Search Results (122)

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

Background/Objectives: Bone turnover markers (BTMs) can provide information on the bone growth of apparently healthy children and adolescents or useful results in the diagnosis and monitoring of the disease condition, comparing them with appropriate reference intervals (RIs). The aim of this study was to establish the RI for the BTM [specific bone alkaline phosphatase (BALP), carboxy-terminal cross-linked collagen type I telopeptide (CTX), N-terminal propeptide pro-collagen type I (PINP), osteocalcin (OC), resistant to acid tartrate phosphatase isoform 5b (TRAcP-5b)] on serum samples from children and adolescents. Method: 202 samples from children and adolescents (ages 1–18 years) (51.48% male), considered apparently healthy. The biomarker was analyzed on automatic immunometric equipment (TGSTA Technogenetics) and the IDS-iSYS automated system kits The RI of the studied parameters was calculated according to CLSI Guideline C28-A3 with stratification by age and sex. Evaluation of the distribution of values and the meaning of the biomarker concentrations were used to calculate general and specific RI for an age group. Results: BTM concentrations vary with pubertal growth. The pattern of change differs for each bone marker. General and age-specific RI were calculated: 1–14 years, 15–18 years for BALP and CTX; 1–13 years, 14–18 years for Oc and PINP and 1–12 years, 13–18 years for TRAcP. Discussion and Conclusions: Concentrations for biomarker studied vary with age and gender. The proof of concentrations with insignificant changes until puberty led to identification of two groups of RI relating to the covariables (age and sex) for each biomarker. Full article

Alkaptonuria (AKU) is a genetically determined disease associated with disorders of tyrosine metabolism. In AKU, the deposition of homogentisic acid polymers contributes to the pathological ossification of cartilage tissue. The controlled use of biomimetics similar to deposits observed in cartilage during AKU potentially may serve the development of new bone regeneration therapy based on the activation of osteoblasts. The proposed biomimetic is pyomelanin (PyoM), a polymeric biomacromolecule synthesized by Pseudomonas aeruginosa. This work presents comprehensive data on the osteoinductive, pro-regenerative, and antibacterial properties, as well as the cytocompatibility, of water-soluble (PyoM_sol) or water-insoluble (PyoM_insol) PyoM. Both variants of PyoM support osteoinductive processes as well as the maturation of osteoblasts in cell cultures in vitro due to the upregulation of bone-formation markers, osteocalcin (OC), and alkaline phosphatase (ALP). Furthermore, the cytokines involved in these processes were elevated in cell cultures of osteoblasts exposed to PyoM: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. The PyoM variants are cytocompatible in a wide concentration range and limit the doxorubicin-induced apoptosis of osteoblasts. This cytoprotective PyoM activity is correlated with an increased migration of osteoblasts. Moreover, PyoM_sol and PyoM_insol exhibit antibacterial activity against staphylococci isolated from infected bones. The osteoinductive, pro-regenerative, and antiapoptotic effects achieved through PyoM stimulation prompt the development of new biocomposites modified with this bacterial biopolymer for medical use. Full article

Background/Objectives: This study aims to investigate the association of movement behaviors with irisin, sclerostin, and bone turnover markers in young pediatric cancer survivors. Methods: A total of 116 young pediatric cancer survivors (12.1 ± 3.3 years; 42% female) were recruited. Time spent in movement behaviors over at least seven consecutive 24 h periods was measured by accelerometers (wGT3x-BT accelerometer, ActiGraph). Blood samples were collected at rest and serum was analyzed for irisin, sclerostin, cross-linked telopeptide of type I collagen (CTX), procollagen type I amino-terminal propeptide (P1NP), total osteocalcin (OC), alkaline phosphatase (ALP), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, phosphorous, and magnesium. Results: Irisin and sclerostin were not significantly correlated with bone turnover markers. Sedentary time was negatively correlated with the P1NP (r = −0.411, p = 0.027) and total OC (r = −0.479, p = 0.015) Z-scores, whereas moderate-to-vigorous physical activity was positively correlated with the P1NP (r = 0.418, p = 0.024) and total OC (r = 0.478, p = 0.016) Z-scores. Moreover, total physical activity was positively correlated with the total OC Z-score (r = 0.448, p = 0.025). Finally, the uncoupling index [CTX/P1NP] was positively correlated with sedentary time (r = 0.424, p = 0.012) and negatively correlated with light physical activity (r = −0.352, 0.041). Conclusions: Reducing sedentary time and increasing physical activity may favor bone formation over resorption in young pediatric cancer survivors. Full article

