A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFβ2 mutation / 中华内科杂志

Objective:Loeys-Dietz syndrome is a rare type of hereditary connective tissue disease. This study was aimed to analyze the clinical characteristics and gene mutations in a family of Loeys-Dietz syndrome with skeletal deformity.Methods:Clinical data of the proband and family members were collected and biochemical measurements and radiological examinations were conducted. Genomic DNA was extracted from peripheral blood of the family members. Whole-exome sequencing was performed to determine the mutation sites in the proband, and Sanger sequencing was applied to verify the candidate mutation in the other family members.Results:The proband is a 34-year-old man with deformities of lower extremities for more than 30 years. Physical examinations showed dolichostenomelia, pes planus, joint laxity and scoliosis. Echocardiography revealed the dilatation of aortic root at the level of the sinuses of Valsalva. A heterozygous missense mutation (c. 220A>C, p.Thr74Pro) in exon 1 of TGFβ2 gene was identified in the proband. The same mutation was detected in his sister and niece with similar clinical features such as deformities of lower extremities and pes planus. This novel mutation has not been reported in ExAC or 1000G and was predicted to be deleterious, supporting a diagnosis of Loeys-Dietz syndrome type 4.Conclusions:Loeys-Dietz syndrome type 4 is caused by TGFβ2 mutations. Skeletal deformity is one of the distinctive features. Genetic testing is helpful for the early diagnosis and differential diagnosis from other connective tissue diseases.

Analysis of clinical characteristics of 5 cases of bisphosphonate associated atypical femoral fractures / 中华内分泌代谢杂志

Objective:To analyze the clinical characteristics of patients with bisphosphonates related atypical femoral fractures(AFFS), thereby to facilitate early diagnosis.Methods:The clinical manifestations, biochemical indexes, imaging features and treatment follow-up of AFFS patients who were diagnosed in the Department of Osteoporosis and Bone Disease, the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from 2011 to 2019 were analyzed retrospectively, and the literature was reviewed.Results:A total of 5 cases of atypical bisphosphonate related femoral fractures were collected, all of them were female, with an average age of 68 years. All the 5 patients were treated with alendronate. Three patients were treated with 70 mg/week throughout the course, and two patients were treated with 10 mg/day at first, and changed to 70 mg/week later. The average course of treatment was 8.7 years, ranging from the shortest 5 years to the longest 17 years. Among the 5 cases, the shortest onset time was 3 years after taking medicine, and the longest was 16 years. The clinical features are as follows: all patients had prodromal pain before fracture which was characterized as dull except for case 4. Case 1 was bilateral thigh pain, the rest were unilateral thigh pain, which began to appear within 2-3 years before fracture. X-ray plain film showed thickening of the lateral bone cortex; radionuclide bone scan(ECT) showed active bone metabolism in the affected area. The abnormal manifestations of ECT were earlier than X-ray and MRI. The recognition of these features is helpful to the early diagnosis of AFFS. All 5 patients stopped bisphosphonates immediately, and continued to take calcium tablets. Active vitamin D was added to 4 cases. One case of incomplete fracture was treated conservatively with Teriparatide for one year, which was helpful to deter it from becoming complete fracture. 4 cases of complete fracture were treated with reduction and fixation, and all healed.Conclusion:Long-term use of bisphosphonates can increase the risk of AFFS. Strengthening the risk assessment during use can reduce the incidence of such fractures. Early diagnosis and reasonable treatment can improve the prognosis.

Generation and phenotype of myeloid cell specific Clcn7-mutation osteopetrosis mouse model / 中华内分泌代谢杂志

