Search

Cardiovascular events among patients with chronic kidney disease (CKD) are associated with vascular calcification (VC). Nevertheless, the process of vascular calcification is complicated. A mechanism of VC is cellular osteogenic transdifferentiation. The mechanism through which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) relieve VC is unknown. For the purpose of this study, we used human aortic vascular smooth muscle cells (HA-VSMCs) stimulated by high phosphate to investigate how BMSC-Exo works. Cell calcification was detected by Alizarin red S staining, AKP activity analysis, and the Ca

Objectives: To assess the associations of biomarkers in serum [highsensitivity C-reactive protein (hs-CRP), serum cartilage oligomeric protein (sCOMP), serum propeptide of type I procollagen (sPINP) and serum osteocalcin (sOC)] and urine [urinary type II collagen telopeptide (uCTX-2)] with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA). Methods: hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1,002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses. Results: hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95% CI 1.01–1.37), with mild and moderate pain while walking (OR 1.17 95% CI 1.01–1.35 and OR 1.56 95% CI 1.29–1.90, respectively) and with progression of nocturnal pain (OR 1.25 95% CI 1.07–1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95% CI 1.05–1.85) and with mild and severe-extreme pain while walking (OR 1.35 95% CI 1.04–1.75 and OR 2.55 95% CI 1.03–6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95% CI 0.25–0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue. Conclusion: This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.

Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of blosozumab versus placebo in perimenopausal and postmenopausal women.This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "blosozumab" to retrieve studies on the relationship between blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC).Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis.The results suggested that blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60-74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 μg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 μg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 μg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 μg/L for 100, 200, and 300 μg supplemental selenium/d, respectively (p 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Postmenopausal osteoporosis is a type of chronic disease with high morbidity and high economic burden. Due to the adverse effects of long-term drug therapy, physical therapy, such as pulsed electromagnetic fields (PEMF), is widely implemented in clinical practice. Therefore, we first conducted the meta-analysis on the efficacy and safety of PEMF in the treatment of postmenopausal osteoporosis. We searched eight databases to acquire potentially eligible studies. Outcome indicators include bone mineral density (BMD), visual analogue scale (VAS), biochemical markers of alkaline phosphatase (ALP), osteocalcin, bone-specific alkaline phosphatase (BSAP), type I collagen carboxy-terminal peptide (CTX), and adverse events. The results showed that a total of 19 studies (1303 patients) were retrieved from eight databases. Compared with conventional medications, PEMF combined with conventional medications significantly increased BMD of lumbar vertebra, femoral, Ward's triangle, bone-specific biochemical indicators of ALP, BSAP, and osteocalcin, and relieved pain. However, The incidence of adverse events was not statistically significant between PEMF combined with conventional medications and conventional medications alone. Compared with conventional medications, PEMF significantly increased the BMD of the femur and reduced the degree of pain, but there was no statistical difference in the BMD of the lumbar spine between PEMF and placebo. Except osteocalcin, BSAP, CTX, and ALP showed no significant difference. In view of its efficacy and safety, PEMF intervention can be considered as a potentially effective complementary therapy for postmenopausal women with osteoporosis. © 2022 Bioelectromagnetics Society.

Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion formation have not been established, making it difficult to investigate and implement preventative therapies. The purpose of this study was to characterize FD lesion progression in children, and to identify clinical variables associated with progressive disease. Clinical data and imaging from an ongoing natural history study at the National Institutes of Health (NIH) were reviewed. 99m-Technetium methylene diphosphonate (99Tc-MDP) scans were used to determine Skeletal Burden Score (SBS), a validated quantitative scoring system. FD progression rate was determined by the change in the SBS in each patient per year. Thirty-one children had serial 99Tc-MDP scans, with a median age at first scan of 6 years (interquartile range [IQR] 4-8, range 2-10), and median follow-up 1.1 years (IQR 1.1-2.1, range 0.7-11.2). The median FD progression rate for the total group was 2.12 SBS units/year (IQR 0.81-2.94, range 0.05-7.81). FD progression rates were highest in children under age 8 years and declined with age (p = 0.03). Baseline disease severity was associated with subsequent disease progression (p = 0.009), with the highest FD progression rates in patients with moderate disease (baseline SBS 16-30), and lowest progression rates in those with severe disease (SBS ≥50). Serum levels of the bone formation marker osteocalcin were positively correlated with subsequent FD progression rate (p = 0.01, R = 0.58). There was no association between FD progression and baseline endocrinopathies, fractures, or surgery rates. FD lesions progress during childhood, particularly in younger children and those with moderate involvement. Osteocalcin may potentially serve as a biomarker for progressive disease. These findings may allow clinicians to investigate preventative therapies, and to identify children with FD who are candidates for early interventions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Background. Bisphosphonate is currently considered one of the drugs for the first-line treatment of osteoporosis because of its ability to inhibit bone resorption, but the molecular mechanism of its effect on osteocyte proliferation and bone formation of diabetic osteoporosis is still unclear. Objective. To confirm the potential effect on of bisphosphonate on osteocyte proliferation and bone formation in patients having diabetic osteoporosis (DO). Methods. Sixty DO patients admitted to our hospital from February 2019 to April 2021 were randomly selected and divided into the bisphosphonate group and the control group. The total incidence, incidence of hip fracture, efficacy, bone mineral density, osteocalcin, pain score, osteocyte proliferation, bone formation index, serum calcium, and phosphorus contents were compared between two groups. Results. The curative effect of bisphosphonic acid group was better than that of control group, and the difference was statistically significant ( P < 0.05 ). Compared with the control group, the bone mineral density and osteocalcin in the bisphosphonic acid group were significantly improved after treatment, and the pain score in the bisphosphonic acid group was significantly lower than that in the control group ( P < 0.05 ). After intervention treatment, the OD and PINP values in the bisphosphonate group were significantly different from those in the control group ( P < 0.05 ). After treatment, the contents of serum calcium and phosphorus in the bisphosphonic acid group were significantly higher than those in the control group ( P < 0.05 ). The incidence of hip fracture, spinal fracture, and other fractures in the bisphosphonic acid group was significantly lower than that in the control group ( P < 0.05 ). Conclusion. The treatment of DO with bisphosphonate is capability of effectively improving bone cell proliferation and bone formation, further alleviating clinical symptoms and promoting the improvement of the disease.

