JBMR Plus最新文献

筛选
英文 中文
Giant cell arteritis associated with intravenous zoledronic acid administration 与静脉注射唑来膦酸有关的巨细胞动脉炎
IF 3.8
JBMR Plus Pub Date : 2024-02-14 DOI: 10.1093/jbmrpl/ziae015
M. L. Balbach, Jennifer R Hewlett, R. Wermers, K. Warrington, S. B. Tanner, Erin Y Chew
{"title":"Giant cell arteritis associated with intravenous zoledronic acid administration","authors":"M. L. Balbach, Jennifer R Hewlett, R. Wermers, K. Warrington, S. B. Tanner, Erin Y Chew","doi":"10.1093/jbmrpl/ziae015","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae015","url":null,"abstract":"\u0000 Bisphosphonates frequently provoke a cytokine-driven acute clinical response (ACR) characterized by fever, chills, arthralgias, and myalgias. More rarely an association between aminobisphosphonates, such as alendronate and zoledronic acid, and rheumatologic and/or immune-mediated syndromes (RIMS) has been described. Herein we report two patients, one with a prior history of rheumatic disease and one without, who developed giant cell arteritis meeting the American College of Rheumatology 2022 criteria following zoledronic acid infusion. We subsequently review existing mechanistic and clinical literature supporting this link. The duration of symptoms and elevation of inflammatory markers may serve as indicators for differentiating between the more common ACR and less frequent but potentially morbid RIMS. Although the benefit of bisphosphonates will outweigh the risk of RIMS for most patients with high fracture risk, clinicians should be aware of this phenomenon to assist earlier diagnosis and treatment in affected individuals.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139963536","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}
引用次数: 0
Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study 前瞻性观察研究:绝经后骨质疏松症患者在使用地诺单抗的同时使用 Romosozumab
IF 3.8
JBMR Plus Pub Date : 2024-02-07 DOI: 10.1093/jbmrpl/ziae016
G. Adami, Elisa Pedrollo, Maurizio Rossini, A. Fassio, V. Braga, Emma Pasetto, Francesco Pollastri, C. Benini, O. Viapiana, Davide Gatti
{"title":"Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study","authors":"G. Adami, Elisa Pedrollo, Maurizio Rossini, A. Fassio, V. Braga, Emma Pasetto, Francesco Pollastri, C. Benini, O. Viapiana, Davide Gatti","doi":"10.1093/jbmrpl/ziae016","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae016","url":null,"abstract":"\u0000 \u0000 \u0000 Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).\u0000 \u0000 \u0000 \u0000 We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators and calcium phosphate metabolism at baseline, month 3 and month 6. Bone mineral density was assessed at baseline and after 6 months.\u0000 \u0000 \u0000 \u0000 Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8% and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and + 99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups and Dkk1 did not change.\u0000 \u0000 \u0000 \u0000 Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD versus denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.\u0000","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139797170","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}
引用次数: 0
Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study 前瞻性观察研究:绝经后骨质疏松症患者在使用地诺单抗的同时使用 Romosozumab
IF 3.8
JBMR Plus Pub Date : 2024-02-07 DOI: 10.1093/jbmrpl/ziae016
G. Adami, Elisa Pedrollo, Maurizio Rossini, A. Fassio, V. Braga, Emma Pasetto, Francesco Pollastri, C. Benini, O. Viapiana, Davide Gatti
{"title":"Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study","authors":"G. Adami, Elisa Pedrollo, Maurizio Rossini, A. Fassio, V. Braga, Emma Pasetto, Francesco Pollastri, C. Benini, O. Viapiana, Davide Gatti","doi":"10.1093/jbmrpl/ziae016","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae016","url":null,"abstract":"\u0000 \u0000 \u0000 Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).\u0000 \u0000 \u0000 \u0000 We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators and calcium phosphate metabolism at baseline, month 3 and month 6. Bone mineral density was assessed at baseline and after 6 months.\u0000 \u0000 \u0000 \u0000 Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8% and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and + 99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups and Dkk1 did not change.\u0000 \u0000 \u0000 \u0000 Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD versus denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.\u0000","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139857002","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}
