RESUMEN
INTRODUCTION: Takayasu's arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. OBJECTIVES: To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. METHODS: This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. RESULTS: In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. CONCLUSION: No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.
Asunto(s)
Biomarcadores , Osteoprotegerina , Polimorfismo de Nucleótido Simple , Arteritis de Takayasu , Humanos , Arteritis de Takayasu/genética , Arteritis de Takayasu/sangre , Osteoprotegerina/sangre , Osteoprotegerina/genética , Estudios Transversales , Femenino , Masculino , Adulto , Estudios de Casos y Controles , Biomarcadores/sangre , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.
Asunto(s)
Remodelación Ósea , Periodontitis , Gases em Plasma , Animales , Periodontitis/terapia , Periodontitis/patología , Periodontitis/sangre , Gases em Plasma/uso terapéutico , Ratas , Masculino , Modelos Animales de Enfermedad , Inflamación , Encía/patología , Ligamento Periodontal/patología , Interleucina-1beta/sangre , Interleucina-1beta/análisis , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/análisis , Interleucina-10/sangre , Interleucina-10/análisis , Ligando RANK/análisis , Ligando RANK/sangre , Ratas Wistar , Osteoprotegerina/análisis , Osteoprotegerina/sangreRESUMEN
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.
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Biomarcadores , Huesos , Factor-23 de Crecimiento de Fibroblastos , Trasplante de Riñón , Osteocalcina , Humanos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios Transversales , Adulto , Huesos/metabolismo , Osteocalcina/sangre , Osteoprotegerina/sangre , Diálisis Renal , Factores de Crecimiento de Fibroblastos/sangre , Osteopontina/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
High serum levels of osteoprotegerin (OPG) are found in patients with obesity, type 2 diabetes, sepsis, or septic shock and are associated with a high mortality rate in stroke. The primary known function of OPG is to bind to the receptor activator of NF-κB ligand (RANKL), and by doing so, it inhibits the binding between RANKL and its receptor (RANK). TLR4 signaling in macrophages involves TRAF6 recruitment and contributes to low-grade chronic inflammation in adipose tissue. LPS is a classical activator of the TLR4 pathway and induces the expression of inflammatory cytokines in macrophages. We have previously observed that in the presence of RANKL, there is no LPS-induced activation of TLR4 in macrophages. In this study, we investigated the crosstalk between RANK and TLR4 pathways in macrophages stimulated with both RANKL and LPS to unveil the role of OPG in inflammatory processes. We found that RANKL inhibits TLR4 activation by binding to RANK, promoting the binding between TRAF6 and RANK, lowering TLR4 activation and the expression of proinflammatory mediators. Furthermore, high OPG levels aggravate inflammation by inhibiting RANKL. Our findings elect RANKL as a candidate for drug development as a way to mitigate the impact of obesity-induced inflammation in patients.
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Macrófagos , Osteoprotegerina , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Factor 6 Asociado a Receptor de TNF , Receptor Toll-Like 4 , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Obesidad/genética , Obesidad/metabolismo , Osteoprotegerina/sangre , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/genética , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismoRESUMEN
BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.