Osteocalcin, an osteoblast-derived hormone, is associated with the development of osteoporosis and arteriosclerosis in the general population. However, its role on the pathogenesis of osteoporosis and vascular calcification in patients with chronic kidney disease (CKD) is unclear. Here, we investigated the connection between osteocalcin, bone mineral density (BMD), and abdominal aortic calcification (AAC) in CKD patients.In total, 95 patients with stage 2 to stage 5 CKD were enrolled. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. BMD was determined by dual-energy X-ray absorptiometry, and AAC scores were generated from lateral lumbar radiograph findings.95 patients were assigned into normal bone density (30.5%, n = 29), osteopenia (45.3%, n = 43), and osteoporosis (24.2%, n = 23) groups. The osteoporosis group was characterized by older age, higher female-to-male ratio, phosphorous levels, calcification scores, osteocalcin levels, and intact parathyroid hormone (PTH) levels, while with lower hemoglobin levels as compared to normal and osteopenia groups. Multivariate multinominal regression analysis showed age, female sex, intact PTH, and serum osteocalcin level were independent determinants of osteoporosis severity in CKD patients. Furthermore, serum osteocalcin level is positively correlated to intact PTH in multivariate linear regression model, indicating that osteocalcin might be a bone turnover marker in patients with CKD. Multivariate stepwise linear regression analysis revealed that age, diabetes mellitus, poorer renal function, rather than osteocalcin, have independent associations with AAC score.Elevated serum osteocalcin levels could be considered as a marker of osteoporosis rather than that of vascular calcification in patients with CKD.

To investigate the changes in bone mineral density, bone metabolism, and efficacy of nutritional intervention combined with calcium carbonate D3 tablets in patients with osteoporosis, a RevMan 5.2 software meta-analysis was conducted in this study. According to the therapeutic direction of nutritional intervention combined with calcium carbonate D3 tablets for osteoporosis patients, relevant literature were searched in Wanfang Medical, CNKI, VIP, and PubMed literature databases at home and abroad. Keywords included bone mineral density, bone metabolism, blood calcium (Ca), blood phosphorus (P), osteocalcin (OC), bone mineral density (BMD), serum alkaline phosphatase (ALP), efficacy, osteoporosis, and nutritional intervention. Literature that met the criteria were deleted, and meta-analysis was performed using RevMan 5.2 software. The results indicate that a total of 10 Chinese literature were included. Compared with the monotherapy group, the clinical efficacy, osteocalcin, BMD, alkaline phosphatase, calcium, and phosphorus were significantly higher in the combination group (P

Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed.To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up.We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis.Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation.This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.

To investigate the relationship between estimated glucose disposal rate (eGDR) and bone turnover markers in patients with type 2 diabetes mellitus (T2DM).This is a cross-sectional study, which recruited 549 patients with T2DM. The eGDRs of patients were calculated based on the presence of hypertension, glycated hemoglobin, and body mass index. All patients were divided into high-eGDR group and low-eGDR group using the median of eGDR as the boundary. The patients were further divided into two subgroups: males and postmenopausal females.The lower the eGDR, the more severe was insulin resistance. The levels of osteocalcin (OC), type I collagen carboxyl-terminal peptide (β-CTX), and type I procollagen amino-terminal peptide (PINP) were significantly lower in the low-eGDR group than those in the high-eGDR group. The eGDR was positively correlated with OC, β-CTX, and PINP in all patients, and in the male subgroups. In the postmenopausal female subgroup, there was no correlation between eGDR and OC, β-CTX, or PINP. In addition, this positive correlation remained after adjusting for other factors in multilinear regression analysis.Our study was the first to demonstrate that eGDR is positively correlated with bone turnover markers in patients with T2DM. This correlation was observed among the male patients with T2DM but not among postmenopausal female patients with T2DM.

