Prevalence of osteoporosis and related factors in postmenopausal women aged 40 and above in China / 中华流行病学杂志

Objective: To understand the prevalence of osteoporosis and related factors in postmenopausal women aged ≥40 years in China and provide scientific evidence for osteoporosis prevention and control. Methods: Data of this study were from the 2018 China Osteoporosis Epidemiological Survey, covering 44 counties (districts) in 11 provinces in China. Related variables were collected by questionnaire survey and physical measurement, and the BMD of lumbar spine and proximal femur was measured by dual-energy X-ray absorption method. The prevalence of osteoporosis and its 95%CI in postmenopausal women aged ≥40 years were estimated with complex sampling weights. Results: A total of 5 728 postmenopausal women aged ≥40 years were included in the analysis and the prevalence of osteoporosis was 32.5% (95%CI: 30.3%-34.7%). The prevalence of osteoporosis in postmenopausal women aged 40-49 years, 50-59 years, 60-69 years, 70-79 years, and ≥80 years were 16.0% (95%CI:4.5%-27.5%), 18.4% (95%CI:15.9%-20.8%), 37.5% (95%CI:34.5%-40.4%), 52.9% (95%CI: 47.5%-58.3%), and 68.0% (95%CI:55.9%-80.1%) respectively. The prevalence of osteoporosis was higher (P<0.001) in those with education level of primary school or below (47.2%, 95%CI: 43.0%-51.3%) and in those with individual annual income less than 10 000 Yuan, (40.3%, 95%CI: 36.9%-43.7%). The prevalence of osteoporosis was 35.1% in rural areas (95%CI: 32.0%-38.1%), which was higher than that in urban areas (P<0.001). The prevalence of osteoporosis in low weight, normal weight, overweight and obese groups were 69.9% (95%CI: 59.0%-80.8%), 42.2% (95%CI: 38.7%-45.7%), 24.2% (95%CI: 21.3%-27.1%) and 14.6% (95%CI: 11.1%-18.0%), respectively. The prevalence of osteoporosis in those with menstrual maintenance years ≤30 years and in those with menopause years ≥11 years were 46.1% (95%CI:40.8%-51.3%) and 48.2% (95%CI:45.0%-51.3%), respectively. Multivariate logistic analysis showed that age ≥60 years, education level of primary school or below, annual household income per capita less than 10 000 Yuan, low body weight, menstrual maintenance years ≤30 years, menopause years ≥11 years were risk factors of osteoporosis in postmenopausal women in China. Conclusions: The prevalence of osteoporosis was high in postmenopausal women aged ≥40 years in China, and there were differences in osteoporosis prevalence among different socioeconomic groups. Effective interventions should be taken for the prevention and control of osteoporosis in key groups in the future.

Genotype-phenotype relationship in a large cohort of osteogenesis imperfecta patients with COL1A1 mutations revealed by a new scoring system / 中华医学杂志(英文版)

BACKGROUND@#Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen. This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI.@*METHODS@#A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study. The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing. A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed. The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses.@*RESULTS@#Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel. These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen. Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs. 218 [136, 284] U/L, P = 0.009) and higher clinical score (12.2 ± 5.3 vs. 7.4 ± 2.4, P < 0.001), denoting more severe phenotypes including shorter stature, lower bone mineral density, higher fracture frequency, more bone deformity, vertebral compressive fractures, limited movement, and dentinogenesis imperfecta (DI). Patients would not present with DI if the glycine substitutions happened before the 79th amino acid in triple helix of α1 chains.@*CONCLUSIONS@#This presented distinctive COL1A1 mutation spectrum in a large cohort of Chinese patients with OI. This new quantitative analysis of genotype-phenotype correlation would be helpful to predict the prognosis of OI and genetic counseling.