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Artritis Reumatoide/sangre , Remodelación Ósea/fisiología , Osteoporosis/sangre , Fracturas Osteoporóticas/diagnóstico , Osteoprotegerina/sangre , Ligando RANK/sangre , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Biomarcadores/sangre , Densidad Ósea , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/etiología , Osteoporosis/patología , Fracturas Osteoporóticas/sangre , Fracturas Osteoporóticas/etiología , Posmenopausia/sangre , PronósticoRESUMEN
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG), known to regulate bone mass by inhibiting osteoclast differentiation and activation, might also play a role in vascular calcification. Increased circulating OPG levels in patients with CKD are associated with aortic calcification and increased mortality. We assessed the predictive role of OPG for all-cause and cardiovascular mortality in patients with CKD stages 3-5 over a 5-year follow-up period. We evaluated the relationship between OPG and all-cause and cardiovascular mortality in 145 CKD patients (stages 3-5) in a prospective observational follow-up study. Inflammation markers, including high-sensitivity C-reactive protein, standard echocardiography, and estimation of intima-media thickness in the common carotid artery, were assessed at baseline, and correlations with OPG levels were determined. The cutoff values for OPG were defined using ROC curves for cardiovascular mortality. Survival was assessed during follow up lasting for up to 5.5 years using Fine and Gray model. A total of 145 (89 men; age 58.9 ± 15.0 years) were followed up. The cutoff value for OPG determined using ROC was 10 pmol/L for general causes mortality and 10.08 pmol/L for CV causes mortality. Patients with higher serum OPG levels presented with higher mortality rates compared to patients with lower levels. Aalen-Johansen cumulative incidence curve analysis demonstrated significantly worse survival rates in individuals with higher baseline OPG levels for all-cause and cardiovascular mortality (p < 0.001). In multivariate analysis, OPG was a marker of general and cardiovascular mortality independent of sex, age, CVD, diabetes, and CRP levels. When CKD stages were included in the multivariate analysis, OPG was an independent marker of all-cause mortality but not cardiovascular mortality. Elevated serum OPG levels were associated with higher all-cause and cardiovascular mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD.
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Enfermedades Cardiovasculares , Osteoprotegerina/sangre , Insuficiencia Renal Crónica , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidadRESUMEN
Biomarkers represent promising aids in periodontitis, host-mediate diseases of the tooth-supporting tissues. We assessed the diagnostic potential of matrix metalloproteinase-8 (MMP-8), tartrate-resistant acid phosphatase-5 (TRAP-5), and osteoprotegerin (OPG) to discriminate between healthy patients', mild and severe periodontitis sites. Thirty-one otherwise healthy volunteers with and without periodontal disease were enrolled at the Faculty of Dentistry, University of Chile. Periodontal parameters were examined and gingival crevicular fluid was sampled from mild periodontitis sites (M; n = 42), severe periodontitis sites (S; n = 59), and healthy volunteer sites (H; n = 30). TRAP-5 and OPG were determined by commercial multiplex assay and MMP-8 by the immunofluorometric (IFMA) method. STATA software was used. All biomarkers showed a good discrimination performance. MMP-8 had the overall best performance in regression models and Receiver Operating Characteristic (ROC) curves, with high discrimination of healthy from periodontitis sites (area under the curve (AUC) = 0.901). OPG showed a very high diagnostic precision (AUC ≥ 0.95) to identify severe periodontitis sites (S versus H + M), while TRAP-5 identified both healthy and severe sites. As conclusions, MMP-8, TRAP-5, and OPG present a high precision potential in the identification of periodontal disease destruction, with MMP-8 as the most accurate diagnostic biomarker.
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Periodontitis Crónica/sangre , Metaloproteinasa 8 de la Matriz/sangre , Osteoprotegerina/sangre , Periodontitis/sangre , Fosfatasa Ácida Tartratorresistente/sangre , Adulto , Biomarcadores/sangre , Periodontitis Crónica/genética , Periodontitis Crónica/patología , Diagnóstico Diferencial , Femenino , Líquido del Surco Gingival/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/genética , Periodontitis/patología , Índice de Severidad de la Enfermedad , Fosfatasa Ácida Tartratorresistente/genéticaRESUMEN
Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)
Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)
Asunto(s)
Animales , Ratas , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/inducido químicamente , Remodelación Ósea/efectos de los fármacos , Enfermedades Renales/fisiopatología , Osteoporosis/prevención & control , Enfermedades Óseas Metabólicas/diagnóstico , Dexametasona/administración & dosificación , Densidad Ósea/efectos de los fármacos , Cloroformo/uso terapéutico , Ratas Wistar , Selectina-P/efectos de los fármacos , Selectina-P/sangre , Galectina 3/efectos de los fármacos , Galectina 3/sangre , Ligando RANK/efectos de los fármacos , Ligando RANK/sangre , Osteoprotegerina/efectos de los fármacos , Osteoprotegerina/sangre , Glucocorticoides/efectos adversos , Glicerol/administración & dosificación , Enfermedades Renales/tratamiento farmacológicoRESUMEN
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.
