Search Results (621)

Background: Chronic kidney disease–mineral and bone disorder contributes to vascular calcification in kidney transplant recipients. However, the relationship between circulating bone turnover markers, Gla-rich protein (GRP), pelvic arterial calcification, and post-transplant outcomes remains uncertain. Methods: In this prospective single-centre study, 79 kidney transplant recipients underwent pre-transplant assessment of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and GRP. Pelvic arterial calcification was quantified using a validated CT-based scoring system. Associations between biomarkers, pelvic calcification severity, graft function, graft survival, patient survival, and major adverse cardiovascular events were evaluated. Results: Serum calcium was associated with serum creatinine (p = 0.039), and serum phosphate was associated with MAG-3 clearance (p = 0.009). OPG concentrations were significantly higher in patients receiving haemodialysis than in those receiving peritoneal dialysis (p = 0.021). No significant associations were observed between pelvic arterial calcification severity and circulating OPG, RANKL, or GRP concentrations. Furthermore, in univariable Cox proportional hazards models, none of the investigated biomarkers was significantly associated with graft or patient survival. Conclusions: Circulating OPG, RANKL, and GRP were not associated with pelvic arterial calcification, graft or patient survival. Larger multicentre studies with longer follow-up are warranted to clarify the prognostic value of these biomarkers. Full article

Background: Bone disease remains a major long-term complication after kidney transplantation. However, the relationship between circulating bone turnover markers (BTMs) and densitometric skeletal parameters in kidney transplant recipients (KTRs) remains incompletely understood. Methods: This single-center, cross-sectional comparative study included 50 stable adult KTRs and 56 non-transplanted individuals with dual-energy X-ray absorptiometry (DXA)-confirmed osteopenia or osteoporosis. Serum bone formation markers, bone-specific alkaline phosphatase (BALP) and procollagen type I N-terminal propeptide (P1NP), and bone resorption markers, β-C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase 5b (TRAP5b), were quantified by enzyme-linked immunosorbent assay (ELISA). Bone mineral density (BMD), Z-scores, and Fracture Risk Assessment Tool (FRAX) estimates were obtained by DXA. Between-group comparisons were adjusted for age, sex, body mass index (BMI) and postmenopausal status, with sensitivity analyses restricted to participants with low bone mass. An exploratory receiver operating characteristic (ROC) analysis was performed to assess the association of BTMs with KTR status. Results: KTRs showed lower DXA-derived Z-scores at the total hip, femoral neck and lumbar spine despite being younger. After adjustment for age, sex, BMI and postmenopausal status, KTRs had significantly higher BALP (adjusted Δ = 129.96 ng/mL, p < 0.001) and PTH, and lower eGFR and magnesium than the reference group, whereas unadjusted differences in P1NP and lumbar spine BMD did not persist; β-CTX and TRAP5b did not differ between groups. BALP remained significantly higher in KTRs across the low-bone-mass restricted and propensity-score overlap analyses. BTMs showed no significant correlations with DXA parameters in KTRs. In the exploratory ROC analysis of study-group status, BALP showed the strongest separation between KTRs and the reference group (AUC = 0.808, p < 0.001). Conclusions: Long-term KTRs exhibit a distinct bone remodeling profile characterized most consistently by elevated BALP, which remained significant after adjustment and showed the strongest separation regarding KTR status. The limited BTM–DXA associations require confirmation in longitudinal studies. Full article

Background: Bone Marrow Edema Syndrome (BMEs) encompasses primary clinical conditions characterized by pain and high-intensity signals on fluid-sensitive magnetic resonance imaging at the subchondral bone level. This study aimed to evaluate bone mineral density (BMD) and turnover markers in BMEs patients compared to a healthy control group. Methods: We selected from the records 165 patients—comprising Complex Regional Pain Syndrome type 1 (CRPS-1, n = 61), hip BMEs (n = 42), and knee BMEs (n = 62)—alongside 150 age- and sex-matched healthy controls. Assessments included bone turnover markers, vitamin D levels, and BMD at the lumbar spine and femur by Dual-Energy X-ray Absorptiometry. Trabecular Bone Score (TBS) was calculated to estimate bone microarchitecture. Results: BMEs patients demonstrated significantly lower BMD across all skeletal sites and reduced TBS values compared to controls. Osteoporosis prevalence was significantly higher in all BMEs subgroups, with CRPS-1 and hip BMES patients showing higher rates than those with knee BMEs. No significant differences were observed in vitamin D or bone turnover markers between groups. Conclusions: Patients with CRPS-1 and BMEs of the hip or knee exhibit a higher prevalence of osteoporosis and compromised bone microarchitecture. These findings highlight a significant association between BME-related conditions and altered BMD/TBS parameters, suggesting a potential shared pathophysiological link. Full article

