Alternated activation with relaxation of periosteum stimulates bone modeling and remodeling.

Gradual elevation of the periosteum from the original bone surface, based on the principle of distraction osteogenesis, induces endogenous hard and soft tissue formation. This study aimed to assess the impact of alternating protocols of activation with relaxation (periosteal pumping) on bone modeling and remodeling. One hundred and sixty-two adult male Wistar rats were used in this study. Four test groups with different pumping protocols were created based on the relaxation applied. Two control groups underwent an activation period without relaxation or only a single activation. One group was sham-operated. Periosteal pumping without period of activation induced gene expression in bone and bone remodeling, and following activation period enhanced bone modeling. Four test groups and control group with activation period equaled the values of bone modeling at the end-consolidation period, showing significant downregulation of Sost in the bone and periosteum compared to that in the sham group (p < 0.001 and p < 0.001, respectively). When all test groups were pooled together, plate elevation from the bony surface increased bone remodeling on day 45 of the observation period (p = 0.003). Furthermore, bone modeling was significantly affected by plate elevation on days 17 and 45 (p = 0.047 and p = 0.005, respectively) and by pumping protocol on day 31 (p = 0.042). Periosteal pumping was beneficial for increasing bone repair when the periosteum remained in contact with the underlaying bony surface during the manipulation period. Following periosteal elevation, periosteal pumping accelerated bone formation from the bony surface by the modeling process.

Changes in the concentration of bone turnover markers in men after maximum intensity exercise.

Background: Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise. Methods: The study involved 33 men aged 20-25, divided into two groups: experimental (n = 15) and control (n = 18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined. Results: When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 (p = 0.025), b-ALP (p < 0.001), OC (p = 0.004) and PINP (p = 0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP (p < 0.001), NTx1 (p < 0.001), OPG (p = 0.001) and PINP (p = 0.002). Conclusion: A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.

PoCOsteo: generic novel platform for bone turnover marker measurement & monitoring.

Despite the increasing efforts in improving bone health assessments, current diagnostics suffer from critical shortcomings. The present article therefore describes a multiplex label-free immunosensor designed and validated for the assessment of two bone turnover markers (BTMs), namely beta isomerized C-terminal telopeptide of type I collagen (CTx) and Procollagen I Intact N-Terminal (PINP), the combination of which is needed to illustrate an accurate overview of bone health. The immunosensor was then tested outside and inside of a microsystem, with the aim of becoming compatible with a point of care system fabricated for automated assessment of these biomarkers later-on at patient side. Custom-made monoclonal antibodies were specifically designed for this purpose in order to guarantee the selectivity of the immunosensor. In the final platform, a finger prick blood sample is introduced into the microfluidic manifolds without any need for sample preparation step, making the tool suitable for near patient and outside of the central laboratory applications. The platform was exploited in 30 real blood samples with the results validated using electrochemiluminescence immunoassay. The results revealed the platform was capable of measuring the target analyte with high sensitivity and beyond the recommended clinical reference range for each biomarker (CTx: 104-1028 ng L-1 and PINP: 16-96 µg L-1, correspondingly). They also showed the platform to have a limit of detection of 15 (ng L-1) and 0.66 (µg L-1), a limit of quantification of 49 (ng L-1) and 2.21 (µg L-1), and an inter- and intra-assay coefficient of variance of 5.39-6.97% and 6.81-5.37%, for CTx and PINP respectively, which is comparable with the gold standard. The main advantage of the platform over the state-of-the art was the capability of providing the results for two markers recommended for assessing bone health within 15 minutes and without the need for skilled personnel or costly infrastructure.

Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

BACKGROUND: Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. MATERIALS AND METHODS: A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. RESULTS: Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. CONCLUSIONS: We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

The role of the Piezo1 channel in osteoblasts under cyclic stretching: A study on osteogenic and osteoclast factors.

OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. RESULTS: CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. CONCLUSIONS: The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement.

