osteoprotegerin and Weight-Loss

To assess if altered bone turnover following bariatric surgery is related to metabolic consequences of the surgical procedure or weight loss. We evaluated serum markers reflecting bone turnover and metabolic pathways at baseline and after 1-year in a controlled non-randomized clinical trial comparing Roux-en-Y gastric bypass surgery (n = 74) with lifestyle intervention (n = 63) on obesity-related comorbidities. The decrease in body mass index (BMI) was larger in the surgery (-14.0 kg/m(2)) compared to lifestyle (-3.7 kg/m(2)). Markedly increased bone turnover was observed following surgery compared to lifestyle intervention and was correlated with change in BMI. Stepwise multivariable regression analysis revealed that group (β = 0.31, p < 0.01), and changes in BMI (β = -0.28, p < 0.01), dickkopf-1 (β = 0.20, p < 0.001) and sclerostin (β = 0.11, p < 0.05) were predictors of change in the bone resorption marker N-terminal telopeptide. Our data support that mechanisms related to the procedure itself and changes in secreted Wnt antagonists may contribute to increased bone turnover following bariatric surgery.

Topics: Adult; Biomarkers; Body Mass Index; Bone Remodeling; Calcium; Female; Gastric Bypass; Humans; Intercellular Signaling Peptides and Proteins; Life Style; Male; Middle Aged; Obesity; Osteoprotegerin; Parathyroid Hormone; Treatment Outcome; Vitamin D; Weight Loss

This study evaluated early and medium-term changes in bone turnover markers, and their associations with weight loss, total bone mineral density (BMD), and hormonal changes after biliopancreatic diversion (BPD).. Ancillary study from a one-year prospective cohort of 16 individuals assessed before, 3 days, 3 and 12 months after BPD. Bone turnover markers (C-terminal telopeptide (CTX), intact osteocalcin (OC), sclerostin, and osteoprotegerin (OPG)) and several hormones were measured at each visit. Total BMD by DXA was assessed at baseline, 3 and 12 months after BPD. Three participants were lost to follow-up.. CTX increased significantly at 3 days (+ 66%), 3 months (+ 219%), and 12 months (+ 295%). OC decreased at 3 days (- 19%) then increased at 3 months (+ 69%) and 12 months (+ 164%). Change in sclerostin was only significant between 3 days and 3 months (+ 13%), while change in OPG was significant between baseline and 3 days (+ 48%) and baseline and 12 months (+ 45%). CTX increase correlated negatively with weight loss at 3 (r = - 0.63, p = 0.009) and 12 months (r = - 0.58, p = 0.039), and total BMD decrease (r = - 0.67, p = 0.033) at 12 months. Change in insulin and adiponectin correlated with changes in bone turnover markers independently of weight loss.. BPD causes an earlier and greater increase in bone resorption over bone formation markers and a decrease in total BMD. Sclerostin did not increase as expected following extensive weight loss. Changes in insulin and adiponectin seem to play a role in the activation of bone remodeling after BPD.

Topics: Adiponectin; Adult; Aged; Biliopancreatic Diversion; Biomarkers; Bone Density; Bone Remodeling; Cohort Studies; Female; Hormones; Humans; Male; Middle Aged; Obesity, Morbid; Osteocalcin; Osteoprotegerin; Weight Loss; Young Adult

Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes.. 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.. 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.. RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.

Topics: Adaptor Proteins, Signal Transducing; Adipocytes; Adipokines; Adult; Anthropometry; Biomarkers; Bone Morphogenetic Proteins; Bone Remodeling; Female; Gastric Bypass; Genetic Markers; Humans; Middle Aged; Obesity; Osteoprotegerin; Prospective Studies; RANK Ligand; Weight Loss; Young Adult

