Bone最新文献

{"title":"Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: A narrative review.","authors":"Dima A Alajlouni, D. Bliuc, Thach Tran, R. Blank, J. Center","doi":"10.2139/ssrn.4281657","DOIUrl":"https://doi.org/10.2139/ssrn.4281657","url":null,"abstract":"Osteoporotic fractures present a major health problem with an increasing prevalence in older people. Fractures are associated with premature mortality, reduced quality of life, subsequent fracture, and increased costs. Hence, it is crucial to identify those at higher risk of fracture. Fracture risk assessment tools incorporated clinical risk factors to improve fracture predictive power over BMD alone. However, fracture risk prediction using these algorithms remains suboptimal, warranting further improvement. Muscle strength and physical performance measurements have been associated with fracture risk. In contrast, the contribution of sarcopenia, the composite condition of low muscle mass, muscle strength and/or physical performance, to fracture risk is unclear. It is uncertain whether this is due to the problematic definition of sarcopenia per se or limitations of the diagnostic tools and cut-off points of the muscle mass component. The recent position statement from the Sarcopenia Definition and Outcomes Consortium confirmed the inclusion of muscle strength and performance in the definition of sarcopenia but not DXA-assessed lean mass. Therefore, clinicians should focus on functional assessment (muscle strength and performance) rather than muscle mass, at least as assessed by DXA, as predictors of fractures. Muscle strength and performance are modifiable risk factors. Resistance exercise improves muscle parameters in the elderly, potentially leading to reduced risk of falls and fractures in the general population and in those who sustained a fracture. Therapists may consider exercise intervention to improve muscle parameters and potentially reduce the risk of fractures. The aim of this review was to explore 1) the contribution of muscle parameters (i.e., muscle mass, strength, and physical performance) to fracture risk in older adults, and 2) the added predictive accuracy of these parameters beyond the existing fracture assessment tools. These topics provide the rationale for investigating strength and physical performance interventions to reduce fracture risk. Most of the included publications showed that muscle mass is not a good predictor of fracture risk, while poor muscle strength and performance are associated with an increased risk of fracture, particularly in men, independent of age, BMD, and other risk factors for fractures. Muscle strength and performance can potentially improve the predictive accuracy in men beyond that obtained by the fracture risk assessment tools, Garvan FRC and FRAX.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116755"},"PeriodicalIF":0.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49058704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of diet and physical activity on bone density of children aged 5-7 years: The Belfast HAPO family study.","authors":"C. Casey, B. Kemp, L. Cassidy, Chris Patterson, M. Tully, A. Hill, D. McCance","doi":"10.2139/ssrn.4328034","DOIUrl":"https://doi.org/10.2139/ssrn.4328034","url":null,"abstract":"OBJECTIVE\u0000Osteoporosis is a global health issue, and modifiable behavioural factors need to be identified in childhood to reduce the risk of osteoporosis in later life. The aim of this study was to investigate the influence of diet and physical activity on bone density of children aged 5-7 years participating in the Belfast Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Family study.\u0000\u0000\u0000DESIGN AND METHODS\u0000Pregnant women were recruited to the Belfast centre of the HAPO study at 24-32 weeks gestation. Offspring were followed up at 5-7 years as part of the Belfast HAPO Family Study. Heel bone mineral density (BMD) and bone mineral apparent density (BMAD) were measured and calculated, respectively. Physical activity in the offspring was measured by accelerometery and dietary intakes were measured using a 4-day food diary.\u0000\u0000\u0000RESULTS\u0000Results from 793 offspring were analysed. Mean age of the offspring ± standard deviation was 6.4 ± 0.5 years. A mean of 48.3 ± 22.4 min each day was spent in moderate to vigorous physical activity (MVPA). Median (interquartile range) dietary calcium and vitamin D intakes were 844 (662-1073) mg/day and 1.7 (1.1-2.5) μg/day, respectively. Neither dietary vitamin D nor calcium intakes were significantly associated with offspring heel BMD or BMAD in multiple regression. However, controlling for confounders, a 30-min greater MVPA was associated with significantly larger heel BMD (0.018 g/cm2 in boys and 0.010 g/cm2 in girls) and BMAD (0.005 g/cm3 in boys and 0.003 g/cm3 in girls).\u0000\u0000\u0000CONCLUSION\u0000Physical activity was associated with better BMD and BMAD in 5-7-year-old children. Dietary calcium and vitamin D were not predictive of BMD and BMAD.