Search Results (129)

Osteocalcin (OC) is a small protein (49 aa) produced by the osteoblast and the most abundant noncollagenous protein in bone. Studies using the osteocalcin-depleted knock-out mouse (OC-/-) reported that osteocalcin affects bone mineral properties and bone strength. Other reports indicated osteocalcin was a hormone regulating glucose metabolism by increasing insulin secretion and sensitivity. These results were controversial. Several years ago, a couple of groups generated osteocalcin knock-out mice using different methods and failed to observe an effect of osteocalcin on bone mineral properties, bone strength or glucose metabolism. One review claimed that the previously reported results from OC-/- mouse studies were inconsistent. Within the last 2 years, additional OC-/- mouse studies have been reported, and they confirm the role of osteocalcin in glucose metabolism, bone mineral properties and strength. Some of the new data reported clears up any controversy. Published studies on the role of osteocalcin in bone and glucose metabolism using OC-/- mice will be reviewed, and results will be compared. It is shown that most of the data on the effect osteocalcin on bone properties and strength is consistent and corroborated when comparing valid data from similar techniques and similar regions of the bone. Data corroborating the role of osteocalcin in glucose metabolism will be presented, and reasons for conflicting results will be discussed. Diabetics and the elderly have reduced osteocalcin levels and are prone to bone fractures, while diabetics are glucose-intolerant. Osteocalcin may be of therapeutic use to these populations. Full article

Background and Objectives: Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those on hemodialysis. Once considered a passive process, VC is now recognized as an active, cell-mediated pathology influenced by mineral dysregulation, chronic inflammation, and oxidative stress. This review aims to synthesize current evidence on the underlying mechanisms of VC in CKD and hemodialysis, with particular focus on emerging biomarkers and therapeutic implications. Materials and Methods: A structured narrative review was conducted by searching PubMed, Web of Science, ScienceDirect, and Google Scholar. The final search was completed on 29 August 2025. A total of 1326 articles were initially retrieved, of which 65 met the inclusion criteria and were analyzed. Studies addressing VC mechanisms, the bone–vascular axis, mineral metabolism, vitamin K–dependent proteins, and biomarkers such as matrix Gla protein (MGP), osteocalcin (OC), and intact parathyroid hormone (iPTH) were included. Results: VC in CKD arises from phenotypic transformation of vascular smooth muscle cells, vesicle-mediated calcification, oxidative stress, and impaired activity of endogenous calcification inhibitors. Disruption of the fibroblast growth factor 23 (FGF23)–Klotho axis and secondary hyperparathyroidism further exacerbate vascular pathology. Among emerging biomarkers, dp-ucMGP reflects vitamin K deficiency and correlates with calcification burden, while OC and iPTH provide insight into bone–vascular crosstalk and mineral turnover. However, biomarker interpretation is limited by assay variability, renal clearance, and clinical heterogeneity. Conclusions: VC in CKD represents a complex process driven by systemic and cellular dysregulation. While biomarkers such as dp-ucMGP, OC, and iPTH offer mechanistic insights and prognostic potential, further validation is required for clinical application. A multimarker approach, combined with individualized management of mineral metabolism, may improve risk stratification and therapeutic targeting in this high-risk population. Full article