The 40-min HIIT acutely induced bone formation which was likely through the increases in muscle derived interleukin 6 and adiponectin activation: The 16 weeks of HIIT intervention, longitudinal randomized controlled trial.

PURPOSE: There is some controversy regarding cytokines released from adipocytes, particularly adiponectin, leptin, and IL6 that regulate bone remodeling. In addition, IL6 is released from muscle contraction, which might have a distinct role in bone remodeling. Hence, this study investigated whether muscle contraction during a session of 40 min of high intensity interval training (40-min HIIT) and after 16 weeks of HIIT (16-wk HIIT) altered the release of those cytokines and bone remodeling in overweight women. METHODS: In total, 22 overweight, premenopausal women were randomly assigned to either the exercise or the control group. The exercise participants engaged in the 40-min HIIT session at 80-90 % of their heart rate reserve (HRR) three times weekly for 16 weeks, while the control participants performed their routine daily activities. Blood was drawn after overnight fasting and immediately after completing the 40-min HIIT sessions to investigate the association of adiponectin, leptin, IL6, CTX, and P1NP through the acute effect of the 40-min HIIT sessions. This process was repeated after the 16-wk intervention program to observe the training effect of HIIT on cytokines linkage. The bone mineral density (BMD) levels of the distal tibia, femur, and lumbar spine were determined prior to and after the 16-wk intervention using dual-energy X-ray absorptiometry. RESULTS: The P1NP level increased by 8.29-20.52 % (95 % CI) and by 2.91-15.54 % after completing the first and last bouts of the 40-min HIIT sessions, respectively. In addition, IL6 increased by 13.39-28.03 % (95 % CI), while serum CTX and adiponectin were unaltered from the acute effect of the 40-min HIIT sessions. There was an association between the increases in P1NP and adiponectin (r = 0.682, p = 0.015); however, the increase in P1NP was mostly associated with the increase in IL6 (r = 0.572, p = 0.054) after completing a 40-min HIIT session. After the 16-wk HIIT program, the resting adiponectin level of the exercise participants increased; however, this was associated with neither bone biomarkers nor BMD. The BMDs of the exercise participants were maintained; however, the tibial BMD of the control participants decreased with an increase in the resting CTX level after 16 weeks. CONCLUSION: Muscle contraction during the 40-min HIIT session elevated the IL6 level, which might have subsequently enhanced bone formation. Furthermore, the association between acute changes in adiponectin and P1NP suggested the possibility of an increase in the sensitivity of the adiponectin receptor in osteoblasts.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

The role of neuropilin in bone/cartilage diseases.

Bone remodeling is the balance between osteoblasts and osteoclasts. Bone diseases such as osteoporosis and osteoarthritis are associated with imbalanced bone remodeling. Skeletal injury leads to limited motor function and pain. Neurophilin was initially identified in axons, and its various ligands and roles in bone remodeling, angiogenesis, neuropathic pain and immune regulation were later discovered. Neurophilin promotes osteoblast mineralization and inhibits osteoclast differentiation and its function. Neuropolin-1 provides channels for immune cell chemotaxis and cytokine diffusion and leads to pain. Neuropolin-1 regulates the proportion of T helper type 17 (Th17) and regulatory T cells (Treg cells), and affects bone immunity. Vascular endothelial growth factors (VEGF) combine with neuropilin and promote angiogenesis. Class 3 semaphorins (Sema3a) compete with VEGF to bind neuropilin, which reduces angiogenesis and rejects sympathetic nerves. This review elaborates on the structure and general physiological functions of neuropilin and summarizes the role of neuropilin and its ligands in bone and cartilage diseases. Finally, treatment strategies and future research directions based on neuropilin are proposed.

