JBMR Plus最新文献

{"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":"2 9","pages":""},"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":"2 5","pages":""},"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":"11 5","pages":""},"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":"39 11","pages":""},"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":"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":"44 24","pages":""},"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}

{"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":"57 7","pages":""},"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":"Prevalence of osteoporosis, sarcopenia, and high falls risk in healthy community-dwelling Thai older adults: a nationwide cross-sectional study","authors":"A. Asavamongkolkul, N. Adulkasem, P. Chotiyarnwong, Ekasame Vanitcharoenkul, Chandhanarat Chandhanayingyong, Panai Laohaprasitiporn, Krabkaew Soparat, A. Unnanuntana","doi":"10.1093/jbmrpl/ziad020","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad020","url":null,"abstract":"\u0000 Thailand has transitioned from an aging society to an aged society, which implies that the prevalence of age-related disorders will increase; however, epidemiological data specific to the prevalence of age-related degenerative musculoskeletal disorders among Thai older adults remain limited. Accordingly, the aim of this study was to investigate the prevalence of age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and high falls risk among healthy community-dwelling Thai older adults. This cross-sectional nationwide study enrolled Thai adults aged ≥60 years from 2 randomly selected provinces from each of the 6 regions of Thailand via stratified multistage sampling during March 2021 to August 2022. All enrolled participants were evaluated for bone mineral density, skeletal muscle mass, grip strength, and gait speed. Osteoporosis was diagnosed according to the World Health Organization definition, and sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Falls risk was determined using the self-rated Fall Risk Questionnaire (FRQ). A total of 2991 eligible participants were recruited. The mean age of participants was 69.2 ± 6.5 years (range: 60–107), and 63.1% were female. The prevalence of osteoporosis, sarcopenia, and high falls risk was 29.7%, 18.1%, and 38.5%, respectively. Approximately one-fifth of subjects (19.1%) had at least 2 of 3 risk factors (i.e., osteoporosis, sarcopenia, and high falls risk) for sustaining a fragility fracture, and 3.4% had all three risk factors. In conclusion, the results of this study revealed a high and increasing prevalence of osteoporosis, sarcopenia, and high falls risk in healthy community-dwelling Thai older adults. Since these conditions are all major risk factors for fragility fracture, modification of Thailand’s national healthcare policy is urgently needed to address the increasing prevalence of these conditions among healthy community-dwelling older adults living in Thailand.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386472","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":"Burosumab versus conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period","authors":"Leanne M. Ward, Wolfgang Högler, Francis H. Glorieux, A. Portale, Michael P. Whyte, C. Munns, Ola Nilsson, Jill H Simmons, Raja Padidela, Noriyuki Namba, H. Cheong, Etienne Sochett, Koji Muroya, Hiroyuki Tanaka, P. Pitukcheewanont, G. Gottesman, Andrew Biggin, Farzana Perwad, Angel Chen, J. Lawrence Merritt, Erik A. Imel","doi":"10.1093/jbmrpl/ziad001","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad001","url":null,"abstract":"\u0000 In a randomized, open-label phase 3 study of 61 children 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to bi-weekly (Q2W) burosumab for 64 weeks improved phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W and had continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for the treatment groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and + 1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and + 0.73 (0.82), and mean (SD) height Z-score + 0.41 (0.50) and + 0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum ALP decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group, and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all six children in the burosumab continuation group and in 14/15 children in the cross-over group. AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Thus, improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"77 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387189","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":"Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta","authors":"Hsiao H Sung, Wyatt Spresser, Joseph P Hoffmann, Zongrui Dai, Peter M Van der Kraan, M. Caird, Esmeralda Blaney Davidson, K. Kozloff","doi":"10.1093/jbmrpl/ziad004","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad004","url":null,"abstract":"\u0000 Craniofacial and dentoalveolar abnormalities are present in all types of Osteogenesis Imperfecta (OI). Mouse models of the disorder are critical to understanding these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. Brtl/+ and G610c/+ are moderately severe and mild type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT scanned heads of 3-week-old, 3-month-old, and 6-month-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT (p < 0.05), whereas G610c/+ skulls are similar in length to their WT counterparts. Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible (p < 0.05). In contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 months (p < 0.05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars (p < 0.05), similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"38 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385780","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":"18F-sodium fluoride PET-CT visualizes disease activity in adult chronic nonbacterial osteitis (CNO)","authors":"A. Leerling, F. Smit, Zita Spӓth, Ana Navas Cañete, L. de Geus-Oei, A. van de Burgt, Olaf M Dekkers, W. van der Bruggen, Natasha M Appelman-Dijkstra, D. Vriens, Elizabeth M Winter","doi":"10.1093/jbmrpl/ziad007","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziad007","url":null,"abstract":"\u0000 \u0000 \u0000 Chronic nonbacterial osteitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride positron emission tomography ([18F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluate the capacities of [18F]NaF-PET/CT to provide structural and functional assessment in adult CNO.\u0000 \u0000 \u0000 \u0000 Cross-sectional study among 43 adult CNO patients and 16 controls (patients referred for suspected, but not diagnosed as CNO) undergoing [18F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values (SUVmax (g/ml)) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUVmax was correlated with clinical disease activity in patients.\u0000 \u0000 \u0000 \u0000 Manubrial and costal sclerosis/hyperostosis, and calcification of the costoclavicular ligament emerged core structural features associated with CNO as visualized by [18F]NaF-PET/CT. SUVmax of CNO lesions was higher compared to in-patient reference bone (mean paired difference 11.4, 95%CI9.4–13.5, p < 0.001) and controls (mean difference 12.4, 95%CI9.1–15.8, p < 0.001). Highest SUVmax values were found in soft tissue and joint areas like the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient 0.546, p < 0.002).\u0000 \u0000 \u0000 \u0000 [18F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue and joint features. At the same time, [18F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF-uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision-making.\u0000","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"26 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139450722","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}