The oral cavity represents one of the most demanding operating environments for biomedical coatings, subjecting materials to constant masticatory shear and tribological stress, dynamic temperature fluctuations, salivary enzymatic activity, and continuous fluid turnover that collectively challenge coating adhesion, durability, and longevity. Thermosensitive hydrogels that undergo reversible sol–gel transitions near body temperature offer a uniquely versatile platform for in situ coating formation on complex oral surfaces, enabling minimally invasive application and conformal coverage of irregular anatomical structures—from periodontal pockets and root canal systems to extraction sockets and bone defects. This review examines the application of thermo-sensitive hydrogel coatings across six major oral disease categories: periodontitis, peri-implantitis, bone defects, endodontic diseases, extraction wounds, and oral cancer. We further discuss practical hurdles facing clinical translation, noting that sterilization often degrades these materials, mechanical properties may prove inadequate under masticatory loads, and long-term biosafety data remains limited. This review critically evaluates how these smart coatings can bridge the gap between laboratory innovation and clinical application, offering insights to guide the development of next-generation precision therapies for oral diseases. Full article

Background and Objectives: The method of femoral canal opening during intramedullary fixation may influence the biological response to surgery. The aim of this study was to compare the early biological responses associated with mechanical canal opening and manual canal opening during Proximal Femoral Nail Antirotation (PFNA) fixation in patients with pertrochanteric femoral fractures, with a particular focus on inflammation, coagulation, organ dysfunction, and bone metabolism. Materials and Methods: This single-centre prospective randomised study consisted of 60 participants (50 women) with a mean age of 80.33 ± 11.13 years, who were randomly assigned to either manual femoral canal opening (n = 30) or mechanical canal opening (n = 30). Outcomes were assessed preoperatively and postoperatively during a 72 h follow-up period. This study was registered at ClinicalTrials.gov (ClinicalTrials.gov ID NCT07648719; registration date: 15 June 2026; study start: 1 March 2025). Results: Across all participants, surgery was associated with a significant decrease in haemoglobin levels, calcium, and estimated glomerular filtration rate, while fibrinogen, urea, creatinine, CRP (C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) significantly increased postoperatively. Patients in the mechanical canal opening group demonstrated significantly higher postoperative levels of leukocytes (p = 0.002), CRP (p = 0.001), NT-proBNP (p = 0.002), fibrinogen (p = 0.026), activated partial thromboplastin time (p = 0.035), urea (p = 0.001), and creatinine (p = 0.018), as well as greater reductions in haemoglobin (p < 0.001), compared with the manual canal opening group. Bone turnover markers also differed between groups: postoperative bone-specific alkaline phosphatase levels were significantly higher in the mechanical canal opening group (p = 0.001), whereas the increase in total procollagen type 1 N-terminal propeptide was more pronounced in the manual canal opening group (p = 0.045). Conclusions: The method of femoral canal opening during PFNA fixation significantly influences early postoperative systemic inflammation, coagulability, organ stress, and bone turnover dynamics. Manual opening of the femoral canal was associated with lower early systemic and bone stress biomarker responses compared with mechanical canal opening. Whether these differences translate into improved clinical outcomes, particularly in elderly patients with limited physiological reserve, remains to be determined. Full article

