Search Results (193)

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a major complication of end-stage renal disease and is associated with increased morbidity and mortality. Sclerostin, an osteocyte-derived glycoprotein that inhibits the Wnt/β-catenin signaling pathway, has been implicated in the dysregulation of bone metabolism in dialysis patients. However, comparative data on sclerostin levels and their clinical determinants between hemodialysis (HD) and peritoneal dialysis (PD) patients remain limited, particularly in Southeast Asian populations. This cross-sectional study was conducted at Hue Central Hospital, Vietnam, between June 2023 and January 2026. A total of 89 end-stage renal disease patients were consecutively enrolled (HD: n = 51; PD: n = 38). Median serum sclerostin levels were 584.21 (IQR: 301.18–1479.50) pg/mL in the HD group and 684.21 (IQR: 407.48–940.35) pg/mL in the PD group, with no significant difference between groups (p = 0.839). Serum sclerostin was inversely correlated with PTH in both HD (r = −0.444, p = 0.001) and PD patients (r = −0.341, p = 0.036). In the HD group, total femur BMD showed a significant inverse correlation with sclerostin (r = −0.304, p = 0.030). In multivariable analysis, Log_PTH remained an independent predictor of sclerostin across all three sequential models in the HD group (Model 1: B = −0.340, p = 0.001; Model 2: B = −0.270, p = 0.035; Model 3: B = −0.268, p = 0.039; adjusted R² range: 0.197–0.217) and in the combined HD + PD cohort (Model 1: B = −0.271, p < 0.001; Model 2: B = −0.263, p < 0.001; Model 3: B = −0.249, p = 0.003; adjusted R² range: 0.141–0.158). In the PD subgroup, Log_PTH was significant in Models 1 and 2 but not in Model 3; none of the models reached overall statistical significance (all p ≥ 0.081), and findings should be considered exploratory given the limited sample size. Serum sclerostin levels did not differ significantly between HD and PD patients. PTH was the most consistent independent predictor of sclerostin across dialysis modalities and analytical models, underscoring its central role in CKD-MBD pathophysiology. Larger prospective multicenter studies are warranted to validate these findings and further clarify the clinical utility of sclerostin in dialysis populations. Full article

Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. Methods: This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. Results: Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls (p < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, p = 0.001) and FT4 (r = 0.43, p = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, p = 0.007). A strong positive correlation was found between DKK-1 and SOST (p < 0.001), while DKK-1 was negatively associated with age (p < 0.05). Conclusions: Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune–bone interactions in thyroid-related changes in bone metabolism. Full article

Peri-implant marginal bone stability remains a major determinant of long-term implant success, yet clinical studies report early marginal bone changes ranging from near-stable conditions in some protocols to approximately 1–2 mm during the first year in more traditional series, underscoring considerable biological variability. In the present review, a remodeling-dominant state refers to turnover-led peri-implant adaptation with limited net cortical gain, whereas modeling-driven apposition refers to uncoupled surface bone addition and cortical reinforcement. We conducted a structured narrative review of PubMed/MEDLINE, Scopus, and Web of Science for literature published between 2000 and February 2026 and qualitatively synthesized direct peri-implant evidence, craniofacial/oral non-implant evidence, and extrapolative mechanobiology from long-bone and systemic models. The available literature supports osteocyte-centered SOST/Wnt regulation as biologically plausible for peri-implant cortical adaptation; however, direct human peri-implant molecular validation remains limited. Based on this synthesis, we propose a hypothesis-generating framework in which mechanical signal profile, microenvironmental stability, and host-related factors influence the probability of transition from a remodeling-dominant to a modeling-dominant peri-implant state. This framework should therefore be interpreted as a testable conceptual model rather than a validated peri-implant mechanism. Its main value lies in organizing current evidence and defining priorities for translational studies that integrate molecular, imaging, and biomechanical endpoints. Full article

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43 hemichannels), and osteocyte paracrine mediators (extracellular vesicles and senescence-associated factors), and examine how each axis modulates tumor cell dormancy, osteolysis, or osteoblastic progression. We then review translational strategies targeting osteocytes, recent preclinical and clinical insights. Emerging biomarkers (e.g., serum sclerostin, DKK1, bone turnover markers) and immune–skeletal imaging approaches are also considered. Controversies, including the paradoxical effects of sclerostin blockade and the identity of in vivo RANKL sources, are discussed. Finally, we outline key knowledge gaps and propose endpoints for future trials. In summary, an osteocyte-centric perspective reveals novel targets and strategies for managing bone metastases, guiding future translational research. Full article

Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM. Full article

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms. Full article

Using colorimetric ELISA, this study aims to assess the impact of Gum Arabica (GA) consumption on functional molecular plasma biomarkers of chronic kidney disease (CKD) via a prospective cohort of GA-consumers (cases) vs. non-consumer (age- and CKD stage-matched) controls. Cohort’s hypertension (92.5%), dyslipidemia (64.8%), and diabetes mellitus (54.8%) were prevalent; the mean CKD duration was 6.94 years (SD 7.8) for both study groups. Comparable eGFR, sCr, ESR, CRP, HbA1c, FPG, UA, and fasting lipid parameters were in both study arms. In consumer cases, the mean duration of GA-consumption was 1.3 ± 1.1 (range 0.25–6) years with a mean dose of 1.7 ± 1.0 (range 0.5–6) spoons per day. Leucine-rich alpha 2-glycoprotein, plasminogen activator inhibitor 1, sirtuin 1, and SOST–sclerostin 1 were significantly (p value < 0.01) of lower concentrations, but lipocalin 2 and uromodulin were invariably (p value < 0.05) greater in the GA-consumer cases than those of controls. Strikingly, cystatin C, myeloperoxidase, orosomucoid 1, and symmetric dimethylarginine lacked any substantial variations in the GA-consumer cases vs. those in controls (p value > 0.05). Proportional correlations of CKD duration–PAI1 levels and sCr-lipocalin 2 levels but inverse correlations of orosomucoid 1-hypertension duration and SDMA-DBP were evident in cases. Full article

Background: Sclerostin, an osteocyte-derived glycoprotein, plays a key role in bone metabolism by inhibiting the Wnt/β-catenin signaling pathway. While it is a recognized therapeutic target in osteoporosis, its relationship with sarcopenia remains unclear. This study aimed to investigate the associations between serum sclerostin levels, sarcopenia, and osteoporosis in older women. Methods: We conducted a cross-sectional study of 79 postmenopausal women aged ≥65 years. Sarcopenia was defined based on grip strength and appendicular skeletal muscle mass (ASM), osteoporosis was diagnosed according to femoral T-scores, and serum sclerostin levels were measured using ELISA. Associations with clinical variables and bone mineral density (BMD) were evaluated using correlation and logistic regression analyses. Results: Sclerostin levels were significantly higher in women with sarcopenia (p = 0.036) and exhibited a negative correlation with grip strength (r = −0.298, p = 0.008) but not with ASM. Positive correlations were found between sclerostin and multiple femoral BMD parameters. In a logistic regression analysis, sclerostin was modestly associated with sarcopenia (p = 0.045); however, no significant association was observed with osteoporosis (p = 0.257). Conclusions: Elevated sclerostin levels are associated with reduced muscle strength and sarcopenia in older women, independent of muscle mass, indicating that sclerostin may reflect a functional decline in musculoskeletal health. Muscle strength should therefore be considered when interpreting sclerostin’s clinical implications in aging populations. Full article

Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and microarchitectural deterioration, leading to increased fracture risk, particularly in aging populations. Postmenopausal osteoporosis (PMOP) remains the most common primary form and results from abrupt estrogen deficiency after menopause, which disrupts bone remodeling by accelerating the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis, suppressing Wnt/β-catenin signaling, and promoting inflammatory cytokine production. In contrast, drug-induced osteoporosis (DIOP) encompasses a heterogeneous group of secondary bone disorders arising from pharmacologic exposures. Glucocorticoids suppress osteoblastogenesis, enhance osteoclast activity, and increase reactive oxygen species; long-term bisphosphonate therapy may oversuppress bone turnover, resulting in microdamage accumulation; denosumab withdrawal triggers a unique rebound surge in RANKL activity, often leading to rapid bone loss and multiple vertebral fractures. Medications including aromatase inhibitors, SSRIs, proton pump inhibitors, heparin, and antiepileptic drugs impair bone quality through diverse mechanisms. Standard antiresorptive agents remain first-line therapies, while anabolic agents such as teriparatide, abaloparatide, and romosozumab provide enhanced benefits in high-risk or drug-suppressed bone states. Transitional bisphosphonate therapy is essential when discontinuing denosumab, and individualized treatment plans—including drug holidays, lifestyle interventions, and monitoring vulnerable patients—are critical for optimizing outcomes. Emerging approaches such as small interfering RNA (siRNA)-based therapeutics, anti-sclerostin agents, digital monitoring technologies, and regenerative strategies show promise for future precision medicine management. Understanding the distinct and overlapping molecular mechanisms of osteoporosis is essential for improving fracture prevention and long-term skeletal health. Full article