Background/Objectives: Orthodontically induced bone remodeling is a complex process, driven by the interaction between osteoblasts, osteoclasts and various biochemical mediators, in response to mechanical forces applied to the teeth. Monitoring this process can be achieved by identifying biomarkers in gingival crevicular fluid (GCF), a dynamic and non-invasive method. Laser therapy, widely used in other medical fields for bio-stimulation and surgery, does not yet benefit from a standardized protocol in orthodontics. The aim of this study was to evaluate the advantages of using laser therapy during orthodontic treatment by analyzing osteocalcin (OC) in gingival crevicular fluid (GCF). Methods: Based on the inclusion and exclusion criteria, we selected 30 patients who presented dentoalveolar disharmony with crowding, who benefited from fixed orthodontic treatment, using edgewise brackets with the same slot size for all subjects. Laser therapy was performed randomly on one hemiarch (HL), right or left, for each patient, randomly chosen at time T0, after activation of the orthodontic appliance. On the other side, the control hemiarch (HC), the same protocol was followed, but without active light. Laser therapy was performed with a dental laser, with a power of 12 watts, setting the periodontology working mode. GCF was collected at baseline, before activation of the orthodontic appliance (time T0) and 14 days after its activation (time T1) from the control hemiarch (HC) and laser hemiarch (HL). Determination of OC levels, as a marker of bone apposition, was performed by the enzyme-linked immunosorbent assay (ELISA) method. To evaluate laser therapy, OC levels were assessed comparatively between HL and HC. Results: Comparing OC values at times T0 and T1 for HL, we obtained a statistically significant difference (p < 0.0001). No statistically significant difference was detected when comparing OC values in HC between T0 and T1 (p = 0.2422). A statistically significant difference was observed between HC and HL at T1 (p < 0.0001). Conclusions: The higher OC levels observed in the hemiarches where laser therapy was applied, compared to the controls, demonstrate its effectiveness as an adjuvant in bone remodeling during orthodontic treatment. Full article

Data on the interplay between muscle, bone, and adipose tissue metabolism in normal-weight children with Prader–Willi syndrome (PWS) undergoing growth hormone (GH) therapy and dietary interventions are limited. This study aimed to assess the myokine profile and explore the associations between myokines, bone markers, adipokines, and body composition in these patients. The study included 26 children with PWS and 26 age-matched healthy controls. Serum levels of irisin, myostatin (MSTN), fibroblast growth factor-2, insulin-like growth factor-I (IGF-I), IGF-binding protein-2, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated OC (Gla-OC), periostin, soluble receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase 5b, leptin/soluble leptin receptor, adiponectin, and proinsulin were measured using immunoenzymatic assays. Children with PWS had significantly lower lean mass (p = 0.047) and a higher fat mass/lean mass ratio (p < 0.001) than controls. Irisin levels were lower in the PWS group (p = 0.031), while MSTN levels were similar between the groups. In patients, irisin positively correlated with BALP (p = 0.025) and negatively correlated with Gla-OC (p = 0.041) and periostin (p = 0.005). MSTN was positively associated with proinsulin (p = 0.001) and negatively associated with lean mass (p = 0.015). OC concentration was lower in the PWS group and correlated positively with lean mass (p = 0.052). Children with PWS exhibit altered myokine, osteokine, and adipokine profiles, as well as differences in body composition. Reduced irisin and osteocalcin levels, along with the negative association between MSTN and lean mass, may impair muscle development and bone metabolism. These imbalances could also contribute to future metabolic disorders in patients with PWS. Full article

Bone mineral density (BMD) is a key indicator of skeletal health in boars that influences their reproductive performance. Systematic research on the relationship between BMD and semen quality in adult boars of different breeds and ages is scarce. This study used quantitative ultrasound (QUS) technology to measure BMD in 492 adult and 208 replacement boars. The boars were divided into four equal groups based on descending BMD rankings to analyze correlations with semen quality. Simultaneously, a 25-hydroxyvitamin D₃ (25-OH-D₃) intervention trial was conducted on 150 adult Duroc boars. A control group and four dose groups (50 μg, 125 μg, 200 μg, and 250 μg) were established. After 90 days, the boars’ semen quality, reproductive hormone levels, and bone metabolism indicators were evaluated. The results showed no significant differences in BMD between adult and replacement boars. However, adult Landrace exhibited significantly higher BMD than Duroc and Yorkshire (p < 0.01). Within the BMD groups, Group D boars had significantly higher rates of sperm abnormality than Groups A and B (p < 0.01), and this trend was consistent across breeds. The 25-OH-D₃ intervention results indicated that the 250 μg dosage produced the optimal effect. In this group, boar semen motility significantly improved while sperm abnormality rates significantly decreased. Concurrently, levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), serum osteocalcin (OC), and BMD all increased to some degree. In summary, boar BMD is significantly influenced by breed and age and is closely correlated with the rate of sperm abnormality rate. Supplementing with 250 μg of 25-OH-D₃ effectively enhances reproductive hormone secretion, improves semen quality, and promotes bone formation. This demonstrates its potential value in breeding and nutritional regulation applications. Full article

