A new biomechanical model of the mammal jaw based on load path analysis.

The primary function of the tetrapod jaw is to transmit jaw muscle forces to bite points. The routes of force transfer in the jaw have never been studied, but can be quantified using load paths--the shortest, stiffest routes from regions of force application to support constraints. Here we use load path analysis to map force transfer from muscle attachments to bite point and jaw joint, and to evaluate how different configurations of trabecular and cortical bone affect load paths. We created three models of the mandible of the Virginia opossum, Didelphis virginiana, each with a cortical bone shell, but with different material properties for the internal spaces: a cortical-trabecular model, in which the interior space is modeled with bulk properties of trabecular bone; a cortical-hollow model, in which trabeculae and mandibular canal are modeled as hollow; and a solid-cortical model, in which the interior is modeled as cortical bone. The models were compared with published in vivo bite force and bone strain data, and the load paths calculated for each model. The cortical-trabecular model, which most closely approximates the actual morphology, was best validated by in vivo data. In all three models the load path was confined to cortical bone, although its route within the cortex varied depending on the material properties of the inner model. Our analysis shows that most of the force is transferred through the cortical, rather than trabecular bone, and highlights the potential of load path analysis for understanding form-function relationships in the skeleton.

Characterization of bone disease in cystic fibrosis.

With the increased life expectancy of people with cystic fibrosis (CF), clinical attention has focused on prevention and treatment of non-pulmonary comorbidities. CF-related bone disease (CFBD) is a common complication and leads to increased fracture rates. Dual energy X-ray absorptiometry (DXA) is the recommended and gold standard technique to identify and monitor bone health. However, DXA has limitations because of its two-dimensional nature. Complementary tools to DXA are available, such as trabecular bone score (TBS) and vertebral fracture assessment (VFA). Quantitative computed tomography (QCT), magnetic resonance imaging (MRI) and quantitative ultrasound (QUS) may also be useful.

Global current research status and future hotspots in osteoporotic fracture based on bibliometric assessment and visualization techniques.

BACKGROUND: In the past decade, the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity, risk assessment of osteoporotic fractures, and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs. AIM: To understand the trends and hotspots in osteoporotic fracture research. METHODS: Original articles were retrieved between January 1, 2010, and December 31, 2019, from the Web of Science Core Collection database. CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends. RESULTS: Nine studies were identified using bibliometric indices, including citation, centrality, and sigma value, which might indicate a growing trend. Through clustering, we identified six major hot subtopics. Using burst analysis, top-5 references with the strongest bursting strength after 2017 were identified, indicating a future hotspot in this field. CONCLUSION: Current hot subtopics in osteoporotic fracture research include atypical femoral fractures, androgen deprivation therapy, denosumab discontinuation, hip fractures, trabecular bone score (TBS), and bone phenotype. Management and prevention of secondary fractures in patients with osteoporotic fractures, TBSs, and long-term administration strategy for zoledronic acid are expected to become research hotspots.

Evaluation of bone mineral density (BMD) and trabecular bone score (TBS) in pheochromocytoma and paraganglioma; a multi-centric case-control study from India.

Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) due to excess sympathetic system stimulation. Our study revealed low BMD and TBS (trabecular bone score) in cases compared to matched controls. Plasma-free nor-metanephrine and hypertension duration found to be most consistent predictive factors. PURPOSE: Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) and increased fracture risks. Sympathetic nervous system stimulation has been shown to increase bone resorption and decrease bone formation via ß2 receptors. Chronic inflammation and increased cytokine production add to more bone loss. TBS (trabecular bone score) is an established surrogate marker for bone histomorphometry. BMD and TBS data in pheochromocytoma and PPGL are scarce. The aim was to assess the BMD and TBS in pheochromocytoma and PPGL and look for clinical and biochemical predictors. METHODS: This case-control study had sample size of 58 (29 cases and controls each). BMI-, age-, and sex-matched controls were taken for comparison. Both cases and controls had undergone DXA scan and BMD {Z-scores and bone mineral concentration (BMC) in g/cm2} and TBS were analyzed. Detailed clinical histories and relevant biochemistry values were noted. RESULTS: The mean age of our case population was 29.5 ± 9.4 years with a mean age of HTN onset at 26.86 ± 6.6 years. Lumbar spine BMC (0.86 ± 0.14 vs 0.96 ± 0.15; p = 0.036), femoral neck Z-score (- 1.23 ± 1.07 vs - 0.75 ± 0.97; p = 0.003), and whole body BMC (0.91 ± 0.14 vs 1.07 ± 0.11; p = 0.000) were significantly low in cases compared to controls. Similarly, TBS was significantly lower in cases compared to controls (1.306 ± 0.113 vs 1.376 ± 0.083; p = 0.001). CONCLUSION: This study establishes both low bone mass and poor bone quality in an Indian pheochromocytoma and PPGL patient's cohort. Plasma-free nor-metanephrine and duration of hypertension were found to be most consistent predictive factors in multivariate regression analysis.

