Potential Role of Bone Metabolism Markers in Kidney Transplant Recipients.

BACKGROUND: The impact of treatments, suppressing the immune system, persistent hyperparathyroidism, and other risk factors on mineral and bone disorder (MBD) after kidney transplantation is well-known. However, there is limited knowledge about their effect on bone metabolism biomarkers. This study aimed to investigate the influence of kidney transplant on these markers, comparing them to patients undergoing hemodialysis and healthy individuals. METHODS: In this cross-sectional study, three groups were included: kidney transplant patients (n = 57), hemodialysis patients (n = 26), and healthy controls (n = 31). Plasma concentrations of various bone metabolism biomarkers, including Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23, were measured. Associations between these biomarkers and clinical and laboratory data were evaluated. RESULTS: A total of 114 patients participated. Transplant recipients had significantly lower levels of Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23 compared to hemodialysis patients. Alkaline phosphatase levels positively correlated with osteopontin (r = 0.572, p < 0.001), while fibroblast growth factor 23 negatively correlated with 25-hydroxyvitamin D (r = -0.531, p = 0.019). The panel of bone biomarkers successfully predicted hypercalcemia (area under the curve [AUC] = 0.852, 95% confidence interval [CI] = 0.679-1.000) and dyslipidemia (AUC = 0.811, 95% CI 0.640-0.982) in transplant recipients. CONCLUSION: Kidney transplantation significantly improves mineral and bone disorders associated with end-stage kidney disease by modulating MBD markers and reducing bone metabolism markers, such as Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, and sclerostin. Moreover, the panel of bone biomarkers effectively predicted hypercalcemia and dyslipidemia in transplant recipients.

[Determination of reference values of CTx and NMID-Osteocalcin and their association with osteoporosis in postmenopausal chilean women]. / Determinación de rangos de BCTx y N-MID Osteocalcina y asociación con Osteoporosis en mujeres chilenas posmenopáusicas.

INTRODUCTION: Bone densitometry (BD) has high specificity in the osteoporosis diagnosis but suboptimal sensitivity to estimate fracture risk. It was proposed that bone turnover markers (BTM) could be included in the osteoporosis risk algorithm, although the extent of its association is unknown. One recommended BTM to assess bone resorption is Beta-Cross Laps (B-CTx), while a BTM to assess bone formation is osteocalcin. AIMS: To establish BCTx and N-MID osteocalcin (N-MID) ranges in postmenopausal women (PM) and compare BTM levels in two groups: control and with abnormal BD. METHODS: PM with BD within the last year were recruited. A questionnaire of risk factors for fractures was applied, and BTM was measured. Volunteers with diseases that would affect bone remodeling were excluded. RESULTS: 117 PM (57 control and 60 with abnormal BD) were recruited. 18% had osteoporosis, and the groups were comparable. The ranges for B-CTx and N-MID were 0.41 ± 0.18 [IC95% 0.37-0.45] and 22.76 ± 7.73 [IC95% 21.29-24.24] ng/mL. The mean levels of B-CTx and N-MID were higher in the group with abnormal BD (0.46 ± 0.19 and 24.29 ± 8.04 ng/mL). A moderate correlation between both BTM was found, but it was weak with abnormal BD. CONCLUSIONS: B-CTx and N-MID ranges were assessed for the first time in Chilean PM, similar to values found in other countries. Slightly higher values of BTM were found in the group with abnormal BD, which the presence of omitted secondary causes could explain. These BTM could be a complementary tool to BD and FRAX in bone evaluation.

Bone Mineral Density in Patients with Hepatic Glycogen Storage Diseases.

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9-20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ -2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ -2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.

The key research of sports in maintaining human health / A pesquisa chave do esporte na manutenção da saúde humana / La investigación clave del deporte para mantener la salud humana

