JBMR Plus最新文献

{"title":"Lower microhardness along with less heterogeneous mineralization in the femoral neck of individuals with type 2 diabetes mellitus indicates higher fracture risk","authors":"Aleksandar Cirovic, Felix N Schmidt, Marko Vujačić, P. Sihota, Bojan Petrovic, Vladimir Živković, Zoran Bascarevic, S. Nikolić, D. Djonic, M. Djuric, Björn Busse, Petar Milovanovic","doi":"10.1093/jbmrpl/ziae005","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae005","url":null,"abstract":"\u0000 There is still limited understanding of the microstructural reasons for the higher susceptibility to fractures in individuals with type 2 diabetes mellitus (T2DM). In this study, we examined bone mineralization, osteocyte lacunar parameters, and microhardness of the femoral neck trabeculae in 18 individuals with T2DM who sustained low-energy fracture (T2DMFx: 78 ± 7 years, 15 women and 3 men) and 20 controls (74 ± 7 years, 16 women and 4 men). Femoral necks of the T2DMFx subjects were obtained at a tertiary orthopedic hospital, while those of the controls were collected at autopsy. T2DMFx individuals had lower trabecular microhardness (p = 0.023) and mineralization heterogeneity (p = 0.001), and a tendency to a lower bone area with mineralization above 95th percentile (p = 0.058) than the controls. There were no significant intergroup differences in the numbers of osteocyte lacunae per bone area, mineralized lacunae per bone area, and total lacunae per bone area (each p > 0.05). After dividing the T2DMFx group based on the presence of vascular complications (VD) to T2DMFxVD (VD present) and T2DMFxNVD (VD absent), we observed that microhardness was particularly reduced in the T2DMFxVD group (vs. control group, p = 0.02), while mineralization heterogeneity was significantly reduced in both T2DMFx subgroups (T2DMFxNVD vs. control, p = 0.002; T2DMFxVD vs. control, p = 0.038). The observed changes in mineralization and microhardness may contribute to the increased hip fracture susceptibility in individuals with T2DM.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621866","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":"Inhibition of RANKL improves the skeletal phenotype of adenine-induced chronic kidney disease in mice","authors":"Corinne E. Metzger, M. Kittaka, Alec N LaPlant, Yasuyoshi Ueki, Matthew R Allen","doi":"10.1093/jbmrpl/ziae004","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae004","url":null,"abstract":"\u0000 Skeletal fragility and high fracture rates are common in chronic kidney disease (CKD). A key component of bone loss in CKD with secondary hyperparathyroidism is high bone turnover and cortical bone deterioration through both cortical porosity and cortical thinning. We hypothesized that receptor activator of nuclear factor-κB ligand (RANKL) drives high bone resorption within cortical bone leading to the development of cortical porosity (Study 1) and that systemic inhibition of RANKL would mitigate the skeletal phenotype (Study 2). In Study 1 we assessed the skeletal properties of male and female Dmp1-cre RANKLfl/fl (cKO) and control genotype (Ranklfl/fl; Con) mice after 10 weeks of adenine-induced CKD (AD; 0.2% dietary adenine). All AD mice regardless of sex or genotype had elevated blood urea nitrogen and high parathyroid hormone (PTH). Con AD mice in both sexes had cortical porosity and lower cortical thickness as well as high osteoclast-covered trabecular surfaces and higher bone formation rate. cKO mice had preserved cortical bone microarchitecture despite high circulating PTH as well as no CKD-induced increases in osteoclasts. In Study 2, male mice with established adenine-induced CKD were given a single injection of an anti-RANKL antibody (5 mg/kg) 8 weeks post-induction or 3x/week dosing with risedronate (1.2 μg/kg) for 4 weeks. Anti-RANKL treatment significantly reduced bone formation rate as well as osteoclast surfaces at both trabecular and cortical surfaces; risedronate treatment had little effect on these bone parameters. In conclusion, these studies demonstrate that bone-specific RANKL is critical for the development of high bone formation/high osteoclasts and cortical bone loss in CKD with high PTH. Additionally, systemic anti-RANKL ligand therapy in established CKD may help prevent the propagation of cortical bone loss via suppression of bone turnover.