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ObjectivesPseudohypoparathyroidism (PHP) is a rare disease, especially when combined with pregnancy. We aimed to explore the changes in serum calcium/parathyroid hormone (PTH) level and medical treatment in a case series of PHP during pregnancy and the postpartum period.MethodsA total of five PHP patients with six pregnancies were enrolled. The classification of PHP was based on (epi)genetic analysis. Clinical characteristics, biochemical indices, and treatment strategies before, during, and after pregnancy were retrospectively collected.ResultsAll patients received calcium and vitamin D agents with nearly normal serum calcium before pregnancy except patient 2 who was found hypocalcemic during gestation. All patients chose Cesarean section, and one suffered preterm delivery due to oligoamnios. The neonatal birth weight ranged from 2,250 to 4,300 g, and all neonates were free of hypocalcemia-related symptoms. The change in calcium metabolism was inconsistent including stable, improved, or worsened during pregnancy. Serum PTH level remained low in the first two trimesters in patients with stable and improved conditions while increased in the last two trimesters in patients with a worsened condition. Serum calcium changed inconsistently while PTH increased consistently during lactation. For patients who did not breastfeed, calcium homeostasis improved after delivery.ConclusionCalcium homeostasis and medicine dosage changed differently in PHP patients during pregnancy and lactation. However, most patients had good pregnancy outcomes. Serum PTH levels might predict changes in calcium metabolism during pregnancy.

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare inherited autoimmune disease, characterized by a classic triad, including chronic mucocutaneous candidiasis, primary adrenocortical insufficiency and hypoparathyroidism. The present study investigated phenotypes and pathogenic variants in a Chinese woman with non-classical APS-1. Disease-associated variants in a patient with APS-1 were identified via targeted next generation sequencing and the variant was confirmed via Sanger sequencing. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and urinary levels of calcium were measured. Blood count assays and bone marrow morphology were investigated. The patient was a 32-year-old woman who had suffered from typical carpopedal spasms since she was 7 years old. She developed syncope, primary amenorrhea, intermittent diarrhea and general fatigue in subsequent years. Hypocalcemia, hyperphosphatemia, low levels of PTH and estradiol, elevated levels of FSH and LH, and absence of erythroblasts were observed, which indicated hypoparathyroidism, primary ovarian insufficiency and pure red cell aplasia. A novel heterozygous missense variant (NM_000383.2: c.623G>T, NP_000374.1: p.Gly208Val) in exon 5 of autoimmune regulator and a reported variant (NM_000383.2: c.371C>T, NP_000374.1: p.Pro124Leu) in exon 3 were detected, of which the c.623G>T variant may be a pathogenic variation that induces APS-1. Under a regular follow-up and therapeutic adjustment of calcium, calcitriol, hormone replacement therapy and methylprednisolone, the endocrine function and clinical symptoms of the patient were notably improved. The results of the present study expand the known genetic and phenotypical spectra of APS-1.

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

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

The carbonic anhydrase II (CAII) deficiency syndrome is a rare autosomal recessive osteopetrosis with renal tubular acidosis (RTA) and cerebral calcifications (MIM259730). CAII deficiency syndrome is caused by mutations in the gene CAII, which encodes the enzyme carbonic anhydrase II. CAII mutations are rarely reported in the Asian population. Here, we described two unrelated CAII deficiency families of Chinese Han origin with clinical and genetic analysis. Altogether, 106 subjects, including 2 probands, 4 unaffected family members from two non-consanguineous Chinese families, and 100 healthy controls were recruited. All seven exons and the exon-intron boundaries of the CAII gene were amplified and directly sequenced. Reverse transcription PCR (RT-PCR) was used to study the effect of splice site mutation. All clinical and biochemical parameters of the probands were collected. Two novel mutations of CAII gene were identified by mutational analysis: A nonsense mutation in exon 4 (c.T381C p.Y127X) in both families; a splice mutation at the splice donor site of intron 3 (c.350+2T>C, IVS3+2T>C) in one family. The splice-site mutation causes exon 3 skipping in patient's mRNA resulting in an in-frame deletion and a novel premature stop codon. These mutations were predicted to result in a loss of function of CAII. This is the first report of CAII deficiency syndrome in Chinese population. Our findings extent the spectrum of CAII mutations observed in patients with CAII deficiency syndrome.