ABSTRACT Introduction One of the evaluation factors of human health is bone health, and an evaluation index of bone health is osteoporosis. Sports are an effective way to improve the human body. Objective The paper discusses the effects of different exercise intensities on human bone health. Methods The thesis selected 51 female college students, designed different exercise intensities of fitness running intervention programs, and conducted a 12-month exercise intervention. We divide female college students into three groups. The subjects' bone mineral density (BMD), serum alkaline phosphatase (ALP), and serum osteocalcin (BGP) were tested before and after the experiment. Results The differences in femoral BMD, serum ALP, serum BGP, and lumbar spine BMD of the three groups of volunteers were significant (P<0.05), while the differences in ulna and radius BMD were not significant. Conclusions Sports can promote human bone health. At the same time, the effect of fitness running on human BMD is site-specific. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução Um dos fatores de avaliação da saúde humana é a saúde óssea, e um índice de avaliação da saúde óssea é a osteoporose. Os esportes são uma forma eficaz de melhorar o corpo humano. Objetivo o artigo discute os efeitos de diferentes intensidades de exercício na saúde óssea humana. Métodos A tese selecionou 51 universitárias, elaborou diferentes intensidades de exercícios em programas de intervenção de corrida de aptidão e conduziu uma intervenção de exercícios de 12 meses. Dividimos as universitárias em três grupos. A densidade mineral óssea (BMD), fosfatase alcalina sérica (ALP) e osteocalcina sérica (BGP) dos indivíduos foram testadas antes e depois do experimento. Resultados As diferenças na DMO femoral, ALP sérica, BGP sérica e DMO da coluna lombar dos três grupos de voluntários foram significativas (P <0,05), enquanto as diferenças na DMO da ulna e rádio não foram significativas. Conclusão O esporte pode promover a saúde óssea humana. Ao mesmo tempo, o efeito da corrida adaptativa na DMO humana é específico do local. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Uno de los factores de evaluación de la salud humana es la salud ósea y un índice de evaluación de la salud ósea es la osteoporosis. Los deportes son una forma eficaz de mejorar el cuerpo humano. Objetivo El artículo analiza los efectos de diferentes intensidades de ejercicio en la salud ósea humana. Métodos La tesis seleccionó a 51 estudiantes universitarias, diseñó diferentes intensidades de ejercicio de programas de intervención para correr y realizó una intervención de ejercicio de 12 meses. Dividimos a las estudiantes universitarias en tres grupos. La densidad mineral ósea (DMO), la fosfatasa alcalina sérica (ALP) y la osteocalcina sérica (BGP) de los sujetos se analizaron antes y después del experimento. Resultados Las diferencias en la DMO femoral, la ALP sérica, la BGP sérica y la DMO de la columna lumbar de los tres grupos de voluntarios fueron significativas (P <0,05), mientras que las diferencias en la DMO del cúbito y del radio no fueron significativas. Conclusión Los deportes pueden promover la salud ósea humana. Al mismo tiempo, el efecto de la actividad física en la DMO humana es específico del sitio. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Impact of metabolic syndrome and its components on bone remodeling in adolescents.

INTRODUCTION: Osteoporosis and metabolic syndrome (MetS) are diseases that have serious public health consequences, reducing the quality of life of patients and increasing morbidity and mortality, with substantial healthcare expenditures. OBJECTIVE: To evaluate the impact of MetS on bone mineral density (BMD) and biochemical markers of bone formation and resorption in adolescents with excess weight. METHOD: A descriptive and analytical cross-sectional study was performed that evaluated 271 adolescents of both sexes (10 to 16 years). From the total sample, 42 adolescents with excess weight and the presence of MetS (14%) were selected. A further 42 adolescents with excess weight and without MetS were chosen, matched for chronological age, bone age, and pubertal developmental criteria to those with MetS, for each sex. Anthropometric measurements, blood pressure collection, and biochemical tests were performed in all adolescents, as well as evaluation of BMD and the bone biomarkers osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal telopeptide (S-CTx). RESULTS: The adolescents with excess weight and MetS exhibited significantly lower transformed BMD and concentrations of BAP, OC, and S-CTx compared to the matched group, except for OC in boys. A negative and significant correlation was observed between total body BMD and BAP (r = -0.55568; p = 0.005), OC (r = -0.81760; p = < .000), and S-CTx (r = -0.53838; p = 0.011) in girls. CONCLUSION: Metabolic syndrome may be associated with reduced bone mineral density and biochemical markers of bone formation and resorption in adolescents with excess weight.

Effect of enhanced masticatory force on OPG, RANKL and MGF in alveolar bone of ovariectomized rats.

