Fracture risk gradient assessed by categories of bone mineral density and trabecular bone score: the Manitoba BMD Registry.

Trabecular bonescore (TBS) helps to predict fracture risk in older adults. In this registry-based cohort study of patients aged 40 years and older, reduction in bone mineral density (BMD) and TBS are complementary for fracture risk prediction enhancement with lower BMD imparting greater risk than reduction in TBS. PURPOSE: Trabecular bone score (TBS) enhances fracture risk prediction independent of bone mineral density (BMD) in older adults. The purpose of this study was to further evaluate the gradient of fracture risk based on TBS tertile categories and WHO BMD categories, adjusted for other risk factors. METHODS: Using the Manitoba DXA registry, patients aged 40 years and older with spine/hip DXA and L1-L4 TBS were identified. Any incident fractures, major osteoporotic fractures (MOF), and hip fractures were identified. Cox regression models were used to estimate unadjusted and covariate-adjusted hazard ratios (HR, 95%CI) for incident fracture by BMD and TBS category and for each SD decrease in BMD and TBS. RESULTS: The study population included 73,108 individuals, 90% female with mean age 64 years. Mean (SD) minimum T-score was - 1.8 (1.1), and mean L1-L4 TBS was 1.257 (0.123). Lower BMD and TBS, both per SD, by WHO BMD category and by TBS tertile category, were significantly associated with MOF, hip, and any fracture (all HRs p < 0.001). However, the quantum of risk was consistently greater for BMD than TBS, with HRs showing non-overlapping CIs. CONCLUSION: TBS is complementary to BMD in prediction of incident major, hip, and any osteoporosis-related fracture, but reductions in BMD impart greater risk than reductions in TBS on both continuous and categorical scales.

Rapid trabecular bone growth in puberty associated with stiffer arteries in adulthood - longitudinal study on healthy young males.

Longitudinal bone content data from puberty to adulthood was assessed in 102 healthy males and associations with arterial health in adulthood was analysed. Bone growth in puberty was related to arterial stiffening and final bone mineral content to decreased arterial stiffness. Relationships with arterial stiffness were dependent on the studied bone regions. INTRODUCTION: Our aim was to assess the relationships between arterial parameters in adulthood and bone parameters in several locations longitudinally from puberty to 18-years and cross-sectionally at 18-years. METHODS: 102 healthy male data from a 7-year follow-up study was used to analyse total body (TB), femoral neck (FN) and lumbar spine (LS) mineral content and density by DXA, carotid intima-media thickness (cIMT) by ultrasound, carotid-femoral pulse wave velocity (cfPWV) and heart rate adjusted augmentation index (AIxHR75) by applanation tonometry. RESULTS: Linear regression analysis revealed negative associations between LS bone mineral density (BMD) and cfPWV [ß=-1.861, CI -3.589, -0.132, p=0.035] which remained significant [ß=-2.679, CI -4.837, -0.522, p=0.016] after adjustment to smoking, lean mass, weight category, pubertal stage, physical fitness, and activity. For AIxHR75 similar results were present [ß=-0.286, CI -0.553, -0.020, p=0.035], but were dependent on confounders. Analysis on pubertal bone growth speed showed independent positive associations to AIxHR75 between Δ FN bone mineral apparent density (BMAD) [ß=672.50, CI 348.07, 996.93, p<0.001] and Δ LS BMAD [ß=700.40, CI 57.384, 1343.423, p=0.033]. Further analysis combining pubertal bone growth and adulthood BMC revealed that the relationships of AIxHR75 with LS BMC and ΔFN BMAD were independent of each other. CONCLUSION: Trabecular bone regions like lumbar spine and femoral neck, showed stronger relationships with arterial stiffness. Rapid bone growth in puberty is related to arterial stiffening, while final bone mineral content relates to decreased arterial stiffness. These results could indicate that bone metabolism is independently associated with arterial stiffness rather than bone and arteries just having common traits of growth and maturation.

Relationship between trabecular bone score, bone mineral density and vertebral fractures in patients with axial spondyloarthritis.