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139530527","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":"Sex-specific effects of Fat-1 transgene on bone material properties, size, and shape in mice","authors":"Beatriz Bermudez, Kenna Brown, G. Vahidi, Ana C F Ruble, Chelsea M Heveran, Cheryl L Ackert-Bicknell, Vanessa Sherk","doi":"10.1093/jbmrpl/ziad011","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad011","url":null,"abstract":"\u0000 Western diets are becoming increasingly common around the world. Western diets have high omega 6 (ω-6) and omega 3 (ω-3) fatty acids and are linked to bone loss in humans and animals. Dietary fats are not created equal; therefore, it is vital to understand the effects of specific dietary fats on bone. We aimed to determine how altering the endogenous ratios of ω-6:ω-3 fatty acids impacts bone accrual, strength, and fracture toughness. To accomplish this, we used the Fat-1 transgenic mice, which carry a gene responsible for encoding an ω-3 fatty acid desaturase that converts ω-6 to ω-3 fatty acids. Male and female Fat-1 positive mice (Fat-1) and Fat-1 negative littermates (WT) were given either a high-fat diet (HFD) or low-fat diet (LFD) at 4 weeks of age for 16 weeks. The Fat-1 transgene reduced fracture toughness in males. Additionally, male bone mineral density (BMD), measured from dual-energy x-ray absorptiometry (DXA), decreased over the diet duration for HFD mice. In males, neither HFD feeding nor the presence of the Fat-1 transgene impacted cortical geometry, trabecular architecture, or whole-bone flexural properties, as detected by main group effects. In females, Fat-1-LFD mice experienced increases in BMD compared to WT-LFD mice, however, cortical area, distal femur trabecular thickness, and cortical stiffness were reduced in Fat-1 mice compared to pooled WT controls. However, reductions in stiffness were caused by a decrease in bone size and were not driven by changes in material properties. Together, these results demonstrate that the endogenous ω-6:ω-3 fatty acid ratio influences bone material properties in a sex-dependent manner. In addition, Fat-1 mediated fatty acid conversion was not able to mitigate the adverse effects of HFD on bone strength and accrual.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440019","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":"Loss of the auxiliary α2δ1 voltage sensitive Calcium Channel subunit impairs bone formation and anabolic responses to mechanical loading","authors":"Madison M Kelly, Karan Sharma, Christian S. Wright, Xin Yi, Perla C. Reyes Fernandez, Aaron T Gegg, Taylor A Gorrell, Megan L. Noonan, A. Baghdady, Jacob A Sieger, Annette C Dolphin, Stuart J Warden, Padmini J. Deosthale, Lilian I Plotkin, Uma Sankar, J. Hum, A. Robling, M. Farach-Carson, William R. Thompson","doi":"10.1093/jbmrpl/ziad008","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad008","url":null,"abstract":"\u0000 Voltage sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1, the gene encoding α2δ1. Dual energy X-ray absorptiometry (DEXA) and microcomputed tomography (μCT) imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female C57BL/6 mice. Structural differences manifested in both trabecular and cortical bone for males, while the absence of α2δ1 affected only cortical bone in female mice. Deletion of α2δ1 impaired skeletal mechanical properties in both sexes, as measured by three-point bending to failure. While no changes in osteoblast number or activity were found for either sex, male mice displayed a significant increase in osteoclast number, accompanied by increased eroded bone surface and upregulation of genes that regulate osteoclast differentiation. Deletion of α2δ1 also rendered the skeleton insensitive to exogenous mechanical loading in males. While previous work demonstrates that VSCCs are essential for anabolic responses to mechanical loading, the mechanism by which these channels sense and respond to force remained unclear. Our data demonstrate that the α2δ1 auxiliary VSCC subunit functions to maintain baseline bone mass and strength through regulation of osteoclast activity, and also provides skeletal mechanotransduction in male mice. These data reveal a molecular player in our understanding of the mechanisms by which VSCCs influence skeletal adaptation.