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PURPOSE: To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts. METHODS: A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts. RESULTS: A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts. CONCLUSION: The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.
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Doenças Ósseas Metabólicas , Fraturas por Compressão , Osteogênese Imperfeita , Fraturas da Coluna Vertebral , Humanos , Osteogênese Imperfeita/genética , Cadeia alfa 1 do Colágeno Tipo I , Colágeno Tipo I/genética , Genótipo , Fenótipo , MutaçãoRESUMO
PURPOSE: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). METHODS: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. RESULTS: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-ß, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05). CONCLUSIONS: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.
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Resistência à Insulina , Osteogênese Imperfeita , Criança , Humanos , Lipocalina-2 , Composição Corporal , HDL-Colesterol , Metabolismo dos Lipídeos , GlicolipídeosRESUMO
PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.
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Neoplasias das Glândulas Suprarrenais , Osteoporose , Paraganglioma , Feocromocitoma , Masculino , Feminino , Humanos , Estudos Transversais , Osso e Ossos , Densidade Óssea/fisiologia , Absorciometria de FótonRESUMO
PURPOSE: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients. METHODS: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing. RESULTS: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = - 0.282), height Z score (r = - 0.292), ALP concentration (r = - 0.304), lumbar BMD (r = - 0.276), BMD Z score of the lumbar spine and femoral neck (r = - 0.32; r = - 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children. CONCLUSION: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.
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OBJECTIVE: Nonsurgical hypoparathyroidism (ns-HP) is a rare disease. There are few studies on Quality of Life (QoL) among patients with ns-HP. This study aimed to investigate the QoL among ns-HP patients with regular conventional treatment, and explore the influence factors affecting QoL among these Chinese ns-HP patients. METHODS: This is a cross-sectional study comparing 101 patients identified as ns-HP and 101 healthy controls. The questionnaires of Short Form 36 Health Survey questionnaire version 2(SF-36v2) were used to evaluate QoL. RESULTS: Scores of all eight subdomains of SF-36v2 and physical component scores (PCS), mental component scores (MCS) were significantly lower in the ns-HP group compared with the healthy controls. The indices of all subdomains of SF-36v2 between Q1 (the lowest quartile) and Q4 (the highest quartile) groups were compared, suggesting higher percentages of detectable parathyroid hormone (PTH) before treatment in Q4 group among all QoL indices except two subdomains (physical function and body pain). CONCLUSION: Both mental and physical QoL were impaired in the ns-HP patients even with regular conventional treatment for hypocalcemia, which were more severe in cases with lower baseline PTH levels.
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Hipocalcemia , Hipoparatireoidismo , Humanos , Qualidade de Vida , Estudos Transversais , Hormônio Paratireóideo , Inquéritos e QuestionáriosRESUMO
PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.
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Densidade Óssea , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Absorciometria de Fóton/métodos , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Vértebras LombaresRESUMO
A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.
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Derivação Gástrica , Osteomalacia , Feminino , Humanos , Adulto , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Cálcio , Osteomalacia/etiologia , Hormônio Paratireóideo , Vitamina DRESUMO
The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.
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Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Nefrocalcinose , Abscesso/tratamento farmacológico , Calcitriol/efeitos adversos , Criança , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Feminino , Humanos , Hipofosfatemia/induzido quimicamente , Hipofosfatemia/tratamento farmacológico , Masculino , Nefrocalcinose/tratamento farmacológico , Fosfatos/efeitos adversos , Estudos ProspectivosRESUMO
Objective: To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation. Methods: A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms. Results: The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG). Conclusions: Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.
