Bone Architecture Research Articles

Humanlike manual activities in Australopithecus

The evolution of the human hand is a topic of great interest in paleoanthropology. As the hand can be involved in a vast array of activities, knowledge regarding how it was used by early hominins can yield crucial information on the factors driving biocultural evolution. Previous research on early hominin hands focused on the overall bone shape. However, while such approaches can inform on mechanical abilities and the evolved efficiency of manipulation, they cannot be used as a definite proxy for individual habitual activity. Accordingly, it is crucial to examine bone structures more responsive to lifetime biomechanical loading, such as muscle attachment sites or internal bone architecture. In this study, we investigate the manual entheseal patterns of Australopithecus afarensis, Australopithecus africanus, and Australopithecus sediba through the application of the validated entheses-based reconstruction of activity method. Using a comparative sample of later Homo and three great ape genera, we analyze the muscle attachment site proportions on the thumb, fifth ray, and third intermediate phalanx to gain insight into the habitual hand use of Australopithecus. We use a novel statistical procedure to account for the effects of interspecies variation in overall size and ray proportions. Our results highlight the importance of certain muscles of the first and fifth digits for humanlike hand use. In humans, these muscles are required for variable in-hand manipulation and are activated during stone-tool production. The entheses of A. sediba suggest muscle activation patterns consistent with a similar suite of habitual manual activities as in later Homo. In contrast, A. africanus and A. afarensis display a mosaic entheseal pattern that combines indications of both humanlike and apelike manipulation. Overall, these findings provide new evidence that some australopith species were already habitually engaging in humanlike manipulation, even if their manual dexterity was likely not as high as in later Homo.

Protective effects of electroacupuncture on senile osteoporosis in rats.

The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms. This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague-Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks. EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups. EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.

Analysis of Bone Phenotype Differences in MEN1-Related and Sporadic Primary Hyperparathyroidism Using 3D-DXA.

Background: The rarity and variability of MEN1-related primary hyperparathyroidism (mPHPT) has led to contradictory data regarding the bone phenotype in this patient population. Methods: A single-center retrospective study was conducted among young age- and sex-matched patients with mPHPT and sporadic hyperparathyroidism (sPHPT). The main parameters of calcium-phosphorus metabolism, bone remodeling markers, and bone mineral density (BMD) measurements were obtained during the active phase of hyperparathyroidism before parathyroidectomy (PTE) and 1 year after. Trabecular Bone Score (TBS) and 3D-DXA analysis of the proximal femur were used to evaluate the differences in bone architecture disruption between groups. Results: Patients with mPHPT had significant lower preoperative BMD compared to sPHPT at lumbar spine-LS (p = 0.002); femur neck-FN (p = 0.001); and total hip-TH (p = 0.002). 3D-DXA analysis showed the prevalence of cortical rather than trabecular bone damage in mPHPT compared to sPHPT: cortical thickness (p < 0.001); cortical surface BMD (p = 0.001); cortical volumetric BMD (p = 0.007); and trabecular volumetric BMD (p = 0.029). One year after, PTE DXA and 3D-DXA parameters were similar between groups, while 3D-visualisation showed more extensive regeneration in cortical sBMD and cortical thickness in mPHPT. Conclusions: mPHPT is associated with lower preoperative BMD values with predominant architecture disruption in the cortical bone. The absence of differences in DXA and 3D-DXA parameters 1 year after PTE between mPHPT/sPHPT combined with significantly lower BMD in mPHPT at the initial stage may indicate faster bone recovery after surgery in mPHPT than in sPHPT.

Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones

Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (n = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes Sclerostin (Sost) and Periostin (Postn) was not impacted by the exercise in long bones. Oppositely, Sost and Postn levels were modulated by exercise in joints, and osteogenic markers (Col10a1, Runx2, Osx, and Dmp1) were downregulated in the exercise group. In addition, the tenogenic markers Scx, Mkx, and Tnmd were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of Bmp2, Bmp4, and Id1 was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.

Nootkatone mitigates periodontal inflammation and reduces alveolar bone loss via Nrf2/HO-1 and NF-κB pathways in rat model of periodontitis.