Aim: To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. Materials & methods: Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and β-isomerized carboxy-telopeptide of type I collagen [β-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. Results: After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum β-CTX and ALP levels than those with TT genotype (all p < 0.001). No significant genotype–treatment interaction was found in hip BMD. Conclusion: The A1330V polymorphism of LRP5 is possibly correlated with response to alendronate treatment in Chinese women with osteoporosis, and the TT genotype could possibly predict a weak response to alendronate. Original submitted 31 October 2013; Revision submitted 13 January 2014

Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by recurrent fragile fractures. Serpin peptidase inhibitor, clade F, member 1 (SERPINF1) is known to cause a distinct, extremely rare autosomal recessive form of type VI OI. Here we report, for the first time, the detection of SERPINF1 mutations in Chinese OI patients. We designed a novel targeted next-generation sequencing panel of OI-related genes to identify pathogenic mutations, which were confirmed with Sanger sequencing and by co-segregation analysis. We also investigated the phenotypes of OI patients by evaluating bone mineral density, radiological fractures, serum bone turnover markers, and pigment epithelium-derived factor (PEDF) concentration. Six patients with moderate-to-severe bone fragility, significantly low bone mineral density, and severe deformities of the extremities were recruited from five unrelated families for this study. Six pathogenic mutations in SERPINF1 gene were identified, five of which were novel: (1) a homozygous in-frame insertion in exon 3 (c.271_279dup, p.Ala91_Ser93dup); (2) compound heterozygous mutations in intron 3 (c.283 + 1G > T, splicing site) and exon 5 (c.498_499delCA, p.Arg167SerfsX35, frameshift); (3) a homozygous frameshift mutation in exon 8 (c.1202_1203delCA, p.Thr401ArgfsX); (4) compound heterozygous missense mutation (c.184G > A, p.Gly62Ser) and in-frame insertion (c.271_279dup, p.Ala91_Ser93dup) in exon 3; and (5) a heterozygous nonsense mutation in exon 4 (c.397C>T + ?, p.Gln133X + ?). Serum PEDF levels were barely detectable in almost all subjects. We identified five novel mutations in SERPINF1 and confirmed the diagnostic value of serum PEDF level for the first time in Chinese patients with the extremely rare OI type VI.

A normal reference value of parathyroid hormone (PTH) was established for the first time in a large sample of healthy Chinese subjects by completely excluding interference of vitamin D deficiency. A high PTH level correlated significantly with an elevated bone turnover and a reduced bone mineral density (BMD). The aims of this study are to establish a normal reference value for serum PTH and to evaluate the effect of parathyroid gland status on bone turnover and BMD. Our cross-sectional study included 1436 healthy individuals from 5 different Chinese cities. Concentrations of serum PTH, 25-hydroxyvitamin D (25OHD), procollagen I N-terminal peptide (P1NP, a bone formation marker), and carboxyl-terminal telopeptide of type I collagen (β-CTX, a bone resorption marker) were measured by electrochemiluminescence immunoassay. BMD was measured by dual-energy X-ray absorptiometry. The relation of PTH concentration to age, gender, height, and weight was examined. Reference values of PTH were established for all subjects and for subjects categorized by serum 25OHD concentrations. Correlations of PTH levels with bone turnover biomarkers and BMD were statistically analyzed. Reference values of PTH were 8.84–69.95 pg/mL in all the subjects and 7.48–60.73 and 5.83–56.78 pg/mL in the subjects with serum 25OHD concentrations of ≥20 and ≥30 ng/mL, respectively. Serum PTH showed a negative linear correlation with 25OHD, and the breakpoint was 18.21 ng/mL, below which the PTH level rapidly increased. The increase in PTH levels with age showed a positive linear correlation with P1NP and β-CTX concentrations and a negative linear correlation with BMD at the lumbar spines and the femoral neck. A reference value of PTH was established in a large sample of healthy Chinese subjects according to 25OHD status, gender, and age. A high PTH level correlated significantly with an elevated bone turnover and a reduced BMD.