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116783"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45127271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosocial and behavioral correlates of self-efficacy in treatment adherence in older patients with comorbid hypertension and type 2 diabetes.","authors":"Antonia Pierobon, Francesco Zanatta, Nicolò Granata, Ekaterina Nissanova, Jacek Polański, Wojciech Tański, Giovanna Callegari, Angelo Caporotondi, Chiara Ferretti, Polańska Beata Jankowska-","doi":"10.5114/hpr/159284","DOIUrl":"10.5114/hpr/159284","url":null,"abstract":"<p><strong>Background: </strong>Adhering to clinical prescriptions is known to protect against the effects of uncontrolled hypertension and of acute and chronic cardiovascular diseases, including diabetes. Contextually, positive associations between self-care behaviors and psychological constructs, such as self-efficacy, are widely acknowledged in the literature. However, still little is known about the psychological factors underlying the patient's self-efficacy. This study aimed to investigate the psychosocial and behavioral correlates of self-efficacy related to treatment adherence in older patients with comorbid hypertension and type 2 diabetes mellitus.</p><p><strong>Participants and procedure: </strong>Italian and Polish patients (≥ 65 years; <i>N</i> = 180) consecutively responded to self-report questionnaires measuring psychosocial (i.e., beliefs about medicines, perceived physician's communication effectiveness, medication-specific social support, self-efficacy) and behavioral factors (i.e., pharmacological adherence, medications refill adherence, intentional non-adherence) related to treatment adherence. Between-group comparisons and regression analyses were performed.</p><p><strong>Results: </strong>Fisher's least significant difference (LSD) test showed significant differences between the Italian and Polish groups in all questionnaires (<i>p</i> < .01) with the Italian patients reporting more satisfactory scores. Younger age (β = .08, <i>p</i> = .045), female gender (β = 1.03, <i>p</i> = .042), higher medication refills adherence (β = -.07, <i>p</i> = .024), lower intentional non-adherence (β = -.03, <i>p</i> = .009), positive beliefs about medications (β = .13, <i>p</i> < .001), better quality of communication with the physician (β = .09, <i>p</i> < .001), and stronger perceived medication-specific social support (β = .06, <i>p</i> = .001) were significantly associated with self-efficacy related to treatment adherence.</p><p><strong>Conclusions: </strong>Future research and interventions should leverage psychosocial and behavioral factors to address self-efficacy contributing to enhancing adherence to clinical prescriptions.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":"24 1","pages":"188-199"},"PeriodicalIF":2.0,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78912999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical value of RANKL, OPG, IL-6 and sclerostin as biomarkers for fibrous dysplasia/McCune-Albright syndrome.","authors":"M. E. Meier, M. Hagelstein-Rotman, T. Streefland, E. Winter, N. Bravenboer, N. Appelman‐Dijkstra","doi":"10.2139/ssrn.4328033","DOIUrl":"https://doi.org/10.2139/ssrn.4328033","url":null,"abstract":"BACKGROUND\u0000Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not correlate with the clinical picture and are not useful to predict or monitor therapy success. This study assessed the correlation of RANKL, OPG, RANKL/OPG ratio, IL-6 and sclerostin with the classic BTMs alkaline phosphatase (ALP), procollagen type 1 propeptide (P1NP) and beta crosslaps (CTX), with pain, skeletal burden score (SBS) and response to bisphosphonate or denosumab treatment.\u0000\u0000\u0000METHODS\u0000Ninety-six serum samples of adult patients >18 years of age with any subtype of FD/MAS were included from the biobank facility of the Leiden University Medical Center, Center for Bone Quality between 2015 and 2021. Standard laboratory assessments were assessed as part of usual care. The concentrations of potential biomarkers RANKL, OPG, sclerostin, IL-6 were analyzed. Data on FD/MAS subtype, age, pain, treatment history and treatment response were retrieved from the electronic patient files. Baseline characteristics were summarized by descriptive statistics. Correlations of the concentrations of the potential biomarkers with classic bone turnover markers, SBS and pain scores were cross-sectionally assessed by Spearman rank order correlation. Correction for multiple testing was performed by Benjamini and Hochberg False Discovery Rate. A sensitivity analyses was performed by excluding patients with SBS below 15 and patients using antiresorptive medication at the time of blood withdrawal or within the wash-out period. In patients treated with bisphosphonates or denosumab after blood withdrawal, pre-treatment concentrations were compared in patients with and without therapy response by Mann Whitney U test.