year, randomized, double-blind, multicenter study we compared the weekly 35-mg and daily 5-mg risedronate dosing regimens in the treatment of Chinese postmenopausal women with osteoporosis or osteopenia.Postmenopausal women with primary osteoporosis or osteopenia were randomly assigned to the weekly group or daily group (n=145 for each) that received oral risedronate 35 mg once a week or 5 mg daily, respectively, for 1 year. The subjects' bone mineral densities (BMDs), bone turnover markers (P1NP and β-CTX), new vertebral fractures, and adverse events were assessed at baseline and during the treatments.All subjects in the weekly group and 144 subjects in the daily group completed the study. The primary efficacy endpoint after 1 year, ie the mean percent changes in the lumbar spine BMD (95% CI) were 4.87% (3.92% to 5.81%) for the weekly group and 4.35% (3.31% to 5.39%) for the daily group. The incidences of clinical adverse events were 48.3% in the weekly group and 54.2% in the daily group.The weekly 35-mg and daily 5-mg risedronate dosing regimens during 1 year of follow-up show similar efficacy in improving BMDs and biochemical markers of bone turnover in Chinese postmenopausal women with osteoporosis or osteopenia. Moreover, the two dosing regimens exhibit similar safety and tolerability.

Calcification of joints and arteries (CALJA; MIM 211800) is an extremely rare mendelian disorder of isolated calcification that is characterized by late onset calcification of the extremity arteries and hand and foot joint capsules. Mutations of NT5E, encoding cluster of differentiation 73, have been implicated in CALJA. Here we report on a Chinese family with CALJA and novel compound heterozygous mutations (c.1360G>A (p.Gly454Arg) and c.1387C>T (p.Arg463X)) in NT5E. Our study represents the second report on patients with CALJA associated with NT5E mutations. The clinical features expand the previously reported phenotype of NT5E mutations. The propositus has calcification of the lower extremity arteries and hand and foot joint capsules similar to those previously reported patients. However, he also has calcification of the upper extremity arteries. By protein structural modeling, we found the mutation p.Gly454Arg may disrupt the folding of β-pleated sheet and destabilize the protein structure. Our findings will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.

Aim: To establish bone mineral density (BMD) reference database in healthy Chinese men of Han ethnicity, and to estimate the prevalence of osteoporosis in the population. Methods: The BMD in the lumbar spine 1-4 (L1-4) and proximal femur was measured using dual energy X-ray absorptiometry in a total of 1 385 healthy Chinese men of Han ethnicity aged 20–89 years old in Shanghai. Results: The highly significant negative correlation between age and BMD at any sites of proximal femur was found in the studied population, wheras no correlation between age and BMD at lumbar spine was observed. The peak BMD of the lumbar spine and any sites of hip in Chinese men was defined as the mean BMD for the subjects aged 20–39 years. According to World Health Organization (WHO) criteria, the BMD cut-off values for osteoporosis of the L1-4, total hip, femoral neck, trochanter and intertrochanter in Chinese men are 0.719, 0.638, 0.575, 0.437 and 0.725 g/cm 2 , respectively. Using the current Chinese reference data, the prevalence of osteoporosis at the L1-4, total hip, femoral neck, trochanter and intertrochanter is 5.4%, 3.8%, 6.3%, 1.8% and 2.8% in 1 084 men aged 50 years or older, respectively. However, using a database for US non-Hispanic white men (NHANES III), the prevalence of osteoporosis or osteopenia at any sites of the hip was significantly higher than that while using the current Chinese reference data. Conclusion: The BMD reference database was established in healthy Chinese men of Han ethnicity, and will facilitate more accurate diagnosis of osteoporosis in Chinese men. (Asian J Androl 2006 Jul; 8: 419–427)