Osteopetrosis is a group of genetic bone disorders. Mutations in the chloride channel 7 gene (CLCN7) lead to chloride channel defect, which results in autosomal dominant osteopetrosis type II (ADO-II), autosomal recessive osteopetrosis (ARO), and intermediate autosomal recessive osteopetrosis (IARO). In the present study, we identified seven novel mutations of the CLCN7 gene and reported the first case of IARO with compound heterozygous mutation in Chinese population. Osteopetrosis is a heritable bone disorder due to the deficiency of or function defect in osteoclasts. Mutations in the CLCN7 lead to chloride channel defects, which result in osteopetrosis with diverse severity ranging from asymptomatic or relatively mild symptoms in ADO-II to the very severe phenotype in ARO. Heterozygous mutations in CLCN7 are associated to ADO-II, while homozygous and compound heterozygous mutations in CLCN7 may result in ARO and IARO. To date, a total of 24 mutations in CLCN7 were identified in ADO-II, and only 3 mutations were identified in IARO. In the present study, we reported seven unrelated ADO-II patients and one IARO patient from Chinese population and elucidated the characteristics of CLCN7 gene mutations in these patients. All 25 CLCN7 exons and exon-intron boundaries from genomic DNA were amplified and sequenced in eight affected individuals suffering from ADO-II/IARO. The clinical, biochemical, and radiographic analysis were evaluated to compare the differences between ADO-II and IARO both in genotype and phenotype. The results showed that there were seven novel CLCN7 mutations identified in these ADO-II/IARO patients, including six heterozygous missense mutations (p.L224R, p.S290Y, p.R326G, p.G347R, p.S473N, and p.L564P) and a novel splice mutation (p.K691FS). The compound heterozygous mutations (p.L224R and p.K691FS) were firstly observed in one IARO patient. The present study would enrich the database of CLCN7 mutations and improve our understanding of this heritable bone disorder.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.

To explore the clinico-genetic characteristics and protein status of parathyroid carcinoma (PC) diagnosed at Peking Union Medical College Hospital from January 1980 to December 2012.Genomic DNA was extracted from peripheral blood lymphocytes and paraffin-embedded tissue for analysis. The mutations of CDC73 gene were detected by direct sequencing. And the expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis.Twenty-four PC patients were recruited. The mean ages at the diagnosis of PHPT and PC were 42.2 and 42.6 years respectively. The serum calcium at the diagnosis of PHPT was 3.78 mmol/L, serum phosphorus 0.65 mmol/L and the median increment of serum parathyroid hormone (PTH) level 20.0. The recurrent rate was 76.2% during a 5-year follow-up.Genetic analysis identified 11 mutations of CDC73 gene (45.8%), among which c.34_35 insCT, c.626_629 delAACA, c.260_261 delGA, c.570 delG, c.40 CT and IVS3+1 GA were novel mutation first identified in our cohort. Nine of them had germline mutations. All tissue samples from normal parathyroid displayed strong positive immunostaining of parafibromin. Complete (55%, 11/20) or partial (45%, 9/20) loss of parafibromin expression was observed in PC tissues. The age at the diagnosis of PHPT, serum calcium, serum phosphorus, PTH, alkaline phosphatase (ALP), bone involvement rate, kidney stone/calcification rate, recurrent rate, metastatic rate and immunostaining level showed no significant difference between the patients with and without CDC73 mutation.In Chinese population, CDC73 mutation and complete/partial loss of immunohistochemical staining for parafibromin occur frequently in PC. Therefore it may be useful in the subset of tumors with equivocal histological examination.

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).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.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 (P0.05).For adult patients with osteomalacia, WB-DWI and SRS can provide mutually supportive data and be used for identifying potential oncogenic osteomalacia.

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.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.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 (P0.001). 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, P0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P0.001). 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.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.