Periodontitis (PD) is a chronic inflammatory disease leading to alveolar bone loss. This study investigated the effect of nootkatone and regulatory mechanism in reducing periodontal inflammation and alveolar bone loss in a rat model. Twenty male Sprague-Dawley rats were divided into control, periodontitis, and nootkatone-treated groups (45 or 90 mg/kg). Ligature induction method was adopted to establish the PD model. After 21 days, rats received daily gavage of either saline or nootkatone for 10 days. Alveolar bone loss was assessed using micro-CT. Histological analyses included hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Masson's trichrome stainings. Immunohistochemistry for heme oxygenase 1 (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2) were performed in periodontal tissues. Content of inflammatory cytokines IL-1β, IL-6, and TNF-α in gingival tissues around ligature were assessed using ELISA kits. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were analyzed and Western blot for NF-κB expression in gingival tissues were performed. Nootkatone significantly reduced the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC), enhanced bone mineral density (BMD), bone volume (BV), and BV/total volume (TV) ratio in ligature-induced rats. Higher dose of nootkatone (90 mg/kg) did not show more significant therapeutic effect than lower dose (45 mg/kg). Histological staining showed decreased osteoclasts' number and improved bone architecture in the nootkatone group. Content of IL-1β, IL-6, and TNF-α and inflammatory cell infiltration level in gingival tissues around the ligature were decreased in the nootkatone-treatment rats. Nootkatone increased Nrf2 and HO-1 protein expression and decreased NF-κB protein level, suppressing MDA levels and enhancing SOD activity. In a rat model, nootkatone effectively mitigates periodontal inflammation and alveolar bone loss through the Nrf2/HO-1 and NF-κB pathways. These findings suggest nootkatone as a promising therapeutic agent for the treatment of periodontitis.

Identification of Postn+ periosteal progenitor cells with bone regenerative potential.

Bone contains multiple pools of skeletal stem/progenitor cells (SSPCs), and SSPCs in periosteal compartments are known to exhibit higher regenerative potential than those in BM and endosteal compartments. However, the in vivo identity and hierarchical relationships of periosteal SSPCs (P-SSPCs) remain unclear due to a lack of reliable markers to distinguish BM SSPCs and P-SSPCs. Here, we found that periosteal mesenchymal progenitor cells (P-MPs) in periosteum can be identified based on Postn-CreERT2 expression. Postn-expressing periosteal subpopulation produces osteolineage descendants that fuel bones to maintain homeostasis and support regeneration. Notably, Postn+ P-MPs are likely derived from Gli1+ skeletal stem cells (SSCs). Ablation of Postn+ cells results in impairments in homeostatic cortical bone architecture and defects in fracture repair. Genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. In summary, our study provides a mechanistic understanding of bone regeneration through the regulation of region-specific Postn+ P-MPs.

Comparative Histological Analysis of Dentine-Derived Tooth Grafts in Maxillary vs Mandibular Socket Preservation: A Retrospective Study of 178 Cases.

(1) Background: In recent years, there has been a growing interest in tooth-derived materials as valuable alternatives to synthetic biomaterials for preventing alveolar ridge dimensional changes. This study aimed to evaluate the histological and clinical differences between alveolar ridge preservation procedures in the maxilla and mandible using demineralized dentin treated with Tooth Transformer®. (2) Methods: A total of 178 patients in good general health were enrolled, with 187 post-extractive sockets lacking buccal and/or palatal bone walls. Alveolar socket preservation procedures and histological evaluations were performed. The sites were divided into two groups: Group A (99 mandibular samples) and Group B (108 maxillary samples). After 5 months (±1 month), single bone biopsies were performed for histologic and histomorphometric analysis. (3) Results: Clinical outcomes demonstrated a good healing of hard and soft tissues with an effective maintenance of bone architecture in both groups. Histomorphometric analysis revealed a total bone volume of 50.33% (±14.86) in Group A compared to 43.53% (±12.73) in Group B. The vital new bone volume was 40.59% (±19.90) in Group A versus 29.70% (±17.68) in Group B, with residual graft dentin material volume at 7.95% (±9.85) in Group A compared to 6.75% (±9.62) in Group B. (4) Conclusions: These results indicate that tooth-derived material supports hard tissue reconstruction by following the structure of the surrounding bone tissue. A 6.8% difference observed between the maxilla and mandible reflects the inherent disparities in natural bone structures in these regions. This suggests that the bone regeneration process after tooth extraction adheres to an anatomical functional pattern that reflects the specific bone characteristics of each area, thus contributing to the preservation of the morphology and functionality of the surrounding bone tissue.