BACKGROUND: In patients with axial spondyloarthritis, vertebral fracture risk is elevated and not always correlated with bone mineral density (BMD). Trabecular bone score (TBS) may offer some advantages in the assessment of vertebral fracture risk in these patients. The primary objective of this study was to compare TBS and BMD between axial spondyloarthritis patients depending on their vertebral fracture status. Secondary objectives were to estimate the prevalence of morphometric vertebral fractures, and to explore factors associated with fracture, as well as the interference of syndesmophytes on BMD and TBS. METHODS: A cross-sectional study was conducted. Data were collected on demographic and clinical characteristics, lab results, imaging findings and treatment. Statistical analysis was performed using SPSS v.13 statistical software. RESULTS: Eighty-four patients (60 men and 24 women; mean age of 59 years) were included. Nearly half (47.6%) of them had lumbar syndesmophytes. The rate of morphometric fracture was 11.9%. TBS showed a higher area under the curve (0.89) than total hip, femoral neck and lumbar BMD (0.80, 0.78, and 0.70 respectively) for classifying patients regarding their fracture status. Nonetheless, the differences did not reach statistical significance. Syndesmophytes affected lumbar spine BMD (p < 0.001), but not hip BMD or TBS. Fractures were associated with TBS, total hip BMD, erythrocyte sedimentation rate and C-reactive protein levels. CONCLUSIONS: We identified decreased TBS and total hip BMD, as well as increased erythrocyte sedimentation rate and C-reactive protein levels as factors associated with morphometric vertebral fractures. Unlike lumbar spine BMD, TBS is not affected by the presence of syndesmophytes.

Protein kinase D3 conditional knockout impairs osteoclast formation and increases trabecular bone volume in male mice.

Studies using kinase inhibitors have shown that the protein kinase D (PRKD) family of serine/threonine kinases are required for formation and function of osteoclasts in culture. However, the involvement of individual protein kinase D genes and their in vivo significance to skeletal dynamics remains unclear. In the current study we present data indicating that protein kinase D3 is the primary form of PRKD expressed in osteoclasts. We hypothesized that loss of PRKD3 would impair osteoclast formation, thereby decreasing bone resorption and increasing bone mass. Conditional knockout (cKO) of Prkd3 using a murine Cre/Lox system driven by cFms-Cre revealed that its loss in osteoclast-lineage cells reduced osteoclast differentiation and resorptive function in culture. Examination of the Prkd3 cKO mice showed that bone parameters were unaffected in the femur at 4 weeks of age, but consistent with our hypothesis, Prkd3 conditional knockout resulted in 18 % increased trabecular bone mass in male mice at 12 weeks and a similar increase at 6 months. These effects were not observed in female mice. As a further test of our hypothesis, we asked if Prkd3 cKO could protect against bone loss in a ligature-induced periodontal disease model but did not see any reduction in bone destruction in this system. Together, our data indicate that PRKD3 promotes osteoclastogenesis both in vitro and in vivo.

Effect of different antiretroviral therapy on muscle mass, bone mineral density, and trabecular bone score in Chinese HIV-infected males.

This is the first study to report both greater BMD loss and muscle loss in Chinese HIV-infected males with lamivudine (3TC)-tenofovir disoproxil fumarate (TDF)-efavirenz (EFV) regimen, which highlights the importance of closely monitoring muscle mass and bone mineral density in patients treated with 3TC-TDF-EFV regimen and provides a foundation for the clinical intervention of sarcopenia and osteoporosis. PURPOSE: To compare the effect initiating different antiretroviral therapy (ART) regimens have on muscle mass, bone mineral density (BMD), and trabecular bone score (TBS). METHODS: We designed a retrospective study of ART-naive Chinese males with HIV (MWH) undergoing two different regimens at 1-year follow-up. All subjects underwent dual-energy absorptiometry (DXA) for BMD and muscle mass prior to ART initiation, and again 1 year later. TBS iNsight software was used for TBS. We analyzed differences in muscle mass, BMD, and TBS after different treatment arms and associations between ART regimens and changes in them. RESULTS: A total of 76 men were included (mean age 31.83 ± 8.75 years). Mean absolute muscle mass decreased significantly from baseline to follow-up after initiation of lamivudine (3TC)-tenofovir disoproxil fumarate (TDF)-efavirenz (EFV), whereas increased significantly after initiation of 3TC-zidovudine(AZT)/Stavudine(d4T)-Nevirapine(NVP). Assignment to 3TC-TDF-EFV resulted in greater percentage loss in BMD at lumbar spine (LS) and total hip (TH) compared to 3TC-AZT/d4T-NVP, but this difference was not statistically significant at the femoral neck BMD and TBS. In the multivariable logistic regression model adjusted for covariates, the 3TC-TDF-EFV regimen was associated with higher odds of decreased appendicular and total muscle mass, LS and TH BMD. CONCLUSIONS: This is the first study to report not only greater BMD loss but also muscle loss in Chinese MWH with 3TC-TDF-EFV regimen. Our work highlights the importance of closely monitoring muscle mass and BMD in patients treated with 3TC-TDF-EFV regimen and provides a foundation for the clinical intervention of sarcopenia and osteoporosis in them.