To investigate the prevalence and characteristics of adrenal lesions in Chinese multiple endocrine neoplasia type 1 (MEN-1) patients.Adrenal CT scan and clinical manifestations were retrospectively reviewed in 32 consecutive MEN-1 patients who were evaluated at our hospital during January 1986 to December 2009.Adrenal lesions were identified in 16 of 32 (50%) MEN-1 patients. Five (31.3%) patents with adrenal involvement showed bilateral lesions, including bilateral adenoma (n=1), bilateral hyperplasia (n=2) and adenoma and hyperplasia on each side (n=2). Unilateral adrenal lesion was presented in 11 (68.7%) patients. Among which, 63.6% had adenomas with a mean diameter of 2.3 cm (0.8-4.0 cm) and the remainder was of hyperplasia or enlargement. In two patients, functioning adrenal abnormalities were detected including Cushing adenoma (n=1) and aldosterone-secreting adenoma (n=1).The prevalence of adrenal lesion in MEN-1 patient is similar between China and western countries. These tumors are mostly benign, small and nonfunctioning. Taking into account a high incidence of adrenal carcinoma in previous foreign studies, routine screening and close surveillance are still recommended for adrenal lesions in MEN-1 patients.

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.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.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; P0.001). 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.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.

To study the efficacy and adverse events of intravenous bisphosphonates in the treatment of patients of primary hyperparathyroidism (PHPT) complicated by hypercalcemia crisis.From October 2003 to December 2007, 14 patients admitted into our hospital were diagnosed as PHPT complicated by hypercalcemia crisis, which was defined as a serum calcium concentration greater than 3.50 mmol/L. Of them, 6 cases had parathyroid adenoma, 1 had hyperplasia and 7 had parathyroid carcinoma. One of the intravenous bisphosphonates including pamidronate, ibandronate and zoledronic acid was given for 29 times in all the 14 cases. Serum calcium, parathyroid hormone, hematology, and other biochemical markers were monitored. Adverse events were recorded.After intravenous bisphosphonates, the serum total calcium (Ca) levels decreased from (3.85 +/- 0.50) mmol/L to (2.86 +/- 0.39) mmol/L in (1.4 +/- 0.6) days, and were kept below 3.50 mmol/L for (10.14 +/- 8.54) days. There was no significant difference of the magnitude of decrease in serum Ca levels among the patients using pamidronate, ibandronate or zoledronic acid. The change of serum Ca level was associated with the serum Ca level before treatment. The response to intravenous bisphosphonates evaluated by the decrease of serum total calcium levels was more significant in patients with parathyroid adenoma or hyperplasia than those with parathyroid carcinoma. The most common adverse event was pyrexia, which occurred 15 times (51.7%) and 75% of the pyrexia events occurred after the first infusion. Other manifestations included fatigue, flu-like symptom, myalgia, arthralgia and diarrhea with an incidence of 3.4% each (one event in the 29 times of treatment). There were 2 events (6.7%) with mild increase of serum creatinine concentration.Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectively with mild adverse events.

To analyze the clinical features of pregnancy and lactation-associated osteoporosis (PLO).The clinical data of 4 patients with PLO were retrospectively analyzed.Bone pain and limitation of motion appeared within 2 months after childbirth in these 4 patients. X-ray films showed multiple vertebral fractures of thoracic and/or lumbar spine. Three of the 4 patients had positive family history of osteoporosis or low trauma fractures. After the diagnosis of PLO was confirmed, lactation was discontinued, and treatment of calcium, active vitamin D analogues, and bisphosphonates were initiated. After these managements, no new fracture occurred and the BMD at L(2-4) was markedly increased by 12.7% - 22.7% during their follow-up period of 1 - 4 years.Women with positive family history of osteoporosis or low trauma fractures may be susceptible to PLO. PLO should be considered when lumbar or back pain occur during pregnancy and lactation. Besides calcium and active vitamin D analogues, anti-resorptive agents (bisphosphonate or calcitonin) may be effective on PLO.

To describe the clinical presentations, radiographic findings and histological pathology of bones, diagnosis, treatment options and prognosis for patients with Gorham-Stout syndrome (GSS).Clinical data of 5 GSS patients seen from January 1980 to January 2008 were reviewed.(1) There were 2 males and 3 females, aged 15 years to 37 years (mean age was 30.2 years). (2) All of them had osteolysis, but the site and extent of involved bones were not the same. Three cases had large amount of bloody pleural effusion and two of them had also chylous effusion. All of the 5 cases had no evidence of malignancies. Four cases accepted bone biopsy. Among them,2 cases having local puncture and open biopsy showed typical bone pathologic manifestations. (3) Various forms of treatment including bisphosphonates, calcium supplementation, active vitD3 treatment, local radiation therapy and surgical ligation of thoracic duct were tried. (4) Follow up and clinical outcomes: the two cases, who had only bone osteolysis remained stable. Of the other three cases who had bone osteolysis associated with pleural effusion, one patient needed interrupted effusion drainage with stable bone impairment and the other two cases were out of contact.GSS is a rare disorder characterized by progressive osteolysis. The clinical presentations of this disease are variable and depend on the sites of involvement. There were no standard therapy available. Prognosis depends on the site of involvement, extent of the disease and presence of complications. Those who have pleural effusion had poor prognosis.