引用次数: 0
Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men. 导致成年白人女性和男性 FN BMD 与全骨强度之间性别特异性关联的结构差异。
IF 3.4
JBMR Plus Pub Date : 2024-01-30 eCollection Date: 2024-04-01 DOI: 10.1093/jbmrpl/ziae013
Karl J Jepsen, Erin M R Bigelow, Robert W Goulet, Bonnie T Nolan, Michael A Casden, Kathryn Kennedy, Samantha Hertz, Chandan Kadur, Gregory A Clines, Aleda M Leis, Carrie A Karvonen-Gutierrez, Todd L Bredbenner
{"title":"Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men.","authors":"Karl J Jepsen, Erin M R Bigelow, Robert W Goulet, Bonnie T Nolan, Michael A Casden, Kathryn Kennedy, Samantha Hertz, Chandan Kadur, Gregory A Clines, Aleda M Leis, Carrie A Karvonen-Gutierrez, Todd L Bredbenner","doi":"10.1093/jbmrpl/ziae013","DOIUrl":"10.1093/jbmrpl/ziae013","url":null,"abstract":"<p><p>Hip areal BMD (aBMD) is widely used to identify individuals with increased fracture risk. Low aBMD indicates low strength, but this association differs by sex with men showing greater strength for a given aBMD than women. To better understand the structural basis giving rise to this sex-specific discrepancy, cadaveric proximal femurs from White female and male donors were imaged using nano-CT and loaded in a sideways fall configuration to assess strength. FN pseudoDXA images were generated to identify associations among structure, aBMD, and strength that differ by sex. Strength correlated significantly with pseudoDXA aBMD for females (<i>R</i><sup>2</sup> = 0.468, <i>P</i> < .001) and males (<i>R</i><sup>2</sup> = 0.393, <i>P</i> < .001), but the elevations (<i>y</i>-intercepts) of the linear regressions differed between sexes (<i>P</i> < .001). Male proximal femurs were 1045 N stronger than females for a given pseudoDXA aBMD. However, strength correlated with pseudoDXA BMC for females (<i>R</i><sup>2</sup> = 0.433, <i>P</i> < .001) and males (<i>R</i><sup>2</sup> = 0.443, <i>P</i> < .001) but without significant slope (<i>P</i> = .431) or elevation (<i>P</i> = .058) differences. Dividing pseudoDXA BMC by FN-width, total cross-sectional area, or FN-volume led to significantly different associations between strength and the size-adjusted BMC measures for women and men. Three structural differences were identified that differentially affected aBMD and strength for women and men: First, men had more bone mass per unit volume than women; second, different cross-sectional shapes resulted in larger proportions of bone mass orthogonal to the DXA image for men than women; and third, men and women had different proportions of cortical and trabecular bone relative to BMC. Thus, the proximal femurs of women were not smaller versions of men but were constructed in fundamentally different manners. Dividing BMC by a bone size measure was responsible for the sex-specific associations between hip aBMD and strength. Thus, a new approach for adjusting measures of bone mass for bone size and stature is warranted.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206918","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}
引用次数: 0
Loss of 24-hydroxylated catabolism increases calcitriol and fibroblast growth factor-23 and alters calcium and phosphate metabolism in fetal mice 24- 羟基分解代谢的缺失会增加降钙三醇和成纤维细胞生长因子-23,并改变胎鼠的钙和磷代谢
IF 3.8
JBMR Plus Pub Date : 2024-01-29 DOI: 10.1093/jbmrpl/ziae012
David Bennin, Sarah A Hartery, B. J. Kirby, Alexandre S Maekawa, René St-Arnaud, Christopher S Kovacs
{"title":"Loss of 24-hydroxylated catabolism increases calcitriol and fibroblast growth factor-23 and alters calcium and phosphate metabolism in fetal mice","authors":"David Bennin, Sarah A Hartery, B. J. Kirby, Alexandre S Maekawa, René St-Arnaud, Christopher S Kovacs","doi":"10.1093/jbmrpl/ziae012","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae012","url":null,"abstract":"\u0000 Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase (CYP24A1). Inactivating mutations of CYP24A1 cause high postnatal levels of calcitriol and the human condition of infantile hypercalcemia type 1, but whether the fetus is disturbed by loss of CYP24A1 is unknown. We hypothesized that loss of Cyp24a1 in fetal mice will cause high calcitriol, hypercalcemia, and increased placental calcium transport. Cyp24a1+/- mice were mated to create pregnancies with WT, Cyp24a1+/- and Cyp24a1 null fetuses. The null fetuses were