Background/Objectives: Orthodontic treatment with a Rapid Maxillary Expander (RME) induces stress on the mid-palatal suture and involves the surrounding craniofacial sutures, leading to significant variations in bone turnover markers (BTMs). The aim of this study was to evaluate whether monitoring biomarkers of bone resorption and deposition in saliva could provide indications for assessing RME treatment effectiveness in pediatric patients. Materials and Methods: The study was conducted at the Dental Clinic of Foggia in collaboration with the Clinical Pathology Unit of the Policlinico-Bari from January 2023 to September 2025. Salivary samples were collected using cotton swabs (SALIVETTE^®, SARSTEDT, Nümbrecht-Elsenroth, Germany) from 47 patients (aged 9–13 years) presenting with Class I dental and skeletal relationships and transverse maxillary deficiency. Samples were collected at five time points: before RME application (t0), and 15 (t1), 30 (t2), 45 (t3), and 60 (t4) days after the start of expansion. For pairwise comparisons of concentrations at different time points the Wilcoxon signed-rank test was used. Analysis of Variance (ANOVA) and Ordinary Least Squares (OLS) multiple regression were used to analyze the relationships between different biomarker concentrations over time. Spearman correlation was used to assess relationships between BTM concentrations at the different time points. Results: The Wilcoxon test showed that the medians of the differences for P1NP measurements were statistically significant at all time points, except between t0 and t1. Differences in PTHrP concentrations were significant, except for the comparison of t2 and t3 relative to t4. No statistically significant differences were observed for TRAcP across any measurement times. ANOVA yielded a high F-value for P1NP (F = 3.6128; p = 0.0128), indicating significant variation, whereas the F-ratios for PTHrP (F = 1.3329; p = 0.2736) and TRAcP (F = 1.3915; p = 0.2534) were close to 1, suggesting non-significant variability. Spearman correlation indicated that P1NP showed the strongest relationships with temporal variables. Discussion and Conclusions: Rapid maxillary expansion results in a significant increase in P1NP levels, reflecting collagen deposition and the onset of bone formation. This preliminary study on saliva highlights how biochemical changes can support clinicians in monitoring and validating the effectiveness of treatment. Full article

Background: Eldecalcitol (ELD) and denosumab are some of the most common therapeutic options for osteoporosis management. ELD effectively increases bone mineral density (BMD) in osteoporotic patients, independent of baseline vitamin D status or calcium intake. However, the efficacy of denosumab combined with either ELD or native vitamin D plus calcium in postmenopausal Chinese women with osteoporosis has not been established. Methods: In this single-center, randomized, open-label, active-controlled clinical trial, postmenopausal women with osteoporosis (defined as a BMD T-score ≤ −2.5 at the lumbar spine [LS], total hip [TH], or femoral neck [FN], or low bone mass with fragility fracture history) were enrolled from Xi’an Honghui Hospital in China and randomized 1:1 to two 12-month treatment regimens: the ELD group received ELD (0.75 μg orally daily) combined with denosumab (60 mg subcutaneously every 6 months), while the control group received the same denosumab regimen plus native vitamin D (800 IU orally daily) and calcium (600 mg orally daily). The primary endpoint was the 12-month percent change in LS BMD from baseline. Secondary endpoints included changes in FN- and TH-BMD from baseline, bone turnover markers, serum parathyroid hormone, quality of life, and the incidence of new fractures. Results: Of the 100 randomized participants, 45 in the ELD group and 46 in the control group were included in the efficacy analysis. After 12 months of treatment, LS-BMD increased significantly in both groups (both p < 0.05), with a greater increase in the ELD group than in the control group (6.75% vs. 4.99%), yielding a statistically significant between-group least-squares mean difference of 1.75% (95% CI, 0.10 to 3.41; p = 0.038). The reduction in serum β-CTX was significantly smaller in the ELD group than in the control group at 3 months (91.00% vs. 93.62%, p = 0.002), with no significant between-group differences thereafter. Seven fractures were reported (one non-vertebral in the ELD group; one vertebral and five non-vertebral in the control group). No significant between-group differences in FN- or TH-BMD, quality of life, or overall adverse event rates were observed. Both regimens were generally well-tolerated, without clinically meaningful calcium-related safety signals. Conclusions: Combination therapy with denosumab and eldecalcitol improved LS-BMD more effectively than denosumab with native vitamin D and calcium in postmenopausal Chinese women with osteoporosis. Clinical trial number: ClinicalTrials.gov identifier NCT05884372, registered on 1 June 2023. Full article