New role of calcium-binding fluorescent dye alizarin complexone in detecting permeability from articular cartilage to subchondral bone.

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by the progressive deterioration of articular cartilage and concomitant alterations in subchondral bone architecture. However, the precise mechanisms underlying the initiation and progression of OA remains poorly understood. In the present study, we explored whether the calcification in the articular cartilage occurred in the early stage of mouse OA model, generated by the surgery destabilization of the medial meniscus (DMM), via the intra-articular injection of alizarin complexone due to its anionic nature for binding calcium-containing crystals. Although we did not observe the calcification in the articular cartilage of early stage of DMM mice, we unexpectedly identified alizarin complexone had the diffusion capacity for detecting the permeability from the articular cartilage to subchondral bone. Our data showed that the diffusion of alizarin complexone from the articular cartilage to calcified cartilage was greater in the early stage of DMM mice than that in sham controls. Additionally, we observed enhanced penetration of alizarin complexone through the periosteum in DMM mice compared to sham mice. In summary, we developed a novel imaging method that offers a valuable tool for further exploration of biochemical communication underlying OA development. Our findings provided new evidence that increased molecular interactions between the articular cartilage and subchondral bone is involved in the pathogenesis of OA progression.

7140 Assessing Bone Mineral Density and Cortical Geometry Using High-resolution Peripheral Quantitative Computed Tomography and Dual Energy X-ray Absorptiometry in Pediatric Survivors of High-risk Neuroblastoma with Growth Failure

Abstract Disclosure: S. Gera: None. M. Guo: None. N. Pollock: None. I. Hampton: None. M. Song: None. D. Weber: None. M. Denburg: None. S. Mostoufi-Moab: None. Introduction: Survival of children with high-risk neuroblastoma (HR-NBL) has increased with multimodal therapy. Cis-retinoic acid (cis-RA), cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure, posing a threat to skeletal structure. HR-NBL survivors demonstrate profound growth failure. DXA measures areal bone mineral density (aBMD). DXA is confounded by short stature and fails to distinguish between trabecular and cortical bone. We previously reported no significant difference in height-per-age adjusted aBMD-Z in HR-NBL survivors compared to healthy controls[1]. However, aBMD-Z in severe short stature may attenuate bone density deficits. High-resolution peripheral quantitative computed tomography (HRpQCT) yields 3D measures of volumetric BMD and bone architecture. Objectives: Assess volumetric BMD (vBMD) and cortical structure using distal tibia HRpQCT and leg lean mass by DXA in HR-NBL survivors compared to healthy controls in a cross-sectional study. Methods: We prospectively enrolled 20 HR-NBL survivors (median age 12.2 yrs, range 9.5 to 15.8, 7 female) treated with cis-RA (median age 2.6 yrs at start of therapy, range 0.3-9.1), and 20 age-, sex-, and race-matched healthy controls. We assessed leg lean mass adjusted for leg length by DXA. For HRpQCT, we compared tibia length (cm), cortical and trabecular vBMD (mg HA/cm3), geometry parameters (cortical and trabecular area [mm2]), and structural parameters (cortical thickness [μm] and porosity, trabecular number [mm-[1]] and separation [μm]). Outcomes were compared using Student’s t-test or Mann-Whitney U test. Linear regression models assessed difference in outcomes of bone microarchitecture and leg lean mass between both groups. Results: Compared to controls, tibia length was significantly shorter in HR-NBL survivors (32.3 ± 0.8 vs. 35.7 ± 0.6, P&amp;lt;0.005). HR-NBL survivors demonstrated lower cortical area (187.6 ± 43.8 vs. 218.7 ± 42.3, P&amp;lt;0.05), cortical perimeter (62.4 ± 7.71 vs. 69.5 ± 8.1, P&amp;lt;0.01), and leg lean mass Z-score (-1.47 ± 1.34 vs. -0.20 ± 0.84, P&amp;lt;0.001) compared to controls. Cortical geometry deficits were explained by muscle deficits (P&amp;lt;0.001). Trabecular area, BMC, areal and volumetric BMD, and measures of bone structure were not significantly different in HR-NBL survivors compared to controls. IGF-1 and 25-OH D levels had no significant effects on DXA or HRpQCT parameters. Conclusion: Bone density is not severely impacted in HR-NBL survivors. Muscle deficits persist years after treatment and explain cortical geometry deficits. HRpQCT substantiates prior DXA evaluation in HR-NBL survivors with significant short stature, demonstrating preserved bone density and structure. 1.Guo et al. Sarcopenia and preserved bone mineral density in pediatric survivors of high-risk neuroblastoma with growth failure. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):1024-1033. Presentation: 6/3/2024