A homozygous mutation in TMEM38B causes rare osteogenesis imperfecta type XIV / 基础医学与临床

Objective To investigate the phenotype of a boy with osteogenesis imperfecta(OI)and detect the path-ogenic gene mutation in his family.Methods The clinical data of a uygur ethnic boy was investigated in detail, who suffered from early onset repeated fragile fractures.Bone turnover biomarkers, bone mineral density(BMD) and bone morphology were evaluated.The pathogenic mutations in this patient were investigated by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing.Results Serum β-cross linked C-te-lopeptide of type Ⅰcollagen was elevated.Radiological assessment revealed a generalized osteoporosis in thoraco-lumbar spine,slender long bone with thin cortices.The pathogenic mutations in TMEM38B were detected as follow:a homozygous mutation c.507G>A transition in exon 4,which would generate a new downstream termination codon (p.W169X).His parents were heterozygous carriers of the mutation.Conclusions Mutation in TMEM38B is iden-tified for the first time in a uygur ethnic boy with extremely rare autosomal recessive OI type XIV.The clinical and genetic findings expands our understanding of rare OI induced by TMEM38B mutation.

Association of GNA11 gene polymorphisms with idiopathic hypoparathyroidism and its complications / 基础医学与临床

Objective To investigate the association of GNA 11 gene polymorphisms with idiopathic hypoparathyroidism (IHP) and its complications. Methods Two hundred and three patients with IHP and 209 control subjects were recruited at Peking Union Medical College Hospital from December 1987 to December 2015. The GNA11 gene polymorphisms were selected and genotyped by Sequenom MassArray iPLEX system.Results The minor allele T of rs308060 was associated with an increased risk of IHP in the additive [OR = 2.505(1.005-6.245) , P＜0.05; OR=3.269(1.264-8.458), P＜0.05]and recessive model[OR= 2.727(1.105-6.727), P＜0.05]. Although no significant difference was found in the incidence of intracranial calcification and cataract in IHP patients, the haplotype CTCGCT consisting of minor allele T of rs308060 was correlated with their 24 hours urinary calcium levels (β = 0. 186, P＜0.05). Conclusions The minor allele T of rs308060 in GNA11 means high risk of IHP, and is positively correlated with urinary calcium excretion in IHP patients after treatment with oral calcium and vitamin D analogs supplements.

Clinical features of hereditary distal renal tubular acidosis and SLC4A1 gene mutation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of two families with distal renal tubular acidosis (dRTA) and mutations in the pathogenic gene SLC4A1.</p><p><b>METHODS</b>Family investigation, medical history collection, and measurement of biochemical parameters were performed to analyze the clinical phenotype and genetic characteristics of dRTA. Direct sequencing was used to detect SLC4A1 gene mutations.</p><p><b>RESULTS</b>Three patients in these two families (two of them were mother and son) were diagnosed with dRTA with typical clinical features, including short stature, metabolic acidosis, alkaline urine, hypokalemia, and nephrocalcinosis. SLC4A1 gene analysis showed that all the three patients had a pathogenic missense mutation R589H (c.1766G>A). The child in family 1 had a de novo mutation of SLC4A1, and the child in family 2 had an SLC4A1 gene mutation inherited from the mother, which met the characteristic of autosomal dominant inheritance.</p><p><b>CONCLUSIONS</b>This study reports the R589H mutation in SLC4A1 gene in families with hereditary dRTA for the first time in China. Clinical physicians should perform gene detection for patients suspected of hereditary dRTA to improve the diagnosis and treatment of this disease.</p>

Association Between Geranylgeranyl Pyrophosphate Synthase Gene Polymorphisms and Bone Phenotypes and Response to Alendronate Treatment in Chinese Osteoporotic Women / 中国医学科学杂志(英文版)

Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women.Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed.Results rs10925503 polymorphism of GGPPS gene was correlated to serum β-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype (all P<0.05). No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly (P<0.01), and without obvious differences between the low dose and standard dose groups (all P>0.05). However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels (all P>0.05).Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.