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Colecalciferol/uso terapéutico , Factores de Crecimiento de Fibroblastos/sangre , Insuficiencia Renal Crónica/terapia , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Grosor Intima-Media Carotídeo , Suplementos Dietéticos , Método Doble Ciego , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Osteopontina/sangre , Osteoprotegerina/sangre , Hormona Paratiroidea/sangre , Diálisis Peritoneal/efectos adversos , Estudios Prospectivos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/etiologíaRESUMEN
BACKGROUND: Coronary artery calcification (CAC) and atherosclerotic inflammation associate with increased risk of myocardial infarction (MI). Vascular calcification is regulated by osteogenic proteins (OPs). It is unknown whether an association exists between CAC and plasma OPs and if they are affected by atherothrombotic inflammation. We tested the association of osteogenic and inflammatory proteins with CAC and assessed these biomarkers after MI. METHODS: Circulating OPs (osteoprotegerin, RANKL, fetuin-A, Matrix Gla protein [MGP]) and inflammatory proteins (C-reactive protein, oxidized-LDL, tumoral necrosis factor-α, transforming growth factor [TGF]-ß1) were compared between stable patients with CAC (CAC ≥ 100 AU, n = 100) and controls (CAC = 0 AU, n = 30). The association between biomarkers and CAC was tested by multivariate analysis. In patients with MI (n = 40), biomarkers were compared between acute phase and 1-2 months post-MI, using controls as a baseline. RESULTS: MGP and fetuin-A levels were higher within individuals with CAC. Higher levels of MGP and RANKL were associated with CAC (OR 3.12 [95% CI 1.20-8.11], p = 0.02; and OR 1.75 [95% CI 1.04-2.94] respectively, p = 0.035). After MI, C-reactive protein, OPG and oxidized-LDL levels increased in the acute phase, whereas MGP and TGF-ß1 increased 1-2 months post-MI. CONCLUSIONS: Higher MGP and RANKL levels associate with CAC. These findings highlight the potential role of these proteins as modulators and markers of CAC. In addition, the post-MI increase in OPG and MGP, as well as of inflammatory proteins suggest that the regulation of these OPs is affected by atherothrombotic inflammation.
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Proteínas de Unión al Calcio/sangre , Enfermedad de la Arteria Coronaria/metabolismo , Proteínas de la Matriz Extracelular/sangre , Infarto del Miocardio/metabolismo , Osteoprotegerina/sangre , Ligando RANK/sangre , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/etiología , Factor de Crecimiento Transformador beta1/sangre , Factor de Necrosis Tumoral alfa/sangre , alfa-2-Glicoproteína-HS/metabolismo , Proteína Gla de la MatrizRESUMEN
The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration. INTRODUCTION: Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters. METHODS: PBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3 weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated. RESULTS: PBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration. CONCLUSION: Monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.
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Monocitos/patología , Osteoclastos/patología , Osteoprotegerina/sangre , Ligando RANK/sangre , Espondilitis Anquilosante/sangre , Adulto , Apoptosis/fisiología , Densidad Ósea/fisiología , Estudios de Casos y Controles , Diferenciación Celular/fisiología , Células Cultivadas , Colágeno Tipo I/sangre , Citocinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , Espondilitis Anquilosante/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). METHODS: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. RESULTS: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). CONCLUSION: OPG was the strongest risk factor associated with new development and rapid progression of AC in incident PD patients.
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Fallo Renal Crónico/terapia , Osteoprotegerina/sangre , Diálisis Peritoneal/efectos adversos , Calcificación Vascular/sangre , Adulto , Factores de Edad , Aorta Abdominal/patología , Biomarcadores/sangre , Diabetes Mellitus/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , México/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Calcificación Vascular/etiología , Adulto JovenRESUMEN
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated ß-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.