7949 Unraveling a Unique Presentation of Paget’s Disease of Bone

Abstract Disclosure: S. Puri: None. L. Bovee: None. R. Narla: None. Background: Paget's Disease of Bone (PDB) is a disorder characterized by rapid bone destruction and repair, which results in distortion of bone architecture. PDB occurs most commonly in adults over 55 and of European descent. PDB presents with both lytic and sclerotic lesions, predominantly in the axial skeleton. Serum alkaline phosphatase (ALP) levels and bone turnover markers (BTMs) are typically elevated in PDB. Clinical Case: A 53-year-old African-American woman with a history of breast cancer, PTSD, depression, and obesity (BMI 37) presented with worsening back pain over the past six months. Her pain would start at the center of her back and radiate to her left lower extremity. She endorsed rapid weight loss and night sweats and had lumbar bony tenderness on exam, prompting a spinal MRI. Spinal MRI was significant for diffuse sclerosis of the L3 vertebral body only. The radiology report provided a broad differential for this finding, including metastases, lymphoma, infection, PDB, and hemangioma. Due to progression of the patient’s back pain and concern for possible malignancy, a whole-body SPECT was completed which showed isolated tracer uptake into the L3 vertebral body extending into the pedicles and spinous process. Similar findings were noted on bone scans dating back to 2001. Per the radiology report, the presence of sclerosis with minimal expansion is most suggestive of PDB. Endocrinology was consulted for guidance on treatment and surveillance imaging for this patient. The endocrinology team discussed the case with radiology, who confirmed that the patient’s imaging findings had classic features of PDB. Bone specific ALP (B-ALP) and procollagen type 1 amino-terminal propeptide (P1NP) as bone turnover markers (BTMs) were within normal limits. A DEXA scan is pending to evaluate for concurrent osteoporosis. Clinical Lessons: PDB was favored as the most likely diagnosis primarily due to the sclerotic appearance of the patient’s vertebral lesion on imaging, radicular symptoms, and exam finding of bony point tenderness. Other diagnoses, such as metastatic disease, were considered and were thought to be unlikely given that the vertebral lesion is monostotic and stable. This case highlights the necessity of carefully evaluating radiographic findings and clinical history in the diagnosis of PDB. In this case, the patient was from a demographic group unlikely to have PDB and, unexpectedly, did not have elevated BTMs. It is important to consider PDB on the differential diagnosis in cases such as this because PDB can present in myriad ways and in a variety of patient populations. Presentation: 6/2/2024

Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Preserving Bone & Tissue Architecture: Socket Shield Case Series

Preserving Bone & Tissue Architecture: Socket Shield Case Series

Metabolic Bone Diseases: Recommendations for Interventional Radiology.

Metabolic bone diseases (MBDs), including osteoporosis, osteomalacia, and Paget's disease, represent a significant challenge in medical imaging and intervention. Interventional radiologists play a pivotal role in managing these conditions, due to the crucial role of detailed and precise imaging in diagnosing and treating MBDs. This article offers comprehensive recommendations aimed at optimizing interventional radiologic practices for patients with MBDs, highlighting the importance of using advanced imaging modalities, including dual-energy X-ray absorptiometry and magnetic resonance imaging, essential for accurate assessment of bone mineral density and architecture, guiding effective intervention strategies. We also discuss the use of minimally invasive procedures like vertebroplasty and biopsy, vital for both diagnostic and therapeutic purposes, to enhance diagnostic accuracy and therapeutic outcomes, ensuring high-quality patient management in the context of MBDs.