Background/Objectives: Discontinuation of long-term denosumab (Dmab) remains a major clinical challenge because of rebound activation of bone remodeling and increased vertebral fracture risk. Intravenous zoledronate (ZOL) is widely recommended as sequential therapy, although evidence after very prolonged Dmab exposure is limited. We report a patient who developed two rare adverse events—acute hepatocellular injury and delayed inflammatory polyarthritis—following a single ZOL infusion administered after 12 years of continuous Dmab treatment. The subsequent management of persistent rebound bone turnover with oral alendronate (ALN) highlights the therapeutic challenges encountered when repeat ZOL administration is not feasible. Methods: A 65-year-old woman with postmenopausal osteoporosis received a single 5 mg ZOL infusion 6 months after her final Dmab injection following 12 years of continuous therapy. Within 24 h, she developed a typical acute phase response. Three days later, marked hepatocellular injury was detected, characterized by substantial elevations in transaminases and gamma-glutamyl transferase, while viral and autoimmune hepatitis were excluded. Liver enzymes normalized within five days with supportive management. Thirty-two days after ZOL administration, she developed inflammatory polyarthritis in the absence of previous rheumatologic disease and with negative immunologic testing. Treatment with low-dose prednisone (5 mg/day) resulted in rapid clinical and biochemical remission. At 6 months, bone turnover markers remained markedly elevated (CTX 0.82 ng/mL, P1NP 95 ng/mL), indicating insufficient suppression of rebound bone turnover after Dmab discontinuation. Because of the adverse events, the patient declined repeat ZOL administration. Results: Weekly oral alendronate (ALN) (70 mg) was initiated and was associated with partial suppression of bone turnover markers. Despite a decline in bone mineral density (BMD) of approximately 5% at both the lumbar spine and total hip over 12 months, BMD remained within the osteopenic range, and no new fragility fractures occurred during follow-up. Conclusions: This case illustrates two rare sequential immune-mediated adverse events following ZOL infusion and underscores the therapeutic challenges of managing Dmab discontinuation after long-term treatment when repeat ZOL administration is contraindicated. Sequential intravenous ZOL and oral ALN therapy was associated with partial suppression of bone turnover markers and protection from incident fractures during follow-up, despite a modest decline in BMD of approximately 5%. Full article

Micro- and nanoplastics (MNPs) are now pervasive in human tissues, yet their biological behavior remains unexplained within conventional pharmacokinetic frameworks. Here, we propose that MNP distribution may follow a bioenergetic logic governed by cellular turnover and metabolic demand, rather than passive diffusion alone. Integrating the human autopsy literature datasets with programmatic biological parameters suggests that MNPs persist intracellularly and are propagated through cycles of cell death and renewal, establishing a previously unrecognized system of retention-driven recirculation. By integrating tissue-specific metabolic rates, macrophage abundance, and intracellular vulnerability indices across 19 organs, we define a hierarchy of susceptibility, with highest accumulation in the spleen, intestinal epithelium, lung, and bone marrow. This hierarchy maps onto clinical patterns of tissue dysfunction and supports a unifying mechanism in which oxidative stress, energetic instability, and chronic inflammation emerge as convergent responses to MNP burden. We further identify a minimal circulating signature—lactate, high-sensitivity C-reactive protein (hsCRP), and lactate dehydrogenase (LDH)—that reflects systemic bioenergetic disruption associated with MNP exposure. Together, this framework offers a conceptual shift from diffusion-limited to turnover-driven accumulation models, providing testable hypotheses for future prospective validation. Full article