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440525","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":"Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice","authors":"Connor Devine, Kenna Brown, Kat O Patton, Chelsea M Heveran, Stephen A Martin","doi":"10.1093/jbmrpl/ziae001","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae001","url":null,"abstract":"\u0000 Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3-months-old) and aged female (20-months-old) C57BL/6 mice. Rapamycin (2 mg/kg body mass) was administered via intraperitoneal injection 1x/5 days for a duration of 8 weeks; this treatment regimen has been shown to induce geroprotective effects while minimizing the side-effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate a short-term, low-dosage, interval, rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440288","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":"Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism","authors":"Aliya A Khan, Lisa G Abbott, Intekhab Ahmed, O. Ayodele, Claudia Gagnon, Richard D Finkelman, Emese Mezosi, Lars Rejnmark, Istvan Takacs, Shaoming Yin, Steven W Ing","doi":"10.1093/jbmrpl/ziad010","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad010","url":null,"abstract":"\u0000 Hypoparathyroidism is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1–84 (rhPTH[1–84]) for treating hypoparathyroidism. The present study (NCT03364738) was a Phase 4, 1-year open-label extension of PARALLAX. Patients received only two doses of rhPTH(1–84) in PARALLAX and were thus considered treatment-naive at the start of the current study. rhPTH(1–84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 years; 81.8% were women, and 90.9% were White. By end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined primary endpoint range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-hour urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402–855 mg/day and 0.8–0.2 μg/day, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2–5 fold from baseline to EOT. HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1–84) once daily for 1 year improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381269","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":"Adaptations of bone and bone vasculature to muscular stretch training","authors":"Julia Eazer, Mina‐Michael Barsoum, Cole Smith, Kazuki Hotta, Brad Behnke, Christina Holmes, Jacob Caldwell, Payal Ghosh, Emily Reid‐Foley, Hyerim Park, Michael Delp, Judy Muller-Delp","doi":"10.1093/jbmrpl/ziad019","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad019","url":null,"abstract":"\u0000 The magnitude of bone formation and remodeling is linked to both the magnitude of strain placed on the bone and the perfusion of bone. It was previously reported that an increase in bone perfusion and bone density occurs in the femur of old rats with moderate aerobic exercise training. This study determined the acute and chronic effects of static muscle stretching on bone blood flow and remodeling. Old male Fischer 344 rats were randomized to either a naïve or stretch-trained group. Static stretching of ankle flexor muscles was achieved by placement of a dorsiflexion splint on the left ankle for 30 min/day, 5d/wk for 4wks. The opposite hindlimb served as a contralateral control (nonstretched) limb. Bone blood flow was assessed during and after acute stretching in naïve rats, and at rest and during exercise in stretch-trained rats. Vascular reactivity of the nutrient artery of the proximal tibia was also assessed in stretch-trained rats. MicroCT analysis was used to assess bone volume and micro-architecture of the trabecular bone of both tibias near that growth plate. In naïve rats, static stretching increased blood flow to the proximal tibial metaphasis. Blood flow to the proximal tibial metaphysis during treadmill exercise was higher in the stretched limb after 4 weeks of daily stretching. Daily stretching also increased tibial bone weight and increased total volume in both the proximal and distal tibial metaphyses. In the trabecular bone immediately below the proximal tibial growth plate, total volume and bone volume increased, but bone volume/total volume was unchanged and trabecular connectivity decreased. In contrast, intravascular volume increased in this region of the bone. These data suggest that blood flow to the tibia increases during bouts of static stretching of the hindlimb muscles, and that 4 weeks of daily muscle stretching leads to bone remodeling and an increase in intravascular volume of the tibial bone.