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.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.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 (P0.01) 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.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.

The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.

To investigate the influence of age on bone mass in Cushing's syndrome patients.Measurement of bone mineral density (BMD) was conducted among 57 women with Cushing's syndrome (CS) and 49 healthy women. There were 14 CS women and 14 healthy women in the group aged 20 - 29; 27 CS women and 15 healthy women in the group aged 30 - 39; and 16 CS women and 20 healthy women in the group aged 40 - 49.Among the healthy women the peak bone mass of lumbar spine was in the group aged 30 - 39, while the peak bone mass of hip was in the group aged 20 - 29. The BMD values of the CS women were lower than those of the healthy women, especially those in lumbar spine and in Ward's triangle. The younger the CS women, the lower the BMD Z-score (for the BMD Z-score of lumbar spine P = 0.021, for the BMD Z-score of femoral neck P = 0.020, and for the BMD Z-score of Ward's triangle P = 0.026). Seventeen of the 57 (29.8%) CS women had osteoporosis, 29 (50.9%) of the 57 had osteopenia, and 15 (26.3%) had fractures. The CS women with bone fractures had lower BMD Z-score than those without fractures (for lumbar fracture P = 0.003).The BMD of CS women is lower than that of the healthy women. Bone loss is more severe in younger CS women than in older ones. CS women with low BMD are prone to have bone fracture.

To investigate the distribution of calcium-sensing receptor (CASR) gene polymorphisms in healthy young women of Han nationality in Beijing area and to explore the association of CASR genotypes and serum calcium, parathormone (PTH) level in healthy women.202 healthy young women aged (27 +/- 5) years of Han nationality in Beijing area were recruited in this study. Whole blood genome DNA was extracted with QIAGEN DNA extraction kit. A986S and G990R genotypes were determined with mutagenically separated polymerase chain reaction (MS-PCR) and PCR-restriction fragment length polymorphisms (RFLP), respectively. Serum calcium, albumin, phosphorus, PTH were determined.(1) There were A986S and G990R polymorphisms in healthy young women of Han nationality in Beijing. The frequencies of genotypes were as follows: SS absent, AA 95.0% and AS 5.0% for A986S, RR21.3%, GR51.0% and GG27.7% for G990R. Hardy-Weinberg equilibrium was evident. (2) In subjects carrying AA and AS genotype, serum Ca was (2.46 +/- 0.09) mmol/L vs (2.45 +/- 0.08) mmol/L, calcium adjusted by albumin was (2.31 +/- 0.10) mmol/L vs (2.30 +/- 0.09) mmol/L, serum P was (1.23 +/- 0.14) mmol/L vs (1.24 +/- 0.11) mmol/L, serum PTH was (41.6 +/- 18.6) ng/L vs (50.0 +/- 25.1) ng/L. There were no significant differences among them. (3) In subjects carrying GG, GR and RR genotype, serum Ca was (2.44 +/- 0.10), (2.46 +/- 0.08) and (2.48 +/- 0.08) mmol/L; calcium adjusted by albumin was (2.30 +/- 0.10), (2.32 +/- 0.09) and (2.32 +/- 0.10) mmol/L; serum P was (1.22 +/- 0.13), (1.24 +/- 0.15) and (1.20 +/- 0.15) mmol/L, serum PTH was (37.6 +/- 16.0), (42.1 +/- 20.2) and (45.9 +/- 18.1) ng/L. There were significant difference in serum Ca, calcium adjusted by albumin and PTH (P = 0.042, 0.020 and 0.014, respectively).(1) There are A986S and G990R polymorphisms in CASR gene in Han nationality in Beijing area. The frequencies of genotypes are as follows: SS absent, AA 95.0% and AS 5.0% for A986S, RR21.3%, GR51.0% and GG27.7% for G990R. Hardy-Weinberg equilibrium is evident. A and G alleles are more common. It is indicated that the distribution of CASR gene polymorphisms in Chinese is different from that in Caucasians. (2) G990R polymorphism is associated with serum calcium and PTH levels in healthy women. Subjects with R allele have higher levels of serum calcium and PTH. There is no correlation between A986S polymorphism and serum calcium or PTH.