\u0000\u0000\u0000RESULTS\u0000The median age of the patients was 41.2 (Q1-Q3 25.9-52.2) years, 62.5 % was female. Median SBS was 2.5 (Q1-Q3 0.5-7.8). RANKL level correlated weakly with ALP (Spearman rho 0.309, p = 0.004, n = 84), but not with P1NP or CTX. The RANKL/OPG ratio, OPG, IL-6 and sclerostin did not correlate with ALP, P1NP or CTX. None of the potential biomarkers correlated with SBS or pain. Results of the sensitivity analyses were comparable. Pre-treatment biomarker levels were similar in patients with and without improvement in pain scores following bisphosphonate therapy. Pre-treatment RANKL and sclerostin were comparable between patients with and without improvement in pain scores after denosumab therapy. Pre-treatment IL-6 level and the RANKL/OPG ratio seemed to be higher in patients with response to denosumab (IL-6: median 0.64 (Q1-Q3 0.53-0.74) pg/mL, n = 6, RANKL/OPG: median 0.062 (Q1-Q3 0.016-0.331), n = 5) compared to patients without response (IL-6: median 0.35 (0.20-0.54) pg/mL, n = 5, RANKL/OPG: 0.027 (0.024-0.046), n = 4). Pre-treatment IL-6 correlated with the improvement in maximum pain scores (rho 0.962, p < 0.001, n = 9) and average pain scores (rho 0.895, p = ","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116744"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44349590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal dominant osteopetrosis.","authors":"L. Polgreen, E. Imel, M. Econs","doi":"10.2139/ssrn.4290887","DOIUrl":"https://doi.org/10.2139/ssrn.4290887","url":null,"abstract":"Autosomal dominant osteopetrosis (ADO) is the most common form of osteopetrosis. ADO is characterized by generalized osteosclerosis along with characteristic radiographic features such as a \"bone-in-bone\" appearance of long bones and sclerosis of the superior and inferior vertebral body endplates. Generalized osteosclerosis in ADO typically results from abnormalities in osteoclast function, due most commonly to mutations in the chloride channel 7 (CLCN7) gene. A variety of debilitating complications can occur over time due to bone fragility, impingement of cranial nerves, encroachment of osteopetrotic bone in the marrow space, and poor bone vascularity. There is a wide spectrum of disease phenotype, even within the same family. Currently, there is no disease specific treatment for ADO, so clinical care focuses on monitoring for disease complications and symptomatic treatment. This review describes the history of ADO, the wide disease phenotype, and potential new therapies.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116723"},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48510041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential bone adaptation to mechanical unloading and reloading in young, old, and osteocyte deficient mice.","authors":"Hailey C. Cunningham, Sophie Orr, D. Murugesh, Allison W. Hsia, B. Osipov, Lauren Go, P. Wu, Alice Wong, G. Loots, G. Kazakia, B. Christiansen","doi":"10.2139/ssrn.4254484","DOIUrl":"https://doi.org/10.2139/ssrn.4254484","url":null,"abstract":"Mechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. Clinically, elderly patients are more prone to musculoskeletal injury and longer periods of bedrest, therefore it is important to understand how periods of disuse will affect overall skeletal health of aged subjects. Bone also undergoes an age-related decrease in osteocyte density, which may impair mechanoresponsiveness. In this study, we examined bone adaptation during unloading and subsequent reloading in mice. Specifically, we examined the differences in bone adaptation between young mice (3-month-old), old mice (18-month-old), and transgenic mice that exhibit diminished osteocyte density at a young age (3-month-old BCL-2 transgenic mice). Mice underwent 14 days of hindlimb unloading followed by up to 14 days of reloading. We analyzed trabecular and cortical bone structure in the femur, mechanical properties of the femoral cortical diaphysis, osteocyte density and cell death in cortical bone, and serum levels of inflammatory cytokines. We found that young mice lost ~10% cortical bone volume and 27-42% trabecular bone volume during unloading and early reloading, with modest recovery of metaphyseal trabecular bone and near total recovery of epiphyseal trabecular bone, but no recovery of cortical bone after 14 days of reloading. Old mice lost 12-14% cortical bone volume and 35-50% trabecular bone volume during unloading and early reloading but had diminished recovery of trabecular bone during reloading and no recovery of cortical bone. In BCL-2 transgenic mice, no cortical bone loss was observed during unloading or reloading, but 28-31% trabecular bone loss occurred during unloading and early reloading, with little to no recovery during reloading. No significant differences in circulating inflammatory cytokine levels were observed due to unloading and reloading in any of the experimental groups. These results illustrate important differences in bone adaptation in older and osteocyte deficient mice, suggesting a possible period of vulnerability in skeletal health in older subjects during and following a period of disuse that may affect skeletal health in elderly patients.