Background/Objectives: Dairy and soybean are important potential dietary sources of bone health. However, their comparative effectiveness and the role of specific components remain unclear. In this network meta-analysis (NMA), we aimed to compare the effects of various dairy and soy products (food level) and their key bioactive components (component level) on bone health in healthy women. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (up to 28 February 2025) for randomized controlled trials. A frequentist random-effects NMA was used to compare interventions for lumbar spine (LS) and total body (TB) bone mineral density (BMD) and bone turnover markers [osteocalcin (OC), deoxypyridinoline (DPD)]. Mean differences (MDs) and 95% confidence intervals were pooled. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Results: Sixty RCTs involving 6284 participants (mean age: 54.2 years) were included. At the food level, no dairy or soy interventions significantly improved outcomes versus control, although milk + yogurt ranked numerically highest based on SUCRA values. At the bioactive-component level, the combination of casein + whey protein (MD 0.04 g/cm², 95% CI 0.01–0.06) and soybean protein (MD: 0.03 g/cm², 95% CI: 0.01–0.05) significantly increased TB BMD. Whey protein alone (SUCRA 74.4% for LS BMD) and casein + whey protein (SUCRA 86.3% for TB BMD and 75.9% for DPD) were among the highest-ranked interventions for bone health. Conclusions: The combination of milk and yogurt may be relatively promising among dairy products for bone health. Whey protein appears to be a key bioactive component beneficial for women’s bone health. Full article

Perilla seed meal (PSM) is a waste biomass of perilla seed extraction that retains flavonoid and phenolic compounds. In this study, we aimed to investigate the potential of PSM extracts (PSMEs) from Perilla frutescens (L.) Britton as a sustainable source of natural active pharmaceutical ingredients (NAPIs) containing rosmarinic acid and luteolin for promoting bone health. PSMEs were obtained through shaking incubation and ultrasonic extraction, with 40% ethanol (PS-E40) and 80% ethanol (PS-E80) being found to be the most effective solvents. The effects of PSMEs on bone formation markers were evaluated in human fetal osteoblast cells (hFOB 1.19) using bone formation parameters. The results demonstrated that PS-E40 and PS-E80 extracts significantly increased alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and osteoprotegerin (OPG) levels while concurrently reducing receptor activator of nuclear factor kappa-Β ligand (RANKL) and reactive oxygen species (ROS) production in a dose-dependent manner, particularly at 100 µg/mL on day 7 and 50 and 100 µg/mL on day 14 of the co-incubation period. Moreover, Alizarin Red S staining demonstrated that PS-E40 enhanced calcium deposition in both normal and osteogenic media, further supporting the effect of PSMEs on mineralization and osteoblast differentiation. Our findings suggest that PSMEs rich in rosmarinic acid and luteolin enhance bone health by promoting osteoblast activity and reducing osteoclastogenesis. Full article

