Associations of different dietary patterns, bone mineral density, and fracture risk among elderly women: the China Osteoporosis Prevalence Study.

Objective: Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men. Methods: Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant. Results: A diet rich in "carnivorous", "vegetarian", "dairy, fruit, and egg" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in "beverage and fried food" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures. Conclusions: Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Orthopedic Surgical Treatment of Patients with Tumor-induced Osteomalacia Located in the Hip Bones: A Retrospective Analysis of 10 Years in a Single Center.

OBJECTIVE: The orthopedic surgical treatment strategies for patients with tumor-induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in-depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor-induced osteomalacia (TIO), whose causative tumors are located in the hip bones. METHODS: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub-professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery-related data, perioperative changes in blood phosphorus levels, and postoperative follow-up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are shown as the means and 25th and 75th interquartile ranges. RESULTS: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. CONCLUSION: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

Identification of rare and novel PHEX variants in X-linked hypophosphatemia.

CONTEXT: X-linked hypophosphatemia (XLH) is a rare metabolic bone disease caused by inactivation mutations in the PHEX gene. Despite the extensive number of reported PHEX variants, only a few cases of chromosomal abnormalities have been documented. OBJECTIVE: We aimed to identify the pathogenic variants in six unrelated families with a clinical diagnosis of XLH and to propose a genetic workflow for hypophosphatemia patients suspected of XLH. METHODS: Multiple genetic testing assays were used to analyze the six families' genetic profiles, including whole exome sequencing, multiplex ligation-dependent probe amplification, whole genome sequencing, reverse transcript polymerase chain reaction, Sanger sequencing, and karyotyping. RESULTS: The study identified six novel pathogenic variants, including one mosaic variant (exon 16-22 deletion), three chromosomal abnormalities (46, XN, inv[X][pter→p22.11::q21.31→p22.11::q21.31 →qter], 46, XN, inv[X][p22.11p22.11], and XXY), a nonclassical intron variant (NM_000444.6, c.1701_31A > G), and a deletion variant (NM_000444.6, c.64_5464-186 del5215) of PHEX. Additionally, a genetic testing workflow was proposed to aid in diagnosing patients suspected of XLH. CONCLUSION: Our research expands the mutation spectrum of PHEX and highlights the significance of utilizing multiple genetic testing methods to diagnose XLH.

Randomized, double-blind, placebo-controlled, multicenter study to evaluate efficacy and safety of the denosumab biosimilar MW031 in Chinese postmenopausal women with osteoporosis.

BACKGROUND: This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included. RESULTS: Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups. CONCLUSION: This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis. TRIAL REGISTRATION: NCT05215977 (ClinicalTrials.gov.).

Preoperative evaluation and orthopedic surgical strategies for tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.

Disruption of FLNB leads to skeletal malformation by interfering with skeletal segmentation through the HOX gene.

Filamin B (FLNB) plays an important role in skeletal development. Mutations in FLNB can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation. In situ hybridization of embryos was performed to examine the transcription of HOX genes during embryonic development. The expression of FLNB was downregulated in FLNBG1586R/G1586R and FLNBWT/G1586R mice, compared to FLNBWT/WT mice. Fusions in tarsal bones were found in FLNBG1586R/G1586R and FLNBWT/G1586R mice, indicating that the skeletal segmentation was interfered with. In the embryo of FLNBG1586R/G1586R mice (E12.5), the transcription levels of HOXD10 and HOXB2 were downregulated in the carpal region and cervical spine region, respectively. This study indicated that the loss-of-function mutation G1586R in FLNB may lead to abnormal skeletal segmentation, and the mechanism was possibly associated with the downregulation of HOX gene transcription during the embryonic period.

Characterization of novel PHEX variants in X-linked hypophosphatemic rickets and genotype-PHEX activity correlation.