Background: Prostaglandin E₂ (PGE₂) is a key lipid mediator involved in inflammation and bone homeostasis. Its systemic production is reliably reflected by 24 h urinary excretion of PGE₂ (U-PGE₂) and its major metabolite (U-PGEM). However, the physiological association between systemic PGE₂ production, calcium-phosphorus homeostasis and bone turnover markers remains unclear. This study aims to elucidate these relationships in a general Chinese adult population. Methods: In this multicenter, cross-sectional study, 737 Chinese adults underwent standardized 24 h urine collection. Multivariable linear regression was used to assess independent associations with bone metabolism markers. Restricted cubic spline models were further employed to examine nonlinear relationships. Results: The median 24 h U-PGE₂ and U-PGEM excretion levels were 133.87 and 246.76 pg/mmol creatinine, respectively, with no significant sex differences (both p > 0.05). Multivariable regression analyses revealed that both 24 h U-PGE₂ and U-PGEM were independently and positively associated with advancing age. Notably, both 24 h U-PGE₂ and U-PGEM maintained a significant inverse association with serum calcium (Overall p < 0.05). Restricted cubic spline analyses further demonstrated a significant non-linear association between both 24 h U-PGE₂ and U-PGEM and total procollagen type 1 N-propeptide (P1NP; both Overall p < 0.05). This relationship was characterized by a steep decline in U-PGE₂ and U-PGEM excretion at lower P1NP concentrations, which subsequently plateaued at higher concentrations (Overall p < 0.05). Additionally, U-PGEM exhibited a significant inverse linear association with intact parathyroid hormone (PTH; Overall p < 0.05). Conclusions: This study provided valuable insights into the clinical determinants of 24 h U-PGE₂ and U-PGEM in Chinese adults and their independent associations with calcium-phosphorus homeostasis and bone turnover markers. Full article

Background: Biomarkers are increasingly used in sport science and sports medicine to monitor training load, recovery, metabolic stress, nutritional status, and potential clinical risk in athletes. However, their interpretation is often limited by overreliance on isolated values, population reference ranges, and simplified thresholds. This narrative review aims to provide a contextual and metabolically informed framework for interpreting routine and emerging biomarkers in athletes. Methods: A critical narrative synthesis was conducted across key physiological domains relevant to athlete monitoring, including exercise intensity, metabolic flexibility, muscle damage, protein catabolism, hydration, hematological and iron status, micronutrient and bone–muscle health, inflammation, endocrine stress, sport-specific interpretation, and emerging metabolomics. The review integrated routine laboratory markers with pathway-level metabolomic interpretation and practical decision-making principles. Results: Routine markers such as lactate, creatine kinase, urea/blood urea nitrogen (BUN), creatinine, electrolytes, ferritin, C-reactive protein, cortisol, testosterone, and vitamin D are useful only when interpreted in relation to individual baseline, sampling conditions, recent workload, nutrition, hydration, sleep, illness, sex-specific physiology, and performance. Metabolomics expands interpretation by identifying pathway-level signatures involving glycolysis, β-oxidation, amino acid turnover, purine degradation, ketone bodies, acylcarnitines, bile acids, oxylipins, kynurenine metabolites, and exercise-induced signaling molecules such as lactate, β-aminoisobutyric acid (BAIBA), and N-lactoyl-phenylalanine (Lac-Phe). However, omics-derived markers require careful standardization and validation before routine applied use. Conclusions: Biomarkers should refine, not replace, clinical reasoning and athlete monitoring. A BASE framework (Baseline, Analytical standardization, Sport-specific context, and Evidence of functional change) may support more precise and proportionate interpretation of both routine blood tests and emerging metabolomic tools in athletes. Full article

Skeletal safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains uncharted, with emerging evidence suggesting a divergence between mono- and dual-agonist therapies. GLP-1RA monotherapy appears bone-neutral, with modest or no adverse effects on bone mineral density (BMD), whilst dual agonists may confer a relatively higher risk of osteoporosis and fractures, plausibly mediated by greater weight loss magnitude and concomitant reductions in lean body mass (LBM) rather than direct osteotoxicity. Intensified surveillance is warranted in susceptible phenotypes, including older adults and postmenopausal women with low baseline BMD under conditions of rapid weight loss. Osteoporosis risk is further amplified by pre-existing osteopenia, nutritional deficiencies, and concomitant exposure to bone-active agents. Given the limitations of serial dual-energy X-ray absorptiometry (DXA), including cumulative radiation exposure and limited sensitivity to early remodeling changes, biochemical markers potentially depict bone turnover more dynamically. Measurement of dynamic bone resorption markers enables early identification of skeletal disturbances, supporting proactive adjustment of therapeutic strategy, dosing, and duration. Specifically, deoxypyridinoline (DPD), a bone-specific collagen crosslink, is a highly sensitive and rapidly responsive urine biomarker of osteoclastic activity. Incorporating DPD urine testing into monitoring frameworks potentially facilitates individualized therapeutic modulation, optimizing the metabolic efficacy of GLP-1RAs while safeguarding skeletal integrity. Full article

