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.

Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology.

As the world population ages, osteoporosis, the most common disease of bone metabolism, affects more than 200 million people worldwide. The etiology is an imbalance in bone remodeling process resulting in more significant bone resorption than bone remodeling. With the advent of the osteoimmunology field, the immune system's role in skeletal pathologies is gradually being discovered. The cytokine interferon-gamma (IFN-γ), a member of the interferon family, is an important factor in the etiology and treatment of osteoporosis because it mediates bone remodeling. This review starts with bone remodeling process and includes the cellular and key signaling pathways of bone remodeling. The effects of IFN-γ on osteoblasts, osteoclasts, and bone mass are discussed separately, while the overall effects of IFN-γ on primary and secondary osteoporosis are summarized. The net effect of IFN-γ on bone appears to be highly dependent on the environment, dose, concentration, and stage of cellular differentiation. This review focuses on the mechanisms of bone remodeling and bone immunology, with a comprehensive discussion of the relationship between IFN-γ and osteoporosis. Finding the paradoxical balance of IFN-γ in bone immunology and exploring the potential of its clinical application provide new ideas for the clinical treatment of osteoporosis and drug development.

Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet.

The aim of the study was to investigate the effect of returning to a balanced diet combined with chromium picolinate (CrPic) or chromium nanoparticles (CrNPs) supplementation at a pharmacologically relevant dose of 0.3 mg/kg body weight on the expression level of selected genes and bone turnover markers in the blood and bones of rats fed an obese diet. The results of the study showed that chronic intake of a high-fat obesogenic diet negatively affects bone turnover by impairing processes of both synthesis and degradation of bones. The switch to a healthy diet proved insufficient to regulate bone metabolism disorders induced by an obesogenic diet, even when it was supplemented with chromium, irrespective of its form. Supplementation with CrPic with no change in diet stimulated bone metabolism only at the molecular level, towards increased osteoclastogenesis (bone resorption). In contrast, CrNPs added to the high-fat diet effectively regulated bone turnover by increasing both osteoblastogenesis and osteoclastogenesis, with these changes directed more towards bone formation. The results of the study suggest that unfavourable changes in bone metabolism induced by chronic intake of a high-fat diet can be mitigated by supplementation with CrNPs, whereas a change in eating habits fails to achieve a similar effect.

The role of bone turnover markers in diagnosis, monitoring, and pathological fractures of osteoporosis.

BACKGROUND: We investigated the utility of specific biomarkers-namely, c-terminal telopeptide (CTX), n-telopeptide (NTX), deoxypyridinoline (DPD), and tartrate-resistant acid phosphatase (TRAP)-compared to conventional diagnostic methods. We hy-pothesized that these novel biomarkers could hold substantial value in the diagnosis, treatment, and monitoring of osteoporosis. METHODS: The study was conducted over a three-year period, from January 1, 2020, to January 1, 2023. We enrolled a total of 520 patients aged 50 years or older who had been diagnosed with osteoporosis. Patients undergoing steroid treatments, which are known to contribute to osteoporosis, were excluded from the study. Additionally, we carefully selected and matched a control group consisting of 500 patients based on demographic characteristics relevant to the diagnosis of osteoporosis. This meticulous selection process resulted in a comprehensive cohort comprising 1,020 patients. Throughout the study, patients were closely monitored for a duration of one year to track the occurrence of pathological fractures and assess their overall prognosis. RESULTS: As a result of our rigorous investigation, we identified CTX, NTX, DPD, and TRAP as pivotal biomarkers that play a crucial role in evaluating bone health, monitoring treatment effectiveness, and detecting pathological fractures in the context of osteoporosis. CONCLUSION: Our study underscores the significance of these biomarkers in advancing the diagnosis and management of osteo-porosis, offering valuable insights into the disease's progression and treatment outcomes.

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins.

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.

Effectiveness of teriparatide in in improving healing rates and bone-turnover markers of osteoporotic hip fracture: a meta-analysis.