To identify the genotype of RET gene in one multiple endocrine neoplasia type 2A (MEN2A) kindred.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.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.The genotype of the family is identified as Cys 634 Trp substitution of RET gene.

To implore the effects of teriparatide (PTH) and alendronate (Alen) on skeletal biomechanical properties of ovariectomized (OVX) osteoporotic rats.70 female Wistar rats of 6 months were randomly divided into 7 groups: (1) Baseline: sacrificed at baseline; (2) OVXb: sacrificed in 6 weeks after OVX; (3) Sham operation; (4) OVXe: sacrificed 14 weeks after OVX; (5) PTH: 40 microg.kg(-1).d(-1); (6) Alen: 100 microg.kg(-1).d(-1); (7) A + P: PTH 40 microg.kg(-1).d(-1) and Alen 100 microg.kg(-1).d(-1). In group (5)-(7), different medicines were injected 5 times per week from 6th to 14th week after OVX. The cancellous biomechanical properties were measured with indentation test and the cortical properties were investigated with three-point bending test.(1) The can load and can stiff of distal femur of OVXb were significantly lower than those of baseline (P0.01). It is indicated that osteoporotic rat models with impaired bone strength were established. (2) The can load and can stiff of distal femur of PTH [(36.3 +/- 9.2) N, (160.7 +/- 48.0) N/mm(2)], Alen [(42.7 +/- 13.0) N, (122.9 +/- 35.6) N/mm(2)] and A + P [(44.3 +/- 18.2) N, (105.2 +/- 58.4) N/mm(2)] groups were all higher than those of OVXe [(19.5 +/- 8.5) N, (83.2 +/- 37.7) N/mm(2), P0.001 or P0.01]. In femoral shaft, maximal load and elastic load in PTH, Alen and A + P groups were higher than those of OVXe (P0.001, P0.01 or P0.05). (3) Can stiff in distal femur was higher in PTH than that in Alen and A + P groups (P0.05). Elastic load, maximal load and energy absorption in femoral shaft were higher in PTH and A + P groups than those in Alen group (P0.05), and maximal stress was higher in PTH than that in A + P and Alen group (P0.05).PTH and Alen were effective in improving the skeletal mechanical properties of OVX rats, but improvement in Alen and A + P was not so good as that in PTH group. It is indicated that anabolic effects of PTH was retarded by Alen's significant inhibition of bone turnover, therefore, PTH and Alen should not be utilized simultaneously.