Background. In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. Methods. Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. Results. Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats ( P < 0.05 ). After castration, captopril decreased serum Ang II concentration ( P < 0.05 ); in female rats, icatibant increased serum Ang II concentration ( P < 0.05 ). Captopril increased serum bradykinin concentration ( P < 0.05 ); in male rats, icatibant decreased serum bradykinin concentration ( P < 0.05 ). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration ( P < 0.05 ). Icatibant decreased urine DPD/Cr in male rats ( P < 0.05 ) and increased osteocalcin concentration in female rats ( P < 0.05 ). Captopril increased cancellous BMD in castrated hypertensive rats ( P < 0.05 ), and icatibant further increased cancellous BMD ( P < 0.05 ), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength ( P < 0.05 ), and icatibant further improved it ( P < 0.05 ). Conclusion. ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.

Osteocalcin has been shown to have an inverse relationship with blood glucose, insulin resistance and adiposity.To determine osteocalcin normal serum concentration in Mexican healthy adults and compare it with values reported in other populations.Carboxylated and undercarboxylated osteocalcin serum concentrations were determined in 100 healthy adults by means of enzyme immunoassay; osteocalcin total concentration was calculated. A descriptive comparison was made with other populations' values reported in the literature.Carboxylated and undercarboxylated osteocalcin median concentrations were 3.22 ng/mL and 1.61 ng/mL, respectively. Mean total osteocalcin was 7.40 ± 5.11 ng/mL. There was no significant difference between the osteocalcin values in our population and those of populations where similar quantification methods to ours were used.Osteocalcin total serum concentration mean in the analyzed population was 7.40 ng/mL. There are subtle variations between populations that are attributable to genetic and population factors; however, the quantification method was the only variable that was shown to significantly influence on osteocalcin levels in healthy populations.Se ha demostrado que la osteocalcina tiene una relación inversa con la glucemia, resistencia a la insulina y adiposidad.Determinar la concentración sérica normal de osteocalcina en adultos sanos mexicanos y compararlos con los reportados en otras poblaciones.Se determinó la concentración sérica de osteocalcina carboxilada y pobremente carboxilada en 100 adultos sanos mediante inmunoensayo enzimático; se calculó la concentración de osteocalcina total. Se hizo una comparación descriptiva con valores de otras poblaciones reportadas en la literatura.Las medianas de las concentraciones de osteocalcina carboxilada y pobremente carboxilada fueron 3.22 ng/mL y 1.61 ng/mL, respectivamente; la media de osteocalcina total fue 7.40 ± 5.11 ng/mL. No hubo diferencia significativa entre los valores de osteocalcina total en nuestra población y los de poblaciones en las que se utilizaron métodos de cuantificación similares al nuestro.La concentración sérica promedio de osteocalcina total en la población analizada fue de 7.40 ng/mL. Las variaciones sutiles entre poblaciones son atribuibles a factores genéticos y poblacionales, sin embargo, el método de cuantificación fue el único que se comprobó influye significativamente en los niveles de osteocalcina en poblaciones sanas.

Objectives Diabetes mellitus (DM) is widely known to have a detrimental effect on bone health and is associated with increased fracture risk. Recently, the Wnt/beta-catenin signaling pathway and its inhibitors sclerostin and dickkopf-1 (Dkk-1) were found to be involved in the control of bone mass. The present study aimed to measure serum sclerostin and Dkk-1 protein levels in children and adolescents with type-1 DM and compare with other bone turnover markers and bone mineral density (BMD). Methods This study was performed on 40 children and adolescents with type-I DM and 40 healthy children and adolescents. Anthropometric measurements and pubertal examination were done. In addition to laboratory analysis, dickkopf-1, sclerostin, cross-linked N-telopeptides of type I collagen (NTx), bone alkaline phosphatase (bALP), and osteocalcin levels were studied. BMD of the participants was measured by calcaneus ultrasonography. Results Dickkopf-1 levels of the children and adolescents with type-1 DM were significantly higher, vitamin D, NTx, osteocalcin, and phosphorus levels were significantly lower than those of the controls (p Conclusions Both bone remodeling and its compensatory mechanism bone loss are lower in children and adolescents with type-1 DM than in the controls. Also, higher levels of Dkk-1 play a role in decreased bone turnover in these patients. Since Dkk-1 and sclerostin seem to take a role in treating metabolic bone diseases in the future, we believe that our findings are significant in this respective.