BACKGROUND: Menopause induces oral bone loss, leading to various oral diseases. Mastication importantly affects bone metabolism in the jawbone. OBJECTIVE: To analyze the effect of enhanced masticatory force on osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), and mechano-growth factor (MGF) in alveolar bone of ovariectomized rats and to study the mechanics mechanism of the alveolar bone of ovariectomized rats response to enhanced masticatory force. METHODOLOGY: Thirty Sprague Dawley rats were randomly divided into three groups: sham-operation group (fat around the removed ovary + normal hard diet), model group (ovariectomy + normal hard diet), and experimental group (ovariectomy + high hard diet). It was a 2-month experiment. Enzyme-linked immunosorbent assay (ELISA) detected serum estradiol (E2), osteocalcin (BGP) and alkaline phosphatase (ALP) in rats. Bone histomorphometric indices in the third molar region of maxilla were detected by micro-CT; protein expressions of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Western blot; and gene expression of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Quantitative Real-Time PCR. RESULTS: Comparing with model group, serum E2 in experimental group increased but not significantly, serum BGP and serum ALP in experimental group decreased but not significantly, OPG in experimental group in alveolar bone increased significantly, RANKL in experimental group in alveolar bone decreased significantly, RANKL/OPG ratio in experimental group decreased significantly, MGF in experimental group in alveolar bone increased significantly, bone volume to total volume fraction increased significantly in experimental group, trabecular thickness increased significantly in experimental group, and trabecular separation decreased significantly in experimental group. CONCLUSION: Enhanced masticatory force affected the expression of OPG, RANKL, and MGF in alveolar bone of ovariectomized rats, improved the quality of jaw bone of ovariectomized rats, and delayed oral bone loss by ovariectomy.

Prevalence and risk factors of medication-related osteonecrosis of the jaw in osteoporotic and breast cancer patients: a cross-sectional study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) has been reported as a side effect of bisphosphonate (BP). The aim of this study was to identify the prevalence of MRONJ in women taking BP for osteoporosis and for metastatic breast cancer and correlate it with risk factors and biochemical markers of bone metabolism. METHODS: Patients taking oral or intravenous BP with osteoporosis (G1; n = 153; median 72.8 years) and with metastatic breast cancer (G2; n = 134; median 58.2 years) had their hospital charts reviewed, were submitted to dental inspection, and answered a health questionnaire. Fasting blood samples were randomly collected from both groups to measure osteocalcin, carboxy-terminal cross-linking telopeptide of type I collagen, intact parathyroid hormone and procollagen type 1 amino-terminal propeptide (P1NP), 25 hydroxyvitamin D (25OHD), creatinine, and total calcium. RESULTS: G1 was older (p = 0.001) and had more cases of diabetes (p = 0.043). P1NP was higher (p = 0.022) and 25OHD lower (p = 0.004) in G2 compared with G1. MRONJ was not found in the G1, whereas 4 cases (3%) were detected in G2. Positive risk factors for MRONJ were number of BP doses and number of visits to the dentist and dental extractions. The biochemical parameters, however, could not identify those who developed MRONJ. CONCLUSIONS: The prevalence of MRONJ was 3% in women with metastatic breast cancer receiving BP. No cases were identified in women receiving oral BP chronically for osteoporosis. P1NP was higher in women with metastatic breast cancer, even during treatment with antiresorptives, but could not differentiate those with MRONJ.

Effect of enhanced masticatory force on OPG, RANKL and MGF in alveolar bone of ovariectomized rats

Abstract Menopause induces oral bone loss, leading to various oral diseases. Mastication importantly affects bone metabolism in the jawbone. Objective: To analyze the effect of enhanced masticatory force on osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), and mechano-growth factor (MGF) in alveolar bone of ovariectomized rats and to study the mechanics mechanism of the alveolar bone of ovariectomized rats response to enhanced masticatory force. Methodology: Thirty Sprague Dawley rats were randomly divided into three groups: sham-operation group (fat around the removed ovary + normal hard diet), model group (ovariectomy + normal hard diet), and experimental group (ovariectomy + high hard diet). It was a 2-month experiment. Enzyme-linked immunosorbent assay (ELISA) detected serum estradiol (E2), osteocalcin (BGP) and alkaline phosphatase (ALP) in rats. Bone histomorphometric indices in the third molar region of maxilla were detected by micro-CT; protein expressions of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Western blot; and gene expression of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Quantitative Real-Time PCR. Results: Comparing with model group, serum E2 in experimental group increased but not significantly, serum BGP and serum ALP in experimental group decreased but not significantly, OPG in experimental group in alveolar bone increased significantly, RANKL in experimental group in alveolar bone decreased significantly, RANKL/OPG ratio in experimental group decreased significantly, MGF in experimental group in alveolar bone increased significantly, bone volume to total volume fraction increased significantly in experimental group, trabecular thickness increased significantly in experimental group, and trabecular separation decreased significantly in experimental group. Conclusion: Enhanced masticatory force affected the expression of OPG, RANKL, and MGF in alveolar bone of ovariectomized rats, improved the quality of jaw bone of ovariectomized rats, and delayed oral bone loss by ovariectomy.