Synergistic effects of calcium and zinc on bio-functionalized 3D Ti cancellous bone scaffold with enhanced osseointegration capacity in rabbit model

The present research aims to develop a Ca-Zn ion-incorporated surface functionalized 3D Ti cancellous bone scaffold for bone defect repair. The scaffold is designed to mimic human cancellous bone architecture through selective laser melting-based additive manufacturing. The chemical-based surface modification approach employed here created a Ca and Zn ions incorporated nano-porous surface layer with enhanced surface roughness and hydrophilicity. The modified biomimetic scaffold improved corrosion resistance behaviour with ICORR and ECORR values of 0.174 and 0.0097 respectively. It is learned that incorporating Zn as ZnO over the scaffold has antibacterial activity against Staphylococcus aureus and Escherichia coli. The cellular response of MG-63 to the modified scaffold was evaluated through in-vitro studies which focus on the cytocompatible properties. The intra-osseous biomimetic Ti-Na-Ca:Zn 3D scaffold revealed significant improvement in the osseointegration capabilities in terms of bone mineral density (BMD) and bone volume/total volume (BV/TV) in the rabbit model. The osseointegration potential at the Ti-Na-Ca:Zn interface was evidenced by histological analysis and micro-CT imaging. In addition to this, the remarkable upregulation of osteogenic genes such as OCN, COL1A1, OPN, ALP, RUNX2, and OSX evidences the dynamics of the osseointegration process at each surgical period. This Ca and Zn surface functionalised porous architecture of the 3D Ti cancellous bone scaffold similar to bone with enhanced biological response and bone integration can potentially allow implant customisation by utilizing additive manufacturing technology with improved clinical outcomes.

DXA: New Concepts and Tools Beyond Bone Mineral Density.

Since its introduction in 1987, dual-energy X-ray absorptiometry (DXA) has revolutionized bone assessment, becoming the gold standard for measuring bone mineral density (BMD). Its low radiation exposure and high accuracy have made it indispensable in diagnosing osteoporosis, aligning with World Health Organization criteria. However, DXA evolution extends beyond BMD measurement, with emerging tools like the Trabecular Bone Score (TBS) and the DXA-based Bone Strain Index (BSI). TBS provides insights into trabecular bone architecture, enhancing the prediction of fracture risk. Despite limitations like body mass index correlation, TBS aids in evaluating patients with conditions such as diabetes and glucocorticoid exposure. BSI, introduced in 2019, evaluates bone strength using finite element analysis, complementing BMD and TBS by assessing bone fatigue.Advancements in DXA-based tools extend to Hip Structural Analysis and three-dimensional DXA software, offering valuable insights into hip fracture risk. Moreover, DXA serves beyond bone assessment, aiding in abdominal aortic calcification assessment, enhancing cardiovascular risk stratification. In summary, the expanding capabilities of DXA promise comprehensive skeletal and cardiovascular health evaluation, contributing significantly to clinical management and prevention strategies.

Evaluation of Functional Components of Lactobacillus plantarum AR495 on Ovariectomy-Induced Osteoporosis in Mice And RAW264.7 Cells

Osteoporosis is a disease characterized by abnormal bone metabolism, where bone resorption outpaces bone formation. In this study, we investigated the key functional components of Lactobacillus plantarum AR495 in mitigating ovariectomy (OVX)-induced osteoporosis in mice. The results indicated that both Lactobacillus plantarum AR495 and its fermentation broth significantly reduced urinary calcium and deoxypyridinoline (DPD) levels in the mice. These interventions inhibited bone resorption and improved trabecular bone architecture by modulating the nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway. Additionally, the L. plantarum AR495 and fermentation broth groups inhibited the RANKL/TRAF-6 and TLR4/MYD88 pathways, leading to enhanced bone metabolism, improved intestinal barrier function, and reduced intestinal inflammation. In vitro experiments revealed that AR495 fermentation supernatant fractions larger than 100 kDa and those between 50–100 kDa significantly decreased the activity of the osteoclast marker TRAP, regulated the expression of the TLR4/MYD88 pathway, and inhibited osteoclast formation, thereby alleviating the OVX-induced osteoporosis phenotype. These findings suggest that these components may be primary functional elements of L. plantarum AR495 in the treatment of osteoporosis.