Pathogenesis and endothelial function in subclinical hypogonadism (SCH) remain unclear. Undercarboxylated osteocalcin (ucOC) participates in atherosclerosis and reproduction. We explored the underlying mechanisms and interplay of endothelial dysfunction, unOC and reproductive hormones in SCH and primary late-onset hypogonadism (LOH).In the SCH, LOH, and healthy eugonadal male groups, we measured serum unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product, and estradiol/T (E/T) as indicators of impaired Leydig cells, androgen sensitivity index (ASI), and aromatase activity, respectively (LH set-point regulators), and assessed flow-mediated dilation of the brachial artery (FMD%), carotid-intima media thickness (CIMT), and aortic stiffness (AS).↑LH/T, ↑ASI, ↓aromatase activity, normal T, follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels, ↑unOC, and enhanced atherosclerotic markers (↓FMD%, ↑CIMT, ↑AS) are characteristics of SCH. Testosterone was positively correlated with FMD% in SCH. The independent predictors were: SHBG and LH for FMD% and CIMT, respectively, and LH/T, ucOC, FSH, estradiol, and E/T ratio for AS in the LOH group; and LH for FMD%AS and LH and LH/T for CIMT in all study subjects.SCH is a distinct clinical entity characterized by impaired androgen sensitivity and aromatase activity, compensatory elevated unOC, endothelial dysfunction, and anti-atherogenic role of testosterone.

The purpose of this research was to investigate the in vitro osteogenic induction of MG-63 cells using topography and collagen protein printed on polydimethyl siloxane (PDMS).ALKALINE PHOSPHATASE (ALP) assay, calcium content, alizarin red staining, immunocytochemistry (ICC), and real-time polymerase chain reaction (PCR) were used to evaluate the osteo-differentiation of human adipose stem cells on the MG-63 cell pattern, MG-63 cells/collagen pattern, and collagen pattern. Also, the differentiated cell shape was studied by crystal violet staining and scanning electron microscopy (SEM).Our results showed that calcium content and ALP activity increased significantly on the MG-63 cells /collagen pattern (P 0.05). The gene expression analysis (ALKALINPHOSPHATASE, COLLAGEN1 and OSTEOCALCIN) and bone marker protein expression (OSTEOCALCIN) confirmed the osteo differentiation of adipose stem cells (ADSCs) seeded on the imprinting substrate.Cell and molecular printing enhanced osteogenic development of adipose stem cells, according to our findings.

To compare concentration and release kinetics of osteocalcin and crestal bone loss under immediate and delayed loading conditions during osseointegration.Forty-one patients who were indicated for rehabilitation with dental implants randomly received either implant with placement of permanent prosthesis after 3 months (delayed loading) or implant with placement of permanent prosthesis within 7 days (immediate loading). Radiographic assessment of crestal bone loss at the mesial and distal surface was done at 3, 6, and 12 months after implant placement. Peri-implant sulcular fluid was collected immediately from the buccal surface at two sites after implant insertion and also, at 7, 15, 30, and 90 days after surgery. The level of osteocalcin was evaluated using ELISA and data were compared using two sample t-test. Differences between two groups were analyzed by unpaired Student's t test. Intragroup comparison was done by repeated measures ANOVA.Mean crestal bone loss was lower in the immediate loading group compared to the delayed loading group at 3, 6, and 12 months (p0.001). Intragroup comparison revealed a statistically significant increase in osteocalcin levels in both group I (delayed loading) (F = 26712.2) and group II (immediate loading) (F = 10497.2) at the predetermined time intervals.Less crestal bone loss and early release of osteocalcin was found in the immediately loaded group than in the delayed loaded group. The study substantiates that immediately loaded implants show less crestal bone as well as early release of osteocalcin facilitating upregulation of bone metabolism, improving long term health of bone and prognosis of implants. Immediately loaded implants can be a better treatment protocol provided there is adequate bone and primary stability.

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR).

The fruit of Prunus mume (ume, also known as Japanese apricot) has been used as a functional food in Japan since ancient times. We previously reported that ume stimulates the differentiation of preosteoblastic cells. Osteocalcin (OCN) is secreted by osteoblasts, and there is known association with glucolipid metabolism and cognitive function. This study sought to clarify the relationship between ume extracts and OCN production both in vitro and in vivo. Alkaline phosphatase activity and OCN level in the ethyl acetate extracts of ume-treated extracts were significantly increased in preosteoblast MC3T3-E1 cells compared with the control group. In human study, serum OCN level was significantly higher in the high ume intake group than in the low intake group in community-dwelling participants over 60 years old. These results suggest that ume has the potential to upregulated OCN production both in vitro and in vivo.

Purpose The effects of aerobic exercise on bone metabolism are still unclear. Thus, the main goal of this study was to explore if there was an effect of the short-term aerobic exercise program on the bone remodeling process and if there were sex differences in the effect of the training program on bone metabolism. Methods Twenty-one participants (men and women) aged 20–23 performed an 8-week aerobic exercise program three times per week in 1-h sessions with increases in the exercise load every 2 weeks. Bone density, bone mineral content and concentration of markers of bone metabolism: osteocalcin, C-terminal procollagen type I peptide, pyridinoline, parathyroid hormone, osteoprotegerin, and the receptor activator of nuclear kappa B ligand by ELISA were measured at the start and at the end of the study, while changes in body composition were assessed by a bioelectric impedance analysis method 6 times during the study. Results The aerobic exercise program increased the concentration of osteocalcin (11.34 vs 14.24 ng/ml), pyridinoline (67.51 vs 73.99 nmol/l), and the receptor activator of nuclear kappa B ligand (95.122 vs 158.15 pg/ml). A statistically significant increase in bone density at neck mean (1.122 vs 1.176 g/cm3) and in bone mineral content at dual femur (33.485 vs 33.700 g) was found in women, while there was no statistically significant change at any site in men. Conclusion 8 weeks of the aerobic exercise program with increment in intensity increased some of bone remodeling biomarkers and showed different effects for men and women.