BACKGROUND: X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. At present, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully understood. METHODS: In this study, we summarized clinical features in a new cohort of 49 HR patients and detected 16 novel PHEX and 5 novel non-PHEX variants. Subsequently, we studied the pathogenesis of new variants by protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. RESULTS: The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering protein length and localization, whereas truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein in cells. Interestingly, no evident correlation was observed between mutation types and clinical phenotypes. However, when we analyzed the relationship between PHEX activity and serum phosphorus level, we found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Following this observation, we established two new knock-in XLHR mouse models with two novel Phex variants (c.T1349C and c.C426G, respectively) using CRISPR/Cas9 technology. Both mouse models demonstrated clinical manifestations of XLHR seen in patients and PhexC426G mice showed more severe phenotype than PhexT1349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. CONCLUSION: Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study facilitates a better understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation, which is of crucial importance for future diagnosis and treatment of XLHR.

Utilization of Nitrogen-Doped Graphene Quantum Dots to Neutralize ROS and Modulate Intracellular Antioxidant Pathways to Improve Dry Eye Disease Therapy.

Purpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED. Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice. Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 µg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels. Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.

Novel 4.18 Mb deletion resulting in 2q37 microdeletion syndrome combined with PTH resistance found in one Chinese patient.

BACKGROUND: 2q37 microdeletion syndrome is a rare clinical condition characterized by a series of physical abnormalities. Its Albright hereditary osteodystrophy (AHO)-like manifestations and possible complication of biochemical abnormalities indicating PTH resistance greatly increased the likelihood of misdiagnosis with classic pseudohypoparathyroidism (PHP) caused by GNAS mutation or methylation alteration, even though there have only been six reports of such clinical occasions. PURPOSE: to investigate the underlying genetic defect in a male patient presenting hypocalcemia, elevated PTH and with a history of kyphosis. METHOD: clinical information was collected, while the DNA was extracted from peripheral blood and subjected to methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and exome sequencing. RESULT: Physical characteristics featuring short stature, obesity, round face, short neck, and shortened 4th metacarpal and laboratory examination of the patient suggested the presence of PTH resistance, which is indicative of PHP. MS-MLPA did not reveal methylation alterations or deletions of GNAS, STX16 or other monogenetic alterations responsible for iPPSDs, but WES revealed a long-range deletion of approximately 4.18 Mb of the 2q37 region that spanned AGAP1 to NDUFA10, indicating that the patient had 2q37 microdeletion syndrome with PTH resistance. CONCLUSION: After undergoing MS-MLPA and exome sequencing, a novel deletion spanning 4.18 Mb on the 2q37 region was identified in one male patient, clarifying the diagnosis of 2q37 microdeletion syndrome with PTH resistance. The new genetic discovery added to our understanding of the molecular defects that cause inactivating PTH/PTH-related protein signaling disorders (iPPSDs).

Efficacy and Safety of Denosumab vs Zoledronic Acid in OI Adults: A Prospective, Open-Label, Randomized Study.

CONTEXT: The comparative effectiveness of denosumab and zoledronic acid for adult patients with osteogenesis imperfecta (OI) has not been established. OBJECTIVE: To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI. METHODS: This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS), and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated. RESULTS: A total of 51 adults with OI (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = .005) and 1.45% (P = .023) in the denosumab group and by 4.92% (P = .006) and 2.02% (P = .016) in the zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of ß-isomerized carboxy-telopeptide of type I collagen and alkaline phosphatase markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS, and BTMs during the treatment were similar between the 2 groups. Patients with OI with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = .030). During the study period, the denosumab group had fewer adverse events than the zoledronic acid group. CONCLUSION: Denosumab effectively increases aBMD in adults with OI, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the antifracture efficacy and safety of denosumab in adult patients with OI.

Safety and Efficacy of Denosumab in Children With Osteogenesis Imperfecta-the First Prospective Comparative Study.

