Explore the vast range of titles available.

BackgroundOsteoporosis has been one of the most common but largely under-diagnosed clinical problems among elderly population. The disease burden is even greater in China because of limited medical resources and large population size. This article is aimed to provide an overview of disease burden, secular trend, and management gap of osteoporosis and related fractures in China.MethodsBased on the related studies published in English and Chinese from 1990 to 2017, we investigated the prevalence/incidence of osteoporosis and osteoporotic fracture in Chinese mainland, Hong Kong, and Taiwan, characterizing the secular trend and disease burden in different regions. Strict inclusion criteria were applied to control the study quality. We further examined the diagnosis and treatment gap of osteoporosis management observed in clinical practice in China and summarized the efforts made by Chinese government and scholars to combat this situation.ResultsTwenty-seven studies concerning osteoporosis prevalence in China (including Chinese mainland, Hong Kong, and Taiwan) met the inclusion criteria and were included in the final analysis. Another 15 studies about hip fracture incidence and 13 studies about vertebral fracture prevalence/incidence were also included. The epidemiological data varied greatly across studies due to different design and population included. A higher prevalence was indicated in female population, older age groups, and residents in northern China compared to their counterparts. Though attenuated increased rates or slight decline patterns have been observed in Hong Kong and Taiwan, osteoporotic fracture incidence still showed steady increase in Chinese mainland. The diagnosis and treatment of osteoporosis as well as post-fracture management were still insufficient in China.ConclusionDue to its silent nature, osteoporosis and its related fractures remain largely under-diagnosed and under-managed in China. It also highlights the scarcity of high-quality studies specifically focus on longtime documentation of disease burden change and male population, especially in mainland area.

Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin’s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE −/− mice and hSOST ki .ApoE −/− mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOST ki mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation. Antibodies targeting sclerostin can ameliorate postmenopausal osteoporosis but present some cardiovascular risk. Here the authors show that the cardiovascular and skeletal effects of sclerostin are mediated by different loops, suggesting ways to preserve the positive effects on bone formation while avoiding the negative cardiovascular consequences.

Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months–90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ − 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences.

Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.

Background Thyroid hormone is a known pivotal factor that affects bone metabolism; however, whether bone microarchitecture is associated with thyroid hormone sensitivity is poorly understood. The trabecular bone score (TBS) serves as an essential indicator for assessing bone microarchitecture. This study aimed to investigate the relationship between sensitivity to thyroid hormones and TBS in euthyroid individuals. Methods This cross-sectional study involved 3320 euthyroid participants from the National Health and Nutrition Examination Survey (NHANES) 2007–2008. Data, including thyroid function, TBS and other related parameters, were extracted and analyzed. The indices of thyroid hormone sensitivity, including the thyrotropin thyroxine resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), thyroid feedback quantile-based index (TFQI) and parametric thyroid feedback quantile-based index (PTFQI), were calculated. Greater values of these indicators indicated a greater degree of impaired thyroid hormone sensitivity. Results Impaired sensitivity to thyroid hormones was associated with degraded bone microarchitecture following adjustments for confounding variables (TT4RI: P  = 0.005, TSHI: P  = 0.008, TFQI: P  = 0.003 and PTFQI: P  = 0.006). The restricted cubic spline model demonstrated a positive relationship between TT4RI, TSHI, TFQI, PTFQI and degraded bone microarchitecture. Similar findings were observed in the analysis of subgroups stratified by age, sex, race, diabetes status, hypertension status and hyperuricemia status. Conclusions In euthyroid individuals, impaired sensitivity to thyroid hormones is associated with degraded bone microarchitecture. However, further studies are required to confirm this relationship.

IntroductionOsteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).Methods and analysisThis study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.Ethics and disseminationThe study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.Trial registration numberNCT05866029.

Background Due to its occult position, complex anatomical structure, and spatial relationships, the causative tumor of Tumor-Induced Osteomalacia (TIO) in the hip region is quite difficult to detect and qualitatively diagnose in clinical practice. In this regard, clinicians often lack sufficient knowledge about such tumors, leading to frequent missed diagnoses, misdiagnoses, and unreasonable treatment. Objective This study aimed to investigate the clinical characteristics of TIO patients with culprit soft tissue tumors in the hip region and evaluate the effect of surgical treatment on these individuals to improve clinicians’ understanding of the rare phenomenon. Methods The clinical data of all patients, from January 2013 to January 2023, who underwent surgical treatment for hip located culprit soft tissue tumors by the subspecialty group on bone and soft tissue tumors at our institution, were retrospectively analysed. Specifically, the clinical characteristics and therapeutic effects were examined and the patients’ clinical experience was summarized. Results Twenty-two patients, who met the inclusion criteria, were included. All patients experienced varying degrees of bone pain, commonly accompanied by weakness (16/22) and limited mobility (21/22), and 10 patients (45.5%) experienced a significant reduction in body height during the course of the disease. All patients underwent orthopedic surgery in the hip region, as hypophosphatemia occurred in all of them. Pathological diagnosis was confirmed to be consistent with causative tumors of TIO. All patients experienced a gradual increase in serum phosphorus postoperatively during short-term follow-up. The follow-up period was between 1 and 10 years, and the postoperative serum phosphorus levels were monitored at our hospital or other facilities close to the patients. Conclusions Oncogenic soft tissue tumors for TIO in the hip region are occult, making clinical misdiagnoses or missed diagnoses highly likely. Therefore, enhancing the clinician’s understanding of this rare condition is imperative. Notably, for TIO patient whose culprit tumor can be located, complete surgical resection of the causative tumor is the best treatment option. Furthermore, close postoperative monitoring of serum phosphorus is necessary, and patients should be subjected to long-term follow-up for prompt detection of recurrent conditions. Highlights Tumor-induced osteomalacia caused by causative soft tissue tumor in the hip region is a rare entity, resulting in great challenges to orthopedists. Qualitative and localized diagnosis led by multi-disciplinary team is a prerequisite for subsequent surgical intervention. For the inguinally located culprit tumors, it may be quite effective after remove the culprit tumor directly and surgical resection may bring huge benefit. Exploring the site of onset of the causative tumor is beneficial for improving the treatment strategy of orthopedic surgery and understanding the prognostic characteristics of TIO patients.