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Remodelación Ósea , Huesos/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Osteocitos/metabolismo , Insuficiencia Renal Crónica/sangre , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Biomarcadores/sangre , Biopsia , Proteínas Morfogenéticas Óseas/metabolismo , Huesos/patología , Calcio/sangre , Estudios de Casos y Controles , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/terapia , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Osteocitos/patología , Osteoprotegerina/sangre , Hormona Paratiroidea/sangre , Fosforilación , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Diálisis Renal , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Índice de Severidad de la Enfermedad , beta Catenina/metabolismoRESUMEN
PURPOSE: Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa ß ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. MATERIALS AND METHODS: This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB). Anthropometric data, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), collagen type 1 C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-VitD), leptin, adiponectin, RANKL, OPG, and sclerostin of 30 menstruating women were measured preoperatively (Pre), and 3, 12, and 24 months (m) after RYGB. RESULTS: Leptin (34.4 (14.7; 51.9) vs. 22.5 (1.9; 52.7) ng/mL) and OPG (3.6 (1.1; 11.5) vs. 3.4 (1.5; 6) pmol/L) decreased, and adiponectin (7.4 (1.7; 18.4) vs. 13.8 (3.0; 34.6) µg/mL), CTX (0.2 (0.1; 2.2) vs. 0.6 (0.4; 6.0) ng/mL), RANKL (0.1 (0.0; 0.5) vs. 0.3 (0.0; 2.0) pmol/L), and sclerostin (21.7 (3.2; 75.1) vs. 34.8 (6.4; 80.5) pmol/L) increased after 3 m. BSAP increased after 12 m (10.1 (5.4; 18.9) vs. 13.9 (6.9; 30.2) µg/mL) (p < 0.005). CTX correlated positively with adiponectin at 24 m and inversely with leptin Pre; OPG at 3 m; weight, FM, FFM, and leptin at 24 m. RANKL correlated directly with weight at 3 m. Sclerostin correlated inversely with weight Pre and FM at 3 m. BSAP correlated negatively with 25-OH-VitD at 12 m, and positively with PTH at 24 m. CONCLUSIONS: RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.
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Adipocitos/metabolismo , Adipoquinas/metabolismo , Proteínas Morfogenéticas Óseas/biosíntesis , Remodelación Ósea/fisiología , Derivación Gástrica , Obesidad/cirugía , Osteoprotegerina/biosíntesis , Ligando RANK/biosíntesis , Proteínas Adaptadoras Transductoras de Señales , Adipoquinas/sangre , Adulto , Antropometría , Biomarcadores/sangre , Biomarcadores/metabolismo , Proteínas Morfogenéticas Óseas/sangre , Femenino , Marcadores Genéticos , Humanos , Persona de Mediana Edad , Obesidad/sangre , Obesidad/metabolismo , Osteoprotegerina/sangre , Estudios Prospectivos , Ligando RANK/sangre , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. INTRODUCTION: Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. METHODS: Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. RESULTS: The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). CONCLUSION: This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.
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Aorta/patología , Calcinosis/patología , Osteoprotegerina/genética , Ligando RANK/genética , Fracturas de la Columna Vertebral/genética , Anciano , Envejecimiento , Densidad Ósea , Brasil , Femenino , Humanos , Masculino , Osteoprotegerina/sangre , Polimorfismo de Nucleótido Simple , Ligando RANK/sangreRESUMEN
UNLABELLED: ⦠BACKGROUND: Vascular calcification is strongly associated with cardiovascular disease and mortality. However, some factors related to vascular calcification in patients with end-stage renal disease receiving peritoneal dialysis (PD) remain unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23), magnesium, and phosphate clearance with vascular calcification in PD subjects, assessed by plain radiographs. ⦠METHODS: Simple vascular calcification scores (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for ≥ 6 months (43 women, median age 39 years, median time on PD 1.4 years). Levels of OPG, OPN, OCN, and FGF-23 were determined by luminometry. ⦠RESULTS: Serum OPG levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3; n = 19 with KI > 7) compared with those with less calcification (p < 0.001). Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had significantly lower renal phosphate clearance. Multiple regression analysis showed that vascular calcification assessed by SVCS was associated with age (r = 0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r = 0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and magnesium were not associated with vascular calcification. ⦠CONCLUSIONS: Higher levels of OPG were consistently associated with vascular calcification in subjects on PD.