The next frontier in postmenopausal osteoporosis management lies not in novel pharmacological agents, but in the systematic integration of mechanism-guided drug selection, fall prevention, and long-term adherence strategies into a unified patient-centered care model. This review is intended for clinicians and clinical researchers involved in the diagnosis, treatment, and long-term management of postmenopausal osteoporosis. We provide a mechanism-to-practice framework that explicitly maps each therapeutic class to the specific molecular pathway it targets: bisphosphonates inhibit osteoclast function downstream of RANKL activation; denosumab blocks RANKL directly at the cytokine level; romosozumab inhibits sclerostin to restore Wnt-mediated bone formation. This mechanistic foundation supports a risk-stratified treatment paradigm in which antiresorptives address accelerated remodeling in moderate-risk patients, while patients at very high fracture risk—characterized by severe bone deficit or recent fragility fractures—benefit from an anabolic-first approach followed by consolidation. Beyond drug selection, we examine the persistent treatment gap in which fewer than 20% of post-fracture patients receive therapy, arguing that fall prevention—responsible for >90% of hip fractures—and medication adherence deserve equal priority in clinical practice. We further analyze key controversies, including T-score- versus FRAX-based intervention thresholds, limitations of the trabecular bone score, cost-effectiveness constraints on anabolic-first sequencing, and evidence gaps in post-denosumab transition strategies. By synthesizing mechanistic insights, guideline recommendations, and critical appraisal of current limitations, this review offers not only an overview of existing knowledge but a coherent decision-support model aimed at improving fracture prevention through comprehensive, individualized care. Full article

Osteoporosis is an aging-related disease characterized by low bone mineral density and deteriorated bone structure, resulting in an increased risk of fractures. Currently, most osteoporosis therapies target osteoclasts to inhibit bone resorption, while the three FDA-approved anabolic agents include parathyroid hormone, parathyroid hormone-related protein, and anti-sclerostin antibody that promote osteoblast function. However, long-term treatment with these agents is associated with potential adverse effects and decreased therapeutic efficacy. This has prompted exploration of novel therapeutic strategies, including microRNAs (miRNAs), which are emerging as promising candidates. miRNAs have been reported to play important roles in regulating pathways involved in bone formation and resorption. In addition to their direct roles in osteoblasts and osteoclasts, miRNAs also serve as key mediators of communication between these cells, which is essential for maintaining bone homeostasis. The complexity of osteoporosis requires versatile regulators such as miRNAs that can modulate multiple biological pathways. Recent studies have demonstrated the potential of miRNA-based therapy to restore bone homeostasis in osteoporotic models. However, further studies are needed to develop tissue-specific delivery systems and evaluate long-term safety to improve the therapeutic potential of miRNAs as new osteoporosis drugs. Full article

Background/Objectives: Changes in sclerostin expression regulated by SOST in osteocytes during spaceflight may be associated with bone loss; however, the underlying mechanisms remain unclear. The aim of this study was to clarify the relationship between SOST expression and bone loss by identifying the gene expression differences between osteocytes with high and low SOST expressions. Methods: We used the NASA GeneLab Database OSD-324, which is a microarray of data about the Ocy454 osteocytic cell line cultured for 2, 4, and 6 days during spaceflight, and the GSE102958 microarray in the Gene Expression Omnibus. We also analyzed the characteristics of SOST gene expression in osteocytes during spaceflight using merged datasets. Results: The findings of Gene Set Enrichment Analysis (GSEA) revealed that five gene sets related with H3K27me3 significantly upregulated with NES > 2.0 during spaceflight compared with ground controls. We also found 77 and 617 differentially expressed genes (DEGs) in flight 6d vs. low and high SOST expression, respectively. We used the transcriptional regulatory relationships unraveled by the sentence-based text-mining (TRRUST) database to determine the most significant upstream transcription factor (TF) of genes downregulated in osteocytes during spaceflight compared with those expressing abundant SOST. We detected that TF Sp7 is the most significant, with FDR < 0.01. Moreover, the GSEA findings indicated that the hypoxic pathway is prolonged in osteocytes during spaceflight compared to those at ground level. Conclusions: The gene expression profiles of osteocytes during spaceflight and in comparatively immature osteocytes with low SOST expression were similar. Furthermore, early osteocyte maturation inhibited by downregulated Sp7 during spaceflight extended the hypoxic response. Full article