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The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling. The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases. Under both physiological and pathological conditions, non-coding RNAs (ncRNAs) play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation. Circular RNAs (circRNAs) are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases. There is accumulating evidence suggesting that circRNAs and microRNAs (miRNAs) serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes. Additionally, recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells (MSCs) differentiate towards the osteoblasts (OB) lineage and the process by which bone marrow-derived macrophages (BMDM) differentiate towards osteoclasts (OC). The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling. Therefore, a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases. Herein, we reviewed the functions of circRNA and microRNA. We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling. This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.

Evaluating the effect of functionally graded materials on bone remodeling around dental implants.

OBJECTIVES: This study evaluates the potential for osseointegration and remodeling of customized dental implants made from Titanium-Hydroxyapatite Functionally Graded Material (Ti-HAP FGM) with optimized geometry, using the finite element method (FEM). METHODS: The study utilized CT scan images to model and assemble various geometrical designs of dental implants in a mandibular slice. The mechanical properties of Ti-HAP FGMs were computed by varying volume fractions (VF) of hydroxyapatite (0-20%), and a bone remodeling algorithm was used to evaluate the biomechanical characteristics of the ultimate bone configuration in the peri-implant tissue. RESULTS: The findings of the FEA reveal that osseointegration improves with changes in the density and mechanical properties of the bone surrounding Ti-HAP implants, which are influenced by the varying VF of hydroxyapatite in the FGM. SIGNIFICANCE: Increasing the hydroxyapatite fraction improves osseointegration, and appropriate length and diameter selection of Ti-HAP dental implants contribute to their stability and longevity.

Subchondral osteoclasts and osteoarthritis: new insights and potential therapeutic avenues.

Osteoarthritis (OA) is the most common joint disease, and good therapeutic results are often difficult to obtain due to its complex pathogenesis and diverse causative factors. After decades of research and exploration of OA, it has been progressively found that subchondral bone is essential for its pathogenesis, and pathological changes in subchondral bone can be observed even before cartilage lesions develop. Osteoclasts, the main cells regulating bone resorption, play a crucial role in the pathogenesis of subchondral bone. Subchondral osteoclasts regulate the homeostasis of subchondral bone through the secretion of degradative enzymes, immunomodulation, and cell signaling pathways. In OA, osteoclasts are overactivated by autophagy, ncRNAs, and Rankl/Rank/OPG signaling pathways. Excessive bone resorption disrupts the balance of bone remodeling, leading to increased subchondral bone loss, decreased bone mineral density and consequent structural damage to articular cartilage and joint pain. With increased understanding of bone biology and targeted therapies, researchers have found that the activity and function of subchondral osteoclasts are affected by multiple pathways. In this review, we summarize the roles and mechanisms of subchondral osteoclasts in OA, enumerate the latest advances in subchondral osteoclast-targeted therapy for OA, and look forward to the future trends of subchondral osteoclast-targeted therapies in clinical applications to fill the gaps in the current knowledge of OA treatment and to develop new therapeutic strategies.

Morpho-functional analysis of the temporomandibular joint following mandible-first bimaxillary surgery with mandible-only patient-specific implants.

The aim of this study was to evaluate condylar and glenoid fossa remodeling after bimaxillary orthognathic surgery guided by patient-specific mandibular implants. In total, 18 patients suffering from dentofacial dysmorphism underwent a virtually planned bimaxillary mandibular PSI-guided orthognathic procedure. One month prior to surgery, patients underwent a CBCT scan and optical scans of the dental arches; these datasets were re-acquired 1 month and at least 9 months postsurgery. Three-dimensional models of the condyles, glenoid fossae, and interarticular surface space (IASS) were obtained and compared to evaluate the roto-translational positional discrepancy and surface variation of each condyle and glenoid fossa, and the IASS variation. The condylar position varied by an average of 4.31° and 2.18 mm, mainly due to surgically unavoidable ramus position correction. Condylar resorption remodeling was minimal (average ≤ 0.1 mm), and affected skeletal class III patients the most. Later condylar remodeling was positively correlated with patient age. No significant glenoid fossa remodeling was observed. No postoperative orofacial pain was recorded at clinical follow-up. The procedure was accurate in minimizing the shift in relationship between the bony components of the TMJ and their remodeling, and was effective in avoiding postoperative onset of orofacial pain. An increase in sample size, however, would be useful to confirm our findings.