Elucidating the mechano-molecular dynamics of TRAP activity using CRISPR/Cas9 mediated fluorescent reporter mice.

Osteoclasts are essential for bone remodeling by adapting their resorptive activity in response to their mechanical in vivo environment. However, the molecular mechanisms underlying this process remain unclear. Here, we demonstrated the role of tartrate-resistant acid phosphatase (TRAP, Acp5), a key enzyme secreted by osteoclasts, in bone remodeling and mechanosensitivity. Using CRISPR/Cas9 reporter mice, we demonstrated bone cell reporter (BCRIbsp/Acp5) mice feature fluorescent TRAP-deficient osteoclasts and examined their activity during mechanically driven trabecular bone remodeling. Although BCRIbsp/Acp5 mice exhibited trabecular bone impairments and reduced resorption capacity in vitro, RNA sequencing revealed unchanged levels of key osteoclast-associated genes such as Ctsk, Mmp9, and Calcr. These findings, in conjunction with serum carboxy-terminal collagen crosslinks (CTX) and in vivo mechanical loading outcomes collectively indicated an unaltered bone resorption capacity of osteoclasts in vivo. Furthermore, we demonstrated similar mechanoregulation during trabecular bone remodeling in BCRIbsp/Acp5 and wild-type (WT) mice. Hence, this study provides valuable insights into the dynamics of TRAP activity in the context of bone remodeling and mechanosensation.

Radiographic texture of the trabecular bone of the proximal phalanx in horses with metacarpophalangeal osteoarthritis.

Osteoarthritis (OA) is a prevalent condition in horses, leading to changes in trabecular bone structure and radiographic texture. Although fractal dimension (FD) and lacunarity have been applied to quantify these changes in humans, their application in horses remains nascent. This study evaluated the use of FD, bone area fraction (BA/TA), and lacunarity in quantifying trabecular bone differences in the proximal phalanx (P1) in 50 radiographic examinations of equine metacarpophalangeal joints with varying OA degrees. In the dorsopalmar view, regions of interest were defined in the trabecular bone of the proximal epiphysis, medial and lateral to the sagittal groove of P1. Lower BA/TA values were observed medially in horses with severe OA (P=0.003). No significant differences in FD and lacunarity were found across OA degrees (P>0.1). FD, BA/TA, and lacunarity were not effective in identifying radiographic texture changes in the P1 trabecular bone in horses with different metacarpophalangeal OA degrees.

An investigation of composition, morphology, mechanical properties, and microdamage accumulation of human type 2 diabetic bone.

This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.

Mechanisms of osteoporosis associated with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic respiratory symptoms due to inflammatory and destructive changes of the lung leading to progressive airflow obstruction. Fragility fractures associated with osteoporosis are among major comorbidities and have significant impacts on quality of life and prognosis of patients with COPD. Evidence suggests that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility and resultant fractures in COPD. Although various clinical risk factors of osteoporosis have been described, mechanisms of COPD-associated osteoporosis are still largely unknown. In addition, its specific treatment has not been established, either. Previous studies have suggested involvement of low BMI and sarcopenia in the pathogenesis of COPD-associated osteoporosis. In this narrative review, we will propose critical roles of vitamin D deficiency and inflammation, both of which are often present in COPD and may underlie the development of osteosarcopenia and impaired bone quality, ultimately causing fractures in COPD patients.

Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

DXA beyond bone mineral density and the REMS technique: new insights for current radiologists practice.

Osteoporosis is the most prevalent skeletal disorder, a condition that is associated with significant social and healthcare burden. In the elderly, osteoporosis is commonly associated with sarcopenia, further increasing the risk of fracture. Several imaging techniques are available for a non-invasive evaluation of osteoporosis and sarcopenia. This review focuses on dual-energy X-ray absorptiometry (DXA), as this technique offers the possibility to evaluate bone mineral density and body composition parameters with good precision and accuracy. DXA is also able to evaluate the amount of aortic calcification for cardiovascular risk estimation. Additionally, new DXA-based parameters have been developed in recent years to further refine fracture risk estimation, such as the Trabecular Bone Score and the Bone Strain Index. Finally, we describe the recent advances of a newly developed ultrasound-based technology known as Radiofrequency Echographic Multi-Spectrometry, which represent the latest non-ionizing approach for osteoporosis evaluation at central sites.