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Hipoparatireoidismo , Anormalidades Urogenitais , Criança , Fator de Transcrição GATA3/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipoparatireoidismo/genética , Mutação , Estudos RetrospectivosRESUMO
By analyzing iron status of 14 ADHR patients, we found that iron deficiency was an important trigger of ADHR. Correcting iron deficiency significantly improved patients' symptoms. Meanwhile, patients' serum phosphate showed positive correlations with iron metabolism parameters and hemoglobin-related parameters, suggesting the necessity of monitoring and correcting the iron status in ADHR. INTRODUCTION: Autosomal dominant hypophosphatemic rickets (ADHR) is unique for its incomplete penetrance, variety of disease onsets, and waxing and waning phenotypes. Iron deficiency is a trigger of ADHR. This study aimed to clarify the role of iron deficiency in ADHR. METHODS: Data of clinical manifestations and laboratory examinations were collected from patients among eight kindreds with ADHR. Multiple regression and Pearson's correlation tests were performed to test the relationships of serum phosphate levels and other laboratory variables during the patients' follow-ups. RESULTS: Among 23 ADHR patients with fibroblast growth factor 23 (FGF23) mutations, 14 patients presented with obvious symptoms. Ten patients had iron deficiency at the onset of ADHR, coinciding with menarche, menorrhagia, pregnancy, and chronic gastrointestinal bleeding. Two patients who did not have their iron status tested presented with symptoms after abortion and pregnancy in one patient each, which suggested that they also had iron deficiency at onset. Patients were treated with ferrous succinate tablets, vitamin C, and neutral phosphate and calcitriol. With correction of the iron status, the patients' symptoms showed notable improvement, with increased serum phosphate levels. Two patients' FGF23 levels also declined to the normal range. There were strong correlations between serum phosphate and serum iron levels (r = 0.7689, p < 0.0001), serum ferritin levels (r = 0.5312, p = 0.002), iron saturation (r = 0.7907, p < 0.0001), and transferrin saturation (r = 0.7875, p < 0.001). We also examined the relationships between serum phosphate levels and hemoglobin-related indices, which were significant (hemoglobin: r = 0.71, p < 0.0001; MCV: r = 0.7589, p < 0.0001; MCH: r = 0.8218, p < 0.0001; and MCHC: r = 0.7751, p < 0.0001). Longitudinal data of six patients' follow-up also showed synchronous changes in serum phosphate with serum iron levels. CONCLUSIONS: Iron deficiency plays an important role in triggering ADHR. Monitoring and correcting the iron status are helpful for diagnosing and treating ADHR. Iron metabolism parameters and hemoglobin-related parameters are positively correlated with serum phosphate levels in patients with ADHR and iron deficiency, and these might serve as good indicators of prognosis of ADHR.
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Anemia Ferropriva , Raquitismo Hipofosfatêmico Familiar , Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Humanos , Ferro , Fosfatos , Gravidez , PrognósticoRESUMO
PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia caused by tumors with excess production of fibroblast growth factor 23 (FGF23). Some reports showed that TIO patients had renal Fanconi syndrome (FS) with unidentified mechanism. In this study, we investigated the association between genetic polymorphisms of phosphate transporters in renal proximal tubules and TIO with FS. METHODS: We recruited 30 TIO patients with FS (TIO-FS) as well as 30 TIO patients (TIO-nonFS) without any urine abnormalities matched by age and gender. We collected clinical manifestations and conducted targeted sequencing of SLC34A1, SLC34A3 and XPR1 genes and the association analysis between variants in TIO with FS and phenotypes. RESULTS: TIO-FS group had lower levels of serum phosphate (0.44 ± 0.12 vs. 0.51 ± 0.07 mmol/L, p < 0.05) than TIO-nonFS group. Among the 16 SNPs in SLC34A1, SLC34A3 and XPR1 genes, GG/GC genotypes of rs148196667 in XPR1 and AA/TA genotypes of rs35535797 in SLC34A3 were associated with a reduced susceptibility to have FS. The G allele of rs148196667 in XPR1 decreased the risk of FS. The GGAA haplotype in SLC34A3 and GCT haplotype in XPR1 were associated with a decreased risk for FS. CONCLUSIONS: The polymorphisms of XPR1 and SCL34A3 are associated with TIO patients with Fanconi syndrome. It provides novel insight to the relationship of phosphate transportation and general functions of renal proximal tubules.
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Síndrome de Fanconi , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/genética , Adulto , China/epidemiologia , Síndrome de Fanconi/epidemiologia , Síndrome de Fanconi/genética , Síndrome de Fanconi/fisiopatologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Hipofosfatemia/diagnóstico , Hipofosfatemia/etiologia , Túbulos Renais Proximais/metabolismo , Masculino , Osteomalacia/complicações , Osteomalacia/diagnóstico , Osteomalacia/epidemiologia , Osteomalacia/metabolismo , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/epidemiologia , Síndromes Paraneoplásicas/metabolismo , Fosfatos/metabolismo , Polimorfismo Genético , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
PURPOSE: Primary hyperparathyroidism (PHPT) is characterized by excessive secretion of parathyroid hormone (PTH). Vitamin D deficiency can stimulate parathyroid secretion. However, whether to correct vitamin D deficiency in patients with PHPT is controversial. We aimed to evaluate the safety and efficacy of vitamin D replacement in patients with PHPT. METHODS: We searched PubMed, Cochrane Library, and Embase. The relevant data were extracted from the included documents. The methodological items for non-randomized studies score entries were used for evaluation of quality. Review Manager 5.3 and Stata 12.0 were used for statistical analysis. RESULTS: A total of 11 articles were included with a total of 388 patients. The serum calcium mean difference (MD) was - 0.06 mg/dL [95% confidence interval (95% CI) - 0.16, 0.04]. Subgroup analysis showed that serum calcium levels did not change if the intervention time exceeded 1 month. The 24-h urinary calcium MD was 36.78 mg/day (95% CI - 37.15, 110.71), which indicated that there was no significant effect of vitamin D supplementation on 24-h urinary calcium levels. The MD of PTH was - 16.01 pg/mL (95% CI - 28.79, - 3.24). Subgroup analysis according to the intervention time showed that vitamin D intervention for more than 1 month significantly reduced PTH levels. The ALP MD was - 10.81 U/L (95% CI - 13.98, - 7.63), which indicated Vitamin D supplementation reduced its level. The MD of 25-hydroxyvitamin D was 22.09 µg/L (95% CI 15.01, 29.17), and no source of heterogeneity was found. CONCLUSION: Vitamin D supplementation in patients with PHPT and vitamin D deficiency significantly reduces PTH and ALP levels without causing hypercalcemia and hypercalciuria.
