Current status of clinical nursing specialists and the demands of osteoporosis specialized nurses in China's Mainland

The clinical nursing specialist(CNS)is an expert who applies an expanded range of practical,theoretical,and research-based competencies to the care of patients within in a specialty clinical area within the larger discipline of nursing.A large number of studies consistently conclude that the CNS is a valuable healthcare resource that provides highquality clinical and evidence-based nursing practice and improves patient outcome.The CNS has been involved in healthcare practices for many years,with an increasingly diverse role.However,the training for the CNS in China is only in a preliminary developmental stage.The aim of this article is to review the history and development of the CNS role.Furthermore,the epidemiologic status of osteoporosis,as well as the feasibility and necessity of developing training programs in China for the osteoporosis CNS,will be discussed.

A Case Report of Alendronate Treatment over 20 Years on Osteoporosis and Literature Review

Osteoporosis is commonly seen in aged people, but not much attention is paid to it. Patient compliance is challenged by many factors, including long-time treatment and high rates of fatality and disability caused by fragility fractures. With age-related changes, the treatment will last for a lifetime. A clinical case of postmenopausal patient who had received incontinuous treatment of alendronate for 20 years was studied in this article. As the level of compliance varied in different treatment phases, the curative outcome of this patient was altered. This study also presented a literature review to discuss the current situation, treatment and compliance of osteoporosis in China and the corresponding influences on bone mineral density (BMD) and prognosis. Hopefully, this study can increase physicians’ awareness of osteoporosis in clinical treatment and its pharmacotherapy and treatment course.

The effect of traditional Chinesemedicine washing combined withmassage for neonataljaundice： a meta-analysis

Objective： To systematically assess the effect of traditional Chinese medicine washing （TCM washing） combined withmassage for the treatment of neonatal jaundice.Methods and analysis： Databases, including PubMed, the Cochrane Library, Embase, Web of Science, the ChineseBiomedical Literature Database （CBM）, CNKI, and Wanfang Data were electronically searched for randomizedcontrolled trials （from inception to July 2017）. The methodological qualities of included trials were evaluated by theCochrane risk of bias assessment tool. The meta-analysis was performed by using RevMan 5.3 software.Results： Overall, thirteen trials with a total of 1998 participants were included. The results of meta-analysis indicatedthat TCM washing combined with massage group was significantly superior to the control group in the first meconiumtime （MD, -16.67; 95% CI, -24.59 to -8.74; P〈0.001）, time for transformation of meconium （MD, -15.44; 95% CI,-23.59 to -7.28; P〈0.001）, transcutaneous bilirubin index changes [after treating three days （MD, -1.99; 95% CI, -2.57 to-1.40; P〈0.001）, after treating four days （MD, -1.86; 95% CI, -2.77 to -0.95; P〈0.001）, after treating five days （MD,-2.44; 95% CI, -3.47 to -1.42; P〈0.001）, after treating six days （MD, -2.23; 95% CI, -3.30 to -1.16; P〈0.001）, and thechanges of serum bilirubin levels [after treating five days （MD, -3.17; 95% CI, -5.83 to -0.50; P=0.02）, after treating sixdays （MD, -1.63; 95% CI, -3.10 to -0.16; P=0.03）, after treating fifteen days （MD,-1.20; 95% CI, -1.99 to -0.41; P=0.003）.Conclusions： TCM washing combined with massage may be an effective therapy for the treatment of neonatal jaundice.It can accelerate the excretion of meconium, shorten the time for transformation of meconium, and decreasetranscutaneous bilirubin index and the level of serum bilirubin. But it should be careful to interpreting these findings.Well-designed RCTs are needed to further clarify the conclusion.

Association between serum estradiol level and appendicular lean mass index in middle-aged postmenopausal women

BACKGROUND Previous studies investigating the association between loss of estrogen at menopause and skeletal muscle mass came to contradictory conclusions.AIM To evaluate the association between serum estradiol level and appendicular lean mass index in middle-aged postmenopausal women using population-based data.METHODS This study included 673 postmenopausal women,aged 40-59 years,from the National Health and Nutrition Examination Survey between 2013 and 2016.Weighted multivariable linear regression models were used to evaluate the association between serum E2 Level and appendicular lean mass index(ALMI).When non-linear associations were found by using weighted generalized additive model and smooth curve fitting,two-piecewise linear regression models were further applied to examine the threshold effects.RESULTS There was a positive association between serum E2 level and ALMI.Compared to individuals in quartile 1 group,those in other quartiles had higher ALMI levels.An inverted U-shaped curve relationship between serum E2 Level and ALMI was found on performing weighted generalized additive model and smooth curve fitting,and the inflection point was identified as a serum E2 level of 85 pg/mL.CONCLUSION Our results demonstrated an inverted U-shaped curve relationship between serum E2 levels and ALMI in middle-aged postmenopausal women,suggesting that low serum E2 levels play an important in the loss of muscle mass in middleaged postmenopausal women.

Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis

Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase （FDPS） in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.Methods The study group comprised 639 postmenopausal women aged （62.2＆#177;7.0） years with osteoporosis or osteopenia who had been randomly assigned to low dose group （70 mg/2w） or standard dose group （70 mg/w） of alendronate in this 1-year study.We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul.Before and after treatment,serum levels of calcium,phosphate,alkaline phosphatase （ALP）,cross linked C-telopeptide of type Ⅰ collagen （β-CTX） were detected.Bone mineral density （BMD） at lumbar spine and proximal femur was measured.The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD,bone turnover biomarkers after the treatment.Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck,and patients with CC genotype had significantly higher baseline femoral neck BMD （（733.6＆#177;84.1） mg/cm2） than those with AC genotypes （（703.0＆#177;86.9） mg/cm2） and AA genotypes （（649.8＆#177;62.4） mg/cm2） （P 〈0.01）.No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS.The percentage change of serum ALP level was significantly lower in patients with CC genotype （-22.9%） than that in those with AC genotype （-24.1%） and AA genotype （-29.8%） of FDPS after 12 months of alendronate treatment （P 〈0.05）.Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline.FDPS gene alleles could predict change percentage of ALP after treatment of alendronate,but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Toll-like receptor 9 defciency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation

Toll-like receptors(TLRs)play pivotal roles in inflammation and provide important links between the immune and skeletal systems.Although the activation of TLRs may affect osteoclast differentiation and bone metabolism,whether and how TLRs are required for normal bone remodeling remains to be fully explored.In the current study,we show for the first time that TLR9^(-/-)mice exhibit a low bone mass and low-grade systemic chronic inflammation,which is characterized by the expansion of CD4^(+)T cells and increased levels of inflammatory cytokines,including TNFα,RANKL,and IL1β.The increased levels of these cytokines significantly promote osteoclastogenesis and induce bone loss.Importantly,TLR9 deletion alters the gut microbiota,and this dysbiosis is the basis of the systemic inflammation and bone loss observed in TLR9^(-/-)mice.Furthermore,through single-cell RNA sequencing,we identified myeloid-biased hematopoiesis in the bone marrow of TLR9^(-/-)mice and determined that the increase in myelopoiesis,likely caused by the adaptation of hematopoietic stem cells to systemic inflammation,also contributes to inflammation-induced osteoclastogenesis and subsequent bone loss in TLR9^(-/-)mice.Thus,our study provides novel evidence that TLR9 signaling connects the gut microbiota,immune system,and bone and is critical in maintaining the homeostasis of inflammation,hematopoiesis,and bone metabolism under normal conditions.

Prevalence of osteoporotic vertebral fracture among community-dwelling elderly in Shanghai

To the Editor:Osteoporosis is becoming a common,serious,and costly health problem,which causes over nine million fractures annually worldwide.[1] Currently,osteoporotic fractures are a considerable burden to public health services and have fairly high morbidity and mortality.[2] Vertebral fractures are the most common osteoporotic fracture and may lead to a high risk of further fracture and could be prevalent in both females and males.[3] Ling et al[4] and Ms.OS studies[5] evaluated the prevalence of vertebral fractures in Beijing and Hong Kong,respectively.However,our knowledge of the descriptive epidemiology and risk factors for vertebral fracture in China still remains poor.

Drug discovery of sclerostin inhibitors

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

Clinical and genetic profiles of 985 Chinese families with skeletal dysplasia

To the Editor:Skeletal dysplasia is a group of clinical and genetic heterogeneous disorders with primary involvement of the musculoskeletal system,including bone,cartilage,tendons,ligaments,and muscles,and is usually characterized by short stature,motion limitation,or fragility fractures,sometimes complicated with extra-skeletal phenotypes.