Proteomics study of bone tissue around ameloblastoma and the potential mechanism of CD36 in bone remodelling.

Ameloblastoma (AM) is characterised by local aggressiveness and bone resorption. To our knowledge, the proteomic profile of bone adjacent to AM has not previously been explored. We therefore looked at the differential proteins in cancellous bone (CB) adjacent to AM and normal CB from the mandible. CB proteins were extracted, purified, quantified, and analysed by liquid chromatography-mass spectrometry (LC-MS) using samples from five patients with AM. These proteins were further investigated using gene ontology for additional functional annotation and enrichment. Proteins that met the screening requirements of expression difference ploidy > 1.5-fold (upregulation and downregulation) and p < 0.05 were subsequently deemed differential proteins. Immunohistochemical staining was performed to confirm the above findings. Compared with normal mandibular CB, 151 differential proteins were identified in CB adjacent to the mandibular AM. These were mainly linked to cellular catabolic processes, lipid metabolism, and fatty acids (FA) metabolism. LC-MS and immunohistochemistry showed that CD36 was one of the notably decreased proteins in CB bordering the AM compared with normal mandibular CB (p = 0.0066 and p = 0.0095, respectively). CD36 expression in CB correlates with bone remodelling in AM, making CD36 a viable target for therapeutic approaches.

Cross-sectional studies of the causal link between asthma and osteoporosis: insights from Mendelian randomization and bioinformatics analysis.

The study, using data from Chongqing, China, and employing Mendelian randomization along with bioinformatics, establishes a causal link between asthma and osteoporosis, beyond glucocorticoid effects. Asthma may contribute to osteoporosis by accelerating bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to osteoporosis. INTRODUCTION: Asthma and osteoporosis are prevalent health conditions with substantial public health implications. However, their potential interplay and the underlying mechanisms have not been fully elucidated. Previous research has primarily focused on the impact of glucocorticoids on osteoporosis, often overlooking the role of asthma itself. METHODS: We conducted a multi-stage stratified random sampling in Chongqing, China and excluded individuals with a history of glucocorticoid use. Participants underwent comprehensive health examinations, and their clinical data, including asthma status, were recorded. Logistic regression and Mendelian randomization were employed to investigate the causal link between asthma and osteoporosis. Furthermore, bioinformatics analyses and serum biomarker assessments were conducted to explore potential mechanistic pathways. RESULTS: We found a significant association between asthma and osteoporosis, suggesting a potential causal link. Mendelian Randomization analysis provided further support for this causal link. Bioinformatics analyses revealed that several molecular pathways might mediate the impact of asthma on bone health. Serum alkaline phosphatase levels were significantly elevated in the asthma group, suggesting potential involvement in bone turnover. CONCLUSION: Our study confirms a causal link between asthma and osteoporosis and highlights the importance of considering asthma in osteoporosis prediction models. It also suggests that asthma may accelerate osteoporosis by increasing bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to bone loss.

Is bone remodelling around fully hydroxyapatite-coated and tapered-wedge stems related to the stem fixation pattern?