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Hiperparatireoidismo Primário , Deficiência de Vitamina D , Vitamina D , Suplementos Nutricionais , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/terapia , Resultado do Tratamento , Vitamina D/sangue , Vitamina D/farmacologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/farmacologiaRESUMO
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , China , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/terapia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/terapiaRESUMO
This study evaluated bone features of PHPT using HR-pQCT. The results showed both cortical and trabecular bones were significantly impaired in PHPT patients. Male and female PHPT patients suffered similar damages in bone. HR-pQCT indices were not observed to differ in MEN1 and sporadic PHPT patients. INTRODUCTION: High-resolution peripheral quantitative CT is a novel imaging technique used to separately assess trabecular and cortical bone status of the radius and tibia in vivo. Using HR-pQCT, we aimed to evaluate bone features of primary hyperparathyroidism patients in a Chinese population and reveal similarities and differences in bone features in multiple endocrine neoplasia type 1-related PHPT and sporadic PHPT patients in the Chinese population. METHODS: A case-control study was designed. In 58 PHPT patients and 58 sex- and age-matched healthy controls, the distal radius and tibia were scanned using HR-pQCT. Areal bone mineral density (aBMD) was also determined in PHPT patients using dual-energy X-ray absorptiometry (DXA). RESULTS: In comparison with controls, PHPT patients were observed to exhibit reduced volumetric BMD at the cortical and trabecular compartments, thinner cortices, and more widely spaced trabeculae. Significant differences were still observed when comparing data of female and male patients with age-matched controls separately. MHPT patients (n = 11) were found to have lower aBMD Z-scores in the lumbar spine, trochanteric region, and total hip compared with sporadic PHPT patients (n = 47), while no differences were observed in HR-pQCT indices between the two groups. In multiple linear regression models, no significant correlations were identified between PTH and HR-pQCT indices. However, height was found to positively correlate with HR-pQCT-derived trabecular indices at both the radius and tibia. CONCLUSIONS: PHPT affects geometry, volumetric density, and microstructure in both the cortical and trabecular bones in both male and female Chinese patients. MHPT patients were observed to have reduced aBMD as determined by DXA in the lumbar spine and hip in comparison with sporadic PHPT patients. However, HR-pQCT indices were not observed to differ.
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Densidade Óssea , Hiperparatireoidismo Primário , Neoplasia Endócrina Múltipla Tipo 1 , Absorciometria de Fóton , Adulto , Idoso , Osso Esponjoso/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/etiologia , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagemRESUMO
There is limited evidence regarding changes in bone microstructure in patients with hypoparathyroidism. In the current study, we used a non-invasive technique to assess bone structure in hypoparathyroidism patients and discovered site-specific changes which were mainly influenced by age and menstrual status. Such changes were more prominent in the trabeculae as well as in non-surgical as opposed to post-surgical patients. INTRODUCTION: Hypoparathyroidism (hypoPT) is a rare disease characterized by the lack of parathyroid hormone. There is limited evidence regarding changes in bone microstructure in patients with non-surgical hypoPT. We investigated bone microstructure of patients with non-surgical hypoPT using a non-invasive technique. METHODS: Patients with hypoPT were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) and compared to age- and sex-matched healthy controls randomly selected from a pre-existing HR-pQCT database in a cross-sectional study. Preliminary comparison between patients with different etiologies of hypoPT was performed. Associations between bone microstructure and clinical parameters were investigated using correlation and regression analyses. RESULTS: A total of 94 patients with non-surgical hypoPT were recruited. Patients displayed an increase in trabecular volumetric BMD of the tibia (170.57 ± 34.32 vs. 156.48 ± 40.55 mg HA/cm3, p = 0.011) and increase in trabecular number of both the radius (1.48 ± 0.29 vs. 1.36 ± 0.22 mm-1, p = 0.003) and tibia (1.42 ± 0.23 vs. 1.24 ± 0.22 mm-1, p < 0.001) compared to healthy controls. Trabecular number was higher for non-surgical hypoPT compared to post-surgical hypoPT (1.37 ± 0.25 and 1.17 ± 0.13 mm-1, p = 0.022). Trends towards increase in cortical volumetric BMD were only present for post-menopausal female and male patients above the age of 50. For female patients, cortical volumetric BMD and area increased with age and decreased after menopause. For males, age had little influence on bone microstructure, but cortical porosity increased with longer treatment durations. CONCLUSIONS: Results from this pilot study suggested that both cortical and trabecular bone were altered in this group of patients with hypoPT. Etiology for hypoPT might influence bone microstructure, mainly on trabeculae. Age, menstrual status, and treatment duration were likely to influence bone microstructure in hypoPT.