Objective: To evaluate the effect of subcutaneous teriparatide therapy on fracture healing rate and change in bone mass density in osteoporotic hip fractures. METHODS: The meta-analysis was done from September to December 2022, and comprised literature search on Wanfang, CNKI, VIP, PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment of the respective database till December 2022. The relevant journals of the library of Macao University of Science and Technology, China, were manually searched for randomised controlled trials of teriparatide in the treatment of osteoporotic hip fractures. The shortlisted studies were subjectd to Cochrane Risk of Bias tool and the Jadad Rating Scale. Meta-analysis was done using the RevMan 5.4 software provided by the Cochrane Collaboration Network. Fracture healing rate and bone mineral density were the primary outcome measures, while mortality, adverse events, malformations, complications, subsequent fractures, timed-up-and-go test, visual analogue scale score, and procollagen type I N-terminal propeptide were the secondary outcome measures. RESULTS: Of the 1,094 articles retrieved, 8(0.7%) randomised controlled trials were analysed. There were 744 patients; 372(50%) in the teriparatide group and 372(50%) in the control group. Fracture healing rate was not significantly different (p=0.82), while bone mineral density was significantly different between the groups (p<0.001). Mortality, adverse events, deformity, and complications were not significantly different (p>0.05), while subsequent fractures, timed-up-and-go score, visual analogue scale score and procollagen type I N-terminal propeptide were significantly different between the groups (p<0.05). Conclusion: The literature did not support teriparatide's ability to improve the healing rate of osteoporotic hip fractures, or to reduce mortality, adverse events, malformations, and complications. In addition, teriparatide could increase bone mineral density of osteoporotic hip fractures and the procollagen type I N-terminal propeptide value, alleviate hip pain, and reduce subsequent fracture rates. This trial is registered with PROSPERO with registration number CRD42022379832.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

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.

Favorable impact of PD1/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation.

BACKGROUND: Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling. METHODS: An exploratory longitudinal study was conducted to assess serum markers of bone resorption (C-terminal telopeptide, CTX) and formation (procollagen type I N-terminal propeptide, PINP, and osteocalcin, OCN) before each ICI application (programmed cell death 1 (PD1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor) for 6 months or until disease progression in patients with advanced cancer and no evidence of bone metastases. To validate the in vivo results, we evaluated osteoclast (OC) and osteoblast (OB) differentiation on treatment with ICIs. In addition, their effect on bone remodeling was assessed by immunohistochemistry, confocal microscopy, and proteomics analysis in a dynamic 3D bone model. RESULTS: During the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation. CONCLUSION: Our study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.

Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities.

Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development and progression of bone loss disorders, but also in the bone-specific aspect of other clinical entities, such as the tumorigenesis of solid organs. Novel treatment options have come into sight that exploit the mechanosensitivity of osteoblasts, osteocytes, and chondrocytes to achieve efficient bone regeneration. In this regard, runt-related transcription factor 2 (Runx2) has emerged as a chief skeletal-specific molecule of differentiation, which is prominent to induction by mechanical stimuli. Polycystins represent a family of mechanosensitive proteins that interact with Runx2 in mechano-induced signaling cascades and foster the regulation of alternative effectors of mechanotransuction. In the present narrative review, we employed a PubMed search to extract the literature concerning Runx2, polycystins, and their association from 2000 to March 2024. The keywords stated below were used for the article search. We discuss recent advances regarding the implication of Runx2 and polycystins in bone remodeling and regeneration and elaborate on the targeting strategies that may potentially be applied for the treatment of patients with bone loss diseases.

Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss.

The existing suite of therapies for bone diseases largely act to prevent further bone loss but fail to stimulate healthy bone formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating bone remodeling in health and disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling to promote their maturation and formation of new bone, leading to enhanced trabecular bone growth and strength. Simultaneously, PEPITEM stimulates an inhibitory paracrine loop: promoting osteoblast release of the decoy receptor osteoprotegerin, which sequesters RANKL, thereby limiting osteoclast activity and bone resorption. In disease models, PEPITEM therapy halts osteoporosis-induced bone loss and arthritis-induced bone damage in mice and stimulates new bone formation in osteoblasts derived from patient samples. Thus, PEPITEM offers an alternative therapeutic option in the management of diseases with excessive bone loss, promoting an endogenous anabolic pathway to induce bone remodeling and redress the imbalance in bone turnover.