The goal of this study was to determine the bone turnover marker (BTM) response to insufficient and subsequent recovery sleep, independent of changes in posture, body weight, and physical activity.Healthy men (N = 12) who habitually slept 7-9 h/night were admitted to an inpatient sleep laboratory for a baseline 8 h/night sleep opportunity followed by six nights of insufficient sleep (5 h/night). Diet, physical activity, and posture were controlled. Serum markers of bone formation (osteocalcin, PINP) and resorption (β-CTX) were obtained over 24 h at baseline and on the last night of sleep restriction, and on fasted samples obtained daily while inpatient and five times after discharge over 3 weeks. Maximum likelihood estimates in a repeated measures model were used to assess the effect of insufficient and subsequent recovery sleep on BTM levels.There was no statistically or clinically significant change in PINP (p = 0.53), osteocalcin (p = 0.66), or β-CTX (p = 0.10) in response to six nights of insufficient sleep. There were no significant changes in BTMs from the inpatient stay through 3 weeks of recovery sleep (all p [Formula: see text] 0.63). On average, body weight was stable during the inpatient stay (Δweight = - 0.55 ± 0.91 kg, p = 0.06).No significant changes in serum BTMs were observed after six nights of insufficient or subsequent recovery sleep in young healthy men. Changes in weight and physical activity may be required to observe significant BTM change in response to sleep and circadian disruptions. Clinical Trials Registration Registered at ClinicalTrials.gov (NCT03733483) on November 7, 2018.

Objective. Diabetes is a chronic disease caused by defective insulin secretion in the body, resulting in metabolic abnormalities with persistent blood glucose elevation. Osteoporosis is the most common diabetes complication. The aim of this study was to perform a meta-analysis of the effects of alendronate combined with atorvastatin compared with alendronate alone in the treatment of osteoporosis in diabetes mellitus. Methods. Two researchers independently used PubMed, ScienceDirect, Cochrane Library, Wanfang Data, CNKI, and VIP databases to search for all relevant studies that met the inclusion criteria and used RevMan 5.3 and STATA 16.0 for data analysis. Results. Fourteen studies that met the inclusion criteria were selected, including 1456 patients. Among the data extracted in this meta-analysis, bone mineral density (BMD) was the primary outcome measurement, while total effective rate, VAS, osteoprotegerin (OPG), bone Gla protein (BGP), bone alkaline phosphatase (BAP), blood P and Ca, and adverse effects were secondary outcome measurements. Our results showed that alendronate combined with atorvastatin is more effective than alendronate alone, with higher BMD, OPG, BGP, and BAP, more significant pain relief, and fewer adverse events. Conclusion. The results of this meta-analysis indicate that alendronate combined with atorvastatin is a better treatment for osteoporosis in diabetes mellitus, showing more effective and higher BMD and fewer adverse events than alendronate alone.

Objectives. To investigate the effect of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its molecular mechanism. Methods. After TSG treatment of rBMSCs, alkaline phosphatase (ALP) activity was compared between the drug treatment group and the control group. The effects of TSG on alkaline phosphatase positive cloning and mineralized nodule formation were also detected. Total mRNA and protein were extracted, and the effects of TSG on the expression levels of osteopontin (OPN), osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), Osterix, and Col1a1 were detected by real-time fluorescence quantitative PCR. Western blotting was used to detect the inhibitory effect of TSG on KDM5A. BMSCs were transfected with small interfering RNA (siRNA) targeting KDM5A (si-KMD5A) and pcDNA3.1 KMD5A. Results. TSG significantly increased the activity of ALP, the number of alkaline phosphatase clones, and calcified nodule formation. The OPN, OCN, Runx2, and Osterix expression levels were significantly increased among the osteoblasts after TSG treatment. A mechanistic study showed that the effect of TSG is realized by inhibiting KDM5A. Conclusions. KDM5A signaling may be involved in the regulation of osteogenic differentiation of rBMSCs. TSG can promote osteogenic differentiation and maturation of rBMSCs at 0.1–50 μmol/L. The mechanism of action was realized by inhibiting the expression of KDM5A.