To investigate the possible association of Q89R, N740N and A1330V polymorphisms in low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD) in postmenopausal Chinese women. Q89R, N740N and A1330V genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 647 unrelated healthy postmenopausal Han Chinese women aged 43–76 years in Shanghai. BMD at lumbar spine 1–4 and the left proximal femur including the femoral neck, trochanter and Ward's triangle were measured by dual-energy X-ray absorptionmetry in all subjects. The distribution of the Q89R, N740N and A1330V genotypes in this population was as follows: QQ 80.5%, QR 18.7%, and RR 0.8%; TT 66.9%, TC31.1%, and CC2.0%; AA 68.0%, AV 29.7%, and VV 2.3%. The frequencies of the Q89R, N740N and A1330V genotypes and alleles did not deviate from the Hardy-Weinberg equilibrium. We found that the Q89R and A1330V polymorphisms were in linkage disequilibrium in our population (χ2=13.50, P

Ellis-van Creveld syndrome (EvC) is a rare autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth. It is caused by biallelic mutations in the EVC or EVC2 gene. Here, we identified a novel nonsense mutation p.W828X (c.2484G>A) in exon 14 and a recurrent nonsense mutation p. R399X (c.1195C>T) in exon 10 of EVC2 gene in a Chinese boy with EvC. Identification of a novel genotype in EvC will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis of EvC but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.

PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor alpha gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-alpha gene may have some minor effects on PBM variation in the Chinese population. Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor alpha (ER-alpha) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER-alpha gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER-alpha XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER-alpha with the hip PBD variation. In conclusion, this study suggests that the ER-alpha gene may have minor effects on PBD variation in our Chinese population.

Osteocalcin, a biochemical marker of bone formation, has been suggested to be involved in the regulation of energy metabolism. The aim of this study was to investigate the possible association between serum osteocalcin and markers of glucose and lipid metabolism in a large sample of healthy Chinese women.A total of 2032 healthy Chinese women in Shanghai, aged 20-94 (including 1396 discovery-study subjects and 636 postmenopausal women for a reduplication analysis) were recruited. Their serum osteocalcin, calcium and the relevant measurements were analyzed. A Spearman correlation analysis was performed between osteocalcin and the other markers of energy metabolism including triglyceride, total cholesterol, fasting plasma glucose (FPG), serum insulin, body mass index and homeostasis model assessment-insulin resistance. Separate multiple regression analyses were performed with data from the discovery and reduplication subjects to determine whether serum osteocalcin concentration was an independent predictor of the glucose or lipid metabolism markers.For the discovery-study subjects, serum osteocalcin was found to be negatively associated with weight (r=-0.08, P=0.002), BMI (-0.13, P0.001) and FPG (r=-0.13, P=0.001). Similar results were also found in the reduplication subjects (weight: r=-0.19, P=0.016; BMI: r=-0.23, P=0.003; FPG: r=-0.28, P0.001). In the multiple regression analysis, serum osteocalcin was revealed as a potential independent predictor for FPG (β=-0.07 and -0.210 for discovery and reduplication, respectively, P0.01) and BMI (β=-0.127 and -0.299 for discovery and reduplication, respectively, P0.01).Serum osteocalcin is negatively associated with weight BMI and FPG in healthy Chinese women. Therefore, osteocalcin might contribute to obesity and diabetes.

OBJECTIVE: X-linked dominant hypophosphatemia (XLH) is the most prevalent form of inherited rickets/osteomalacia in humans. The aim of this study was to identify PHEX gene mutations and describe the clinical features observed in 6 unrelated Chinese families and 3 sporadic patients with hypophosphatemic rickets/osteomalacia. METHODS: For this study, 45 individuals from 9 unrelated families of Chinese Han ethnicity (including 16 patients and 29 normal phenotype subjects), and 250 healthy donors were recruited. All 22 exons and exon-intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: The PHEX mutations were detected in 6 familial and 3 sporadic hypophosphatemic rickets/osteomalacia. Altogether, 2 novel mutations were detected: 1 missense mutation c.1183G>C in exon 11, resulting in p.Gly395Arg and 1 missense mutation c.1751A>C in exon 17, resulting in p.His584Pro. No mutations were found in the 250 healthy controls. CONCLUSIONS: Our study increases knowledge of the PHEX gene mutation types and clinical phenotypes found in Chinese patients with XLH, which is important for understanding the genetic basis of XLH. The molecular diagnosis of a PHEX genetic mutation is of great importance for confirming the clinical diagnosis of XLH, conducting genetic counseling, and facilitating prenatal intervention, especially in the case of sporadic patients.