Expression of Ki-67, galectin-3, fragile histidine triad, and parafibromin in malignant and benign parathyroid tumors / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Our study aimed to investigate the differential expression of Ki-67, galectin-3, fragile histidine triad (FHIT) gene, and parafibromin in PC, parathyroid adenoma (PA), parathyroid hyperplasia (PH), and normal parathyroid (NP) tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors.</p><p><b>METHODS</b>Data of 15 cases with PC, 19 PAs, and 8 PHs were retrospectively analyzed for their clinical characteristics. The expression of Ki-67, galectin-3, FHIT, and parafibromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control.</p><p><b>RESULTS</b>Complete loss of parafibromin expression was seen in 9 of 15 (60%) carcinomas, and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one (4%) adenoma. Galectin-3 staining was positive in 11 of 15 (73%) carcinomas, 5 of 19 (26%) adenomas, 1 of 8 (12%) hyperplasias, and 0 of 6 normal tissues. The Ki-67 proliferative index was high in 4 of 15 (27%) carcinomas, 1 of 19 (5%) adenomas, and none of the hyperplasia or normal tissues. FHIT expression did not differ appreciably among the tumor types. The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87%, while the specificity of both positive galectin-3 and positive Ki-67 could reach 100%.</p><p><b>CONCLUSIONS</b>These data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors. And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.</p>

Comparison of whole body diffusion weighted magnetic resonance imaging and somatostatin receptor scintigraphy for oncogenic osteomalacia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the accuracy of whole body diffusion weighted magnetic resonance imaging (WB-DWI) with that of somatostatin receptor scintigraphy (SRS) in the detection and localization of the lesions in patients with oncogenic osteomalacia (OOM).</p><p><b>METHODS</b>Totally 6 patients with clinically suspected oncogenic osteomalacia were enrolled. All of them underwent WB-DWI and SRS within 2 weeks to evaluate the possible presence of tumors that lead to osteomalacia. Surgical and pathological findings were considered as the gold standard. The sensitivity, specificity, and accuracy were calculated.</p><p><b>RESULTS</b>Pathology confirmed the diagnosis of two soft tissue tumors (including 1 angiolipoma and 1 mesenchymal tumor) and one bone tumor of malignant neurofibroma. The sensitivity, specificity, and accuracy in the identification of lesions in patients with oncogenic osteomalacia were 33.33%, 100%, 66.67% for WB-DWI and 33.33%, 66.67%, 50% for SRS (P>0.05).</p><p><b>CONCLUSION</b>For adult patients with osteomalacia, WB-DWI and SRS can provide mutually supportive data and be used for identifying potential oncogenic osteomalacia.</p>

Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of autosomal recessive polycystic kidney disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disease, which is a disorder with multiple organ involvement, mainly the kidney and liver. It is caused by mutations in the PKHD1 gene. Here, we reported the clinical characteristics of a case with ARPKD and analyze the genetic features of this patient as well as of his father using targeted exome sequencing and Sanger sequencing.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes obtained from a patient with ARPKD. The mutations were identified using exome sequencing and confirmed by Sanger sequencing.</p><p><b>RESULTS</b>The patient was diagnosed as ARPKD based on ultrasonography and abdominal computed tomography which showed polycystic changes, multiple calcinosis of both kidneys, and multiple dilated bile ducts of the liver. Compound heterozygous PKHD1 gene mutations A979G and G5935A, which lead to substitution of an asparagine for an aspartate at amino acid 327 (N327D) and a glycine for an arginine at amino acid 1979 (G1979R) respectively, were identified using targeted exome sequencing and confirmed by Sanger sequencing for the patient. In addition, the father of the patient was identified to be a carrier of heterozygous A979G mutation of this gene.</p><p><b>CONCLUSIONS</b>We identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD. Targeted exome sequencing is suitable for genetic diagnosis of single-gene inherited diseases like ARPKD in which the pathogenic gene is a large.</p>