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Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Osteoprotegerina/sangre , Diálisis Peritoneal/efectos adversos , Calcificación Vascular/diagnóstico , Calcificación Vascular/etiología , Adulto , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Osteopontina/sangre , Calcificación Vascular/sangreRESUMEN
SUMMARY Introduction: osteoprotegerin has emerged as a new candidate for the treatment of osteoporosis. However, high levels of osteoprotegerin have been linked to vascular calcification, an independent and well-defined risk factor for cardiovascular disease (CVD) and mortality. Thus, the action of osteoprotegerin in these situations has been questioned. Objective: to evaluate the effect of osteoprotegerin (OPG) on the human body, especially in bone tissue and in vascular diseases. Methods: the scientific databases consulted were PubMed-Medline and Cochrane, using keywords (MeSH terms) grouped into the following syntaxes: (Osteoprotegerin OR Osteoclastogenesis Inhibitory Factor OR Receptors, Tumor Necrosis Factor, Member 11b OR Tumor Necrosis Factor Receptor Superfamily, Member 11b OR FDCR-1 Protein OR FDCR 1 Protein OR OCIF Protein OR Follicular Dendritic Cell-Derived Receptor-1) AND (Bones AND Bone OR Bones AND Bone Tissue OR Bones OR Bone Tissue OR Cardiovascular Diseases). Results: Osteoprotegerin is present in various organs and binds to two ligands: nuclear factor kB (RANKL) related to the differentiation of osteoclasts, and tumor necrosis factor related to the apoptosis-inducing ligand (TRAIL). OPG inhibits the regulation effects of nuclear factor kB on inflammation and on the skeletal and vascular systems, preventing the apoptosis induced by TRAIL, being related to the preservation of bone tissue. Conclusion: a deeper knowledge of the mechanisms involved in the association between OPG serum levels, bone integrity and cardiovascular disease can provide important data for future therapeutic interventions.
RESUMO Introdução: a osteoprotegerina (OPG) tem surgido como uma nova candidata para o tratamento da osteoporose; no entanto, níveis elevados de OPG têm sido relacionados à calcificação vascular, um fator de risco independente e bem definido para doença cardiovascular (DCV) e mortalidade. Assim, a ação da OPG nessas situações tem sido questionada. Objetivo: avaliar a ação da OPG no corpo humano, em especial no tecido ósseo e nas doenças vasculares. Métodos: as bases de informação científica consultadas foram PubMed-Medline e Cochrane, utilizando-se palavras-chave (MeSH terms) agrupadas nas seguintes sintaxes: (Osteoprotegerin OR Osteoclastogenesis Inhibitory Factor OR Receptors, Tumor Necrosis Factor, Member 11b OR Tumor Necrosis Factor Receptor Superfamily, Member 11b OR FDCR-1 Protein OR FDCR 1 Protein OR OCIF Protein OR Follicular Dendritic Cell-Derived Receptor-1) AND (Bones AND Bone OR Bones AND Bone Tissue OR Bones OR Bone Tissue OR Cardiovascular Diseases). Resultados: a OPG está presente em vários órgãos e une-se a dois ligantes: o fator nuclear kB (RANKL), relacionado com a diferenciação dos osteoclastos, e o fator de necrose tumoral, relacionado ao ligante indutor de apoptose (TRAIL). Assim, a OPG inibe os efeitos da regulação do fator nuclear kB na inflamação e nos sistemas esquelético e vascular, prevenindo a apoptose induzida pelo TRAIL, estando relacionada com a preservação do tecido ósseo. Conclusão: um conhecimento mais aprofundado sobre os mecanismos envolvidos na associação entre os níveis séricos da OPG, integridade óssea e doenças cardiovasculares podem proporcionar dados importantes para futuras intervenções terapêuticas.