Vertebral Level Variations in Trabecular Bone Score and Effect on Fracture Prediction: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. TBS is reportedly insensitive to degenerative changes, and it is uncertain whether the same rules for excluding lumbar vertebral levels from BMD measurement should be applied to TBS. The current analysis was performed to explore inter-vertebral variation in TBS measurements from L1 to L4, how this relates to clinically identified structural artifact resulting in vertebral level exclusion from BMD reporting, and area under the curve (AUC) for incident fracture. The study population comprised 70,762 individuals aged 40 years and older at the time of baseline spine DXA assessment (mean age 64.1 years, 89.7% female), among whom 24,289 (34.3%) had one or more vertebral exclusions. Both TBS and BMD showed a similar cranial/caudal inter-vertebral gradient. Compared with L1-4, TBS from L1 alone was lower (mean difference -0.096; -7.6%) while TBS from L4 alone was 0.046 (3.6%) greater, similar in those without and with visual structural artifact. During mean follow-up of 8.7 years, 6744 (9.5%) individuals sustained incident major osteoporotic fractures. TBS from L1 alone gave significantly higher AUC for incident fracture than L1-4, which was in turn significantly higher than L2, L3 and L4 alone, seen in those without and with visual structural artifact. In contrast, AUCs for BMD showed minimal variation from L1 to L4, and was higher for L1-4 than for any individual lumbar vertebral level. In summary, we found inter-vertebral TBS variations within the lumbar spine are overall similar to BMD but are relatively unaffected by visual structural artifact. Fracture outcomes showed the strongest association with TBS measured from L1 alone. Further investigation is need to understand the cause and clinical application of these differences.

CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury.

In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.

Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

Arthroscopic versus open cancellous bone grafting for scaphoid delayed/nonunion in adults (SCOPE-OUT): study protocol for a randomized clinical trial.

BACKGROUND: Scaphoid non-union results in pain and decreased hand function. Untreated, almost all cases develop degenerative changes. Despite advances in surgical techniques, the treatment is challenging and often results in a long period with a supportive bandage until the union is established. Open, corticocancellous (CC) or cancellous (C) graft reconstruction and internal fixation are often preferred. Arthroscopic assisted reconstruction with C chips and internal fixation provides minimal trauma to the ligament structures, joint capsule, and extrinsic vascularization with similar union rates. Correction of deformity after operative treatment is debated with some studies favouring CC, and others found no difference. No studies have compared time to union and functional outcomes in arthroscopic vs. open C graft reconstruction. We hypothesize that arthroscopic assisted C chips graft reconstruction of scaphoid delayed/non-union provides faster time to union, by at least a mean 3 weeks difference. METHODS: Single site, prospective, observer-blinded randomized controlled trial. Eighty-eight patients aged 18-68 years with scaphoid delayed/non-union will be randomized, 1:1, to either open iliac crest C graft reconstruction or arthroscopic assisted distal radius C chips graft reconstruction. Patients are stratified for smoking habits, proximal pole involvement and displacement of > / < 2 mm. The primary outcome is time to union, measured with repeated CT scans at 2-week intervals from 6 to 16 weeks postoperatively. Secondary outcomes are Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH), visual analogue scale (VAS), donor site morbidity, union rate, restoration of scaphoid deformity, range of motion, key-pinch, grip strength, EQ5D-5L, patient satisfaction, complications and revision surgery. DISCUSSION: The results of this study will contribute to the treatment algorithm of scaphoid delayed/non-union and assist hand surgeons and patients in making treatment decisions. Eventually, improving time to union will benefit patients in earlier return to normal daily activity and reduce society costs by shortening sick leave. TRIAL REGISTRATION: ClinicalTrials.gov NCT05574582. Date first registered: September 30, 2022. Items from the WHO trial registry are found within the protocol.