Consensus on clinical management of tumor-induced osteomalacia

Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23(FGF23)production by a tumor,which often arises from a mesenchymal origin.[1-3]Most clinical symptoms of TIO are the consequences of prolonged FGF23-mediated hypophosphatemia as muscle weakness,bone pain,impaired mobility,and fractures.[4]Clinical diagnosis and management of TIO are challenging because knowledge about this condition is still restricted to a few specialized centers,leading to delay in diagnosis and appropriate treatment.The scope of the present consensus is to provide up-to-date guidance on the assessment and treatment of TIO.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles:Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus

Diabetic wound healing has become a serious healthcare challenge.The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction,resulting in chronic inflammation,abnormal vascular function,and tissue necrosis.To solve these issues,we developed a double-network hydrogel,constructed with pluronic F127 diacrylate(F127DA)and hyaluronic acid methacrylate(HAMA),and enhanced by SS31-loaded mesoporous polydopamine nanoparticles(MPDA NPs).As components,SS31,a mitochondria-targeted peptide,maintains mitochondrial function,reduces mitochondrial reactive oxygen species(ROS)and thus regulates macrophage polarization,as well as promoting cell proliferation and migration,while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation,but also control release of SS31 in response to ROS.This F127DA/HAMA-MPDA@SS31(FH-M@S)hydrogel has characteristics of adhesion,superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31(M@S)NPs.In addition,in a diabetic rat full thickness skin defect model,the FH-M@S hydrogel promoted macrophage M2 polarization,collagen deposition,neovascularization and wound healing.Therefore,the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Unexpected vertebral metastasis of parathyroid carcinoma

To the editor：Parathyroid carcinoma is an uncommon cause of parathyroid hormone （PTH）-dependent hypercalcemia and its timely diagnosis and treatment remains a clinical challenge.1 Here,we report a case in which extremely rare distinct metastatic foci of parathyroid carcinoma within the fourth lumbar vertebra was found.A 53-year-old man was admitted to a local hospital with persistent symptoms of generalized weakness,nausea,and vomiting on February 8,2012.Primary hyperparathyroidism and right sided parathyroid adenoma was diagnosed and right parathyroidectomy was performed.But,the patient＆#39;s hypercalcemia remained and he underwent en bloc resection.Unfortunately,his calcium level still fluctuated between 3.08-4.60 （normal,2.08-2.60） mmol/L and the PTH level was 283.9 （normal,15-65） ng/L.The patient was transferred to our hospital on May 2 and he was found severely hypercalcemic upon admission （serum calcium：4.43 mmol/L;PTH：3 235 ng/L）.10.3760/cma.j.issn.0366-6999.20132122.

Small extracellular vesicles in combination with sleep-related circRNA3503:A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis

Osteoarthritis(OA),characterized by chondrocyte apoptosis and disturbance of the balance between catabolism and anabolism of the extracellular matrix(ECM),is the most common age-related degenerative joint disease worldwide.As sleep has been found to be beneficial for cartilage repair,and circular RNAs(circRNAs)have been demonstrated to be involved in the pathogenesis of OA,we performed RNA sequencing(RNA-seq),and found circRNA3503 was significantly increased after melatonin(MT)-induced cell sleep.Upregulation of circRNA3503 expression completely rescued the effects of interleukin-1β(IL-1β),which was used to simulate OA,on apoptosis,ECM degradation-and synthesis-related genes.Mechanistically,circRNA3503 acted as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p.Moreover,as we previously showed that small extracellular vesicles(sEVs)derived from synovium mesenchymal stem cells(SMSCs)can not only successfully deliver nucleic acids to chondrocytes,but also effectively promote chondrocyte proliferation and migration,we assessed the feasibility of sEVs in combination with sleep-related circRNA3503 as an OA therapy.We successfully produced and isolated circRNA3503-loaded sEVs(circRNA3503-OE-sEVs)from SMSCs.Then,poly(D,L-lactide)-b-poly(ethylene glycol)-b-poly(D,L-lactide)(PDLLA-PEG-PDLLA,PLEL)triblock copolymer gels were used as carriers of sEVs.Through in vivo and in vitro experiments,PLEL@circRNA3503-OE-sEVs were shown to be a highly-effective therapeutic strategy to prevent OA progression.Through multiple pathways,circRNA3503-OE-sEVs alleviated inflammation-induced apoptosis and the imbalance between ECM synthesis and ECM degradation by acting as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p.In addition,circRNA3503-OE-sEVs promoted chondrocyte renewal to alleviate the progressive loss of chondrocytes.Our results highlight the potential of PLEL@circRNA3503-OE-sEVs for preventing OA progression.

Primary hypertrophic osteoarthropathy:an update

Digital clubbing,which has been recognized as a sign of systemic disease,is one of the most ancient diseases.However,the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood.The study of a clinically indistinguishable idiopathic form(primary hypertrophic osteoarthropathy,PHO)provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy.Current advances in the study of PHO are discussed.The impaired metabolism of prostaglandin E2(PGE2)plays a central role in its pathogenesis.