hypercalcemic, modestly hypophosphatemic (compared to Cyp24a1+/- fetuses only), with 3.5-fold increased calcitriol, 4-fold increased FGF23, and unchanged PTH. qPCR confirmed absence of Cyp24a1 and 2-fold increases in S100g, Ncx1 and Casr in null placentas but not fetal kidneys; these changes predicted an increase in placental calcium transport. However, placental 45Ca and 32P transport were unchanged in null fetuses. Fetal ash weight and mineral content, placental weight, crown-rump length, and skeletal morphology did not differ among the genotypes. Serum P1NP and bone expression of Sost and Blgap were reduced while Calcr was increased in nulls. In conclusion, loss of Cyp24a1 in fetal mice causes hypercalcemia, modest hypophosphatemia, increased FGF23, but no alteration in skeletal development. Reduced incorporation of calcium into bone may contribute to the hypercalcemia without causing a detectable decrease in skeletal mineral content. The results predict that human fetuses bearing homozygous or compound heterozygous inactivating mutations of CYP24A1 will also be hypercalcemic in utero but with normal skeletal development.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139591755","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}
引用次数: 0
Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study. 阿巴帕肽治疗男性腰椎、全髋和股骨颈骨矿物质密度的应答率:ATOM 研究的结果。
IF 3.8
JBMR Plus Pub Date : 2024-01-27 eCollection Date: 2024-02-01 DOI: 10.1093/jbmrpl/ziae009
Ruban Dhaliwal, David Kendler, Kenneth Saag, Steven W Ing, Andrea Singer, Robert A Adler, Leny Pearman, Yamei Wang, Bruce Mitlak
{"title":"Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study.","authors":"Ruban Dhaliwal, David Kendler, Kenneth Saag, Steven W Ing, Andrea Singer, Robert A Adler, Leny Pearman, Yamei Wang, Bruce Mitlak","doi":"10.1093/jbmrpl/ziae009","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae009","url":null,"abstract":"<p><p>Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 μg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], <i>P</i> = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], <i>P</i> < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], <i>P</i> < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10945712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174719","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}
引用次数: 0
Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts 成骨细胞中表达的人类组织-非特异性碱性磷酸酶的糖蛋白组图谱
IF 3.8
JBMR Plus Pub Date : 2024-01-22 DOI: 10.1093/jbmrpl/ziae006
Diana Atanasova, Ekaterina Mirgorodskaya, Lavanya Moparthi, Stefan Koch, Mathias Haarhaus, S. Narisawa, José Luis Millán, Eva Landberg, Per Magnusson
{"title":"Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts","authors":"Diana Atanasova, Ekaterina Mirgorodskaya, Lavanya Moparthi, Stefan Koch, Mathias Haarhaus, S. Narisawa, José Luis Millán, Eva Landberg, Per Magnusson","doi":"10.1093/jbmrpl/ziae006","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae006","url":null,"abstract":"\u0000 Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate (PPi) and ATP to provide inorganic phosphate (Pi), thus controlling the PPi/Pi ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has five potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303 and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and liquid chromatography with tandem mass spectrometry (LC/MS–MS). The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all five sites of TNALP, as well as core fucosylation on four out of five sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139607976","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}
引用次数: 0
Wnt Pathway Inhibition with the Porcupine Inhibitor LGK974 Decreases Trabecular Bone but not Fibrosis in a Murine Model with Fibrotic Bone 用箭毒抑制剂 LGK974 抑制 Wnt 通路可降低纤维化骨小鼠模型中的骨小梁数量,但不会降低其纤维化程度
IF 3.8
JBMR Plus Pub Date : 2024-01-21 DOI: 10.1093/jbmrpl/ziae011
H. Lung, K. Wentworth, T. Moody, Ariane Zamarioli, Apsara Ram, Gauri Ganesh, Misun Kang, Sunita Ho, Edward C. Hsiao
{"title":"Wnt Pathway Inhibition with the Porcupine Inhibitor LGK974 Decreases Trabecular Bone but not Fibrosis in a Murine Model with Fibrotic Bone","authors":"H. Lung, K. Wentworth, T. Moody, Ariane Zamarioli, Apsara Ram, Gauri Ganesh, Misun Kang, Sunita Ho, Edward C. Hsiao","doi":"10.1093/jbmrpl/ziae011","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae011","url":null,"abstract":"\u0000 G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD.\u0000 The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single cell RNA sequencing on long-bone stromal cells of 9-week-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or down-regulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139609764","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}