Background/Objective: In patients with acute lymphoblastic leukemia (ALL), it has been demonstrated that the treatment has a negative effect on bone health. The n-3 polyunsaturated fatty acids (LCPUFAs-ω3) may attenuate bone resorption. We evaluated the effects of LCPUFAs-ω3, vitamin D, and calcium supplementation on bone turnover markers and changes in vitamin D concentrations during 6 weeks of supplementation and during 6 weeks of post-intervention follow-up in pediatric patients with ALL. Methods: Thirty-six pediatric patients with ALL were randomly assigned to the ω-3VDCa group (100 mg/kg/d LCPUFAs-ω3 + 4000 IU vitamin D + 1000 mg calcium) or the VDCa group (4000 IU vitamin D + 1000 mg calcium) for 6 weeks. Blood samples were collected to determine 25(OH)D, PTH, ICTP, and TRAP-5b (biomarkers of bone resorption) and osteocalcin (OC, a biomarker of bone production) levels at baseline, 6 weeks, and 12 weeks after supplementation. The 25(OH)D analysis was performed using ultra-high-performance liquid chromatography coupled to a mass spectrometer, and PTH and bone turnover markers were measured by ELISA. Results: The 25(OH)D concentration increased in both groups (ω3VDCa group: 19.4 ng/mL vs. 44.0 ng/mL, p < 0.0001; VDCa group: 15.3 ng/mL vs. 42.8 ng/mL, p = 0.018) and remained significantly higher at 12 weeks. At 12 weeks, ICTP showed lower concentrations in the ω-3VDCa group than in the VDCa group (0.74 ng/mL vs. 1.05 ng/mL, p = 0.024). Conclusions: Combined omega-3 and 4000 IU vitamin D supplementation for 6 weeks had a positive effect on bone health, as indicated by serum ICTP, with no effect on serum 25(OH)D levels over vitamin D supplementation alone. Full article

Bone tissue regeneration is a complex process that takes place at the level of osteoblasts derived from mesenchymal cells and occurs under the action of multiple signaling pathways and through the expression of osteoregenerative markers. The leaf extract of Juglans regia L. (JR) is rich in polyphenols with demonstrated osteoregeneration effects. In the present study, we investigated the extract’s effects on three types of cells with various stages of differentiation: adult mesenchymal stem cells (MSCs), osteoblasts at low passage (O6) and osteoblasts at advanced passage (O10). To assess the efficacy of the walnut leaf extract, in vitro treatments were performed in comparison with ellagic acid (EA) and catechin (CAT). The osteoregenerative properties of the leaf extract were evaluated in terms of cell viability, bone mineralization (by staining with alizarin red) and the expression of osteogenesis markers such as osteocalcin (OC), osteopontin (OPN), dentin matrix acidic phosphoprotein 1 (DMP1) and collagen type 1A. Another compound implicated in oxidative stress response, but also a bone homeostasis regulator, nuclear factor erythroid 2-related factor 2 (NRF2), was studied by immunocytochemistry. Together with collagen amount, alkaline phosphatase (ALP) activity and NF-kB levels were measured in cell lysates and supernatants. The obtained results demonstrate that JR treatment induced osteogenic differentiation and bone mineralization, and it showed protective effects against oxidative stress. Full article

Background/Objectives: Recent data on long-term consequences of prematurity on bone health are conflicting. The aim of this study was to assess the metabolic bone profile and bone mineral density (BMD) in prepubertal children born prematurely and to examine possible associations between bone health parameters and perinatal morbidity factors. Methods: This cross-sectional observational study included 144 children of mean (SD) age 10.9 (1.6) years: 49 children born very preterm (≤32 gestational weeks), 37 moderate-to-late preterm (32⁺¹ to 36⁺⁶ gestational weeks), and 58 born at term (controls). Serum levels of calcium/Ca, phosphorus/P, alkaline phosphatase/ALP, 25-hydroxyvitamin D/25(OH)D, bone formation markers (osteocalcin/OC, procollagen type I C-terminal propeptide/PICP, and insulin growth factor-1/IGF-1), and bone resorption markers (serum tartrate-resistant acid phosphatase 5b/bone TRAP5band urinary calcium-to-creatinine ratio) were measured. Total-body and lumbar-spine BMD and BMD Z-scores were calculated using dual-energy X-ray absorptiometry/DXA. Results: Children born very preterm showed significantly higher ALP, OC, PICP, and bone TRAP5b levels compared to controls, as well as compared to children born moderate-to-late preterm. Total-body and lumbar-spine BMD Z-scores were significantly lower in the very preterm-born group compared to controls. Gestational diabetes, preeclampsia, and bronchopulmonary dysplasia were associated with lower total-body BMD in the very preterm-born population. Conclusions: Preterm birth is associated with impaired metabolic bone profile and lower total-body and lumbar-spine BMD in childhood. Moderate-to-late preterm-born children exhibit altered metabolic bone parameters compared to very preterm-born children. Further research in children might allow better insight into the long-term impact of preterm birth on bone health. Full article