Evaluation of decellularization process for developing osteogenic bovine cancellous bone scaffolds in-vitro.

Current immunological issues in bone grafting regarding the transfer of xenogeneic donor bone cells into the recipient are challenging the industry to produce safer acellular natural matrices for bone regeneration. The aim of this study was to investigate the efficacy of a novel decellularization technique for producing bovine cancellous bone scaffold and compare its physicochemical, mechanical, and biological characteristics with demineralized cancellous bone scaffold in an in-vitro study. Cancellous bone blocks were harvested from a bovine femoral head (18-24 months old) subjected to physical cleansing and chemical defatting, and further processed in two ways. Group I was subjected to demineralization, while Group II underwent decellularization through physical, chemical, and enzymatic treatments. Both were then freeze-dried, and gamma radiated, finally producing a demineralized bovine cancellous bone (DMB) scaffold and decellularized bovine cancellous bone (DCC) scaffold. Both DMB and DCC scaffolds were subjected to histological evaluation, scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), fourier-transform infrared spectroscopy (FTIR), quantification of lipid, collagen, and residual nucleic acid content, and mechanical testing. The osteogenic potential was investigated through the recellularization of scaffolds with human osteoblast cell seeding and examined for cell attachment, proliferation, and mineralization by Alizarin staining and gene expression. DCC produced a complete acellular extracellular matrix (ECM) with the absence of nucleic acid content, wider pores with extensive interconnectivity and partially retaining collagen fibrils. DCC demonstrated a higher cell proliferation rate, upregulation of osteogenic differentiation markers, and substantial mineralized nodules production. Our findings suggest that the decellularization technique produced an acellular DCC scaffold with minimal damage to ECM and possesses osteogenic potential through the mechanisms of osteoconduction, osteoinduction, and osteogenesis in-vitro.

Sostdc1 Suppression in the Absence of Sclerostin Potentiates Anabolic Action of Cortical Bone in Mice.

The development of Wnt-based osteoanabolic agents has progressed rapidly in recent years, given the potent effects of Wnt modulation on bone homeostasis. Simultaneous pharmacologic inhibition of the Wnt antagonists sclerostin and Dkk1 can be optimized to create potentiated effects in the cancellous bone compartment. We looked for other candidates that might be co-inhibited along with sclerostin to potentiate the effects in the cortical compartment. Sostdc1 (Wise), like sclerostin and Dkk1, also binds and inhibits Lrp5/6 coreceptors to impair canonical Wnt signaling, but Sostdc1 has greater effects in the cortical bone. To test this concept, we deleted Sostdc1 and Sost from mice and measured the skeletal effects in cortical and cancellous compartments individually. Sost deletion alone produced high bone mass in all compartments, whereas Sostdc1 deletion alone had no measurable effects on either envelope. Mice with codeletion of Sostdc1 and Sost had high bone mass and increased cortical properties (bone mass, formation rates, mechanical properties), but only among males. Combined administration of sclerostin antibody and Sostdc1 antibody in wild-type female mice produced potentiation of cortical bone gain despite no effect of Sostdc1 antibody alone. In conclusion, Sostdc1 inhibition/deletion can work in concert with sclerostin deficiency to improve cortical bone properties. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Bone density and trabecular bone score to predict fractures in adults aged 20-39 years: a registry-based study.

Trabecular bone score (TBS) enhances fracture risk assessment in older adults; whether this is true in younger people is uncertain. In this registry-based study of adults aged 20-39 years, low BMD, but not low TBS, predicted fracture. PURPOSE: Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40 years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults. METHODS: Women and men aged 20-39 years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS. RESULTS: The study included 2799 individuals (77% female, mean age 32 years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures. CONCLUSION: In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults.

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension.

In postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories. PURPOSE: To investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score (TBSTT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE). METHODS: Postmenopausal women with lumbar spine (LS) or total hip BMD T-score <-2.5 and ≥-4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBSTT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1-6, 8, and 10. RESULTS: In long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBSTT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBSTT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBSTT were poorly correlated during denosumab treatment. CONCLUSION: In postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBSTT, independently of BMD, and shifted more patients to lower fracture-risk categories.

Accuracy of osseointegrated screw-bone construct stiffness and peri-implant loading predicted by homogenized FE models relative to micro-FE models.