Background Current research on osteoporosis (OP) in hemophilia is insufficient. The suitability of high-resolution peripheral quantitative computed tomography (HR-pQCT) for evaluating osteoporosis in hemophilia remains unclear. Aim To investigate the current status of osteoporosis and the applicability of HR-pQCT in adult hemophilia patients. Methods Thirty three hemophilia patients aged 23–49 years were recruited. X-ray examinations were performed on the bleeding joints. Dual energy X-ray absorptiometry (DXA) and HR-pQCT were used to assess bone mineral density (BMD). The HR-pQCT values of the distal tibia and radius were compared between hemophilia patients and healthy controls(HCs). Results All bleeding joints showed local osteoporosis on X-ray. Only 33.3% of patients had a hip BMD lower than the expected value according to DXA. The Tb.vBMD(98.5 ± 44.2 mg/cm 3 ), Tt.Ar(612.5 ± 163.5mm 2 ),Tb.Ar(487.0 ± 175.6mm 2 ), Ct.Ar(117.0 ± 25.7mm 2 ), Tb.BV/TV(0.2 ± 0.1), Tb.N(0.9 ± 0.3 1/mm), Ct.Pm(96.3 ± 13.8 mm) of the distal tibia and Tt.Ar(248.4 ± 53.1mm 2 ),Tb.Ar(186.0 ± 55.1mm 2 ), Ct.Ar(66.1 ± 14.4 mm 2 ), Ct.Pm(68.1 ± 7.1 mm) of the distal radius in the hemophilia group was significantly lower than the HCs(tibia Tb.vBMD:186.4 ± 44.3mg/cm 3 , Tt.Ar:906.8 ± 135.0mm 2 ,Tb.Ar:743.7 ± 137.6mm 2 , Ct.Ar:169.3 ± 21.9mm 2 ,Tb.BV/TV:0.3 ± 0.1, Tb.N:1.5 ± 0.2 1/mm,Ct.Pm:117.8 ± 8.2 mm; radius Tt.Ar:285.7 ± 35.6 mm 2 , Tb.Ar:83.8 ± 7.9mm 2 , Ct.Ar:0.3 ± 0.1mm 2 , Ct.Pm:80.2 ± 4.3 mm) with statistically significant differences ( p  < 0.05). Correlation analysis showed a positive correlation ( r  = 0.768, p  = 0.016) between femoral neck BMD with DXA and total volumetric BMD(Tt.vBMD) at the distal tibia. Conclusion The bone health status of adult hemophilia patients in China is worrying. The occurrence of OP may be accompanied by varying degrees of bone loss, bone destruction, and structural abnormalities observed in both trabecular and cortical bones of the upper and lower limbs. The condition of the trabecular bones in the lower limbs is particularly severe. The correlation between BMD measurements obtained from HR-pQCT and DXA is strong.

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. 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. , 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. These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H O -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. 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.

PurposeThe increased social and economic burdens make osteoporosis in men an emerging public health issue. However, the quality of life among men with osteoporosis is still unclear. This systematic review and meta-analysis aimed to evaluate the health-related quality of life (HRQoL) among men with osteoporosis or osteoporotic fracture.MethodsPubMed, EMBASE, and the Cochrane Library database were systematically searched from inception to May 2021. Studies were included if they used validated questionnaires to measure HRQoL among osteoporotic men. A meta-analysis was performed using a random-effects model or fixed-effects model to calculate the standard mean difference (SMD) or mean difference (MD) with 95% confidential interval (95% CI).Results14 studies involving 6338 male participants were chosen for systematic review, of which 10 were included in the meta-analysis. Men with osteoporosis had poorer global HRQoL and multiple dimensions of HRQoL than men without osteoporosis. Hip fracture, vertebral fractures, or wrist fractures dramatically impaired HRQoL of men, and physical function was declined even before hip fracture (SMD = −0.60, 95% CI, −0.82 to −0.39). Femoral and lumbar BMD was positively correlated with HRQoL, and a number of fragility fractures and time since fracture had negative effects on HRQoL. Effective anti-osteoporotic drugs could improve HRQoL of men.ConclusionThe health-related life quality of men was significantly impaired by osteoporosis and fracture of the hip, vertebral, or wrist. We should pay more attention to the diagnosis and treatment of male osteoporosis to improve the life quality of men.