Objectives: The aim of this observational study was to evaluate whether the presence of periapical inflammatory cysts (PIC) is accompanied by a state of vitamin D (25OHD) 25(OH)D insufficiency or deficiency and biochemical variations in biomarkers of bone metabolism such as osteocalcin (OC), isoenzyme of bone alkaline phosphatase (BALP), and C-terminal telopeptide of type 1 collagen (CTX). Methods: A total of 56 patients (group P), 36 males and 20 females, of which 42 had one cyst (group P1) and 14 had multiple periapical cysts (group P2), alongside 56 healthy subjects (group H) were recruited. Rx-OPT and clinical evaluation were used to evaluate the presence of PIC. At the first visit, all subjects underwent venous sampling (group P and H) to measure bone biomarkers by the chemiluminescence method. The Mann–Whitney test was used to compare the different biomarkers in the H vs. P, H vs. P1, H vs. P2, and P1 vs. P2 groups. The Mann–Whitney test was used to compare biomarker levels between the study groups. ROC curves were used to search for the concentration of the different biomarkers in which the best sensitivity and specificity were found. Results: 25OHD and CTX showed a difference between H vs. P, H vs. P1, H vs. P2, and P1 vs. P1 groups (p < 0.05). The study of the ROC curves with a comparison between concentrations in the H vs. P group showed the best sensitivity and specificity for 25OHD at a concentration <19 ng/mL, highlighting a picture of 25OHD deficiency. Conclusions: The presence of apical cysts could be indicative of a vitamin D deficiency that should be appropriately treated. The findings suggest that vitamin D deficiency, given its role in bone metabolism and mineralisation, may contribute to a biological environment that favours the development or persistence of periapical cystic lesions. Full article

Childhood leukemia survivors are at risk of long-term complications. Data on bone remodeling in childhood acute lymphoblastic leukemia (ALL) are limited. This 2-year prospective longitudinal study investigated bone remodeling and bone turnover markers at diagnosis, during treatment, and until stopping treatment, in ALL patients < 18 years, to clarify the influence of leukemia itself and/or chemotherapy on bone. Methods: A total of 22 ALL children (12 males, age 5.5 ± 3.6 years) underwent blood sampling at the 5 time point (T0−T4). Osteoprotegerin (OPG), receptor-activator-NF-B-ligand (RANKL), osteocalcin (OC), C-terminal-telopeptide-type-I-collagen (CTX), bone-alkaline-phosphatase (bALP), tartrate-resistant acid-phosphatase-5b (TRACP5b), procollagen-type-I-N-terminal-propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Data from patients at T0 were compared to a control group of healthy children. We used the principal component analysis (PCA) for statistics. Results: Levels of CTX, OC, P1NP, and bALP resulted lower in ALL children than controls (p = 0.009 for CTX and p < 0.001 for the others), also DKK1 and sclerostin (p < 0.0001 and p = 0.023). RANKL ed OPG were higher in patients. During T0−T4, CTX, OC, P1NP, TRACP5b, and bALP showed a significant increase, in particular at T0−T1 (end-of-induction). Less evident changes were detected onwards. Conclusions: The onset of leukemia has been revealed as a key point in determining a slowing of bone remodeling in ALL children. Full article

Sambucus javanica subsp. javanica (SJ) has been used in traditional medicine in the northern region of Thailand for healing bone fractures; however, studies on how this plant stimulates bone formation are still scarce. The present study aimed to investigate the potential of crude extracts and fractions obtained from SJ leaves for osteoporotic protection. All samples were investigated in murine preosteoblast MC3T3-E1 cells for bone formation and resorption biomarkers, namely alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), and the OPG/RANKL ratio. Additionally, calcium deposits were determined using the alizarin red S staining technique. The results indicated that the crude water and the crude ethanol extracts contained gallic acid, rutin, and chlorogenic acid as major compounds. The extracts stimulated osteoblastic cell differentiation and enhanced osteoprotective activity, as measured by a significant increase in ALP activity, OC, OPG, the OPG/RANKL ratio, and the degree of calcification. Additionally, they exhibited a negative impact on bone resorption by significantly reducing RANKL and reactive oxygen species (ROS) production. Therefore, our findings add novel evidence indicating that the SJ crude extracts from water and ethanol extraction could be further utilized as a natural active pharmaceutical ingredient (NAPI) for the development of bone health products. Full article