Computational predictions of stiffness and peri-implant loading of screw-bone constructs are highly relevant to investigate and improve bone fracture fixations. Homogenized finite element (hFE) models have been used for this purpose in the past, but their accuracy has been questioned given the numerous simplifications, such as neglecting screw threads and modelling the trabecular bone structure as a continuum. This study aimed to investigate the accuracy of hFE models of an osseointegrated screw-bone construct when compared to micro-FE models considering the simplified screw geometry and different trabecular bone material models. Micro-FE and hFE models were created from 15 cylindrical bone samples with a virtually inserted, osseointegrated screw (fully bonded interface). Micro-FE models were created including the screw with threads (=reference models) and without threads to quantify the error due to screw geometry simplification. In the hFE models, the screws were modelled without threads and four different trabecular bone material models were used, including orthotropic and isotropic material derived from homogenization with kinematic uniform boundary conditions (KUBC), as well as from periodicity-compatible mixed uniform boundary conditions (PMUBC). Three load cases were simulated (pullout, shear in two directions) and errors in the construct stiffness and the volume average strain energy density (SED) in the peri-implant region were evaluated relative to the micro-FE model with a threaded screw. The pooled error caused by only omitting screw threads was low (max: 8.0%) compared to the pooled error additionally including homogenized trabecular bone material (max: 92.2%). Stiffness was predicted most accurately using PMUBC-derived orthotropic material (error: -0.7 ± 8.0%) and least accurately using KUBC-derived isotropic material (error: +23.1 ± 24.4%). Peri-implant SED averages were generally well correlated (R2 ≥ 0.76), but slightly over- or underestimated by the hFE models and SED distributions were qualitatively different between hFE and micro-FE models. This study suggests that osseointegrated screw-bone construct stiffness can be predicted accurately using hFE models when compared to micro-FE models and that volume average peri-implant SEDs are well correlated. However, the hFE models are highly sensitive to the choice of trabecular bone material properties. PMUBC-derived isotropic material properties represented the best trade-off between model accuracy and complexity in this study.

Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare bone disease that is associated with fractures and low bone mass. Sclerostin inhibition is being evaluated as a potential approach to increase bone mass in OI. We had previously found that in Col1a1Jrt/+ mice, a model of severe OI, treatment with an anti-sclerostin antibody had a minor effect on the skeletal phenotype. In the present study, we assessed the effect of genetic sclerostin inactivation in the Col1a1Jrt/+ mouse. We crossed Col1a1Jrt/+ mice with Sost knockout mice to generate Sost-deficient Col1a1Jrt/+ mice and assessed differences between Col1a1Jrt/+ mice with homozygous Sost deficiency and Col1a1Jrt/+ mice with heterozygous Sost deficiency. We found that Col1a1Jrt/+ mice with homozygous Sost deficiency had higher body mass, femur length, trabecular bone volume, cortical thickness and periosteal diameter as well as increased biomechanical parameters of bone strength. Differences between genotypes were larger at the age of 14 weeks than at 8 weeks of age. Transcriptome analysis of RNA extracted from the tibial diaphysis revealed only 5 differentially regulated genes. Thus, genetic inactivation of Sost increased bone mass and strength in the Col1a1Jrt/+ mouse. It appears from these observations that the degree of Sost suppression that is required for eliciting a beneficial response can vary with the genetic cause of OI.

The gas bladder of Heterotis niloticus (Cuvier, 1829).

This work reports on the structural characteristics of the respiratory gas bladder of the osteoglossiform fish Heterotis niloticus. The bladder-vertebrae relationships are also analyzed. A slit-shaped orifice in the mediodorsal pharyngeal wall is surrounded by a muscle sphincter and serves as a glottis-like opening to the gas bladder. The dorsolateral internal surface of the gas bladder is lined by a parenchyma of highly vascularized trabeculae and septa displaying an alveolar-like structure. The trabeculae contain, in addition to vessels, numerous eosinophils probably involved in immune responses. The air spaces are endowed with a thin exchange barrier indicating a good potential for respiratory gas exchange. The ventral wall of the gas bladder is a well-vascularized membrane that exhibits an exchange barrier in the luminal face and an inner structure dominated by the presence of a layer of richly innervated smooth muscle. This is suggestive of an autonomous adjustability of the gas bladder ventral wall. The trunk vertebrae show large transverse processes (parapophyses) and numerous surface openings that lead into intravertebral spaces that become invaded by the bladder parenchyma. Curiously, the caudal vertebrae show a regular teleost morphology with neural and hemal arches, but have similar surface openings and intravertebral pneumatic spaces. The African Arowana hence rivals the freshwater butterfly fish Pantodon in its exceptional role of displaying postcranial skeletal pneumaticity outside of Archosauria. The possible significance of these findings is discussed.