Assuntos
Densidade Óssea , Hipoparatireoidismo , Adulto , Estudos Transversais , Feminino , Humanos , Hipoparatireoidismo/diagnóstico por imagem , Hipoparatireoidismo/etiologia , Masculino , Projetos Piloto , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagemRESUMO
This study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%. INTRODUCTION: The purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective. METHODS: We developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model. RESULTS: Treatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%. CONCLUSIONS: Using real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.
Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Idoso , Conservadores da Densidade Óssea/economia , Conservadores da Densidade Óssea/uso terapêutico , China/epidemiologia , Análise Custo-Benefício , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Pós-Menopausa , Estudos Prospectivos , Medição de Risco , Fatores de RiscoRESUMO
This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. INTRODUCTION: This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. RESULTS: Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. CONCLUSIONS: This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients.
Assuntos
Densidade Óssea , Articulações dos Dedos , Osteoartropatia Hipertrófica Primária , Tomografia Computadorizada por Raios X , Osso e Ossos , Extremidades , Feminino , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/patologia , Humanos , Masculino , Osteoartropatia Hipertrófica Primária/diagnóstico por imagemRESUMO
Objective: To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT). Methods: Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3'untranslated region (3'UTR) of GNA11 gene, respectively. Results: Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion: The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.
Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP/genética , Predisposição Genética para Doença , Hipoparatireoidismo/genética , Adulto , Alelos , Povo Asiático , Estudos de Casos e Controles , China , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Frequência do Gene , Genótipo , Humanos , Hipoparatireoidismo/diagnóstico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Objective: To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated. Methods: This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tcm -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results: Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) (P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI (P = 0.04) or US (P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions: 4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.
Assuntos
Tomografia Computadorizada Quadridimensional , Hiperparatireoidismo Primário , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Tecnécio Tc 99m SestamibiRESUMO
In this large-sample study, we demonstrated that osteogenesis imperfecta (OI) significantly impaired the quality of life (QoL) in children. Moderate/severe OI patients had worse QoL scores than patients with mild OI. Furthermore, the QoL for OI patients was correlated with the presence of pathogenic gene mutations. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary disease characterized by multiple fragility fractures and progressive skeletal deformities. No detailed investigations about the quality of life (QoL) have been carried out in a large sample of patients with OI. We evaluated the QoL and its influencing factors in a large and well-characterized OI cohort. METHODS: We used a validated questionnaire of PedsQL 4.0 to evaluate the health-related quality of life (HRQoL) of children and adolescents with OI. We compared HRQoL among patients with OI types I, III, and IV. The relationship between HRQoL and pathogenic mutations in candidate OI genes was investigated. We also evaluated the influencing factors of HRQoL in OI patients. RESULTS: A total of 138 children with OI and 138 healthy controls were enrolled in this study. The HRQoL scores of OI patients were 64.4 ± 30.0, 71.9 ± 22.2, 75.7 ± 24.8, 63.7 ± 24.5, and 68.9 ± 22.0 in physical, emotional, social, school functioning, and total score, respectively, which were significantly lower than those of healthy children (86.5 ± 12.7, 83.3 ± 16.0, 92.1 ± 11.8, 87.5 ± 11.8, and 87.3 ± 10.7, all p < 0.01). Moderate and severe OI (type III/IV) patients had poorer HRQoL scores than patients with mild OI (type I). Gene mutations inducing qualitative defects in type I collagen led to worse HRQoL scores than those with quantitative defects in type I collagen, except in emotional functioning. The total HRQoL score was positively correlated with family income, lumbar, and femoral bone mineral density (BMD) Z-scores and negatively correlated with disease severity and fracture frequency. CONCLUSION: HRQoL was significantly impaired in OI patients, and patients with more severe OI had poorer HRQoL scores. For the first time, we found that children with qualitative defects in type I collagen had poorer HRQoL scores than those with quantitative defects in type I collagen.