BACKGROUNDS Alveolar bone and cementum share many biological and developmental similarities. The mineralizing effect of calcitriol has been previously reported. Yet, its cementoinductivity has not been confirmed. This study evaluated the potential cementoinductivity effect of calcitriol and enamel matrix derivative (EMD) on human periodontal ligament-ligament derived cells (hPDCs). METHODS Human PDCs obtained from extracted third molars or premolars were cultured with calcitriol, or EMD. Cementogenic gene expression was examined using RT-qPCR. Expression analysis also included cementoblast-specific markers, Cementum Protein 1 (CEMP1), cementum attachment protein (CAP), and recently reported cementoblast-enriched genes, secreted frizzled related protein 1 (SFRP1), and Dickkopf-related protein 1 (DKK1). Mineralization capacities were evaluated by alkaline phosphatase (ALP) activity, Alizarin Red and Von Kossa staining followed by scanning electron microscope imaging and element mapping. RESULTS Among tested conditions, 10 nM calcitriol enhanced most cementogenic gene expression, Trans-forming growth factor-β1 (TGF-β1), bone morphogenetic proteins (BMP-2 and BMP-4), Core-binding factor subunit alpha-1/Runt-related transcription factor 2 (Cbfa1/RUNX2), Type I collagen (Col-1), Alkaline phosphatase (ALP), Bone sialoprotein (BSP), osteopontin (OPN/SPP1), osteocalcin (OCN), CEMP1 and CAP, and Wnt signaling negative modulators, SFRP1 and DKK1, along with highest ALP activity and mineralization formation in hPDCs. However, only moderate CEMP-1 protein was observed. In contrast, EMD stimulated stronger CEMP-1 and CAP protein, but presented weaker mineralization capacity, hinting at the possibility that strong stimulation of mineralization might dominate cemetogenic specific factors and vice versa. CONCLUSION Calcitriol demonstrated not only great osteoinductivity, but also the potential to induce cementogenic gene expression by initiating hPDC differentiation and promoting mineralization. Compared to calcitriol, EMD promoted cementoinductivity in hPDCs at a later time point via highly expressed CEMP1 and CAP protein, but with less mineralization. Thus, calcitriol and EMD could provide differential enhancement of cementoinduction and mineralization, likely acting at various differentiation stages. This article is protected by copyright. All rights reserved.

The present study compared the first (EC1) and second (EC2) bouts of whole-body eccentric exercises to examine the effects of the magnitude of muscle damage on changes in blood bone markers. Fifteen sedentary young men performed nine eccentric exercises of arm, leg, and trunk muscles, and repeated them 2 weeks later. Blood samples were taken before and 2 h and 1-5 days following each bout to analyze plasma creatine kinase (CK) activity and myoglobin concentration, serum tartrate-resistant acid phosphatase (TRAP), type 1 C-terminal telopeptide (CTX-1), procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BAP), undercarboxylated-osteocalcin (ucOCN), carboxylated-osteocalcin (cOCN), and leptin concentrations. All except ucOCN changed significantly (p 0.05) after both bouts. When comparing bouts for peak changes, P1NP (bone formation marker) and CTX-1 (bone resorption marker) increased less after EC2 (peak: 137±96% and 7±6%, respectively) than after EC1 (146 ± 80% and 30 ± 21%, respectively), whereas BAP (bone formation marker) increased more after EC2 (18 ± 16%) than after EC1 (4 ± 15%) (p 0.05). Leptin (49 ± 58%) and cOCN (14 ± 10%) increased more (p 0.05) after EC2 than after EC1 (-30 ± 15%, 9 ± 26%). Significant (p 0.05) correlations were evident between peak CK activity and peak CTX-1 (r = 0.847), P1NP (r = 0.815), BAP (r = -0.707), ucOCN (r = 0.627), cCON (r = -0.759), and leptin (r = -0.740) changes after EC1, but many of these correlations disappeared after EC2. This was also found for the relationships between other muscle damage markers (myoglobin, muscle soreness, and muscle strength) and the bone markers. It was concluded that bone turnover was affected by eccentric exercise, but muscle damage was unfavorable for bone formation.

Objective The role of circadian clock in cementogenesis is unclear. This study examines the role of REV-ERBs, one of circadian clock proteins, in proliferation, migration and mineralization of cementoblasts to fill the gap in knowledge. Methods Expression pattern of REV-ERBα in cementoblasts was investigated in vivo and in vitro. CCK-8 assay, scratch wound healing assay, alkaline phosphatase (ALP) and alizarin red S (ARS) staining were performed to evaluate the effects of REV-ERBs activation by SR9009 on proliferation, migration and mineralization of OCCM-30, an immortalized cementoblast cell line. Furthermore, mineralization related markers including osterix (OSX), ALP, bone sialoprotein (BSP) and osteocalcin (OCN) were evaluated. Results Strong expression of REV-ERBα was found in cellular cementum around tooth apex. Rev-erbα mRNA oscillated periodically in OCCM-30 and declined after mineralization induction. REV-ERBs activation by SR9009 inhibited proliferation but promoted migration of OCCM-30 in vitro. Results of ALP and ARS staining suggested that REV-ERBs activation negatively regulated mineralization of OCCM-30. Mechanically, REV-ERBs activation attenuated the expression of OSX and its downstream targets including ALP, BSP and OCN. Conclusions REV-ERBs are involved in cementogenesis and negatively regulate mineralization of cementoblasts via inhibiting OSX expression. Our study provides a potential target regarding periodontal and cementum regeneration.