To investigate the effects of teriparatide (hPTH1-34, PTH) and alendronate (Alen) on bone turnover rate and bone mineral density (BMD) of ovariectomized (OVX) osteoporotic rats.70 female 6-month-old Wistar rats were randomly divided into 7 groups: (1) baseline group: killed immediately as baseline controls; (2) sham operation group: injected subcutaneously with normal saline (NS) as normal controls; (3) OVXb group: underwent ovarietomy (OVX) and killed 6 weeks after OVX as pre-therapeutic controls; (4) OVXe group: injected with NS subcutaneously and then sacrificed 14 weeks after OVX as controls by the end of treatment; (5) PTH group: PTH 40 microg.kg(-1).d(-1) was administered; (6) Alen group: Alen 100 microg.kg(-1).d(-1) was administered; (7) A + P group: PTH 40 microg.kg(-1).d(-1) and Alen 100microg.kg(-1).d(-1) were administered. In groups 4 approximately 7, different medicines were injected subcutaneously QD 5 times per week from the 6th week to the 14th week after OVX and then the rats were killed and their right femurs, lumbar vertebrae, and samples of blood and urine were collected. Absorptometry was used to measure the BMD of the right femur and lumbar vertebrae. The serum calcium, phosphate, creatinine, alanine transaminase, and alkaline phosphatase (ALP) activity were measured by automatic biochemical analysis. The bone resorption marker urine deoxypyridinoline/creatinine (UDpd/Cr) level was measured by enzyme-linked immuosorbent assay.Six weeks after OVX the ALP and UDpd/Cr levels in the OVXb group were 101 U/L +/- 59 U/L and (118 +/- 32) x 10(-6) respectively, both significantly higher than those of the baseline group (58 U/L +/- 10 U/L and (48 +/- 34) x 10(-6) respectively, both P0.01) and the BMD results of the OVXb group were all significantly lower than those in the baseline group (all P0.01), which indicated that an OVX osteoporotic rat model was established successfully. The ALP and UDpd/Cr levels of the Alen group were 61 U/L +/- 28 U/L and (17 +/- 39) x 10(-6), significantly lower than those of the PTH group 120 U/L +/- 36 U/L and (111 +/- 26) x 10(-6) respectively, both P0.01) and the UDpd/Cr levels of the A + P group were between those of the Alen group and those of the PTH group. The BMD levels of the femur and lumbar vertebrae of the PTH, Alen, and A + P groups were all significantly higher than those of the control groups (all P0.01), and were similar to or higher than those of the sham operation group without significant differences between the PTH and Alen groups. The BMD level of the lumber vertebrae of the A + P group were significantly higher than those in the PTH group (all P0.05), and the femoral BMD results of the A + P group were significantly higher than those in the PTH and Alen groups (all P0.01).PTH and Alen are all effective on osteoporosis. In particular, the combination of PTH and Alen is more effective on increasing the BMD level.

To investigate the association between bone mineral density (BMD) and leptin receptor (LEPR) polymorphism (Gln223 Arg) in young women and postmenopausl osteoporotic women.BMD values were determined by dual energy X-ray absorptiometry. The Gln223 Arg genotypes of LEPR were analyzed by using polymerase chain reaction-restriction fragment length polymorphism method.Hardy-Weinberg equilibrium was evident for LEPR polymorphism. The subjects carrying the GG genotype of LEPR had significantly higher BMD at lumbar spine as compared with the subjects with GA and AA genotype in young women [(1.213 +/- 0.127) g/cm(2) vs (1.154 +/- 0.124) g/cm(2), P0.05]. There were no significant differences in BMD at the proximal femur among GG, GA and AA genotype in young women. No significant differences in BMD at all sites were observed among GG, GA and AA genotype in postmenopausl osteoporotic women. Correlation was found between BMD and leptin receptor polymorphism (Gln223 Arg) at lumbar spine (r = -0.151, P0.05).Leptin receptor polymorphism (Gln223 Arg) has association with peak bone mass in young women, which may be used as genetic marker in predicting the risk of developing osteoporosis in Chinese women of Han nationality.

To determine the efficacy of pamidronate disodium (pamidronate) in treatment of Paget's disease of bone.Intravenous drip of pamidronate was given at the dose of 30 - 60 mg per day for 2 - 3 weeks with a total dosage of 90 - 270 (168 +/- 84) mg to 5 patients with Paget's disease of bone, 2 males and 3 females, aged 27 - 74 (61 on average) with the course of disease of 4 - 48 years (24 years on average), all of them having multiple bone lesions, 2 being in grade 4 of pain assessment and bedridden and 3 being in grade 3 with impaired mobility. Pain assessment, biochemical markers of bone turnover, including serum alkaline phosphatase (ALP), carboxy-terminal propeptide of type I collagen (PICP), carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and urinary hydroxyproline (HOP), and side effects of pamidronate were observed before treatment, by the end of treatment, and 4, 12, 24, and 48 weeks after treatment.The Pagetic bone pain was significantly reduced by the end of treatment in all patients. The degree of pain assessment declined from grade 4 to grade 2 in 2 patients, and from grade 3 to grade 1 in 3 patients. The mobility was markedly improved without bone pain 12 weeks after treatment and relief of pain lasted for 1 year in all patients. Serum ALP, PICP, ICTP and urinary HOP concentrations were significant decrease by the end of treatment. Moreover, the mean percentage decreases for above biochemical markers at 12 and 24 weeks after treatment were 50% or over. The values of serum ALP, PICP, ICTP and urinary HOP decreased from 398 u/L (median), 818 ng/L (median), (29 +/- 14) ng/L and (71 +/- 16) mg/24 h urine respectively to 159 u/L, 129 ng/L, (12 +/- 4) ng/L and (34 +/- 7) mg/24 h urine respectively 48 weeks after treatment (all P0.05). Side effects, including a transient increase in body temperature, skin eruption and pruritus, and a transient increase of serum aspartate aminotransferase concentration, were negligible.Intravenous infusion of pamidronate is effective on Paget's disease of bone. Pamidronate of the dose of 90 - 270 mg administered within 2 - 3 weeks produces a year-long remission. Side effects of pamidronate are slight and transient.