Upper Zone of Growth Plate and Cartilage Matrix (UCMA) Levels in Patients with Chronic Kidney Disease

Abstract Chronic kidney disease (CKD) is an important health problem across the world affecting the adult population with an enormous social and economic burden. Calcium regulation is also affected in patients with CKD, and related to several disorders including vascular calcifications, mineral bone disorders, and cardiovascular diseases (CVD). Upper zone of growth plate and cartilage matrix (UCMA) is vitamin K-dependent protein (VKDP) and acts as a calcification inhibitor in the cardiovascular system. The molecular mechanism of UCMA action remains unclear in CKD. In the current study, we aimed to investigate serum total UCMA levels and its association with calcium metabolism parameters in CKD patients including hemodialysis (HD) patients. Thirty-seven patients with CKD stage 3-5, 41 HD patients, and 34 healthy individuals were enrolled in this cross-sectional study. Serum UCMA and calcification related protein levels (Matrix Gla Protein (MGP), Osteocalcin (OC), and Fetuin-A) were analyzed with enzyme-linked immunosorbent assay (ELISA). Calcium mineral disorder parameters (Serum Ca, P, iPTH) were quantified with routine techniques. We, for the first time, report the potential biomarker role of UCMA in CKD including HD. Serum total UCMA levels were significantly higher in patients with CKD including HD patients than the healthy controls. Also, serum UCMA levels showed negative correlations with serum calcium, and eGFR, while showed positive relationships with P, iPTH, MGP, OC. Increased total UCMA levels may have a role in the Ca metabolism disorder and related to the pathogenesis of Vascular Calcification in patients with CKD.

Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health. OBJECTIVE AND RATIONALE: This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk. SEARCH METHODS: A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR). OUTCOMES: Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle-Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, -0.04; 95% CI, -0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, -0.07; 95% CI, -0.13 to -0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, -0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, -0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, -2.68; 95% CI, -4.70 to -0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls. WIDER IMPLICATIONS: On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.

Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial.

BACKGROUND: Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial. METHODS: Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6. RESULTS: Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels. CONCLUSIONS: Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice.

BACKGROUND/AIMS: Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice. METHODS: To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model. RESULTS: VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX. CONCLUSION: VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients.

OBJECTIVE: The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. METHODS: Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. RESULTS: In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. CONCLUSION: Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

A prospective study of the influence of the skeleton on calcium mass transfer during hemodialysis.

BACKGROUND: Calcium gradient, the difference between serum calcium and dialysate calcium d[Ca], is the main contributor factor influencing calcium transfer during hemodialysis. The impact, however, of bone turnover, on calcium mass transfer during hemodialysis is still uncertain. METHODS: This prospective cross-sectional study included 10 patients on hemodialysis for a 57.6±16.8 months, with severe hyperparathyroidism. Patients were submitted to 3 hemodialysis sessions using d[Ca] of 1.25, 1.5 and 1.75 mmol/l in three situations: pre-parathyroidectomy (pre-PTX), during hungry bone (early post-PTX), and after stabilization of clinical status (late post-PTX). Biochemical analysis and calcium mass transfer were evaluated and serum bone-related proteins were quantified. RESULTS: Calcium mass transfer varied widely among patients in each study phase with a median of -89.5, -76.8 and -3 mmol using d[Ca] 1.25 mmol/L, -106, -26.8 and 29.7 mmol using d[Ca] 1.50 mmol/L, and 12.8, -14.5 and 38 mmol using d[Ca] 1.75 mmol/L during pre-PTX, early post-PTX and late post-PTX, respectively, which was significantly different among d[Ca] (p = 0.0001) and among phases (p = 0.040). Ca gradient and delta of Ca also differed among d[Ca] and phases (p<0.05 for all comparisons), whether ultrafiltration was similar. Serum Osteocalcin decreased significantly in late post-PTX, whereas Sclerostin increased earlier, in early post-PTX. CONCLUSIONS: The skeleton plays a key role in Ca mass transfer during dialysis, either by determining pre-dialysis serum Ca or by controlling the exchangeable Ca pool. Knowing that could help us to decide which d[Ca] should be chosen in a given patient.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.