The short-chain fatty acid receptors Gpr41/43 regulate bone mass by promoting adipogenic differentiation of mesenchymal stem cells.

Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate. SCFAs exert various metabolic functions, which in part can be explained by activation of G protein-coupled receptors (Gpr) 41 and 43. However, the potential relevance of a SCFA-Gpr41/43 signaling axis for bone metabolism has not been established. The aim of our study is to investigate the role of Gpr41/43 in bone metabolism and osteogenic differentiation of mesenchymal stem cells. For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. In addition, we isolated bone marrow derived mesenchymal stem cells from WT and Gpr41/43 dKO mice and differentiated them into osteoblasts in the absence or presence of acetate. MicroCT scanning of femoral bones of Gpr41/43 dKO mice revealed a significant increase of trabecular bone volume and trabecular compared to WT controls. Treatment of WT bone marrow-derived osteoblasts with acetate resulted in decreased mineralization and substantial downregulation of bone formation markers such as Phex, Ptgs2 and Col1a1. Notably, this effect was strongly attenuated in differentiated osteoblasts lacking Gpr41/43. Inversely, acetate supplementation resulted in higher levels of adipocyte marker genes including Pparg, Lpl and Adipoq in bone marrow-derived cells from WT mice, an effect blunted in differentiated cells isolated from Gpr41/43 dKO mice. Overall, these data indicate that acetate regulates bone architecture via SCFA-Gpr41/43 signaling by modulating the osteogenic versus adipogenic differentiation of mesenchymal stem cells.

Changes in bone density and microarchitecture following treatment of Graves' disease and the effects of vitamin D supplementation. A randomized clinical trial.

Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves' disease (GD). Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70µg/day (2800IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. Eighty-six GD patients were included (age 41 ± 14years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1-4%). Cortical porosity decreased in tibia (- 7% [95%CI: - 12 to - 2%]) and radius [- 14% [95%CI: - 24 to - 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 - 9%]) and radius (4% [95%CI: 1-7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. In newly diagnosed GD, 9months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. NCT02384668.

Clinical and Radiographic Evaluation of Soft Tissue and Bone Status in Immediate Loaded Implants Placed Following Their Extraction in the Maxillary Anterior Region.

In the maxillary anterior region, teeth extraction leads to significant soft and hard tissue changes. Immediate implant placement following extraction aims to reduce bone loss and overall treatment time. However, it may result in adverse soft tissue changes impacting esthetics. This study evaluates the clinical and radiographic outcomes of immediately loaded implants in the maxillary anterior region, focusing on soft tissue preservation and bone status. This study, conducted from April 2022 to August 2024 at the Department of Oral and Maxillofacial Surgery, Ragas Dental College and Hospital, included 10 immediately loaded implants in seven patients. Following atraumatic extraction, implants were placed and loaded with functional provisional crowns fabricated using three-dimensional (3D) rapid prototyping models. Parameters such as crestal bone loss, buccal and palatal bone width, and interdental papilla thickness were evaluated preoperatively and postoperatively using radiographsand clinical assessments. The study found significant crestal bone loss at both mesial and distal sites over time, with the greatest loss observed at the three-month follow-up. Buccal and palatal bone width showed no significant differences preoperatively and postoperatively. Interdental papilla thickness and overall pink esthetic scores also showed no significant differences between preoperative and postoperative evaluations. Immediate implant placement in the maxillary anterior region, using 3D rapid prototyping for custom splint fabrication, demonstrated effective preservation of soft tissue profile and bone architecture. This approach provides functional and esthetic benefits, although careful monitoring of crestal bone loss is necessary.

Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial

IntroductionPersons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that...