CONTEXT: Denosumab is a potential therapeutic agent for osteogenesis imperfecta (OI), but its efficacy and safety remain unclear in children with OI. OBJECTIVE: We aimed to investigate the effects of denosumab on bone mineral density (BMD), spinal morphometry, and safety in children with OI compared with zoledronic acid. METHODS: In this prospective study, 84 children or adolescents with OI were randomized to receive denosumab subcutaneous injection every 6 months or zoledronic acid intravenous infusion once. Changes of BMD and its Z-score, vertebral shape, serum levels of calcium and bone turnover biomarkers were assessed during the 1-year treatment. RESULTS: After 12 months of treatment, BMD at the lumbar spine, femoral neck, and total hip significantly increased by 29.3%, 27.8%, and 30.2% in the denosumab group, and by 32.2%, 47.1%, and 41.1% in the zoledronic acid group (all P < .001 vs baseline). Vertebral height and projection area significantly increased after denosumab and zoledronic acid treatment. Rebound hypercalcemia was found to be a common and serious side effect of denosumab, of which 14.3% reached hypercalcemic crisis. Rebound hypercalcemia could be alleviated by switching to zoledronic acid treatment. CONCLUSION: Treatment with denosumab or zoledronic acid is beneficial in increasing BMD and improving the spinal morphometry of children with OI. However, denosumab should be used with caution in pediatric patients with OI because of its common and dangerous side effect of rebound hypercalcemia. The appropriate dosage and dosing interval of denosumab need to be further explored in children with OI.

Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants.

OBJECTIVE: Deficiency of cartilage-associated protein (CRTAP) can cause extremely rare autosomal recessive osteogenesis imperfecta (OI) type VII. We investigated the pathogenic mechanisms of CRTAP variants through functional studies on bones of patients with OI. METHODS: Two nonconsanguineous families with CRTAP mutations were included and their phenotypes and genotypes were evaluated. Bone specimens were obtained from 1 patient with OI and a normal control during orthopedic surgery. The impacts of the novel variant on the CRTAP transcript were confirmed. The expression levels of CRTAP mRNA and CRTAP protein were analyzed. The quantification of prolyl 3-hydroxylation in the α1 chain of type I collagen was evaluated. RESULTS: Patients with OI type VII had early-onset recurrent fractures, severe osteoporosis, and bone deformities. The c.621 + 1G > A and c.1153-3C > G mutations were identified in CRTAP in the patients with OI. The c.621 + 1G > A variant was a novel mutation that could impair mRNA transcription, leading to a truncated CRTAP protein. In a patient with c.621 + 1G > A and c.1153-3C > G mutations in CRTAP, the mRNA and protein levels of CRTAP in osteoblasts were significantly decreased and the osteoid volume and osteoblast numbers were markedly reduced compared with those in the normal control individual. This was simultaneously accompanied by significantly reduced prolyl 3-hydroxylation at Pro986 in the α1 chain of type I collagen and invisible active bone formation in bone. CONCLUSION: The novel c.621 + 1G > A mutation in CRTAP expands the genotypic spectrum of type VII OI. Biallelic mutations of c.621 + 1G > A and c.1153-3C > G in CRTAP can lead to reduced CRTAP mRNA and deficient CRTAP protein in osteoblasts, which reduces 3-hydroxylation in Pro986 of the α1 chain of type I collagen and impairs bone formation, thus contributing to severe OI type VII.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

BACKGROUND: Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. OBJECTIVE: This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. METHOD: 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum ß-isomer of C-terminal telopeptides of type I collagen (ß-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. RESULTS: Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. CONCLUSION: All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

Early bone loss in patients with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism. METHODS: Male participants aged 30-59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia. RESULTS: Ninety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius. CONCLUSIONS: In non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.

Explorative research on glucolipid metabolism and levels of adipokines in pseudohypoparathyroidism type 1 patients.

BACKGROUND: Pseudohypoparathyroidism type 1 (PHP1) is a rare disease featuring hypocalcemia and elevated PTH level. Though disturbed calcium and phosphorus metabolism under PTH resistant have been widely studied, glucolipid metabolism abnormalities observed in PHP1 patients have received little attention. The aim of this research is to explore the glucolipid metabolism features in a rather large cohort of PHP1 patient. In the current study, PHP1 patients and primary hyperparathyroidism patients as well as normal control were recruited for the investigation. Glucolipid metabolic indices as well as the level of four adipokines were examined. RESULTS: A total of 49 PHP1 patients, 64 PHPT patients and 30 healthy volunteers were enrolled. A trend of higher HOMA-ß index was found in PHP1 patients than normal controls (median 97.08% vs 68.19%, p = 0.060). Both the PHP1 and PHPT group presented with significantly lower TNFα level compared to normal controls (average 10.74 pg/ml and 12.53 pg/ml vs 15.47 pg/ml, p = 0.002 and 0.041, respectively). FGF21 level was significantly higher in PHPT group than in PHP1 group (median 255.74 pg/ml vs 167.46 pg/ml, p = 0.019). No significant difference in glucolipid metabolic indices and adipokines was found between PHP1A or PHP1B patients and normal controls, while overweight/obese PHP1 patients tended to have higher leptin than normal-BMI cases (p = 0.055). Multiple linear regression analysis showed BMI rather than PTH or HOMA-IR to be an independent variable of leptin in PHP1. CONCLUSION: Metabolic stress given upon especially overweight PHP1 patients may resulted in possible ß-cell compensation. Elevated TNFα may be related with hyper-PTH level regardless of calcium level.