Bone-derived proteins, including carboxylated osteocalcin (cOC), are thought to play a role in cardiovascular and metabolic health. cOC is recognized for its strong affinity for calcium hydroxyapatite and its possible involvement in vascular calcification and lipid metabolism. Although the undercarboxylated form of osteocalcin (ucOC) has been widely researched, the connections between cOC and cardiovascular risk markers, such as mean arterial pressure (MAP), pulse pressure (PP), and the atherogenic index, are still not well understood. This cross-sectional study comprised 81 adults from Western Mexico; selection was based on rigorous inclusion criteria. Participants underwent various measurements, including anthropometric, biochemical, and cardiovascular assessments, such as the body mass index (BMI), body fat percentage, serum glucose, insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), lipid profile, creatinine, blood pressure parameters, and the atherogenic index. Serum cOC levels were determined using an enzyme-linked immunosorbent assay (ELISA). The study examined the relationships between cOC and cardiovascular/metabolic markers using inferential statistics and correlation coefficients. Multivariate linear analysis was performed to identify factors independently associated with the serum levels of cOC. Multivariate analysis revealed that MAP (B coefficient: 0.138, 95% CI: 0.028–0.247, p = 0.015) and the atherogenic index (B coefficient: 0.599, 95% CI: −0.039–1.161, p = 0.037) are independent predictors of cOC levels. A positive correlation was observed between cOC, PP, the atherogenic index, and HbA1, as well as an inverse correlation between cOC and HDL-c among the participants. Additionally, PP was positively correlated with HOMA-IR. Participants with elevated cOC levels showed higher MAP and atherogenic index values, indicating a potential connection between cOC and cardiovascular risk. cOC is independently associated with MAP and the atherogenic index, suggesting it may play a role in vascular remodeling and lipid metabolism. These results emphasize the importance of the bone–vascular axis in cardiovascular health and indicate that cOC might be a useful biomarker for assessing cardiovascular risk. Additional research is necessary to confirm these findings in larger, long-term studies and to investigate the mechanisms that connect cOC with cardiovascular outcomes. Full article

Hypertension is a global health concern not only correlated with cardiovascular complications, but also with impaired bone metabolism, potentially affecting healing at the bone–implant interface. Losartan, an angiotensin II receptor blocker (ARB) commonly prescribed for hypertension, has shown beneficial effects on bone healing in spontaneously hypertensive rats (SHRs). However, the influence of hypertension and ARBs like losartan on the bone cellular response at the bone–implant interface remains underexplored. Methods: A total of 32 rats were included in this study: 16 SHRs, with 8 receiving losartan (30 mg/kg daily) and 8 receiving no treatment, and 16 normotensive Wistar rats, with 8 receiving losartan and 8 receiving no treatment. After one week of treatment, titanium implants were placed into the tibia of all the animals. The bone–implant interface was assessed 60 days post-implantation using micro-computed tomography (µCT) and an immunohistochemical analysis. Results: (i) The ARB treatment significantly increased the bone volume and bone–implant contact in the SHRs receiving losartan compared to the untreated SHRs. (ii) Consistent with the µCT findings, the immunohistochemistry further confirmed regular bone turnover and increased osteocalcin (OC) mineralization in the treated SHRs. In contrast, no alterations in the bone microarchitecture were noted in the Wistar rats treated with losartan. Conclusions: The results suggest that losartan, an ARB drug, improves bone volume and bone turnover at the bone–implant interface in SHRs. Full article