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.(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.(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 (P0.001). (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 (P0.001).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.

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.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.OVX resulted in increasing of UDpd/Cr 133.3% (P0.01). The ratio of UCa/Cr also increased in OVX groups but without any significant compared with Sham (P0.05). UDpd/Cr were reduced by 54.6% and 51.8% (P0.01) 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.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.

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.

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).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.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.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.

To evaluate the value of peripheral quantitative computed tomography (pQCT) in measuring bone architecture and biomechanic properties.50 virgin female Wistar rats six months old were randomly divided into 4 groups: (1) 8 rats were killed as baseline group; (2) 8 rats underwent sham operation and then were killed 14 weeks after (sham operation group); (3) 16 rats underwent bilateral ovariectomy (OVX) without further intervention. Six and 14 weeks after the operation each 8 rats were killed (OVX group); and (4) 18 rats underwent OVX too. After the OVX 9 of the 18 rats were treated with 17beta-estradiol 20 micro g/kg/d IH and 9 rats were treated with estradiol valerate 800 micro g/kg/d po for 8 weeks respectively. Then the 18 rats were killed (OVX plus estrogen group, O + E group). The right tibiae of the rats were taken for histomorphometric analysis, and the right femora were prepared for pQCT scanning and bone biomechanical measurement with indentation test and three-point bending test.Histomorphometric analysis showed that the trabecular volume of proximal tibia (Cn-BV/TV) in the OVX group was 8.1 +/- 1.4%, significantly lower than that in the sham operation group (19.5 +/- 1.5%, P0.01). pQCT scanning showed that the femoral trabecular bone mineral content (Trab BMC) in the OVX group was 1.7 +/- 0.3 mg/mm, significantly lower than that in the sham operation group (3.2 +/- 0.5 mg/mm, P0.01) and the femoral trabecular bone mineral density (Trab BMD) in the OVX group was 158 +/- 32 mg/mm(3), significantly lower than that in the sham operation group (320 +/- 39 mg/mm(3), P0.01). The cancellous maximal load (Can load) of the distal shaft of femur in the OVX group was 12.5 +/- 2.5 N, significantly lower than that in the sham operation group (45.9 +/- 3.2 N, P0.01). The cancellous stiffness (Can Stiff) of the distal shaft of femur in the OVX group was 226 +/- 48 N/mm, significantly lower than that in the sham operation group (396 +/- 72 N/mm, P0.01). The Can load of O + E group was 21.8 +/- 3.7 N, significantly higher than that in the OVX group (P0.05). The Can Stiff of the O + E group was 382 +/- 54 N/mm, significantly higher than that in the OVX group (P0.05). There were no significant differences in cortical bone determined by pQCT as well as biomechanic properties in measured by three point test after OVX and estrogen treatment. A significant positive correlation was shown between Trab BMD and Cn-TV/BV and between Trab BMD and Tb N (r = 0.88 and 0.73, both P0.01). Similarly, both Trab BMC and Trab BMD of the femur were significantly correlated with the Can load and Can Stiff determined by indentation test (r = 0.47 - 0.68, all P0.01). There was also a significant correlation of parameters measured by pQCT in cortical bone with the maximal load and stiffness for the femur midshaft, and the best correlation was found between the maximal load of femur midshaft and Crt BMC and Crt A (both r = 0.76 and P0.01).The geometric, densitometric and mechanical properties in cortical and trabecular bones of rat can be well described by pQCT.

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.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.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) (P0.001), and cross-genotype of Fok I and Taq I was also significantly associated with BMD at the Neck and Troch sites (P0.05). 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.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.