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"167 1","pages":"116646"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46397281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hindlimb unloading in C57BL/6J mice induces bone loss at thermoneutrality without change in osteocyte and lacuno-canalicular network.","authors":"Laura Peurière, Carmelo J Mastrandrea, A. Vanden‐Bossche, M. Linossier, M. Thomas, Myriam Normand, M. Lafage-Proust, L. Vico","doi":"10.2139/ssrn.4232740","DOIUrl":"https://doi.org/10.2139/ssrn.4232740","url":null,"abstract":"Impaired mechanical stimuli during hindlimb unloading (HLU) are believed to exacerbate osteocyte paracrine regulation of osteoclasts. We hypothesized that bone loss and deterioration of the osteocyte lacuno-canalicular network are attenuated in HLU mice housed at thermoneutrality (28 °C) compared with those housed at ambient temperature (22 °C). Following acclimatization, 20-week-old male C57BL/6J mice were submitted to HLU or kept in pair-fed control cages (CONT), for 5 days (5d) or 14d, at 22 °C or 28 °C. In the femur distal metaphysis, thermoneutral CONT mice had higher bone volume (p = 0.0007, BV/TV, in vivo μCT, vs. 14dCONT22) whilst osteoclastic surfaces of CONT and HLU were greater at 22 °C (5dCONT22 + 53 %, 5dHLU22 + 50 %, 14dCONT22 + 186 %, 14dHLU22 + 104 %, vs matching 28 °C group). In the femur diaphysis and at both temperatures, 14dHLU exhibited thinner cortices distally or proximally compared to controls; the mid-diaphysis being thicker at 28 °C than at 22 °C in all groups. Expression of cortical genes for proteolytic enzyme (Mmp13), markers for osteoclastogenic differentiation (MCSF, RANKL), and activity (TRAP, Ctsk) were increased following 22 °C HLU, whereas only Ctsk expression was increased following 28 °C HLU. Expression of cortical genes for apoptosis, senescence, and autophagy were not elevated following HLU at any temperature. Osteocyte density at the posterior mid-diaphysis was similar between groups, as was the proportion of empty lacunae (<0.5 %). However, analysis of the lacuno-canalicular network (LCN, fluorescein staining) revealed unstained areas in the 14dHLU22 group only, suggesting disrupted LCN flow in this group alone. In conclusion, 28 °C housing influences the HLU bone response but does not prevent bone loss. Furthermore, our results do not show osteocyte senescence or death, and at thermoneutrality, HLU-induced bone resorption is not triggered by osteoclastic activators RANKL and MCSF.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116640"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42369205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α mediates osteoclast-induced disuse osteoporosis via cytoophidia in the femur of mice.","authors":"M. Bie, Yi Tang, Yuxing Xia, Q. Zhang, Yuanye Tian, Chun Cheng, Xinzhao Li, Xin Qi, F. Kang","doi":"10.2139/ssrn.4263596","DOIUrl":"https://doi.org/10.2139/ssrn.4263596","url":null,"abstract":"Osteoporosis induced by disuse because of bed rest or the aerospace industry has become one of the most common skeletal disorders. However, mechanisms underlying the disuse osteoporosis remain largely unknown. We validated the tail-suspended model in mice and demonstrated that there is bone loss in the trabecular and cortical bones of the femur. Importantly, we showed that genetical deletion of hypoxia-inducible factor-1α (HIF-1α) in osteoclasts ameliorated osteoclastic bone resorption in the trabecular bone whereas pharmacological treatment with HIF-1α inhibitor protected the hindlimb-unloaded mice from disuse-induced osteoporosis in the trabecular and cortical bones. The HIF-1α knockout RAW264.7 cells and RNA-sequencing proved that HIF-1α is vital for osteoclastogenesis and bone resorption because it regulated the level of inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) via cellular myelocytomatosis (c-Myc) oncogene. The IMPDH and CTPS are vital nucleotide metabolic enzymes which have an important functional role in cell metabolism, and they can assemble into intracellular linear or ring-shaped structures to cope with cell stress. Interestingly, both in vitro and in vivo, the IMPDH and CTPS cytoophidia were found in osteoclasts, and the level of HIF-1α correlated with osteoclastogenesis and bone-resorbing activity. Our data revealed that HIF-1α/c-Myc/cytoophidia signalling might be required for osteoclasts to mediate cell metabolism in disuse-induced osteoporosis. Overall, our results revealed a new role of HIF-1α/c-Myc/cytoophidia in supporting osteoclastogenesis and bone resorption and exposed evidence for its role in the pathogenesis of disuse osteoporosis, which might provide promising therapeutic targets.