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387496","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":"Osteoclast-specific Plastin 3 knockout in mice fail to develop osteoporosis despite dramatic increased osteoclast resorption activity","authors":"Ilka Maus, M. Dreiner, Sebastian Zetzsche, F. Metzen, Bryony C Ross, D. Mählich, M. Koch, Anja Niehoff, Brunhilde Wirth","doi":"10.1093/jbmrpl/ziad009","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad009","url":null,"abstract":"\u0000 PLS3 loss-of-function mutations in humans and mice cause X-linked primary osteoporosis. However, it remains largely unknown how PLS3 mutations cause osteoporosis and which function PLS3 plays in bone homeostasis. A recent study showed that the ubiquitous Pls3 KO in mice results in osteoporosis with decreased bone thickness and stiffness. In these mice, mainly osteoclasts were impacted in their function, exhibiting increased resorptive activity and altered podosome formation through a misregulation of the NFκB pathway. Specifically, Pls3 KO caused the decreased nuclear localization of its interaction partner NFκB repressing factor, NKRF, thereby augmenting Nfatc1 transcription. However, it has not been proven if, indeed, the osteoclasts are the major cell type affected and responsible for the osteoporosis development in ubiquitous Pls3 KO mice.\u0000 Here, we generated osteoclast-specific Pls3 KO female (Pls3fl/fl; LysMCretg/0) and male (Pls3fl;LysMCretg/0) mice and demonstrate specific PLS3 loss in cultured osteoclasts. In addition, we developed a novel polyclonal PLS3 antibody that showed for the first time specific PLS3 loss in immunofluorescence staining of osteoclasts in contrast to previously available antibodies against PLS3 that failed to show PLS3-specificity in mouse cells. Moreover, we demonstrate that the osteoclast-specific Pls3 KO causes a dramatic increase in the resorptive activity of osteoclasts in vitro. Despite this pronounced effect on osteoclast resorption activity, osteoclast-specific Pls3 KO in vivo failed to cause any osteoporotic phenotype in 12-, 24-, and 48-week-old mice as proven by micro-CT and three-point bending test. These results demonstrate that the pathomechanism of PLS3-associated osteoporosis is highly complex and cannot be reproduced in a system singularly focused on one cell type, leading us to conclude that the loss of PLS3 in alternative bone cell types, such as osteoblasts and osteocytes contributes to the osteoporosis phenotype in ubiquitous Pls3 KO mice.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450710","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":"Advanced Glycation End Products Are Not Associated With Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers in Adults With and Without Type 1 Diabetes: A Cross-Sectional Study","authors":"J. Coll, Anne-Frédérique Turcotte, William D Leslie, Laëtitia Michou, S. J. Weisnagel, Fabrice Mac-Way, Caroline Albert, Claudie Berger, Suzanne N Morin, Rémi Rabasa-Lhoret, Claudia Gagnon","doi":"10.1093/jbmrpl/ziad018","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad018","url":null,"abstract":"\u0000 It is unclear if advanced glycation end products (AGEs) are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: C-terminal crossed-linked telopeptide of type 1 collagen, CTX; procollagen type 1 N-terminal propeptide, P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman’s correlations. Data are mean±SD or median(interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43±15 years, BMI 26.6±5.5 kg/m2). Participants with T1D had diabetes for 27.6±12.3 years, a mean 3-year HbA1C of 7.5±0.9% and skin AGEs of 2.15±0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2-32.0] ng/mL) and CML [48.0±16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs, or between AGEs and 3-year HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450656","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":"A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss","authors":"Christopher de la Bastide, Lissa Soares, L. Lui, James Harrington, Peggy Cawthon, Eric Orwoll, Deborah Kado, Jaymie Meliker","doi":"10.1093/jbmrpl/ziad006","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad006","url":null,"abstract":"\u0000 Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older U.S men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function, however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed U.S. studies of bone health in older men and women: The Osteoporotic Fractures in Men (MrOS) Study and the Study of Osteoporotic Fractures (SOF). We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long term cadmium exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful the proposed studies could be influential in directing future U.S policy to decrease Cd exposure in the U.S population similar to recent policies adopted by the European Union to limit Cd in fertilizers.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387003","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}