Background/Objectives: Sclerostin is a glycoprotein produced by osteocytes that regulates osseous remodeling, particularly in the context of orthodontic tooth movement. The purpose of the current systematic review is to assess the effect of orthodontic tooth movement (OTM) on sclerostin expression (SE) in the alveolar bone matrix (ABM). Methods: Indexed databases including PubMed, Embase and Web of Science were searched without time and language restrictions up to and including March 2025. Results: Seven studies performed on 8- to 12-week-old male rodents were included. The magnitude of orthodontic forces ranged from 10–120 g. Distalization and mesialization of the maxillary first molar were performed in one and six studies, respectively. In two studies, SE was increased on the compression and tension sides during OTM. In one study, SE is increased and decreased on the compression and tension sides, respectively; and another reported no difference in SE on the compression and tension sites during OTM. Two studies did not report data on SE on the control-sites (sites unexposed to OTM). Sample-size estimation was not performed in any of the included studies. All studies had a high risk of bias (RoB) and low certainty of evidence (CoE). Conclusions: Sclerostin may play a regulatory role in ABM during OTM. However, current evidence is limited by methodological inconsistencies, high RoB, and low CoE. Well-designed, power-adjusted studies using standardized protocols are required to establish reproducible findings and assess the translational potential of SE in orthodontics. Full article

Hormonal alterations associated with polycystic ovary syndrome (PCOS) also impact bone metabolism, though it is unclear if this is bone-protective or not. Bone marker dysfunction has been reported in PCOS and appears to be associated with obesity. This study sought to determine whether a panel of bone marker proteins (BMPs) would be dysregulated in PCOS stratified by BMI as a potential biomarker for bone in PCOS. In this exploratory cross-sectional study, plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin resistant population (24 with PCOS and 24 controls). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for the following BMPs: sclerostin; Dickkopf-related protein-1; glycogen synthase kinase-3 alpha/beta; periostin; tumor necrosis factor ligand superfamily member 11; fibroblast growth factor 23; sphingosine kinase 1; sphingosine kinase 2; cathepsins A, B, D, E, G, L2, S and Z; parathyroid hormone; osteocalcin; tumor necrosis factor ligand superfamily member 11 (sRANKL) and interleukin-1 beta. Four BMPs differed in the PCOS cohort (whole set without matching for body mass index (BMI) or insulin resistance (IR)): periostin (p = 0.05), cathepsin L (p = 0.05) and osteocalcin (p = 0.02) decreased in PCOS, whilst cathepsin D (p = 0.02) increased; however, linear regression showed that only cathepsins D and L and osteocalcin differed. None of the BMPs differed in the nonobese women with and without PCOS, nor in obese PCOS and controls stratified by BMI greater than 30 kg/m². In subgroup analysis, periostin (p = 0.001), sphingosine kinase 2 (p = 0.01) and cathepsin L (p = 0.001) were higher in obese versus nonobese PCOS (p = 0.01). Cathepsin Z (p = 0.02), sphingosine kinase 2 (p = 0.04) and lysosomal protective protein (p = 0.05) were lower in obese versus nonobese controls. Changes in BMPs indicative of impaired bone physiology were associated with BMI in both controls and PCOS, but did not differ between women with and without PCOS when BMI was matched. Hyperandrogenemia in PCOS did not affect BMP levels. Full article

Immunosenescence refers to the set of immunoendocrinological alterations underlying the progressive decline in innate and adaptive immune function that occurs with aging. It is closely linked to the concept of inflammaging, a state of low-grade chronic systemic inflammation that contributes to age-related diseases. In the elderly, key features of diseases such as rheumatoid arthritis, particularly in its elderly onset form, and senile osteoporosis are characterized by a decline in sex hormones and the immunoregulatory IL-2; an increase in serum autoantibodies and pro-inflammatory mediators such as TNF-α, IL-6; and upregulation of bone-related factors RANKL, DKK1, and sclerostin, including the dysregulation of the IL-33/IL-31 axis. The aim of this review is to examine the key molecular pathways of immunosenescence in osteoimmunology, as well as the potential for therapeutic modulation of inflammaging through biologic and target synthetic disease-modifying antirheumatic drugs, denosumab and romosozumab, with particular attention to their management in elderly patients. Full article