Trabecular Bone Score (TBS) Varies with Correction for Tissue Thickness Versus Body Mass Index: Implications When Using Pediatric Reference Norms.

Trabecular bone score (TBS) derived from secondary analysis of lumbar spine dual-energy X-ray absorptiometry (DXA) scans improves fracture prediction independent of bone mineral density (BMD) in adults. The utility of TBS to assess fracture risk in younger patients has not been established because pediatric norms have been lacking. Robust TBS reference data from the Bone Mineral Density in Childhood Study (BMDCS) have been published. TBS values for the BMDCS study were derived using an algorithm that accounts for tissue thickness (TBSTH ) rather than the commercially available algorithm that adjusts for body mass index (BMI; TBSBMI ). We examined the magnitude of differences in TBSTH and TBSBMI in a cohort of 189 healthy youth. TBS values using both algorithms increased with age and pubertal development in a similar pattern. However, TBSBMI values were systematically and significantly higher than TBSTH (mean = 0.06, p < 0.0001). The difference between calculated TBSBMI and TBSTH was not uniform. Differences were greater at lower TBS values, in males, in older individuals, in those at later Tanner stages, and in those with a greater BMI Z-score. These systematic differences preclude the development of a simple formula to allow conversion of TBSBMI to TBSTH "equivalents." Because of these systematic differences in these two algorithms, using an individual's TBSBMI to calculate a Z-score using the BMDCS TBSTH reference values results in a falsely higher TBS Z-score (differences mean = 0.73, interquartile range [IQR] = 0.3 to 1.6). Until TBSTH software for Hologic DXA equipment becomes commercially available, BMDCS TBS reference norms should not be used. © 2023 American Society for Bone and Mineral Research (ASBMR).

Effects of joint immobilization and treadmill exercise on marrow adipose tissue and trabecular bone after anterior cruciate ligament reconstruction in the rat proximal tibial epiphysis.

Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocols after anterior cruciate ligament (ACL) reconstruction affects trabecular bone and MAT is unclear. We aimed to examine the effects of joint immobilization and treadmill exercise on trabecular bone and MAT after ACL reconstruction. Rats received unilateral knee ACL transection and reconstruction surgery. After surgery, rats were reared without intervention, with joint immobilization, or with treadmill exercise (12 m/min, 60 min/day, six days/week), with untreated rats as controls. At two or four weeks after starting experiments, we examined histological changes in trabecular bone and MAT in the proximal tibial epiphysis. After ACL reconstruction, there were no significant changes in trabecular bone area and MAT area at both time points. Joint immobilization after ACL reconstruction resulted in reduced trabecular bone area and MAT accumulation due to adipocyte hyperplasia and hypertrophy within four weeks. Treadmill exercise after ACL reconstruction did not affect any parameters in trabecular bone and MAT. We detected a moderate negative correlation between trabecular bone area and MAT area. Therefore, MAT accumulation induced by joint immobilization may contribute, at least in part, to reducing trabecular bone area. To minimize trabecular bone loss and MAT accumulation, joint immobilization after ACL reconstruction should be minimized. Exercise after ACL reconstruction did not alter trabecular bone and MAT.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Bone health evaluation in primary hyperparathyroidism using dual-energy X-ray absorptiometry and trabecular bone score.

Bone involvement in primary hyperparathyroidism (PHPT) is characterized by reduced bone mineral density (BMD) using dual X-ray absorptiometry (DXA). A hallmark of PHPT is BMD loss at cortical sites while trabecular bone remains relatively preserved. PHPT is associated with increased fracture risk at both trabecular and cortical skeletal sites, which cannot be explained based on BMD values alone. The application of the trabecular bone score (TBS), an index of the lumbar spine DXA bone microarchitecture, showed lower TBS values and increased risk of fractures in PHPT patients, independent of BMD. Although further prospective studies are needed, promising data have been published with the use of TBS and some advanced DXA-based imaging modalities in patients with PHPT.