Weight-adjusted waist index is a potential early predictor of degraded bone microarchitecture: A cross-sectional study of the national health and nutrition examination survey 2007-2008.

PURPOSE: This study aimed to investigate the association between weight-adjusted waist index (WWI) and trabecular bone score (TBS) and to assess the ability of WWI to identify individuals with degraded bone microarchitecture (DBMA). METHODS: This cross-sectional study included participants aged 20 and older from the National Health and Nutrition Examination Survey. Furthermore, WWI was calculated by waist circumference and body weight. In addition, linear regression models were employed to investigate the association between WWI and TBS, while logistic regression models were employed to determine the association between WWI and the risk of DBMA. Finally, the performance of WWI in identifying individuals with DBMA was using the receiver operating characteristic (ROC) curves with area under the ROC curve. RESULTS: A total of 4,179 participants with a mean age of 49.90 years were included in the final analysis. WWI was negatively associated with TBS and positively associated with an increased risk of DBMA. Furthermore, the associations between WWI and TBS, as well as DBMA risk, were stable regardless of stratification by age, sex, race, or body mass index (BMI). Moreover, WWI achieved good performances in identifying individuals with DBMA or low TBS. In addition, the combination of WWI and BMI showed better performances in identifying individuals with DBMA or low TBS than WWI or BMI alone. CONCLUSION: WWI established a negative association with TBS and a positive association with the risk of DBMA. Clinicians should be alert to the potential risk of DBMA among individuals with high WWI. Moreover, WWI, alone or in combination with BMI, has the potential to serve as an early screening strategy in identifying individuals with DBMA.

Computationally efficient dominant load-based local bone microstructure reconstruction method using topology optimization.

The bone microstructure of the human proximal femur is clinically crucial for diagnosing skeletal pathologies, such as osteoporosis and bone metastases. The topology optimization-based bone microstructure method obtains these bone microstructures by converting low-resolution (LR) images into high-resolution images. However, this method is inherently computationally inefficient as it requires numerous finite elements, iterative analyses, and parallel computations. Therefore, this study proposes a novel topology optimization-based localised bone microstructure reconstruction method using the dominant load, which highly affects the selected region of interest (ROI), for efficient resolution enhancement. The load dependency of selected ROIs is quantified with a load dependency score. Then, the localised finite element model is constructed based on the local load estimation. Finally, the selected dominant load is applied as an input for the topology optimization-based bone microstructure reconstruction method. The reconstructed bone microstructure was similar to that of the conventional method. The localised finite element model applied by the dominant load effectively and accurately reconstructed the bone morphology and exhibited high computational efficiency. In conclusion, the dominant load-based approach can be used to construct a reasonable trabecular bone structure for ROI with high computational efficiency. The predictive performance of the proposed method was validated and showed promise for accurate trabecular bone structure prediction without additional radiation exposure.

Association of trabecular bone score with disease parameters and vertebral fractures in axial spondyloarthritis.

Objectives: We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis. Methods: Patients diagnosed with axial spondyloarthritis were included in this cross-sectional study. Dual-energy X-ray absorptiometry was used to measure BMD in the lumbar spine and TBS. Low TBS was defined as ≤1.31. The association between TBS and disease parameters including Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, BASFI and BASMI was studied using logistic regressions. Results: Our study included 56 patients, with a mean age of 38.9 ± 13.5 years and a mean disease duration of 12.7 ± 7.7 years. Patients with low TBS were significantly older and had higher waist circumference and body mass index. These patients also showed greater clinical activity, as evidenced by higher ASDAS-CRP, BASFI and BASMI scores (P < 0.05). In multivariate logistic regression, low TBS was associated with all disease parameters, except for BASMI: BASDAI (OR [95% CI] = 3.68 [1.48-9.19], P = 0.005), ASDAS-CRP (OR [95% CI] = 2.92 [1.20-7.10], P = 0.018), BASFI (OR [95% CI] = 1.04 [1.01-1.08], P = 0.018), BASMI (OR [95% CI] = 1.36 [0.99-1.87], P = 0.062). However, no association was observed between TBS and VFs. Conclusion: TBS was associated with active spondyloarthritis, suggesting increased bone fragility in these patients. However, TBS failed to demonstrate an association with VFs.