PURPOSE: This study aimed to compare bone mineral density (BMD) changes around the femoral component after total hip arthroplasty (THA) in a fully hydroxyapatite-coated stem (CORAIL) and in a tapered-wedge stem (Taperloc complete) and identify predictors of BMD changes. METHODS: This retrospective study compared 43 hips in the CORAIL group and 40 hips in the Taperloc group. The relative changes in BMD at 2 years after THA measured using dual-energy X-ray absorptiometry and the three-dimensional quantified contact states of the stem with the femoral cortical bone were assessed. Predictors of the relative change in the BMD around the proximal part of the stem were examined using multiple regression analysis. RESULTS: The decrease in BMD in Gruen zone 7 was significantly less in the CORAIL group than in the Taperloc group (P = 0.02). In the CORAIL group, the contact area in any zone was not a significant predictor of the relative changes in BMD. The contact area between the Taperloc stem and the femoral cortical bone in zones 2 and 6 was a positive predictor of the relative changes in BMD in zones 1 (P = 0.02 and P = 0.04, respectively) and 2 (P = 0.008 and P = 0.004, respectively). CONCLUSION: The CORAIL stem suppressed the postoperative BMD loss around the stem, irrespective of the contact state. The Taperloc complete stem required contact with the proximal femoral metaphysis to suppress the postoperative BMD loss around the stem.

Aging impairs the osteocytic regulation of collagen integrity and bone quality.

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFß signaling (TßRIIocy-/-) that suppresses PLR. The control aged bone displayed decreased TGFß signaling and PLR, but aging did not worsen the existing PLR suppression in male TßRIIocy-/- bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFß. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFß-dependent maintenance of collagen integrity.

Mechanobiochemical bone remodelling around an uncemented acetabular component: influence of bone orthotropy.

Mechanical loosening of an implant is often caused by bone resorption, owing to stress/strain shielding. Adaptive bone remodelling elucidates the response of bone tissue to alterations in mechanical and biochemical environments. This study aims to propose a novel framework of bone remodelling based on the combined effects of bone orthotropy and mechanobiochemical stimulus. The proposed remodelling framework was employed in the finite element model of an implanted hemipelvis to predict evolutionary changes in bone density and associated orthotropic bone material properties. In order to account for variations in load transfer during common daily activities, several musculoskeletal loading conditions of hip joint corresponding to sitting down/up, stairs ascend/descend and normal walking were considered. The bone remodelling predictions were compared with those of isotropic strain energy density (SED)-based, isotropic mechanobiochemical and orthotropic strain-based bone remodelling formulations. Although similar trends of bone resorption were predicted by orthotropic mechanobiochemical (MBC) and orthotropic strain-based models across implanted acetabulum, more volume (10-20%) of bone elements was subjected to bone resorption for the orthotropic MBC model. Higher bone resorption (75-85%) was predicted by the orthotropic strain-based and orthotropic MBC models compared to the isotropic MBC and SED-based models. Higher bone apposition (35-160%) across the implanted acetabulum was predicted by the isotropic MBC model, compared to the SED-based model. The remodelling predictions indicated that a reduction in estrogen level might lead to an increase in bone resorption. The study highlighted the importance of including mechanobiochemical stimulus and bone anisotropy to predict bone remodelling adequately.

Comparison of disc position stability and condylar bone remodelling between two open disc repositioning surgeries: a retrospective single-centre cohort study.

BACKGROUND AND OBJECTIVE: Open suturing (OSu) and mini-screw anchor (MsA) are two commonly used open disc repositioning surgeries for anterior disc displacement (ADD) of the temporomandibular joint (TMJ). This study assesses the differences in disc position stability (DPS) and condylar bone remodelling (CBR) between these two surgical procedures in a single centre. METHODS: A retrospective cohort study using MRI scans (pre-operation, 1 week and 12 months post-operation) of all patients who had open TMJ disc repositioning surgery from January 2016 to June 2021 at one centre through two surgical techniques (OSu and MsA) was performed. The predictor variable was technique (OSu and MsA). Outcome variables were DPS and CBR. During follow-up, DPS was rated as good, acceptable and poor, and CBR was graded as improved, unchanged, and degenerated. Multivariate analysis was used to compare the DPS and CBR at 12 months after adjusting five factors including age, sex, Wilkes stage, preoperative bone status (normal, mild/moderate abnormal) and the degree of disc repositioning (normal, overcorrected, and posteriorly repositioned). Relative risk (RR) for DPS and CBR was calculated by multivariate logistic regression. RESULTS: Three hundred eighty-five patients with 583 joints were included in the study. MRIs at 12 months showed that 514 joints (93.5%) had good DPS, and 344 joints (62.5%) had improved CBR. Multivariate analysis revealed that OSu had higher DPS (RR=2.95; 95% CI, 1.27-6.85) and better CBR (RR=1.58; 95% CI, 1.02-2.46) than MsA. Among the factors affecting DPS, females had better results than males (RR=2.63; 95% CI, 1.11-6.26) and overcorrected or posteriorly repositioned discs were more stable than normally repositioned discs (RR=5.84; 95% CI, 2.58-13.20). The improvement in CBR decreased with age increasing (RR=0.91; 95% CI, 0.89-0.93). Preoperative mild/moderate abnormal bone status had a higher probability of improved CBR compared to normal preoperative bone status (RR=2.60; 95% CI, 1.76-3.83). CONCLUSION: OSu had better DPS and CBR than MsA. Sex and the degree of disc repositioning impacted DPS, while age and preoperative bone status affected CBR.