Effects of online continuing medical education on perspectives of shared decision-making among Chinese endocrinologists.

BACKGROUND: Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. METHODS: In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians' perspectives during the process of SDM, which was conducted before and after the CME course was provided. RESULTS: In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants' age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). CONCLUSIONS: Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician's educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.

Genotype-phenotype correlations in pseudohypoparathyroidism type 1a patients: a systemic review.

BACKGROUND: Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding protein (Gsα) resulting from maternal GNAS gene variation. The clinical manifestations are related to PTH resistance (hypocalcemia, hyperphosphatemia, and elevated serum intact PTH) in the presence or absence of multihormone resistance, and Albright's hereditary osteodystrophy (AHO). OBJECTIVES: To summarize the molecular genetics results and clinical characteristics as well as to explore the correlations between them. METHODS: Articles pertaining to PHP1a until May, 31, 2021 were reviewed and 527 patients with genetic diagnosis were included in the data analysis. The clinical characteristics and molecular genetics results of these patients were analyzed and compared to explore the correlations between them. RESULTS: A total of 258 GNAS rare variants (RVs) were identified in 527 patients. The RVs were most commonly found in exons 1 and 7 (17.6% each), with frameshift (36.8%), and missense (31.3%) being the main types of RVs. The median age of onset was 5.0 years old. The most common clinical manifestations were elevation of PTH (86.7%) and AHO (87.5%). Thyroid stimulating hormone resistance was the most common hormone resistance (75.5%) other than PTH resistance. Patients with missense and in-frame RVs had lower incidence rates of the round face (P = .001) and subcutaneous ossifications (P < .001) than those with loss-of-function (non-sense, frameshift, splicing site variants, and large deletions) variants. CONCLUSIONS: This study revealed the correlation between loss-of-function RVs with round faces and subcutaneous ossifications in PHP 1a patients. Further exploration of genotype-phenotype correlations through more standardized and prospective studies with long-term follow-up is necessary.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

Influence of Obesity and Changes in Weight or BMI on Incident Fractures in Postmenopausal Women: From Peking Vertebral Fracture Study.

This study aims to investigate the influence of overweight/obesity and change in weight or body mass index (BMI) on incident fractures among Chinese postmenopausal women. According to BMI, 754 postmenopausal women were categorized into normal weight (NW), overweight (OW), and obesity (OB) groups, respectively. We used data from the baseline and the second survey for statistical analysis, including anthropometric data, clinical fractures, and morphometric vertebral fractures (MVFs) assessed by X-rays. The prevalence of previous MVFs was 32.7% and 21.8% in the OB and NW groups, respectively (p < 0.05). All incident fractures and incident MVFs accounted for 10.7 and 6.3% among all participants within five years. Overweight/obesity and increase in weight or BMI during the follow-up had no associations with all incident fractures, incident MVFs, and incident clinical non-VFs among all participants. However, after multivariate adjustment, the increased BMI at baseline was the risk factor of incident MVFs in the OW group (odds ratio, OR 2.06, 95% confidence interval, 95% CI 1.16-3.66, p = 0.014), and increase in weight (OR 0.89, 95% CI 0.79-0.99, p = 0.036) or BMI (OR 0.77, 95% CI 0.59-0.99, p = 0.045) during the follow-up were the protective factors of all incident fractures in the NW group. Overweight/obesity and change in weight or BMI do not correlate with fracture risk in postmenopausal women, but an increase in weight is the protective factor against incident fractures in normal-weight participants. Overweight postmenopausal women with a higher BMI should pay attention to the risk of MVFs.