Objective:To construct a myeloid cell specific Clcn7-G763R mutant mouse model and characterize its phenotype.Methods:A mouse conditional knocked in p. G763R mutation in Clcn7 gene was constructed and bred with LysM cre mice to obtain osteopetrosis mice with myeloid cell specific Clcn7-G763R mutation. The differences of bone mass in mice with different genotypes were analyzed using Micro CT and the changes of histology were observed with HE staining. Osteoclasts were cultured and the expression levels of osteoclasts differentiation and maturation-related genes were detected by real-time PCR. The functions of osteoclasts were examined through bone resorption assay.Results:The body weight of homozygous mutant mice at 4 weeks old was reduced compared with the wild type mice [(12.000±1.666)g vs(15.630±2.314)g, P=0.021], with shorter femur length [(1.160±0.096)cm vs (1.300±0.082)cm, P=0.037]. Micro CT showed that bone mineral density of homozygous mutant mice was remarkably increased at 4 weeks old [(0.753±0.002)g/cm 3vs(0.143±0.034)g/cm 3, P=0.003], while bone mineral density of heterozygous mutant mice increased significantly at 8 weeks old [(0.236±0.021)g/cm 3vs(0.180±0.020)g/cm 3, P=0.030]. HE staining revealed increased trabecula bone volume in the mutant mice, especially in homozygous mutant mice with narrow bone marrow cavity and wider hypertrophic zone of chondrocytes. There was no significant difference in the number of osteoclasts between wild type mice and heterozygous mice in vitro( P=0.358), while total area of osteoclasts increased in heterozygous mutant mice [(3.590×10 6±0.911×10 6)μm 2vs(1.352×10 6±0.260×10 6)μm 2, P=0.043]. Impaired function of resorption was unveiled by bone resorption assay. There were no significant differences in the expressions of osteoclast differentiation and maturity-related genes including NFATc1, c-fos, Ctsk, and Acp5 between the two groups. Conclusion:A myeloid cell specific Clcn7-G763R mutation mice with impaired osteoclasts and increased bone mass is successfully constructed.

Interpretation of Guidelines for the Diagnosis and Treatment of Male Osteoporosis / 中华内分泌代谢杂志

In October 2020, Chinese Society of Osteoporosis and Bone Mineral Research issued the Guidelines for Diagnosis and Treatment of Male Osteoporosis. Taken together with the Guideline for Diagnosis and Treatment of Primary Osteoporosis (2017), this article interprets guideline for male osteoporosis from the aspects of osteoporosis epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, and treatment.

Drug discovery of sclerostin inhibitors

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.

Prenatal diagnosis of monogenic skeletal disorders in 22 pedigrees / 中华内分泌代谢杂志

Objective:To evaluate the clinical value of prenatal molecular diagnostic technology in preventing hereditary diseases through analysis of prenatal diagnostic characteristics in 22 monogenic skeletal disorders pedigrees.Methods:This study retrospectively analyzed prenatal molecular diagnostic results of 22 pedigrees with monogenic skeletal disorders who were admitted to Department of Osteoporosis and Bone Diseases in our hospital from January 2014 to July 2021.Results:Among 22 pedigrees, there were 10 pedigrees with X-linked hypophosphatemic rickets due to PHEX gene mutations, in which 8 fetuses were found to carry pathogenic variants; 6 pedigrees with osteopetrosis, including 3 cases of CLCN7 gene mutation, 2 TCIRG1 gene mutation, and 1 CTSK gene mutation, were detected to have 2 affected fetuses and 1 carrier. There were 4 cases of osteogenesis imperfecta, including 2 cases of COL1A1 gene mutation, 1 case of COL1A2 gene mutation, and 1 case of SERPINF1 gene mutation, in which 1 affected fetus and 1 carrier were found; only one case of osteoarthritis with mild chondrodysplasia caused by COL2A1 gene mutation was found to harbor pathogenic variant in fetus; 1 case of hypophosphatasia due to ALPL gene mutation was not detected to carry pathogenic variant in fetus. By the time of follow-up, all 12 affected fetuses were terminated, and the remaining 10 fetuses except for one case still in pregnancy were born in good condition.Conclusion:Prenatal molecular diagnosis may confirm whether the fetus carries pathogenic variants at the first and second trimesters. For monogenic skeletal disorders that comply with Mendel′s law of separation, prenatal diagnosis can be determined by calculating the probability of recurrence of offspring. In addition, for families with de novo mutations in the offspring, it is necessary to pay attention to whether there are mosaic mutations in the parents.