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality.We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function.17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values.Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

Made available in DSpace on 2022-04-28T19:43:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The objective of this study was to identify predictors of 12-mo areal bone density accrual in different body segments, lean soft tissue, and osteogenic characteristics attributed to sports participation among adolescent girls and boys. Adolescents (Girls [n = 64], [aged = 14.7]); Boys [n = 129], [aged = 14.6]) were stratified into three groups according to their engagement in different sports (Control [n = 68], Swimming [n = 25], and Weight-bearing sports [n = 100]). Areal bone density (aBMD [g/cm²]) and lean soft tissue (LST) [kg] were measured by dual-energy x-ray absorptiometry (DXA; Lunar DPX-NT; General Electric Healthcare, Little Chalfont, Buckinghamshire, United Kingdom). The ground reaction force (GRF) index attributed to sports participation (Sport-GRF) was created considering the GRF attributed to each sport, body weight of the adolescent, and the amount of time spent in sports participation. Osteocalcin levels (ng/mL) were estimated from a venous blood sample. Multiple regression analysis showed that after adjusting for covariates, the models involving sport-GRF, LST (Δ), and osteocalcin explained 15.8% to 76.2% of the aBMD gains. Specifically in girls, OC was only associated with lower limb aBMD accrual. In boys, however, sport ground reaction forces were positively associated with total spine aBMD accrual. Furthermore, the LST (Δ) was positively associated with aBMD accrual in all body sites (β = 0.003 to 0.011) in both sexes. Increases in LST contributed significantly to gains in aBMD accrual in both sexes, being a more important predictor of changes in bone outcomes than ground reaction forces and osteocalcin. Post-Graduation Program in Movement Sciences Sao Paulo State University (UNESP) Laboratory of InVestigation in Exercise LIVE Department of Physical Education Sao Paulo State University (UNESP) Amsterdam UMC Amsterdam Public Health Research Institute Post-Graduation Program in Movement Sciences Sao Paulo State University (UNESP) Laboratory of InVestigation in Exercise LIVE Department of Physical Education Sao Paulo State University (UNESP)

MicroRNAs (miRNAs) regulate osteogenic differentiation and influence osteoporosis (OP). The aim of this study was to determine the potential role of miR-874-3p in OP. The expression levels of miR-874-3p and leptin (LEP) in the femoral neck trabeculae of 35 patients with or without OP were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of miR-874-3p or LEP on the cell proliferation and alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) levels were observed by upregulating miR-874-3p in human bone marrow mesenchymal stem cells (hBMSCs). Additionally, calcium deposition levels were evaluated using alizarin red staining (ARS). Molecular mechanisms of miR-874-3p and LEP underlying the osteogenic differentiation of hBMSCs were also evaluated using bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays. The miR-874-3p levels were significantly lower in the femoral neck trabeculae of patients with OP than those of the control group, while the opposite was observed regarding the levels of LEP. Expression levels of miR-874-3p in hBMSCs were upregulated during osteogenic differentiation, while those of LEP were downregulated. Moreover, miR-874-3p upregulation promoted ALP, RUNX2, OCN, and OSX mRNA expression, cell proliferation, and calcium deposition in hBMSCs. LEP was found to be a target gene of miR-874-3p. Overexpression of LEP inhibited the expression of osteoblast markers and reversed the effect of osteogenic differentiation induced by the upregulation of miR-874-3p. In conclusion, miR-874-3p promoted the proliferation and differentiation of hBMSCs by downregulating the expression of LEP, thus inhibiting OP. Abbreviations : miRNAs: microRNAs; OP: osteoporosis; hBMSCs: human Bone Marrow Mesenchymal stem cells; LEP: leptin; DEGs: differentially expressed genes