Benefit of infusions with ibandronate treatment in children with osteogenesis imperfecta / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteogenesis imperfecta (OI) is a rare bone disease and its effective treatment is relatively deficient. We tried to assess the effects of new bisphosphonate, ibandronate on children with OI.</p><p><b>METHODS</b>In this open-label, prospective, controlled study, 30 children with OI were enrolled. They received either infusions of ibandronate (2 mg) in every three months or oral calcitriol 0.25 µg daily for 24 months. All patients took 500 mg calcium plus 200 U vitamin D daily together. The endpoints were the change of annual new fracture rate (observed by case history and X ray films of spine), bone mineral density (BMD, measured by dual energy X-ray absortiometry), serum concentration of carboxy-telopeptide cross-links of type I collagen (CTX, bone resorption marker) and alkaline phosphatase (ALP, bone formation marker) during the follow-up.</p><p><b>RESULTS</b>After the cyclic infusions of ibandronate, the annual new fracture rate was significantly decreased from 1.9 to 0.13 time, obviously lower than that of calcitriol group, which decreased from 1.8 to 1.0 time after the treatment (P < 0.001). The significant increase of BMD at the lumbar spine, femoral neck, trochanter, total hip was found in the group of ibandronate by 59.0%, 42.0%, 47.5% and 36.6% in time dependent manner (compared with the baseline, P < 0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P < 0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P < 0.001). The tolerance of the children to ibandronate was quite well. Mild fever and muscle pain were found in 9 cases within 1 - 3 days after the first infusion of ibandronate, which could relieve after 1 - 2 days without special management.</p><p><b>CONCLUSIONS</b>The benefits of cyclic infusions of ibandronate to children with OI are significant because ibandronate could significantly reduce annual bone fracture rate, increase lumbar and hip BMD, preserve vertebral morphometry of patients through inhibition of bone resorption.</p>

Levels and dynamic changes of serum fibroblast growth factor 23 in hypophosphatemic rickets/osteomalacia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast growth factor 23 (FGF-23) in the regulation of phosphate homeostasis, we measured the circulating concentrations of this growth factor in healthy individuals and in patients with hypophosphatemic rickets/osteomalacia.</p><p><b>METHODS</b>Nineteen patients with hypophosphatemic rickets/osteomalacia were included in hypophosphatemic group (HP, 12 female and 7 male, mean age was 30 years), and 19 healthy age-matched individuals served as the control group. Full length FGF-23 fragments were measured by two-site enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Mean FGF-23 concentrations were significantly higher in the HP group ((87.4 +/- 43.6) pg/ml) compared with the control group ((19.2 +/- 6.16) pg/ml; P < 0.001). In 1 patient with tumour-induced osteomalacia, serum FGF-23 concentrations were 84.1 pg/ml; these concentrations were normalized 2 hours after a hemangiopericytoma resection (7.8 pg/ml). Subsequently, serum 1,25(OH)(2) vitamin D3 concentrations significantly increased from 21.3 pg/ml to 89.3 pg/ml, and serum phosphorus levels were normalized.</p><p><b>CONCLUSIONS</b>Serum FGF-23 concentrations were markedly elevated in patients with hypophosphatemic rickets. FGF-23 plays an important role in the pathogenesis of hypophosphatemic rickets/osteomalacia.</p>

Treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism with domestic-made calcitriol: a prospective and self-controlled clinical trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these patients. Here we reported a prospective and open-label trial to investigate the efficacy and safety of domestic-made calcitriol in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism.</p><p><b>METHODS</b>Twenty-four patients with confirmed hypoparathyroidism or pseudohypoparathyroidism aged (36.5 +/- 11.0) years old were studied. Among them, 16 patients had idiopathic hypoparathyroidism, 2 had pseudohypoparathyroidism and 6 had hypoparathyroidism secondary to cervical surgery. Serum calcium levels were lower than 1.88 mmol/L. Oral calcitriol was administered twice or three times with elemental calcium 1.2 g per day. All patients were followed every 4 weeks throughout the 12-week period. Dose adjustments of calcitriol were based on serum and urinary calcium levels and symptoms of hypocalcemia.</p><p><b>RESULTS</b>Twenty patients were included by the end of this study. Muscular weakness, cramps, extremity paresthesia, Chovestek's sign and Trousseau's sign were relieved in 76.9%, 100%, 94.4%, 93.3% and 78.9% of patients, respectively. Serum calcium, plasma ionized calcium and serum phosphorus levels were (1.54+/-0.25) mmol/L, (0.64+/-0.10) mmol/L and (2.00+/-0.46) mmol/L at baseline, and reached (2.20+/-0.20) mmol/L, (0.95+/-0.06) mmol/L and (1.68+/-0.25) mmol/L (P<0.01) at the 12th week of treatment, respectively. Eighty percent of patients were assessed as effective and 20% as partly effective. Three, four and eight patients had hypercalciuria at the 4th, 8th and 12th week of treatment, respectively, which were reduced by thiazide diuretics. The final dose of calcitriol was (1.09+/-0.50) microg/d.</p><p><b>CONCLUSIONS</b>Calcitriol combined with calcium can be used in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism effectively and safely. Serum and urinary calcium levels should be monitored during the course of the therapy.</p>