Early predictive value of bone turnover markers for the changes of bone mineral densities in postmenopausal patients with osteoporosis treated with alendronate / 中华内分泌代谢杂志

Objective:To investigate the effect of alendronate treatment and assess the value of bone turnover markers (BTMs) in predicting the changes of bone mineral densities (BMDs) in postmenopausal women with osteoporosis.Methods:In this retrospective study, 409 postmenopausal women with osteoporosis aged (64.86±7.21) years in the Department of Osteoporosis and Bone Disease, Shanghai Sixth People′s Hospital were enrolled from 2012 to 2020. BMDs at lumbar spine 1-4, femoral neck, and total hip, serum β cross-linked C-telopeptide of type 1 collagen (β-CTX), and osteocalcin (OC) were measured before and after treatment.Results:After alendronate treatment for 1 year, BMDs at lumbar spine 1-4, femoral neck and total hip increased 4.84%, 2.13%, and 2.89%, respectively ( P<0.05). At 6 months and 1 year on treatment, β-CTX and OC levels decreased by 77.7%, 42.3% and 78.2%, 49.5%, respectively ( P<0.05). Linear regression analysis showed that for every 10% decrease in the change of β-CTX at 6 months after alendronate treatment, the rate changes in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.417%, 0.127%, and 0.213% at 1 year after alendronate treatment; for every 10% decrease in OC, the change rates in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.582%, 0.258%, and 0.375%. Conclusions:Alendronate significantly increases BMDs and decreases BTMs levels in elderly women with osteoporosis. BTMs have a predictive value for the changes of BMDs, allowing early monitoring for the effect of alendronate treatment.

Autosomal recessive hypophosphatemic rickets 1 caused by DMP1 mutation: one pedigree study / 中华内分泌代谢杂志

In the present study, the clinical features of a patient with autosomal recessive hypophosphatemic rickets 1 caused by dentin matrix protein 1(DMP1)gene mutation and her family members were investigated. DMP1 gene from peripheral blood was sequenced by Sanger sequencing, and the known mutation was verified among her family members and 250 healthy populations. The proband was a 42-year-old female with bone deformity of both lower limbs, bone pain, and short stature. The results of X-rays and laboratory examination were consistent with the hypophosphatemic rickets reported before. A homozygous mutation(c.2T> C)in DMP1 was identified by Sanger sequencing in the proband, her son and daughter were heterozygous for c. 2T> C.

Proximal symphalangism caused by NOG gene novel mutation: A family report / 中华内分泌代谢杂志

Proximal symphalangism is a rare hereditary bone disease caused by NOG or GDF5 gene mutations, of which NOG gene mutations account for the majority. A family of SYM1 was reported. Patient was a man with proximal interphalangeal joint stiffness of bilateral fingers for more than 20 years. Combined with laboratory and imaging examinations, the patient was diagnosed with proximal symphalangism. 4 other subjects in this family are affected. The detection of NOG gene mutations of the proband and his mother and son showed that there were heterozygous missense mutations in exon 1, c.667C>T, resulting in p. Pro223Ser. The pathogenesis, clinical and imaging manifestations of SYM1 were reviewed in combination with literature to improve clinicians′ understanding of the disease.

One case of hypercalcemic crisis after parathyroidectomy in primary hyperparathyroidism / 中华内分泌外科杂志

Hypercalcemic crisis (HC) is a rare but critical electrolyte disorder, which may result in death if rapid correct management is not given due to the injury of the neurologic, cardiovascular and renal systems. Severe primary hyperthyroidism (PHPT) is listed as the most common cause of hypercalcemic crisis. Prompt surgical removal of the parathyroid glands is the most effective cure for HC. Nevertheless, hypercalcemic crisis after a successful parathyroidectomy is infrequent. Now, we report a case admitted to the Department of General Surgery of the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital about a successful therapy of hypercalcemic crisis postparathyroidectomy in Sep. 2019, aiming to remind clinicians of the individualized program of calcium supplement after surgery of hyperparathyroidism and emphasize the value of renal dialysis in HC.

Clinical features and gene mutation analysis of COMP in eight patients with pseudoachondroplasia / 中华内分泌代谢杂志

The clinical features and the mutation of cartilage oligomer matrix protein (COMP) gene were analyzed in 8 patients with pseudoachondroplasia (PSACH).The clinical data and the peripheral blood from 5 male and 3 female probands,their pedigree members,and 250 unrelated volunteers were collected.Eight patients who were sporadic cases,had been detected mutation of COMP gene by DNA sequencing.PSACH is a skeletal disorder characterized by short stature,joint laxity,and early-onset osteoarthritis.The heights of 8 patients were significantly lower than the average level by 3 standard deviations,with short limbs and deformities of legs.Radiographs showed flattening of vertebrae with anterior beaking or tonguing in children and osteoarthritis in adults.As to the patients with short limb dwarfism,short toes,and abnormal radiography findings,PSACH should be suspected and could be confirmed by detection of COMP gene mutation.