To investigate in vitro the impact of fibroblast growth factor 1 (FGF1) in comparison to ascorbic acid (AscA) on human periodontal ligament fibroblast (HPdLF) growth, their osteogenic differentiation, and modulation of their inflammatory reaction to mechanical stress.The influence of different concentrations of FGF1 (12.5-200 ng/mL) on growth and proliferation of HPdLF cells was analyzed over 20 days by counting cell numbers and the percentage of Ki67-positive cells. Quantitative expression analysis of genes encoding the osteogenic markers alkaline phosphatase (ALPL), Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OSP), as well as the fibroblast markers vimentin (VIM) and fibroblast-specific protein 1 (FSP1), was performed after 2 and 20 days of cultivation. Metabolic activity was determined by MTT assay. For comparison with AscA, 50 ng/mL FGF1 was used for stimulation for 2 and 20 days. Cell number, percentage of Ki67-positive cells, and expression of osteoblast- and fibroblast-specific genes were examined. Alkaline phosphatase activity was visualized by NBT/BCIP and calcium deposits were stained with alizarin red. Cytokine (IL‑6, IL‑8, COX2/PGE2) expression and secretion were analyzed by qPCR and ELISA in 6 h mechanically compressed HPdLF cultured for 2 days with FGF1 or ascorbic acid.Higher concentrations of FGF1 promoted cell proliferation upon short-term stimulation, whereas prolonged treatment induced the expression of osteogenic markers even with low concentrations. AscA promotes cell growth more markedly than FGF1 in short-term cultures, whereas FGF1 induced osteogenic cell fate more strongly in long-term culture. Both factors induced an increased inflammatory response of HPdLF to mechanical compression.Our data suggest that FGF1 promotes an osteogenic phenotype of HPdLF and limits inflammatory response to mechanical forces compared to AscA.ZIELSETZUNG: In-vitro-Evaluation des Einflusses von Fibroblastenwachstumsfaktor 1 (FGF1) im Vergleich zu Ascorbinsäure (AscA) auf das Wachstum, das osteogene Differenzierungspotenzial und die inflammatorische Stressreaktion humaner Parodontalligamentfibroblasten (HPdLF).Der Einfluss von verschiedenen Konzentrationen von FGF1 (12,5–200 ng/ml) auf das Wachstum und die Proliferation von HPdLF-Zellen wurde über 20 Tage anhand von Zellzahlen und dem Anteil an Ki67-positiven Zellen analysiert. Die quantitative Expressionsanalyse von Genen, welche für die osteogenen Marker alkalische Phosphatase (ALPL), „runt-related transcription factor 2“ (RUNX2), Osteocalcin (OCN) und Osteopontin (OSP) sowie für die Fibroblastenmarker Vimentin (VIM) und „fibroblast-specific protein 1“ (FSP1) kodieren, wurde nach 2 und 20 Tagen Kultivierung durchgeführt. Die metabolische Aktivität wurde mittels MTT-Assay bestimmt. Für den Vergleich mit AscA wurde 50 ng/ml FGF1 zur Stimulation für 2 und 20 Tage verwendet. Die Zellzahl, der Anteil Ki67-positiver Zellen und die Expression von osteoblasten- und fibroblastenspezifischen Genen wurden untersucht. Die Aktivität der alkalischen Phosphatase wurde mittels NBT/BCIP visualisiert und Kalziumablagerungen mit Alizarin-Rot angefärbt. Die Expression und die Sezernierung von Zytokinen (IL‑6, IL‑8, COX2/PGE2) wurden mittels qPCR und ELISA in 6 h mechanisch komprimierten HPdLF analysiert, die 2 Tage mit FGF1 oder Ascorbinsäure kultiviert wurden.Höhere Konzentrationen von FGF1 förderten die Zellproliferation bei Kurzzeitstimulation, während bei längerer Behandlung auch mit niedrigen Konzentrationen die Expression osteogener Marker induziert wurde. AscA förderte das Zellwachstum in Kurzzeitkulturen deutlicher als FGF1, wohingegen FGF1 den osteogenen Phänotyp bei Langzeitkultivierung stärker hervorrief. Beide Faktoren induzierten eine erhöhte inflammatorische Reaktion von HPdLF auf mechanische Kompression.Unsere Daten deuten darauf hin, dass FGF1 den osteogenen Phänotyp von HPdLF bei Langzeitkultivierung fördert und die immunologische Stressreaktion auf mechanische Kräfte im Vergleich zu AscA mindert.

Background: Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. Objectives: To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. Methods: In a 2 × 2-factorial trial, 200 healthy, 6-to 8-year-old, Danish, children with light skin (55°N) were randomized to 20 μg/d vitamin D3 or placebo and to substitute 260 g/d dairy with HP (10 g protein/100 g) or NP (3.5 g protein/100 g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. Results: In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased by 7.2 ± 14.1 nmol/L and decreased by 32.3 ± 17.5 nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4 ± 2.4 energy percentage (E%), which increased to 18.3 ± 3.4 E% with HP. There were no vitamin D-yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. Conclusions: Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20 μg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732.

The objective of this study was to assess the efficacy of calcitonin spray on bone healing following open reduction internal fixation (ORIF) of mandibular fractures. Fourteen patients were subdivided into a study group and a control group. A standardized surgical protocol for ORIF was followed. Postoperatively, salmon calcitonin nasal spray was administered to only the study group. The outcome parameters assessed were serum osteocalcin, pain, and radiographic bone healing. Serum osteocalcin was assessed pre- and postoperatively. Postoperative pain was documented using a visual analogue scale (VAS) on the 7th, 14th, 23rd, and 30th days. An orthopantomogram was used to score fracture healing at four time intervals, as follows: 1 — absence of callus; 2 — presence of minimal callus; 3 — considerable callus; and 4 — complete fusion of fracture. Pain scores were lower for the study group, with no pain from the fifth day, while the control group produced a mean score for day 5 of 2.43 ± 0.98 (p = 0.001). Mean postoperative serum osteocalcin levels were higher for the study group (67.82 ± 8.89) compared with the control group (57.69 ± 6.22; p = 0.029). Bone healing at 12 weeks postoperatively was level 4 for 28.6% of patients in the study group and level 3 for 71.4%. In comparison, 85.7% in the control group demonstrated level 3 healing, while 14.3% remained at level 2 (p = 0.462). Within the limitations of the study, it can be concluded that intranasal salmon calcitonin spray reduces postoperative pain and facilitates fracture healing, although its economic efficiency is still to be proven.