Effect of fibroblast growth factor 9 on Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibroblast growth factor 9 (FGF9), expressed in brain, kidney and developing skeletal tissues, can physiologically inhibit endochondral ossification; but little is known about how FGF9 affects osteoblasts and its detailed regulatory mechanism. Here we examined the effect of FGF9 on the activity of the murine Runt-related transcription factor 2 (Runx2) gene promoter in preosteoblast MC3T3-E1 and premyoblast C2C12 cells.</p><p><b>METHODS</b>Plasmids containing the Runx2 promoter region were transfected into MC3T3-E1 and C2C12 cells and stably transfected cell lines were established. The method of luciferase reporter gene activation was used to examine the effects of FGF9 on the promoter activity.</p><p><b>RESULTS</b>FGF9 (10 ng/ml) increased Runx2 promoter activity in MC3T3-E1 cells. When MC3T3-E1 cells were treated with FGF9 plus the various inhibitors or activator of the intracellular signaling transducation pathways, including 10 micromol/L U0126 (the inhibitor of mitogen-activated protein kinase kinase), 10 micromol/L SB203580 (the inhibitor of p38/mitogen activated protein kinase), or 1 micromol/L C6 ceramide (an activator of mitogen activated protein kinase), the luciferase expression did not change significantly compared with that of the cells treated with FGF9 only. However, when C2C12 cells were treated with 10 ng/ml FGF9, Runx2 gene promoter activity first decreased and then increased over a period of 1 to 5 days. Among the above inhibitors, only U0126 (10 micromol/L) completely blocked the effects of FGF9 on Runx2 gene promoter activity.</p><p><b>CONCLUSIONS</b>Our data showed that FGF9 can affect Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells. The action of FGF9 appears to depend partly on the mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathways in C2C12 cells.</p>

RET gene cys 634 trp mutation in a multiple endocrine neoplasia type 2A kindred / 中国医学科学院学报

<p><b>OBJECTIVE</b>To identify the genotype of RET gene in one multiple endocrine neoplasia type 2A (MEN2A) kindred.</p><p><b>METHODS</b>Genome DNA was extracted from peripheral blood leucocytes. The DNA sequence of gel-purified polymerase chain reaction (PCR) products was determined with the previously reported 6 pairs of primers of PCR amplification of 10, 11, 13, 14, 15, and 16 exons of RETgene.</p><p><b>RESULTS</b>No abnormalities were found in exon 10, 13, 14, 15, and 16. C to G replacement in nucleotide 14 996 of exon 11 was identified in DNA samples obtained from both peripheral blood of 2 affected brothers. This missense point mutation arisen in heterozygosity and caused a substitution of Cys to Trp residue at codon 634 ( Cys 634 Trp) in RET protein.</p><p><b>CONCLUSION</b>The genotype of the family is identified as Cys 634 Trp substitution of RET gene.</p>

Effects of different human parathyroid hormone 1-34 administration on SaoS-2 cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effects of different human parathyroid hormone 1-34 (hPTH1-34) administration on SaoS-2 cells, and explore the mechanism of bone formation improvement.</p><p><b>METHODS</b>Each cycle covered 48 h. SaoS-2 cells were continuously or intermittently stimulated by 50 ng/ml hPTH1-34 for 1, 3, 6, 12, and 24 h in each cycle. Total RNA was extracted by Trizol kit. Alkaline phosphatase (ALP), osteocalcin or bone Gla-containing protein (BGP) and cyclic adenosine monophosphate (cAMP) levels were measured by chemical method, radioimmunoassay and competitive protein binding method, respectively. c-fos gene expression was semi-quantified by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>ALP level was time-dependently increased in 1, 3 and 6 h stimulation, especially in 3 and 6 h (compared with control, P < 0.01; P < 0.05 or P < 0.01 compared with continuous stimulation). The cAMP level was time-dependently increased in 3 and 6 h incubation (P < 0.05 compared with control and continuous stimulation). Intermittent hPTH1-34 stimulation had more effects on cAMP level than continous action (P < 0.001). hPTH1-34 intermittent stimulation of 1, 3, and 6 h enhanced c-fos gene expression time-dependently.</p><p><b>CONCLUSIONS</b>Intermittent hPTH1-34 stimulation has a stronger effect on osteoblast than continuous action, especially in 3, 6 h in each cycle intermittent stimulation. The synchronous responses of c-fos, ALP and cAMP to hPTH1-34 suggest that hPTH1-34 affect Saos-2 cells through cAMP dependent protein kinase A (PKA) pathway and c-fos gene paly an important role.</p>