Seize the opportunity and strive to do well in clinical research of bone mineral diseases / 中华内分泌代谢杂志

How to inherit and develop the Society of Osteoporosis and Bone Mineral Disease Research, Chinese Medical Association is not only a challenge for the committee, but also an opportunity for development. We must seize the opportunity and strive to do well the clinical research of bone mineral diseases.

Comparative study of laparoscopic and open repair of gastroduodenal ulcer perforation / 国际外科学杂志

Objective@#To compare the clinical effects of laparoscopic repair and open repair of gastroduodenal ulcer perforation.@*Methods@#Retrospective analysis was performed on 117 patients with perforated gastroduodenal ulcer admitted to Sijing Hospital of Shanghai Songjiang District from October 2005 to February 2018, including 86 males and 31 females. The average age was 35.56 years with a range from 17 to 68 years. Patients were divided into two groups according to different surgical methods: laparoscopic group (n=56) and open group (n=61). Patients in the laparoscopic group were received laparoscopic repair for perforated gastroduodenal ulcer, while patients in the open group received open repair for perforated gastroduodenal ulcer. Comparison of two groups of patients with operation time, intraoperative blood loss, postoperative first anal exhaust time, analgesic utilization rate, length of hospital stay, the body′s inflammatory response [preoperative and 24 h, 72 h, 120 h of postoperative peripheral white blood cell (WBC)], C-reactive protein level (CRP), postoperative complications (postoperative incision infection, incision dehiscence, gastric duodenal fistula, abdominal abscess, adhesion intestinal obstruction and lung infection). Measurement data were expressed as mean±standard deviation (Mean±SD), and t-test was used for comparison between groups; count data were compared by Chi-square test.@*Results@#All the patients in the two groups successfully completed the operation, and there were no cases transferred to laparotomy in the laparoscopic group. Intraoperative blood loss[(15.3±9.5) ml vs (30.5±11.3) ml, P<0.001], time of first anal exhaust[(56.5±9.8) h vs (83.8±15.6) h, P<0.001], analygesic utilization rate (10.71% vs 52.46%, P<0.005), and length of hospital stay [(7.5±1.5) d vs (10.0±3.4) d, P<0.001] of the laparoscopic group were significantly better in the open group, the differences were statistically significant. The WBC and CRP at 24 h, 72 h and 120 h after surgery of the laparoscopic group were also significantly better than in the open group [WBC: 24 h, (14.55±3.44) ×109/L vs (16.02±4.12) ×109/L, P=0.020; 72 h, (10.25±2.32) ×109/L vs (14.22±3.29) ×109/L, P<0.001; 120 h, (8.12±3.11)×109/L vs (11.58±2.33) ×109/L, P<0.001. CRP: 24 h, (50.35±13.73) mg/L vs (80.11±13.56) mg/L, P<0.001; 72 h, (29.37±7.81) mg/L vs (53.57±8.05) mg/L, P<0.001; 120 h, (17.71±7.01) mg/L vs (34.35±7.72) mg/L, P<0.001], the differences were statistically significant. There was no significant difference in operation time and postoperative complications between the two groups (P>0.05).@*Conclusion@#Compared with open gastroduodenal ulcer perforation repair, laparoscopic gastroduodenal ulcer perforation repair surgery trauma are smaller, and the body′s inflammatory response are lighter, postoperative complications is no statistical significance, but will look from actual data, the cases of complications is less, is now a better surgical treatment of gastroduodenal ulcer perforation.