引用次数: 0
Association of secondhand smoke with fracture risk in community-dwelling non-smoking adults in Korea 韩国社区居住的非吸烟成年人中二手烟与骨折风险的关系
IF 3.8
JBMR Plus Pub Date : 2024-01-21 DOI: 10.1093/jbmrpl/ziae010
Junyeong Ahn, H. Park, Sung Joon Cho, Seungjin Baek, Yumie Rhee, N. Hong
{"title":"Association of secondhand smoke with fracture risk in community-dwelling non-smoking adults in Korea","authors":"Junyeong Ahn, H. Park, Sung Joon Cho, Seungjin Baek, Yumie Rhee, N. Hong","doi":"10.1093/jbmrpl/ziae010","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae010","url":null,"abstract":"\u0000 Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 non-smokers aged 40–69 years, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high versus low groups). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4 years (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P = 0.028) after adjusting for multiple covariates including age, sex, body mass index, household income, bone density of mid-shaft tibia, c-reactive protein, alcohol consumption, and history of fracture. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P = 0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P = 0.025) whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P = 0.253), suggesting a potential dose–response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P = 0.008) or non-vertebral non-hip fractures (aHR: 1.36, P = 0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P = 0.908). Secondhand smoke was associated with an elevated risk of fracture in non-smokers, independent of clinical risk factors.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139609836","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}
引用次数: 0
Post-fracture survival in a population-based study of adults aged ≥ 66 years: a call to action at hospital discharge 对年龄≥ 66 岁的成年人进行的基于人口的骨折后存活率研究:呼吁在出院时采取行动
IF 3.8
JBMR Plus Pub Date : 2024-01-20 DOI: 10.1093/jbmrpl/ziae002
Geneviève Vincent, J. Adachi, Emil Schemitsch, J. Tarride, Nathan Ho, Rajvi J Wani, Jacques P. Brown
{"title":"Post-fracture survival in a population-based study of adults aged ≥ 66 years: a call to action at hospital discharge","authors":"Geneviève Vincent, J. Adachi, Emil Schemitsch, J. Tarride, Nathan Ho, Rajvi J Wani, Jacques P. Brown","doi":"10.1093/jbmrpl/ziae002","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae002","url":null,"abstract":"\u0000 Post-fracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 years. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 years with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to non-fracture individuals based on sex, age, and comorbidities. All-cause 1- and 5-year overall survival and relative survival ratios (RSRs) were assessed and time trends in survival changes were characterized starting immediately after a fracture. In both sexes, overall survival was markedly decreased over 6 years of follow-up after hip, vertebral, and pNHNV fractures, and as expected, worse survival rates were observed in older patients and males. The lowest 5-year RSRs were observed after hip fractures in males (66–85 years, 51.9%–63.9%; ≥86 years, 34.5%), followed by vertebral fractures in males (66–85 years, 53.2%–69.4%; ≥86 years, 35.5%), and hip fractures in females (66–85 years, 69.8%–79.0%; ≥86 years, 52.8%). Although RSRs did not decrease as markedly after dNHNV fractures in younger patients, relatively low 5-year RSRs were observed in females (75.9%) and males (69.5%) aged ≥86 years. The greatest reduction in survival occurred within the initial month after hip, vertebral, and pNHNV fractures, indicating a high relative impact of short-term factors, with survival-reduction effects persisting over time. Therefore, the most critical period for implementing interventions aimed at improving post-fracture prognosis appears to be immediately after a fracture; however, considering the immediate need for introducing such interventions, primary fracture prevention is also crucial to prevent the occurrence of the initial fracture in high-risk patients.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139610553","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信