Association of polymorphisms of vitamin D receptor gene start codon and 3'-end region with bone mineral density in postmenopausal women / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine whether vitamin D receptor(VDR) gene start codon polymorphisms and 3'-end region polymorphisms exerted a combined influence on bone mineral density(BMD) in Han postmenopausal women in Beijing area.</p><p><b>METHODS</b>The VDR Fok I and 3'-end region genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 110 unrelated postmenopausal women. BMD was measured at the lumbar spine (L(2-4)), femoral neck(Neck), Ward's triangle(Ward's) and trochanter (Troch) using duel-energy X-ray absorptiometry.</p><p><b>RESULTS</b>The frequencies distribution of Fok I, Apa I, Bsm I and Taq I alleles in this cohort all followed the Hardy-Weinberg equilibrium. No significant association of Fok I, Apa I or Taq I genotype with BMD in postmenopausal women was found when these polymorphisms were considered independently, except for Bsm I genotype. When a combined analysis of VDR gene Fok I and 3'-end region polymorphisms was carried out, cross-genotyping Fok I and Apa I polymorphisms was significantly associated with BMD at the L(2-4) (P<0.001), and cross-genotype of Fok I and Taq I was also significantly associated with BMD at the Neck and Troch sites (P<0.05). However, cross-genotyping Fok I and Bsm I polymorphisms was not significantly associated with BMD. Cross-genotyping Apa I and Bsm I or Taq I polymorphisms was not associated with BMD in postmenopausal women, either.</p><p><b>CONCLUSION</b>Although Fok I polymorphisms of VDR gene were not significantly associated with BMD in postmenopausal women, VDR gene Fok I and 3'-region polymorphisms (Apa I and Taq I) had a combined effect on the BMD in postmenopausal women.</p>

Steroids hormone and bone / 中国医学科学院学报

Bone is an active tissue in which the processes of remodeling are continuous to ensure normal bone integrity and strength. Steroids play an important role in regulating bone growth, development and remodeling. Glucocorticoids excess will induce bone damages especially osteoporosis. Otherwise, estrogen and androgen are bone protective steroids in both female and male. To develop a new selective steroid receptor modulator is one of the targets in future study to treat osteoporosis.

Changes of urinary deoxypyridinoline crosslink/creatinine in rats after ovariectomy and anti-osteoporotic intervention / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the changes of urinary deoxypyridinoline crosslink/creatinine (UDpd/Cr) in rats after OVX and intervention by estrogen and bisphosphonate and investigate the possible application of deoxypyridinoline in osteoporosis diagnosis and treatment.</p><p><b>METHODS</b>40 female 6-month-old virginal Wistar rats were divided into 5 groups, ovariectomized or sham ovariectomized. (1) Ovxb (n = 8): sacrificed at 6 weeks after OVX; (2) Sham (n = 8): sham ovariectomized; (3) Ovxe (n = 8): sacrificed at 14 weeks after OVX; (4) O + E (n = 9):OVX + 17 beta estradiol [20 micrograms/(kg.d) ih]; (5) O + C (n = 7):OVX + cimadronate [0.2 mg/(kg.d)]; Treatment started 6 weeks after OVX and lasted 8 weeks. Rats in group 2-5 were sacrificed at 14 weeks after OVX. Urinary and serum biochemical parameters were measured, pQCT scanning of femur, bone biomechanical test in femur were determined.</p><p><b>RESULTS</b>OVX resulted in increasing of UDpd/Cr 133.3% (P < 0.01). The ratio of UCa/Cr also increased in OVX groups but without any significant compared with Sham (P > 0.05). UDpd/Cr were reduced by 54.6% and 51.8% (P < 0.01) in O + E, O + C group respectively compared with Ovxe. The significant negative correlationships were found between UDpd/Cr and bone mass, BMD and biomechanic characteristics.</p><p><b>CONCLUSIONS</b>UDpd/Cr ratio is a sensitive bone resorption marker, a marked changes were observed when the rats ovariectomized or treated with estradiol and cimadronate. There were best correlation between UDpd/Cr and bone mineral density and bone biomechanic characteristics. It is fair to apply UDpd/Cr ratio for osteoporosis diagnosis and treatment.</p>