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"168 1","pages":"116648"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42434262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic markers of metabolic bone disease of prematurity in preterm infants.","authors":"Kui-lin Lü, Shuang-shuang Xie, Qi-Feng Hu, Zhang-Ya Yang, Qiong-li Fan, Enhao Liu, Yu-Ping Zhang","doi":"10.2139/ssrn.4259998","DOIUrl":"https://doi.org/10.2139/ssrn.4259998","url":null,"abstract":"Due to the higher birth rate of preterm infants and improvements in their management, metabolic bone disease of prematurity (MBDP) has a high incidence and is receiving increasing attention. Bone growth and mineralization are important for normal growth and development. However, clear indicators for the early diagnosis of MBDP are lacking. We aimed to explore simple and feasible early warning indicators for diagnosing MBDP. Our study collected case data of premature infants from two medical centers in Chongqing from January 2020 to February 2022. According to the inclusion and exclusion criteria, data from 136 cases were collected. The correlation between 14 variables in each case and the occurrence of MBDP was analyzed. According to the area under the receiver operating characteristic curve (AUROC) analysis, the best cutoff value for each variable was determined. Potential predictors were selected and LASSO regression analysis was used to establish the association of two models with MBDP, whose results were used to develop a diagnostic nomogram. Furthermore, a model decision curve was analyzed. Four predictors were selected from 14 clinical variables by LASSO regression, and Model I was established, including the following characteristics: height (>36 cm), head circumference (≤29.49 cm), and Ca2+ (>2.13 mmol/L) and alkaline phosphatase (ALP) (>344 U/L) levels. A single predictor, the ALP level (>344 U/L), was used to establish Model II. The AUROC values of the two models were 0.959 for Model I and 0.929 for Model II. In conclusion, in this study, two diagnostic models of MBDP were developed using four combinations of predictors and ALP as a single predictor. Both models showed a strong sensitivity and specificity for the early diagnosis of metabolic bone disease (MBD) and an ALP level of 344 U/L was defined as a simple and effective diagnostic threshold. In future studies, the evaluation of larger sample sizes, the establishment of diagnostic threshold values of ALP for premature infants of different ages, and internal and external validations are needed to improve the adaptability of the model.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116656"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44353501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLCN7, a gene shared by autosomal recessive and autosomal dominant osteopetrosis.","authors":"T. Stauber, Lena Wartosch, Svenja Vishnolia, A. Schulz, U. Kornak","doi":"10.2139/ssrn.4207532","DOIUrl":"https://doi.org/10.2139/ssrn.4207532","url":null,"abstract":"After the discovery of abundant v-ATPase complexes in the osteoclast ruffled membrane it was obvious that in parallel a negative counter-ion needs to be transported across this membrane to allow for efficient transport of protons into the resorption lacuna. While different candidate proteins were discussed the osteopetrosis phenotype of Clcn7 knockout mice suggested that the chloride/proton-exchanger ClC-7 might be responsible for transporting the negative charge. In the following, individuals with autosomal recessive osteopetrosis (ARO) were found to carry biallelic CLCN7 pathogenic variants. Shortly thereafter, heterozygous pathogenic variants were identified as the exclusive cause of autosomal dominant osteopetrosis type 2 (ADO2). Since in most cell types other than osteoclasts ClC-7 resides in late endosomes and lysosomes, it took some time until the electrophysiological properties of ClC-7 were elucidated. Whereas most missense variants lead to reduced chloride currents, several variants with accelerated kinetics have been identified. Evidence for folding problems is also known for several missense variants. Paradoxically, a heterozygous activating variant in ClC-7 was described to cause lysosomal alteration, pigmentation defects, and intellectual disability without osteopetrosis. The counter-intuitive 2 Cl-/H+ exchange function of ClC-7 was shown to be physiologically important for intravesicular ion homeostasis. The lysosomal function of ClC-7 is also the reason why individuals with CLCN7-ARO can develop a storage disorder and neurodegeneration, a feature that is variable and difficult to predict. Furthermore, the low penetrance of heterozygous pathogenic CLCN7 variants and the clinical variability of ADO2 are incompletely understood. We aim to give an overview not only of the current knowledge about ClC-7 and its related pathologies, but also of the scientists and clinicians that paved the way for these discoveries.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116639"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42002337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}