Effect of trabecular architectures on the mechanical response in osteoporotic and healthy human bone.

Research at the mesoscale bone trabeculae arrangement yields intriguing results that, due to their clinical resolution, can be applied in clinical field, contributing significantly to the diagnosis of bone-related diseases. While the literature offers quantitative morphometric parameters for a thorough characterization of the mesoscale bone network, there is a gap in understanding relationships among them, particularly in the context of various bone pathologies. This research aims to bridge these gaps by offering a quantitative evaluation of the interplay among morphometric parameters and mechanical response at mesoscale in osteoporotic and non-osteoporotic bones. Bone mechanical response, dependent on trabecular arrangement, is defined by apparent stiffness, computationally calculated using the Gibson-Ashby model. Key findings indicate that: (i) in addition to bone density, measured using X-ray absorptiometry, trabecular connectivity density, trabecular spacing and degree of anisotropy are crucial parameters for characterize osteoporosis state; (ii) apparent stiffness values exhibit strong correlations with bone density and connectivity density; (iii) connectivity density and degree of anisotropy result the best predictors of mechanical response. Despite the inherent heterogeneity in bone structure, suggesting the potential benefit of a larger sample size in the future, this approach presents a valuable method to enhance discrimination between osteoporotic and non-osteoporotic samples.

Trabecular Bone Component Assessment under Orthodontic Loads and Movements during Periodontal Breakdown-A Finite Elements Analysis.

This numerical analysis, by employing Tresca and Von Mises failure criteria, assessed the biomechanical behavior of a trabecular bone component subjected to 0.6, 1.2, and 2.4 N orthodontic forces under five movements (intrusion, extrusion, tipping, rotation, and translation) and during a gradual horizontal periodontal breakdown (0-8 mm). Additionally, they assessed the changes produced by bone loss, and the ischemic and resorptive risks. The analysis employed eighty-one models of nine patients in 405 simulations. Both failure criteria showed similar qualitative results, with Tresca being quantitatively higher by 1.09-1.21. No qualitative differences were seen between the three orthodontic loads. Quantitatively, a doubling (1.2 N) and quadrupling (2.4 N) were visible when compared to 0.6 N. Rotation and translation followed by tipping are the most stressful, especially for a reduced periodontium, prone to higher ischemic and resorptive risks. In an intact periodontium, 1.2 N can be safely applied but only in a reduced periodontium for extrusion and intrusion. More than 0.6 N is prone to increasing ischemic and resorptive risks for the other three movements. In an intact periodontium, stress spreads in the entire trabecular structure. In a reduced periodontium, stress concentrates (after a 4 mm loss-marker for the stress change distribution) and increases around the cervical third of the remaining alveolar socket.

Usefulness of DXA-based bone strain index in postmenopausal women with type 2 diabetes mellitus.

Bone Strain Index (BSI) is a new dual-energy x-ray absorptiometry (DXA)-based index. We retrospectively evaluated data from 153 postmenopausal women with a history of type 2 diabetes mellitus (T2DM). Lumbar spine and femoral Bone Strain Index (BSI) were sensitive to skeletal impairment in postmenopausal women suffering from T2DM. PURPOSE: Bone Strain Index (BSI) is a new dual-energy X-ray absorptiometry (DXA)-based measurement. We evaluated the performance of BSI in predicting the presence of fragility fractures in type 2 diabetes mellitus (T2DM) postmenopausal women. METHODS: We retrospectively evaluated data from a case-control study of 153 postmenopausal women with a history of at least 5 years of T2DM (age from 40 to 90 years). For each subject, we assessed the personal or familiar history of previous fragility fractures and menopause age, and we collected data about bone mineral density (BMD), BSI, and Trabecular Bone Score (TBS) measurements. Statistical analysis was performed having as outcome the history of fragility fractures. RESULTS: Out of a total of 153 subjects, n = 22 (14.4%) presented at least one major fragility fracture. A negative correlation was found between lumbar BSI and lumbar BMD (r = - 0.49, p < 0.001) and between total femur BSI and total femur BMD (r = - 0.49, p < 0.001). A negative correlation was found between femoral neck BSI and femoral neck BMD (r = - 0.22, p < 0.001). Most DXA-based variables were individually able to discriminate between fractured and non-fractured subjects (p < 0.05), and lumbar BSI was the index with the most relative difference between the two populations, followed by femoral BSI. CONCLUSION: Lumbar spine and femoral BSI are sensitive to skeletal impairment in postmenopausal women suffering from T2DM. The use of BSI in conjunction with BMD and TBS can improve fracture risk assessment.