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.

Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Exercise and osteoimmunology in bone remodeling.

Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-ß, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.

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.

Plasma serotonin precursors and metabolite are correlated with bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis.

BACKGROUND: Serotonin (5-HT) precursors regulate bone remodeling. This study aims to investigate the correlation of plasma 5-HT precursors and metabolite with bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporosis (PMOP) patients. METHODS: The age, body mass index (BMI), and years since menopause (YSM) were documented for 348 postmenopausal women in normal/osteopenia/osteoporosis (OP) groups, with lumbar spine and femoral neck BMD measured. Serum bone turnover markers (PINP/ß-CTX) and plasma 5-HT, 5-HT precursors (Trp/5-HTP) and metabolite (5-HIAA) were measured by ELISA. OP patients were allocated to high/low expression groups following ROC analysis of 5-HT/Trp/5-HTP/5-HIAA. The relationship of plasma 5-HT/Trp/5-HTP/5-HIAA, BMD, and bone turnover markers with PMOP was analyzed using logistic regression analysis. The correlation of plasma 5-HT/Trp/5-HTP/5-HIAA with BMD and bone turnover markers was analyzed using Pearson's correlation analysis, followed by logistic regression analysis of the relationship between plasma 5-HT/Trp/5-HTP/5-HIAA and BMD, bone turnover markers and PMOP. RESULTS: BMI, YSM, BMD and PINP, and ß-CTX levels differed among groups. Levels of plasma 5-HT precursors/metabolite were increased in OP patients. Individuals with high 5-HT precursors/metabolite levels had low BMD and high PINP/ß-CTX levels. The 5-HT precursors/metabolite negatively-correlated with BMD and positively-correlated with PINP/ß-CTX. BMI, YSM, BMD, and PINP/ß-CTX/Trp/5-HTP/5-HT related to PMOP and were independent risk factors for OP. CONCLUSION: Plasma 5-HT precursors and metabolite negatively-correlate with BMD and positively-correlate with PINP/ß-CTX in PMOP patients. Peripheral 5-HT precursors and metabolite level may be a new direction of treatment of PMOP and bone metabolism-related disorders.

Incretins Beyond the Pancreas: Exploring the Impact of GIP and GLP-1/2 on Bone Remodeling.

Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 and 2 (GLP-1, 2), belong to the group of gastrointestinal hormones. Their actions occur through interaction with GIP and GLP-1/2 receptors, which are present in various target tissues. Apart from their well-established roles in pancreatic function and insulin regulation, incretins elicit significant effects that extend beyond the pancreas. Specifically, these hormones stimulate osteoblast differentiation and inhibit osteoclast activity, thereby promoting bone anabolism. Moreover, they play a pivotal role in bone mineralization and overall bone quality and function, making them potentially therapeutic for managing bone health. Thus, this review provides a summary of the crucial involvement of incretins in bone metabolism, influencing both bone formation and resorption processes. While existing evidence is persuasive, further studies are necessary for a comprehensive understanding of the therapeutic potential of incretins in modifying bone health.

PTH treatment before cyclic joint loading improves cartilage health and attenuates load-induced osteoarthritis development in mice.

Osteoarthritis (OA) treatment is limited by the lack of effective nonsurgical interventions to slow disease progression. Here, we examined the contributions of the subchondral bone properties to OA development. We used parathyroid hormone (PTH) to modulate bone mass before OA initiation and alendronate (ALN) to inhibit bone remodeling during OA progression. We examined the spatiotemporal progression of joint damage by combining histopathological and transcriptomic analyses across joint tissues. The additive effect of PTH pretreatment before OA initiation and ALN treatment during OA progression most effectively attenuated load-induced OA pathology. Individually, PTH directly improved cartilage health and slowed the development of cartilage damage, whereas ALN primarily attenuated subchondral bone changes associated with OA progression. Joint damage reflected early transcriptomic changes. With both treatments, the structural changes were associated with early modulation of immunoregulation and immunoresponse pathways that may contribute to disease mechanisms. Overall, our results demonstrate the potential of subchondral bone-modifying therapies to slow the progression of OA.