JBMR Plus最新文献

{"title":"When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit","authors":"Eva M. Wölfel,&nbsp;Benjamin Bartsch,&nbsp;Jasmin Koldehoff,&nbsp;Imke A. K. Fiedler,&nbsp;Sofie Dragoun-Kolibova,&nbsp;Felix N. Schmidt,&nbsp;Johannes Krug,&nbsp;Mei-Chun Lin,&nbsp;Klaus Püschel,&nbsp;Benjamin Ondruschka,&nbsp;Elizabeth A. Zimmermann,&nbsp;Hans Jelitto,&nbsp;Gerold Schneider,&nbsp;Bernd Gludovatz,&nbsp;Björn Busse","doi":"10.1002/jbm4.10839","DOIUrl":"10.1002/jbm4.10839","url":null,"abstract":"<p>Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age-related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case-control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back-scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three-point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J-integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138625747","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":"The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult-Onset Hypophosphatasia","authors":"Naoko Hidaka,&nbsp;Hiroaki Murata,&nbsp;Kanako Tachikawa,&nbsp;Keiichi Osaki,&nbsp;Takashi Sekiyama,&nbsp;Yuka Kinoshita,&nbsp;Hajime Kato,&nbsp;Yoshitomo Hoshino,&nbsp;Soichiro Kimura,&nbsp;Takashi Sunouchi,&nbsp;So Watanabe,&nbsp;Masaomi Nangaku,&nbsp;Noriko Makita,&nbsp;Toshimi Michigami,&nbsp;Nobuaki Ito","doi":"10.1002/jbm4.10842","DOIUrl":"10.1002/jbm4.10842","url":null,"abstract":"<p>Hypophosphatasia (HPP) is an inherited disease caused by variants of the <i>ALPL</i> gene encoding tissue-nonspecific alkaline phosphatase. Adult-onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18 years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first-line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64-year-old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the <i>ALPL</i> gene (c.319G &gt; A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6 months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6-minute walk test (525 to 606 m). The EQ-5D-5L index was also improved (0.757 to 0.895). Within a follow-up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04 μM, uPPi/Cre: 226.8 to 75.4 nmol/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the <i>ALPL</i> gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822505","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":"Utility and Limitations of TALLYHO/JngJ as a Model for Type 2 Diabetes–Induced Bone Disease","authors":"Lejla Emini,&nbsp;Juliane Salbach-Hirsch,&nbsp;Johannes Krug,&nbsp;Katharina Jähn-Rickert,&nbsp;Björn Busse,&nbsp;Martina Rauner,&nbsp;Lorenz C. Hofbauer","doi":"10.1002/jbm4.10843","DOIUrl":"10.1002/jbm4.10843","url":null,"abstract":"<p>Type 2 diabetes mellitus (T2DM) increases risk of fractures due to bone microstructural and material deficits, though the mechanisms remain unclear. Preclinical models mimicking diabetic bone disease are required to further understand its pathogenesis. The TALLYHO/JngJ (TH) mouse is a polygenic model recapitulating adolescent-onset T2DM in humans. Due to incomplete penetrance of the phenotype ~25% of male TH mice never develop hyperglycemia, providing a strain-matched nondiabetic control. We performed a comprehensive characterization of the metabolic and skeletal phenotype of diabetic TH mice and compared them to either their nondiabetic TH controls or the recommended SWR/J controls to evaluate their suitability to study diabetic bone disease in humans. Compared to both controls, male TH mice with T2DM exhibited higher blood glucose levels, weight along with impaired glucose tolerance and insulin sensitivity. TH mice with/without T2DM displayed higher cortical bone parameters and lower trabecular bone parameters in the femurs and vertebrae compared to SWR/J. The mechanical properties remained unchanged for all three groups except for a low-energy failure in TH mice with T2DM only compared to SWR/J. Histomorphometry analyses only revealed higher number of osteoclasts and osteocytes for SWR/J compared to both groups of TH. Bone turnover markers procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase (TRAP) were low for both groups of TH mice compared to SWR/J. Silver nitrate staining of the femurs revealed low number of osteocyte lacunar and dendrites in TH mice with T2DM. Three-dimensional assessment showed reduced lacunar parameters in trabecular and cortical bone. Notably, osteocyte morphology changed in TH mice with T2DM compared to SWR/J. In summary, our study highlights the utility of the TH mouse to study T2DM, but not necessarily T2DM-induced bone disease, as there were no differences in bone strength and bone cell parameters between diabetic and non-diabetic TH mice. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822438","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":"Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1–84)","authors":"Pernille van Dijk Christiansen,&nbsp;Tanja Sikjær,&nbsp;Christina Møller Andreasen,&nbsp;Jesper Skovhus Thomsen,&nbsp;Annemarie Brüel,&nbsp;Ellen Margrethe Hauge,&nbsp;Jean-Marie Delaisse,&nbsp;Lars Rejnmark,&nbsp;Thomas Levin Andersen","doi":"10.1002/jbm4.10829","DOIUrl":"10.1002/jbm4.10829","url":null,"abstract":"<p>In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1–84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1–84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 μg rhPTH(1–84) a day (<i>n</i> = 21) (PTH) or similar placebo (<i>n</i> = 21) (PLB) for 6 months as add-on to conventional therapy. This was followed by an open-label extension, where patients extended their rhPTH(1–84) (PTH) (<i>n</i> = 5), continued conventional treatment (CON) (<i>n</i> = 5), or withdrew from rhPTH(1–84) and resumed conventional therapy (PTHw) for an additional 24 months (<i>n</i> = 8). Bone biopsies were collected at months 6 (<i>n</i> = 42) and 30 (<i>n</i> = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH-treated patients. In the rhPTH(1–84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1–84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822437","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":"Increased Osteoblast GαS Promotes Ossification by Suppressing Cartilage and Enhancing Callus Mineralization During Fracture Repair in Mice","authors":"Kathy K Lee,&nbsp;Adele Changoor,&nbsp;Marc D Grynpas,&nbsp;Jane Mitchell","doi":"10.1002/jbm4.10841","DOIUrl":"10.1002/jbm4.10841","url":null,"abstract":"<p>Gα_S, the stimulatory G protein α-subunit that raises intracellular cAMP levels by activating adenylyl cyclase, plays a vital role in bone development, maintenance, and remodeling. Previously, using transgenic mice overexpressing Gα_S in osteoblasts (G_S-Tg), we demonstrated the influence of osteoblast Gα_S level on osteogenesis, bone turnover, and skeletal responses to hyperparathyroidism. To further investigate whether alterations in Gα_S levels affect endochondral bone repair, a postnatal bone regenerative process that recapitulates embryonic bone development, we performed stabilized tibial osteotomy in male G_S-Tg mice at 8 weeks of age and examined the progression of fracture healing by micro-CT, histomorphometry, and gene expression analysis over a 4-week period. Bone fractures from G_S-Tg mice exhibited diminished cartilage formation at the time of peak soft callus formation at 1 week post-fracture followed by significantly enhanced callus mineralization and new bone formation at 2 weeks post-fracture. The opposing effects on chondrogenesis and osteogenesis were validated by downregulation of chondrogenic markers and upregulation of osteogenic markers. Histomorphometric analysis at times of increased bone formation (2 and 3 weeks post-fracture) revealed excess fibroblast-like cells on newly formed woven bone surfaces and elevated osteocyte density in G_S-Tg fractures. Coincident with enhanced callus mineralization and bone formation, G_S-Tg mice showed elevated active β-catenin and Wntless proteins in osteoblasts at 2 weeks post-fracture, further substantiated by increased mRNA encoding various canonical Wnts and Wnt target genes, suggesting elevated osteoblastic Wnt secretion and Wnt/β-catenin signaling. The G_S-Tg bony callus at 4 weeks post-fracture exhibited greater mineral density and decreased polar moment of inertia, resulting in improved material stiffness. These findings highlight that elevated Gα_S levels increase Wnt signaling, conferring an increased osteogenic differentiation potential at the expense of chondrogenic differentiation, resulting in improved mechanical integrity. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10841","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822395","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":"Fruit and Vegetable Consumption and the Risk of Bone Fracture: A Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)-Assessed Systematic Review and Dose–Response Meta-Analysis","authors":"Sheida Zeraattalab-Motlagh,&nbsp;Seyed Mojtaba Ghoreishy,&nbsp;Arman Arab,&nbsp;Sara Mahmoodi,&nbsp;Amirhossein Hemmati,&nbsp;Hamed Mohammadi","doi":"10.1002/jbm4.10840","DOIUrl":"10.1002/jbm4.10840","url":null,"abstract":"<p>Researchers have examined the link between consuming fruit and vegetables and the incidence of fractures for many years. Nevertheless, their findings have been unclear. Furthermore, the dose-dependent relationship has not been examined, and the level of certainty in the evidence was not evaluated. We carried out a dose-dependent meta-analysis examining the relation between fruit and vegetables intake and fracture incidence. PubMed, Web of Sciences, and Scopus were searched until April 2023 for cohort studies evaluating the relation between fruit and vegetables and fracture incidence. Summary relative risks (RRs) were computed from complied data by applying random effects analysis. To examine the level of evidence, we utilized the approach called the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Ten cohort studies comprising 511,716 individuals were entered. There was a nonsignificant relation between fruit and vegetables, as well as only fruit intake and any fracture risk. In contrast, high versus low analysis presented that vegetables consumption was linked to a 16% decrease in any type of fracture incidence (RR 0.84; 95% confidence interval [CI], 0.75 to 0.95; <i>I</i>² = 83.1%; <i>n</i> = 6). Also, per one serving/day (200 g/day) increments in vegetables consumption, there was a 14% decline in the fracture risk (RR 0.86; 95% CI, 0.77 to 0.97; <i>I</i>² = 84.7%; <i>n</i> = 5; GRADE = moderate). With moderate certainty, a greater consumption of only vegetables, but not total fruit and vegetables or only fruit, might reduce the risk of fracture. These associations were also evident in dose–response analysis. Large intervention trials are demanded to approve our findings. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135138191","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":"Trends in Serum Cytokine Expression in Pediatric Skeletal Dysplasia","authors":"David A. O'Connell,&nbsp;Ricki S. Carroll,&nbsp;Angela L. Duker,&nbsp;Andrea J. Schelhaas,&nbsp;Marjorie M. Postell,&nbsp;Paul T. Fawcett,&nbsp;Michael B. Bober","doi":"10.1002/jbm4.10816","DOIUrl":"10.1002/jbm4.10816","url":null,"abstract":"<p>The skeletal dysplasias are a heterogeneous group of genetic conditions caused by abnormalities of growth, development, and maintenance of bone and cartilage. Little is known about the roles that cytokines play in the inflammatory and non-inflammatory pathophysiology of skeletal dysplasia. We sought to test our hypothesis that cytokines would be differentially expressed in children with skeletal dysplasia as compared to typically growing controls. Cytokine levels were analyzed using the Cytokine Human Magnetic 25-Plex Panel (Invitrogen, Waltham, MA, USA); 136 growing individuals with skeletal dysplasia and compared to a cohort of 275 healthy pediatric control subjects. We focused on the expression of 12 cytokines across nine dysplasia cohorts. The most common skeletal dysplasia diagnoses were: achondroplasia (58), osteogenesis imperfecta (19), type II collagenopathies (11), multiple epiphyseal dysplasia (MED: 9), diastrophic dysplasia (8), metatropic dysplasia (8), and microcephalic osteodysplastic primordial dwarfism type II (MOPDII: 8). Of the 108 specific observations made, 45 (41.7%) demonstrated statistically significant differences of expression between controls and individuals with skeletal dysplasia. Four of the 12 analyzed cytokines demonstrated elevated expression above control levels in all of the dysplasia cohorts (interleukin 12 [IL-12], IL-13, interferon γ-induced protein 10 kDa [IP-10], regulated on activation, normal T cell expressed and secreted [RANTES]) and two demonstrated expression below control levels across all dysplasia cohorts (monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1β [MIP-1β]). The highest levels of overexpression were seen in MOPDII, with expression levels of IP-10 being increased 3.8-fold (<i>p</i> &lt; 0.0001). The lowest statistically significant levels of expressions were in type II collagenopathies, with expression levels of MCP-1 being expressed 0.43-fold lower (<i>p</i> &lt; 0.005). With this data, we hope to lay the groundwork for future directions in dysplasia research that will enhance our understanding of these complex signaling pathways. Looking forward, validating these early trends in cytokine expression, and associating the observed variations with trends in the progression of dysplasia may offer new candidates for clinical biomarkers or even new therapeutics. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135241086","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":"Changes in Vertebral Bone Density and Paraspinal Muscle Morphology Following Spaceflight and 1 Year Readaptation on Earth","authors":"Jennifer C. Coulombe,&nbsp;Fjola Johannesdottir,&nbsp;Katelyn A. Burkhart,&nbsp;Henriette Brummer,&nbsp;Brett T. Allaire,&nbsp;Mary L. Bouxsein","doi":"10.1002/jbm4.10810","DOIUrl":"10.1002/jbm4.10810","url":null,"abstract":"<p>Astronauts have an increased risk of back pain and disc herniation upon returning to Earth. Thus, it is imperative to understand the effects of spaceflight and readaptation to gravity on the musculoskeletal tissues of the spine. Here we investigated whether ~6 months of spaceflight led to regional differences in bone loss within the vertebral body. Additionally, we evaluated the relationships between vertebral bone density and paraspinal muscle morphology before flight, after flight, and after readaptation on Earth. We measured vertebral trabecular bone mineral density (Tb.BMD), paraspinal muscle cross-sectional area (CSA), and muscle density in 17 astronauts using computed tomography (CT) images of the lumbar spine obtained before flight (before flight, <i>n</i> = 17), after flight (spaceflight, <i>n</i> = 17), and ~12 months of readaptation to gravitational loading on Earth (follow-up, <i>n</i> = 15). Spaceflight-induced declines in Tb.BMD were greater in the superior region of the vertebral body (−6.7%) than the inferior (−3.1%, <i>p</i> = 0.052 versus superior region) and transverse regions (−4.3%, <i>p</i> = 0.057 versus superior region). After a year of readaptation to Earth's gravity, Tb.BMD in the transverse region remained significantly below preflight levels (−4.66%, <i>p</i> = 0.0094). Paraspinal muscle CSA and muscle density declined −1.0% (<i>p</i> = 0.005) and −0.83% (<i>p</i> = 0.001) per month of spaceflight, respectively. Ultimately, bone loss in the superior vertebral body, along with fatty infiltration of paraspinal muscles and incomplete recovery even after a year of readaptation on Earth, may contribute to spinal pathology in long-duration astronauts. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135341669","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":"Anisotropy, Anatomical Region, and Additional Variables Influence Young's Modulus of Bone: A Systematic Review and Meta-Analysis","authors":"Krisztián Kovács,&nbsp;Szilárd Váncsa,&nbsp;Gergely Agócs,&nbsp;Andrea Harnos,&nbsp;Péter Hegyi,&nbsp;Viktor Weninger,&nbsp;Katinka Baross,&nbsp;Bence Kovács,&nbsp;Gergely Soós,&nbsp;György Kocsis","doi":"10.1002/jbm4.10835","DOIUrl":"10.1002/jbm4.10835","url":null,"abstract":"<p>The importance of finite element analysis (FEA) is growing in orthopedic research, especially in implant design. However, Young's modulus (<i>E</i>) values, one of the most fundamental parameters, can range across a wide scale. Therefore, our study aimed to identify factors influencing <i>E</i> values in human bone specimens. We report our systematic review and meta-analysis based on the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. We conducted the analysis on November 21, 2021. We included studies investigating healthy human bone specimens and reported on <i>E</i> values regarding demographic data, specimen characteristics, and measurement specifics. In addition, we included study types reporting individual specimen measurements. From the acquired data, we created a cohort in which we performed an exploratory data analysis that included the explanatory variables selected by random forest and regression trees methods, and the comparison of groups using independent samples Welch's <i>t</i> test. A total of 756 entries were included from 48 articles. Eleven different bones of the human body were included in these articles. The range of <i>E</i> values is between 0.008 and 33.7 GPa. The <i>E</i> values were most heavily influenced by the cortical or cancellous type of bone tested. Measuring method (compression, tension, bending, and nanoindentation), the anatomical region within a bone, the position of the bone within the skeleton, and the bone specimen size had a decreasing impact on the <i>E</i> values. Bone anisotropy, specimen condition, patient age, and sex were selected as important variables considering the value of <i>E</i>. On the basis of our results, <i>E</i> values of a bone change with bone characteristics, measurement techniques, and demographic variables. Therefore, the evaluation of FEA should be performed after the standardization of in vitro measurement protocol. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135862998","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":"Antiresorptive Versus Anabolic Therapy in Managing Osteoporosis in People with Type 1 and Type 2 Diabetes","authors":"Tatiane Vilaca,&nbsp;Richard Eastell","doi":"10.1002/jbm4.10838","DOIUrl":"https://doi.org/10.1002/jbm4.10838","url":null,"abstract":"<p>Diabetes is characterized by hyperglycemia, but the two main types, type 1 diabetes (T1D) and type 2 diabetes (T2D), have distinct pathophysiology and epidemiological profiles. Individuals with T1D and T2D have an increased risk of fractures, particularly of the hip, upper arm, ankle, and nonvertebral sites. The risk of fractures is higher in T1D compared to T2D. The diagnosis of osteoporosis in individuals with T1D and T2D follows similar criteria as in the general population, but treatment thresholds may differ. Antiresorptive therapies, the first-line treatment for osteoporosis, are effective in individuals with T2D. Observational studies and post hoc analyses of previous trials have indicated that antiresorptive drugs, such as bisphosphonates and selective estrogen receptor modulators, are equally effective in reducing fracture risk and increasing bone mineral density (BMD) in individuals with and without T2D. Denosumab has shown similar effects on vertebral fracture risk but increases the risk of nonvertebral fractures. Considering the low bone turnover observed in T1D and T2D, anabolic therapies, which promote bone formation and resorption, have emerged as a potential treatment option for bone fragility in this population. Data from observational studies and post hoc analyses of previous trials also showed similar results in increasing BMD and reducing the risk of fractures in people with or without T2D. However, no evidence suggests that anabolic therapy has greater efficacy than antiresorptive drugs. In conclusion, there is an increased risk of fractures in T1D and T2D. Reductions in BMD cannot solely explain the relationship between T1D and T2D and fractures. Bone microarchitecture and other factors play a role. Antiresorptive and anabolic therapies have shown efficacy in reducing fracture risk in individuals with T2D, but the evidence is more robust for antiresorptive drugs. Evidence in T1D is scant. Further research is needed to fully understand the underlying mechanisms and optimize management strategies for bone fragility in T1D and T2D. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134815480","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}