Electrical stimulation-induced muscle contraction (ESMC) has demonstrated various physiological benefits, but its effects on the secretion of undercarboxylated osteocalcin (ucOC), a bone-derived cytokine, remain unclear. This study explored the relationship between ESMC, bone strain, and ucOC secretion through two experiments. In the first, young male Fischer 344 rats were divided into three groups: low-frequency ES (LF, 10 Hz), high-frequency ES (HF, 100 Hz), and control (CON). Acute 30-min transcutaneous ES was applied, and both bone strain and ucOC levels were measured. In the second experiment, rats underwent LF or HF long-term ES (two sessions per week for 4 weeks), with ucOC and insulin levels monitored. Results revealed a significant peak in ucOC at 6 h post-acute LF-ESMC. Despite HF-ESMC generating greater bone strain, LF-ESMC, with smaller but repetitive bone strain, proved more effective in stimulating ucOC secretion. In the long-term study, both ESMC groups exhibited early increases in ucOC, with a positive correlation to insulin levels. In conclusion, bone strain induced by ES-mediated muscle contraction promotes ucOC secretion, with both the magnitude and frequency of strain playing critical roles. Full article

Background/Objectives: Stroke survivors have a significantly increased likelihood of developing osteoporosis, a condition characterized by weak and brittle bones as well as an elevated risk of bone fractures. However, previous studies on exercise intervention have mostly been on stroke survivors who are able to walk. The objective of this study was to examine the effect of walking exercise on bone health in non-ambulatory stroke survivors. Methods: This pre- and post-test study enrolled a group of chronic non-ambulatory stroke survivors. They were instructed to complete an 8-week aerobic walking exercise program, three sessions per week. Serum concentrations of osteocalcin (OC) and carboxy-terminal telopeptides of type I collagen (ICTP) were evaluated at baseline and after completing the walking exercise program. In addition, we assessed the ambulation capacity and balance control using the functional ambulation category (FAC) and Berg Balance Scale (BBS), respectively. Results: A total of 9 out of 10 non-ambulatory stroke survivors who were recruited completed the intervention. The serum concentration of OC significantly increased from 8.51 ± 2.28 ng/mL to 9.39 ± 2.97 ng/mL (p < 0.10). The serum concentration of ICTP significantly increased from 4.45 ± 2.58 ng/mL to 5.31 ± 2.92 ng/mL (p < 0.10). Both FAC and BBS scores significantly improved from 1.0 ± 0 to 1.33 ± 0.5 (p < 0.1) and from 7.22 ± 10.02 to 15.78 ± 14.81 (p < 0.01), respectively. Conclusions: The findings of this pilot study suggest that walking exercise may improve bone health by initiating a bone remodeling process in chronic non-ambulatory stroke survivors. Full article

Gingival crevicular fluid (GCF) and oral fluid have emerged as promising diagnostic tools for detecting biomarkers. This review aimed to evaluate the existing literature on using oral fluids as a source of biomarkers for bone turnover diseases affecting the jawbone. A comprehensive search strategy was executed between August 2014 and August 2024 across five major databases (Web of Science, EBSCOhost Dentistry & Oral Sciences Source, Cochrane Library, Scopus, and PubMed) and grey literature sources. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was applied. The screening was facilitated using Rayyan at rayyan.ai and Endnote X20 software tools, culminating in the evaluation of 14,965 citations from databases and 34 from grey literature. Following rigorous scrutiny, 37 articles were selected for inclusion in this review, encompassing diseases such as periodontitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoporosis. The quality of the included observational studies was assessed using the Revised Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS 2). Interleukin-1 beta (IL-1β), sclerostin, osteoprotegerin (OPG), and interleukin-34 (IL-34) emerged as significant biomarkers in GCF, and they were mainly from periodontitis and osteoporosis. Osteocalcin (OC), IL-1β, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), OPG, and matrix metalloproteinase-9 (MMP-9) were significant in oral fluid or saliva, and they were from periodontitis, MRONJ, and osteoporosis. These findings underscore the potential use of oral fluids, which are regarded as non-invasive tools for biomarker identification in bone turnover. Many biomarkers overlap, and it is important to identify other specific biomarkers to enable accurate diagnosis of these conditions. Full article

The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery. Full article