Comparative study of laparoscopic and open repair of gastroduodenal ulcer perforation / 国际外科学杂志

Objective To compare the clinical effects of laparoscopic repair and open repair of gastroduodenal ulcer perforation.Methods Retrospective analysis was performed on 117 patients with perforated gastroduodenal ulcer admitted to Sijing Hospital of Shanghai Songjiang District from October 2005 to February 2018,including 86 males and 31 females.The average age was 35.56 years with a range from 17 to 68 years.Patients were divided into two groups according to different surgical methods:laparoscopic group (n =56) and open group (n =61).Patients in the laparoscopic group were received laparoscopic repair for perforated gastroduodenal ulcer,while patients in the open group received open repair for perforated gastroduodenal ulcer.Comparison of two groups of patients with operation time,intraoperative blood loss,postoperative first anal exhaust time,analgesic utilization rate,length of hospital stay,the body's inflammatory response [preoperative and 24 h,72 h,120 h of postoperative peripheral white blood cell (WBC)],C-reactive protein level (CRP),postoperative complications (postoperative incision infection,incision dehiscence,gastric duodenal fistula,abdominal abscess,adhesion intestinal obstruction and lung infection).Measurement data were expressed as mean ± standard deviation (Mean ± SD),and t-test was used for comparison between groups;count data were compared by Chi-square test.Results All the patients in the two groups successfully completed the operation,and there were no cases transferred to laparotomy in the laparoscopic group.Intraoperative blood loss [(15.3 ± 9.5) ml vs (30.5 ±11.3) ml,P ＜ 0.001],time of first anal exhaust [(56.5 ± 9.8) h vs (83.8 ± 15.6) h,P ＜ 0.001],analygesic utilization rate (10.71％ vs 52.46％,P ＜ 0.005),and length of hospital stay [(7.5 ± 1.5) d vs (10.0 ±3.4) d,P ＜ 0.001] of the laparoscopic group were significantly better in the open group,the differences were statistically significant.The WBC and CRP at 24 h,72 h and 120 h after surgery of the laparoscopic group were also significantly better than in the open group [WBC:24 h,(14.55 ± 3.44) × 109/L vs (16.02 ± 4.12) × 109/ L,P =0.020;72 h,(10.25 ± 2.32) × 109/L vs (14.22 ± 3.29) × 109/L,P ＜ 0.001;120 h,(8.12 ±3.11) ×109/Lvs (11.58 ±2.33) × 109/L,P ＜0.001.CRP:24 h,(50.35 ± 13.73) mg/L vs (80.11 ±13.56) mg/L,P＜0.001;72 h,(29.37 ±7.81) mg/Lvs (53.57 ±8.05)mg/L,P＜0.001;120h,(17.71 ±7.01) mg/L vs (34.35 ± 7.72) mg/L,P ＜ 0.001],the differences were statistically significant.There was no significant difference in operation time and postoperative complications between the two groups (P ＞ 0.05).Conclusion Compared with open gastroduodenal ulcer perforation repair,laparoscopic gastroduodenal ulcer perforation repair surgery trauma are smaller,and the body's inflammatory response are lighter,postoperative complications is no statistical significance,but will look from actual data,the cases of complications is less,is now a better surgical treatment of gastroduodenal ulcer perforation.

Seize the opportunity and strive to do well in clinical research of bone mineral diseases / 中华内分泌代谢杂志

How to inherit and develop the Society of Osteoporosis and Bone Mineral Disease Research, Chinese Medical Association is not only a challenge for the committee, but also an opportunity for development. We must seize the opportunity and strive to do well the clinical research of bone mineral disease.

A clinical study of Proteus syndrome caused by a mosaic somatic mutation in AKT1 gene / 中华内科杂志

Objective Proteus syndrome is a rare disease. The aim of the present study was to analyze the clinical characteristics and gene mutations of Proteus syndrome with a case report and relevant literature review. Methods Clinical data of the patient with Proteus syndrome were collected in detail and biochemical measurements and radiological examinations were conducted. Tissues from phalanges with lesions were obtained to extract DNA, and Sanger sequencing of AKT1 gene was carried on. The pathogenic mutation was further tested in peripheral blood samples of the patient, his parents and 250 healthy volunteers. Orthopaedic surgery was performed on the affected limbs of the patient. Results The patient was presented with progressive overgrowth of the right extremity, scoliosis, cerebral connective tissue nevus and lower extremity venous. A heterozygous mutation of AKT1 gene (c. 49G>A) was identified in DNA extracted from the affected bone tissue of the patient, but not be found in genomic DNA of peripheral blood samples from the patient, his parents and 250 healthy volunteers. Movement function of the affected limb improved significantly after the operations. Conclusions The prominent features of Proteus syndrome are overgrowth of one extremity and cerebral connective tissue nevus. A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease.