OBJECTIVES: Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. SUBJECTS AND METHODS: Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). RESULTS: Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. CONCLUSIONS: It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

Waist circumference is an effect modifier of the association between bone mineral density and glucose metabolism.

OBJECTIVE: The role of bone markers on insulin resistance (IR) remains controversial. The objective of this study is to evaluate the association between bone mineral density (BMD) and glucose metabolism and investigate if visceral hyperadiposity, evaluated by waist circumference (WC), is an effect modifier of this association. SUBJECTS AND METHODS: Cross-sectional analysis with 468 young adults from the fourth follow-up of the 1978/79 Ribeirão Preto prospective birth cohort, Brazil. BMD, total osteocalcin (OC), fasting plasma glucose and insulin concentrations were assessed. IR, sensitivity (S) and secretion (ß) were estimated by homeostasis model assessment (HOMA) indexes. Multiple linear regression models were constructed to estimate the association between BMD and glucose metabolism. Beta coefficient, R2 and p-values were provided. WC was tested as an effect modifier and OC as a confounder. The covariates were selected based on Direct Acyclic Graph. RESULTS: Significant interaction between BMD (femoral neck and proximal femur areas) and WC on glucose metabolism was observed in the adjusted models. Subjects with increased WC presented a positive association between BMD and log HOMA1-IR while an inverse association was found in those with normal WC (femoral neck R2 = 0.17, p = 0.036; proximal femur R2 = 0.16, p = 0.086). BMD was negatively associated with log HOMA2-S in individuals with increased WC and positively in those with normal WC (femoral neck R2 = 0.16, p = 0.042; proximal femur R2 = 0.15, p = 0.097). No significant associations between BMD, log HOMA2-ß and OC and glucose metabolism markers were observed. CONCLUSIONS: BMD was associated with glucose metabolism, independently of OC, and WC modifies this association.

Osteocalcin levels in a healthy population of western Mexico and comparison with populations from around the world. / Niveles de referencia de osteocalcina en población sana de México.

Introduction: Osteocalcin has been shown to have an inverse relationship with blood glucose, insulin resistance and adiposity. Objective: To determine osteocalcin normal serum concentration in Mexican healthy adults and compare it with values reported in other populations. Method: 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. Results: 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. Conclusion: 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.

Introducción: Se ha demostrado que la osteocalcina tiene una relación inversa con la glucemia, resistencia a la insulina y adiposidad. Objetivo: Determinar la concentración sérica normal de osteocalcina en adultos sanos mexicanos y compararlos con los reportados en otras poblaciones. Método: 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. Resultados: 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. Conclusión: 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.

Waist circumference is an effect modifier of the association between bone mineral density and glucose metabolism

ABSTRACT Objective: The role of bone markers on insulin resistance (IR) remains controversial. The objective of this study is to evaluate the association between bone mineral density (BMD) and glucose metabolism and investigate if visceral hyperadiposity, evaluated by waist circumference (WC), is an effect modifier of this association. Subjects and methods: Cross-sectional analysis with 468 young adults from the fourth follow-up of the 1978/79 Ribeirão Preto prospective birth cohort, Brazil. BMD, total osteocalcin (OC), fasting plasma glucose and insulin concentrations were assessed. IR, sensitivity (S) and secretion (β) were estimated by homeostasis model assessment (HOMA) indexes. Multiple linear regression models were constructed to estimate the association between BMD and glucose metabolism. Beta coefficient, R2 and p-values were provided. WC was tested as an effect modifier and OC as a confounder. The covariates were selected based on Direct Acyclic Graph. Results: Significant interaction between BMD (femoral neck and proximal femur areas) and WC on glucose metabolism was observed in the adjusted models. Subjects with increased WC presented a positive association between BMD and log HOMA1-IR while an inverse association was found in those with normal WC (femoral neck R2 = 0.17, p = 0.036; proximal femur R2 = 0.16, p = 0.086). BMD was negatively associated with log HOMA2-S in individuals with increased WC and positively in those with normal WC (femoral neck R2 = 0.16, p = 0.042; proximal femur R2 = 0.15, p = 0.097). No significant associations between BMD, log HOMA2-β and OC and glucose metabolism markers were observed. Conclusions: BMD was associated with glucose metabolism, independently of OC, and WC modifies this association.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy

ABSTRACT Objectives: Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. Subjects and methods: Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). Results: Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. Conclusions: It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.