Piezo1 contributes to alveolar bone remodeling by activating ß-catenin under compressive stress.

INTRODUCTION: The mechanosensitive ion channel, Piezo1, is responsible for transducing mechanical stimuli into intracellular biochemical signals and has been identified within periodontal ligament cells (PDLCs). Nonetheless, the precise biologic function of Piezo1 in the regulation of alveolar bone remodeling by PDLCs during compressive forces remains unclear. Therefore, this study focused on elucidating the role of the Piezo1 channel in alveolar bone remodeling and uncovering its underlying mechanisms. METHODS: PDLCs were subjected to compressive force and Piezo1 inhibitors. Piezo1 and ß-catenin expressions were quantified by quantitative reverse transcription polymerase chain reaction and Western blot. The intracellular calcium concentration was measured using Fluo-8 AM staining. The osteogenic and osteoclastic activities were assessed using alkaline phosphatase staining, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and Western blot. In vivo, orthodontic tooth movement was used to determine the effects of Piezo1 on alveolar bone remodeling. RESULTS: Piezo1 and activated ß-catenin expressions were upregulated under compressive force. Piezo1 inhibition reduced ß-catenin activation, osteogenic differentiation, and osteoclastic activities. ß-catenin knockdown reversed the increased osteogenic differentiation but had little impact on osteoclastic activities. In vivo, Piezo1 inhibition led to decreased tooth movement distance, accompanied by reduced ß-catenin activation and expression of osteogenic and osteoclastic markers on the compression side. CONCLUSIONS: The Piezo1 channel is a key mechanotransduction component of PDLCs that senses compressive force and activates ß-catenin to regulate alveolar bone remodeling.

Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience.

Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment. Before the initiation of zoledronate (T0) and after six months of treatment (T1), serum levels of five BTM were measured, and patients (N = 47) underwent DXA evaluation. Standard radiological imaging was performed to assess bone tumor response to medical anti-cancer treatment. High tumor burden in bone correlated with higher serum CTX (p = 0.007) and NTX (p = 0.005) at baseline. Low concentrations of OPG at T0 predicted BM progression with a sensitivity and specificity of 63% and 77%, respectively, when a cutoff of 5.2 pmol/l was used; such a predictive meaning was stronger in patients with lytic BM (sensitivity: 88%, specificity: 80%; p = 0.0006). As for the risk of SREs, we observed an association between low baseline OC (p = 0.04) and OPG (p = 0.08) and the onset of any-time SREs, whereas an increase in OPG over time was associated with reduced risk of on-study events (p = 0.03). Moreover, a statistically significant correlation emerged between low baseline lumbar T-score and femur BMD and on-study SREs (p < 0.001 in both instances). These findings suggest that addition of DXA to BTM dosage could help stratifying the risk of SREs at the time of BM diagnosis but does not enhance our capability of detecting bone progression, during zoledronate treatment.