JBMR Plus最新文献

The importance of finite element analysis (FEA) is growing in orthopedic research, especially in implant design. However, Young's modulus (E) values, one of the most fundamental parameters, can range across a wide scale. Therefore, our study aimed to identify factors influencing E 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 E 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 t 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 E values is between 0.008 and 33.7 GPa. The E 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 E values. Bone anisotropy, specimen condition, patient age, and sex were selected as important variables considering the value of E. On the basis of our results, E 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. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Clinical studies indicate that microvascular disease (MVD) affects bone microstructure and decreases bone strength in type 2 diabetes mellitus (T2D). Osteocytes are housed in small voids within the bone matrix and lacunae and act as sensors of mechanical forces in bone. These cells regulate osteoclastic bone resorption and osteoblastic bone formation as well as osteocytic perilacunar remodeling. We hypothesized that MVD changes morphometric osteocyte lacunar parameters in individuals with T2D. We collected iliac crest bone biopsies from 35 individuals (10 female, 25 male) with T2D with MVD (15%) or without MVD (21%) with a median age of 67 years (interquartile range [IQR] 62–72 years). The participants were included based on c-peptide levels >700 pmol L⁻¹, absence of anti-GAD65 antibodies, and glycated hemoglobin (HbA1c) levels between 40 and 82 mmol mol⁻¹ or 5.8% and 9.7%, respectively. We assessed osteocyte lacunar morphometric parameters in trabecular and cortical bone regions using micro-computed tomography (micro-CT) at a nominal resolution of 1.2 μm voxel size. The cortical osteocyte lacunar volume (Lc.V) was 7.7% larger (p = 0.05) and more spherical (Lc.Sr, p < 0.01) in the T2D + MVD group. Using linear regression, we found that lacunar density (Lc.N/BV) in trabecular but not cortical bone was associated with HbA1c (p < 0.05, R² = 0.067) independently of MVD. Furthermore, Lc.V was larger and Lc.Sr higher in the center than in the periphery of the trabecular and cortical bone regions (p < 0.05). In conclusion, these data imply that MVD may impair skeletal integrity, possibly contributing to increased skeletal fragility in T2D complicated by MVD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997–2002) to the median IRs of the last 5 years (2012–2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (p-trend <0.05). The median IRs decreased 6.4% in women with T1D (p-trend = 0.35) and 25.6% in women with T2D (p-trend <0.05) but increased 2.3% in women without diabetes (p-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin-deficient, streptozotocin (STZ)-induced diabetes is protective for bone and skeletal muscle. DBA/2J male mice were injected with low-dose STZ (diabetic) or vehicle (non-diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647-MyoAb) or control (REGN1945-ConAb) antibody was administered for 8 weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX-I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro-computed tomography evaluations of femur) and cortical bone strength was assessed (three-point bending test of femur diaphysis). In diabetic mice, the combination of insulin/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin/MyoAb-treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross-sectional area (CSA) was lower with diabetes and the combination treatment with insulin/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross-sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X-ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49–22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02–2.04) and competing risk analyses (HR = 1.46; CI 1.02–2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99–2.06; p = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Heterotopic ossification (HO) consists of extraskeletal bone formation. One form of HO is acquired and instigated by traumas or surgery, and another form is genetic and characterizes fibrodysplasia ossificans progressiva (FOP). Recently, we and others showed that activin A promotes both acquired and genetic HO, and in previous studies we found that the retinoid agonist palovarotene inhibits both HO forms in mice. Here, we asked whether palovarotene's action against HO may include an interference with endogenous activin A expression and/or function. Using a standard mouse model of acquired HO, we found that activin A and its encoding RNA (Inhba) were prominent in chondrogenic cells within developing HO masses in untreated mice. Single-cell RNAseq (scRNAseq) assays verified that Inhba expression characterized chondroprogenitors and chondrocytes in untreated HO, in addition to its expected expression in inflammatory cells and macrophages. Palovarotene administration (4 mg/kg/d/gavage) caused a sharp inhibition of both HO and amounts of activin A and Inhba transcripts. Bioinformatic analyses of scRNAseq data sets indicated that the drug had reduced interactions and cross-talk among local cell populations. To determine if palovarotene inhibited Inhba expression directly, we assayed primary chondrocyte cultures. Drug treatment inhibited their cartilaginous phenotype but not Inhba expression. Our data reveal that palovarotene markedly reduces the number of local Inhba-expressing HO-forming cell populations. The data broaden the spectrum of HO culprits against which palovarotene acts, accounting for its therapeutic effectiveness. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dual-energy X-ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate fracture risk in a cohort of adults with at least one known fall and age-matched healthy controls. DXA images of the entire body as, well as isolated images of the hip, forearm, and spine (1488 total), were obtained from 478 fallers and 48 non-faller controls. A modeling pipeline was developed for fracture risk prediction using the DXA images and clinical data. First, self-supervised pretraining of feature extractors was performed using a small vision transformer (ViT-S) and a convolutional neural network model (VGG-16 and Resnet-50). After pretraining, the feature extractors were then paired with a multilayer perceptron model, which was used for fracture risk classification. Classification was achieved with an average area under the receiver-operating characteristic curve (AUROC) score of 74.3%. This study demonstrates ViT-S as a promising neural network technique for fracture risk classification using DXA scans. The findings have future application as a fracture risk screening tool for older adults at risk of falls. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25-hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, p < 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long-standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Osteogenesis imperfecta (OI) is a genetic, collagen-related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy n = 1, OI type I n = 1, OI type III n = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm³) were manufactured and loaded quasi-statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro–computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted R² of 0.556 (p = 2.65e−05) and 0.46 (p = 2.2e−04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site-matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM (R² = 67.4%, p = 7.73e−07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.