DNA preservation in compact and trabecular bone.

Significant variation exists in the molecular structure of compact and trabecular bone. In compact bone full dissolution of the bone powder is required to efficiently release the DNA from hydroxyapatite. In trabecular bone where soft tissues are preserved, we assume that full dissolution of the bone powder is not required to release the DNA from collagen. To investigate this issue, research was performed on 45 Second World War diaphysis (compact bone)-epiphysis (trabecular bone) femur pairs, each processed with a full dissolution (FD) and partial dissolution (PD) extraction method. DNA quality and quantity were assessed using qPCR PowerQuant analyses, and autosomal STRs were typed to confirm the authenticity of isolated DNA. Our results support different mechanisms of DNA preservation in compact and trabecular bone because FD method was more efficient than PD method only in compact bone, and no difference in DNA yield was observed in trabecular bone, showing no need for full dissolution of the bone powder when trabecular bone tissue is processed. In addition, a significant difference in DNA yield was observed between compact and trabecular bone when PD was applied, with more DNA extracted from trabecular bone than compact bone. High suitability of trabecular bone processed with PD method is also supported by the similar quantities of DNA isolated by FD method when applied to both compact and trabecular bone. Additionally similar quantities of DNA were isolated when compact bone was extracted with FD method and trabecular bone was extracted with PD method. Processing trabecular bone with PD method in routine identification of skeletonized human remains shortens the extraction procedure and simplifies the grinding process.

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

Bibliometric analysis of publications on trabecular bone score (TBS).

Purpose: Trabecular bone score (TBS), as a texture indicator of bone microarchitecture, predicts the risk of fracture. This study aims to explore the knowledge map of TBS. Methods: We searched Scopus for "trabecular bone score" or "trabecular score" from the beginning to 2021. Our inclusion criteria were original articles and reviews that were related to TBS and our exclusion criteria were non-English articles, non-related to TBS, and document type other than original articles and reviews. and related documents were included for bibliometric analysis. Excel, VOS viewer, and Science of Science (Sci2) software were used for data synthesis. Results: From 749 retrieved articles, 652 articles were included for analysis. These documents were cited 12,153 times and had an H-index of 56. The most productivity belonged to the USA (n = 130 documents), Switzerland (n = 101), and Italy (n = 67). "Osteoporosis International" (n = 80) had the highest participation in publishing. The research topics of interest were mainly related to the applicability of TBS for fracture risk assessment in chronic endocrine disorders such as osteoporosis and diabetes mellitus. Bursting analysis of the title and abstract revealed the initial focus of the discriminative power of TBS for osteoporotic fracture and the more recent focus on comparing bone mineral density (BMD) and TBS in a variety of chronic diseases. Conclusion: The number of annual publications on TBS has increased, especially after 2016. These publications highlight the importance of in-depth knowledge of TBS in predicting fracture risk and also its strengths and limitations of treatment monitoring in different health conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01338-7.

Conditional loss of CaMKK2 in Osterix-positive osteoprogenitors enhances osteoblast function in a sex-divergent manner.

Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a multi-functional, serine/threonine protein kinase with predominant roles in inflammation, systemic energy metabolism, and bone remodeling. We previously reported that global ablation of CaMKK2 or its systemic pharmacological inhibition led to bone mass accrual in mice by stimulating osteoblasts and inhibiting osteoclasts. However, a direct, cell-intrinsic role for the kinase in the osteoblast lineage has not been established. Here we report that conditional deletion of CaMKK2 from osteoprogenitors, using the Osterix 1 (Osx1) - GFP::Cre (tetracycline-off) mouse line, resulted in increased trabecular bone mass due to an acute stimulation of osteoblast function in male and female mice. The acute simulation of osteoblasts and bone formation following conditional ablation of osteoprogenitor-derived CaMKK2 was sustained only in female mice. Periosteal bone formation at the cortical bone was enhanced only in male conditional knockout mice without altering cortical bone mass or strength. Prolonged deletion of CaMKK2 in early osteoblasts was accompanied by a stimulation of osteoclasts in both sexes, indicating a coupling effect. Notably, alterations in trabecular and cortical bone mass were absent in the doxycycline-removed "Cre-only" Osx1-GFP::Cre mice. Thus, the increase in osteoblast function at the trabecular and cortical bone surfaces following the conditional deletion of CaMKK2 in osteoprogenitors is indicative of a direct but sex-divergent role for the kinase in osteoblasts.