Osteoradionecrosis of the jaw (ORNJ) remains one of the most severe late complications of head and neck radiotherapy. Current evidence suggests that ORNJ is a progressive and biologically heterogeneous disorder driven by microvascular injury, chronic hypoxia, oxidative stress, fibro-atrophic remodeling, impaired bone turnover, immune dysregulation, and systemic susceptibility factors. Within this complex pathogenic network, heat shock protein 27 (HSP27) emerges as a biologically plausible but unexplored mediator. HSP27 regulates multiple stress-response pathways, including redox homeostasis, cytoskeletal stabilization, endothelial protection, apoptosis control, fibroblast activation, and osteoblast–osteoclast function, all of which overlap with key mechanisms implicated in ORNJ. However, no studies have directly investigated HSP27 expression, activation, or functional significance in irradiated mandibular tissues or ORNJ-specific cohorts. This review summarizes current knowledge of ORNJ pathobiology, examines potential mechanistic links with HSP27, and outlines future research priorities involving biomarker development, tissue-level characterization, preclinical modeling, and therapeutic targeting. Integrating HSP27 into ORNJ research may improve understanding of pathogenesis, risk stratification, and the development of novel preventive and therapeutic strategies. Full article

Tendon injury, tendon–bone interface disruption, and rotator cuff pathology involve inflammatory signaling, oxidative stress, extracellular matrix turnover, cellular senescence, and impaired differentiation. Plant-derived bioactive compounds, including curcumin, quercetin, and other flavonoids and botanical formulations, have been investigated across these pathways in preclinical tendon and enthesis models, but interpretation is complicated by heterogeneous models, formulations, delivery platforms, and endpoints. This review distinguishes preclinical and formulation-specific tissue-response signals from evidence sufficient to support patient-facing clinical or nutraceutical claims. It synthesizes 31 articles using an evidence-tiering framework separating preclinical plausibility (Tier 3), limited human-facing translational evidence (Tier 2), and robust clinical efficacy (Tier 1). The corpus was predominantly Tier 3, with two Tier 2 articles providing human tissue or clinically oriented evidence and no Tier 1 evidence identified. An evidence-calibrated translational proximity map and an overclaim prevention checklist are provided to guide interpretation. The proposed proximity map reflects relative translational position within a focused narrative corpus and was not based on systematic review methods, formal risk-of-bias assessment, or clinical intervention evidence. The limited human-facing evidence does not represent patient-intervention evidence and does not support clinical, supplementation, or treatment recommendations. These compounds remain candidates for staged translational investigation rather than established interventions. Full article

Background: Selective estrogen receptor modulators (SERMs) are widely used for postmenopausal osteoporosis, yet whether treatment response attenuates with aging in routine practice remains unclear. We examined age- and site-specific responses to SERM therapy. Methods: We retrospectively analyzed postmenopausal women with primary osteoporosis treated with a SERM for 1 year (2017–2021). Participants were stratified by age (50–64, 65–74, and ≥75 years). We evaluated changes in bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck and changes in urinary NTX and serum BAP. Multivariable linear regression modeled BMD change ratios (1-year/baseline) adjusting for baseline site-specific BMD, estimated glomerular filtration rate (eGFR), and active vitamin D co-therapy (none, alfacalcidol, or eldecalcitol). The primary endpoint was the 1-year change in lumbar spine BMD; secondary endpoints included femoral neck BMD and bone turnover markers. Results: Lumbar spine BMD increased significantly across all age groups, whereas femoral neck BMD increased significantly only in women aged 50–64 years. However, BMD change ratios did not differ among age groups at either site. In adjusted models, age was not independently associated with BMD change at the lumbar spine or femoral neck. Lower baseline BMD predicted larger relative gains at both sites, and eldecalcitol co-therapy was independently associated with femoral neck BMD response. Conclusions: In real-world practice, BMD changes observed during SERM treatment were site-specific rather than clearly age-dependent. Lumbar spine BMD improved across age groups, whereas femoral neck changes were smaller and less consistent. Full article