Assessment of preoperative localization techniques for patients with primary hyperparathyroidism / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the sensitivity and usefulness of 99mTc-sestamibi scintigraphy (SS) and neck ultrasonography (US) as preoperative localization procedures in patients with primary hyperparathyroidism (pHPT).</p><p><b>METHODS</b>160 patients with proved pHPT in Peking Union Medical College Hospital from June 1983 to June 2002 were studied. There were 107 women(66.9%) and 53 men (33.1%), with a mean age of 38.9 years (10-73 years). 100 patients were underwent SS and 148 patients were underwent US prior to surgery, and the results were compared with operative and histological findings.</p><p><b>RESULTS</b>The sensitivity of SS and US in localization of the enlarged parathyroid glands was 94.0% and 85.1% respectively, and the positive predictive value of SS and US was 100% and 89.1% respectively, the overall sensitivity was 98.9% by combination of SS and US. In solitary parathyroid adenomas group (n = 145), the sensitivity of SS and US was 93.3% and 84.7% respectively; There was no significant difference (P = 0.428) in sensitivity of SS between the parathyroid glands correctly identified and undetected in classical neck location as compared with ectopic parathyroid glands, whereas significantly (P = 0.026) influenced by the US sensitivity.</p><p><b>CONCLUSIONS</b>Different sensitivity exit between SS and VS in preoperative localization in patients with pHPT undergoing parathyroidectomy. The combined use of SS and US could increase the sensitivity of localization technique. Ectopic parathyroid had no influence on the sensitivity of 99mTc-MIBI scanning, but decreased the sensitivity of ultrasonography. The size of parathyroid tumors had effects on the sensitivity of ultrasonography. Otherwise, various conditions causing SS false negative were observed. Some interfere factors should be excluded when SS negative results were encountered in clinical practice.</p>

Precision of rat BMD measurements by dual-energy X-ray absorptiometry in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the precision of rat bone mineral density (BMD) measurements by Norland Excellplus dual-energy X-ray absorptiometry (DXA) and to investigate the BMD changes in ovariectomized (Ovx) rats in vitro.</p><p><b>METHODS</b>(1) The coefficients of variation (CV) for BMD measurements at various skeletal regions were repeatedly determined by DXA in 10 Wistar rats in vitro. (2) BMD in lumbar vertebra (L5) and both sides of femurs was measured in total 90 rats. And (3) changes in BMD between Ovx and sham rats were compared.</p><p><b>RESULTS</b>(1) The short-term CVs of BMD measurements in different regions by DXA were as follows, 1.58% for lumbar vertebra (L5), 0.90% for left femur, and 0.86% for right femur, respectively. The long-term CVs were 2.22% for lumbar vertebra (L5), 1.09% for left femur, and 1.20% for right femur. (2) The BMD values in 90 Wistar rats were (127.5 +/- 12.3) in lumbar vertebra (L5), (82.6 +/- 11.3) in corpus vertebra (L5'), (150.7 +/- 10.6) in left femur and (149.9 +/- 10.6) mg/cm2 in right femur, respectively. The correlation coefficient of BMD measurements between left and right femurs was 0.792 (P < 0.001). (3) In Ovx group, the BMD values of corpus vertebra (L5') and distal femurs were significantly decreased, that was 10.0%-17.5% lower in comparison with sham group (P < 0.001).</p><p><b>CONCLUSIONS</b>Measurement of rat BMD in vitro by Norland Excellplus DXA is a useful method, and it can reflect the changes in rat bone masses with good precision.</p>