Pycnodysostosis caused by CTSK mutation:one pedigree study / 中华内分泌代谢杂志

The purpose of this study was to analyze the clinical characteristics of a patient with pycnodysostosis caused by cathepsin K ( CTSK ) gene mutation and his family members in order to improve the understanding of this rare diseases. A pediatric patient with pycnodysostosis was referred to us when he was eight years old. He presented with elevated bone mineral density, short stature, dentition abnormality and multiple fractures of right tibia. Next generation sequencing ( NGS) and Sanger sequencing confirmed that the proband carried carrying compound heterozygous mutations of cathepsin K(CTSK) gene, including a missense mutation c.440C>T in exon 5 (p.Ala147Val) and a deletion mutation c. 778delA in exon 6 ( p. Ser260AlafsX15) which was inherited from his father. His mother and sister did not carry the above variations. Clinically, it is necessary to differentiate pycnodysostosis from osteopetrosis and other osteosclerotic diseases.

Clinical features and identification of LEMD3 gene mutation in 4 osteopoikilosis patients / 中华内分泌代谢杂志

Objective To analyze the clinical features and the mutation of LEMD3 gene in four osteopoikilosis patients.Methods Clinical data of 4 patients were collected, peripheral blood samples were obtained for DNA extract, and LEMD3 gene mutation was analyzed by direct DNA sequencing.Results 4 patients with osteopoikilosis included a male aged 44, a female aged 42, a 26-year-old male, a 21-year-old female.All these patients were from families of non-consanguineous marriage.The main complaint of these patients was pain on arthrosis.Abnormal X-ray radiography was found in medical examination, while markers of bone metabolism were normal.The results of X-ray examination showed that numerous, discrete round or ovoid calcification were scattered throughout the wrist, pelvis and scapula.A de novo mutation c.595delG(NM_014319.4) localized in exon1 of the LEMD3 gene resulting in p.Ala199ProfsX46 of Case 3, while the mutation is not found in his parents and the remaining 3 patients.Conclusions A de novol LEMD3 mutation led to osteopoikilosis was found, and the pathogenesis of molecular mechanism in Chinese remained further exploration.

Adult hypophosphatasia caused by ALPL mutation: one pedigree study / 中华内分泌代谢杂志

An adult patient with hypophosphatasia caused by compound heterozygous mutations in alkaline phosphatase,liver /bone /kidney(ALPL)gene was investigated through comprehensively reviewing the medical history and clinical records of the proband and her family members in order to better understand the disease.The proband and her older sister had mild decreased serum alkaline phosphatase level accompanied with frequently nontraumatic fractures at limbs and all the teeth fell off at the age of 20 and 7, respectively.Both of them carried a missense mutation c.407G>A(p.Arg136His)in exon 5 and a deletion mutation c.1318_1320delAAC(p.Asn440del)in exon 12 simultaneously.Other four family members were p.Arg136His mutation carriers and two members were p.Asn440del mutation carriers.We found that p.Asn440del mutation was associated with the oral disorders.In this family, compound heterozygous manifested more serious symptoms, while heterozygous showed relatively mild symptoms.In addition, it is necessary to differentiate it from primary osteoporosis and other diseases of disturbed bone mineralization.

Diagnosis and treatment of 6 cases with Paget′s disease of bone / 中华内分泌代谢杂志

Six cases of Paget′s disease of bone, including 5 males and 1 female, aged (57. 7 ±11. 8) years old, were recruited. Mean duration of disease was (7. 5±6. 5) years. Clinical manifestations were bone pain and bone deformity. The lesions mainly reside in the pelvis and femur. X-ray film showed typical lesion of Paget′s disease of bone, such as impaired bone trabecular structure with coarseness and disorder, cortical thickening, medullary cavity narrowing and skeletal deformation. Bone scan revealed abnormal radionuclide concentration in the involved bone. Serum alkaline phosphatase ( ALP) in 6 patients was increased ( median 235 U/ L). 5 patients received zoledronic acid sodium intravenous infusion therapy. Bone pain was relieved obviously in 5 patients after treatment for 2-3 months. Physical activity was greatly improved, and serum ALP levels significantly decreased.