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Femenino , Humanos , Huesos/metabolismo , Osteoprotegerina/sangre , Remodelación Ósea/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Factores de Riesgo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Calcificación Vascular/sangre , Calcificación Vascular/metabolismoRESUMEN
ABSTRACT Objective The aim of this study was to investigate the in vitro and in vivo biological responses to nanostructured carbonated hydroxyapatite/calcium alginate (CHA) microspheres used for alveolar bone repair, compared to sintered hydroxyapatite (HA). Material and Methods The maxillary central incisors of 45 Wistar rats were extracted, and the dental sockets were filled with HA, CHA, and blood clot (control group) (n=5/period/group). After 7, 21 and 42 days, the samples of bone with the biomaterials were obtained for histological and histomorphometric analysis, and the plasma levels of RANKL and OPG were determined via immunoassay. Statistical analysis was performed by Two-Way ANOVA with post-hoc Tukey test at 95% level of significance. Results The CHA and HA microspheres were cytocompatible with both human and murine cells on an in vitro assay. Histological analysis showed the time-dependent increase of newly formed bone in control group characterized by an intense osteoblast activity. In HA and CHA groups, the presence of a slight granulation reaction around the spheres was observed after seven days, which was reduced by the 42nd day. A considerable amount of newly formed bone was observed surrounding the CHA spheres and the biomaterials particles at 42-day time point compared with HA. Histomorphometric analysis showed a significant increase of newly formed bone in CHA group compared with HA after 21 and 42 days from surgery, moreover, CHA showed almost 2-fold greater biosorption than HA at 42 days (two-way ANOVA, p<0.05) indicating greater biosorption. An increase in the RANKL/OPG ratio was observed in the CHA group on the 7th day. Conclusion CHA spheres were osteoconductive and presented earlier biosorption, inducing early increases in the levels of proteins involved in resorption.
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Humanos , Animales , Masculino , Alginatos/farmacología , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Durapatita/farmacología , Nanoestructuras/uso terapéutico , Recuento de Células , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/farmacología , Ensayo de Materiales , Osteoblastos/efectos de los fármacos , Osteoprotegerina/sangre , Ratas Wistar , Receptor Activador del Factor Nuclear kappa-B/sangre , Reproducibilidad de los Resultados , Factores de Tiempo , Alveolo Dental/efectos de los fármacos , Difracción de Rayos XRESUMEN
This study aimed to explore serum adiponectin and osteoprotegerin levels in patients with coronary heart disease (CHD) and their correlation with inflammatory and ischemia factors. From September 2010 to Augest 2010, 347 CHD patients were enrolled for a retrospective analysis. Serum lipoprotein phospholipase A2 (Lp-PLA2), hypersensitive C-reactive protein (hs-CRP), ischemia modified albumin (IMA), and adiponectin and osteoprotegerin levels were detected and analyzed. Serum adiponectin levels (ng/mL, CV was 4.3% at 250 ng/mL) were found to be negatively correlated with Lp-PLA2 (r = -0.958, P = 0.014) and hs-CRP (r = -0.958, P = 0.015) and positively correlated with IMA (r = 0.962, P = 0.025). Serum osteoprotegerin levels were positively correlated with Lp-PLA2 (r = 0.933, P = 0.027) and hs-CRP (r = 0.932, P = 0.022) and negatively correlated with IMA (r = -0.924, P = 0.017). In addition, serum adiponectin levels negatively correlated with osteoprotegerin levels. In conclusion, serum adiponectin level was negatively correlated with CHD progression, whereas serum osteoprotegerin level was positively correlated with CHD progression. Combined detection of adiponectin and osteoprotegerin levels may be of potential value in the clinical determination of CHD severity.
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Adiponectina/sangre , Enfermedad Coronaria/sangre , Osteoprotegerina/sangre , Anciano , Secuencia de Bases , Biomarcadores/sangre , Enfermedad Coronaria/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
CONTEXT: Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population. OBJECTIVE: To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis. DESIGN: Cross-sectional study nested within the Multicenter AIDS Cohort Study. SETTING: Four US academic medical centers. PARTICIPANTS: There were 578 HIV-infected and 344 HIV-uninfected men. MAIN OUTCOME MEASURES: Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors. RESULTS: OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque. CONCLUSIONS: OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.