Osteoprotegerin (OPGN) is a bone-remodeling marker that is associated with various metabolic and vascular complications. Cross-sectional studies in humans have demonstrated an inverse association between leptin, a marker of energy sufficiency, and OPGN. The physiology of OPGN has not been fully elucidated to date. We thus aim to elucidate 1) whether OPGN levels exhibit any gender dimorphism or day/night secretion pattern; and 2) whether there is any effect of acute and/or chronic energy deprivation on its circulating levels and whether such effects are mediated through leptin.. Study A: To evaluate OPGN secretion patterns and OPGN response to acute energy deprivation, we studied 12 healthy subjects under three different conditions for 72 h-in the isocaloric fed state, and during a fasting state with administration of either placebo or metreleptin in replacement doses. Blood samples were obtained every 15 min and pooled hourly during the last 24 h of the study. Study B: To evaluate the effect of chronic energy deprivation on OPGN secretion, we measured its levels in 14 obese subjects before and during weight loss after bariatric surgery.. OPGN levels exhibited a statistically significant (P < 0.01), albeit clinically limited in magnitude, day/night variation pattern in both genders (R(2) = 14.68%; 10.7-14.8% reduction with lower levels around 1600-1800 h; P < 0.01). Males had lower OPGN levels compared to females (1.81 ± 0.04 vs. 3.65 ± 0.07 pmol/liter; P < 0.001). Three days of fasting with either placebo or metreleptin administration did not change OPGN levels. OPGN levels did not change during bariatric surgery-induced weight loss.. OPGN levels are lower in men and exhibit a statistically significant, albeit clinically limited in magnitude, day/night secretion pattern. Neither acute nor chronic energy deprivation leading to significant weight loss has any effects on OPGN levels. Nomenclature Comment: Use of the terms "circadian" and "day/night variation" is meant as follows: Circadian pattern is a functional term that implies a rhythm that has been proven to be regulated by the innate circadian apparatus (anatomical and/or molecular). Conversely, day/night variation pattern is a descriptive term that refers to serum levels that vary during a day, usually in a periodic fashion. It is not known whether this variation is an innate property of the organ that secretes this hormone or whether it is determined by exogenous factors.

Topics: Adult; Bariatric Surgery; Energy Intake; Fasting; Female; Humans; Leptin; Male; Osteoprotegerin; Weight Loss; Young Adult

We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects.. In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/male=2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery.. OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P<0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (P=0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (r=0.295, r=0.20, P<0.05) and after adjustment for age (r=0.28, r=0.20, P<0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (r=0.30, P<0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (P=0.02, P=0.006, P=0.007, P<0.001, P<0.001, P<0.001 respectively) and a significant increase in adiponectin and HDL values (P<0.001 for both variables).. Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.

Topics: Adipokines; Adult; Alanine Transaminase; Bariatric Surgery; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Osteoprotegerin; Regression Analysis; Risk Factors; Triglycerides; Weight Loss

To assess the influence of weight reduction therapy on serum osteoprotegerin (OPG) concentration in obese patients and compare these results with normal-weight controls.. Forty-three obese women (BMI, 36.7 +/- 4.1 kg/m2; mean age, 50.1 +/- 4.5 years) were studied. The control group consisted of 19 normal-weight women (BMI, 24.2 +/- 2.1 kg/m2; mean age, 53.8 +/- 5.2 years). In all patients, serum concentrations of OPG, C telopeptide of type I collagen containing the cross-linking site (CTX), osteocalcin, parathormone, 25-(OH)-D3 (vitamin D), and total calcium and phosphorus were assessed before and after a 3-month weight reduction therapy.. In obese subjects, serum concentrations of OPG, 25-(OH)-D3, osteocalcin, total calcium, and phosphorus were significantly lower, and serum concentration of parathormone was significantly higher, before weight reduction therapy in comparison with normal-weight controls. After weight reduction, a significantly higher serum concentration of 25-(OH)-D3 and CTX and significantly lower concentration of OPG were found.. Serum concentration of OPG was significantly lower in obese patients in comparison with normal-weight controls. Weight reduction therapy resulted in further decrease in OPG serum concentrations. Therefore, OPG cannot be treated as a protective factor from bone loss in obese patients.

Topics: Body Mass Index; Bone Density; Calcifediol; Calcium; Collagen Type I; Female; Humans; Middle Aged; Obesity; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; Peptides; Phosphorus; Weight Loss; X-Rays

Transfer of CD4+CD45RBHi T cells into semi syngeneic immunodeficient mice represents a model of inflammatory bowel disease (IBD). As patients with IBD often suffer from osteopenia, we studied if this T cell transfer in mice results in osteopenia in addition to colitis, and if treatment with osteoprotegerin (OPG) has effects on the bone mineral density of T cell transferred mice. We also investigated whether osteopenia was due to malabsorption as a result of a dysregulated digestive tract or as a consequence of the inflammatory process.. CD4+CD45RBHi or CD4+CD45RBLo T cells (4 x 10(5)) were sorted from CB6F1 and transferred into C.B.17 scid/scid mice. Recipient mice were treated with human IgG1 Fc (control) or Fc-OPG three times per week in a prophylactic regimen as well as a therapeutic regimen (after 10% body weight loss) and were evaluated for osteopenia and colitis.. Mice that received CD4+CD45RBHi T cells developed osteopenia (as indicated by decreased bone density accompanied by decreased osteoblasts and increased osteoclasts) and colitis (as indicated by histological changes in the large intestine). Mice that received CD4+CD45RBLo T cells developed neither osteopenia nor colitis. All animals consumed, on average, the same amount of food and water over the course of the study. Prophylactic treatment with Fc-OPG increased bone density in mice that received either CD4+CD45RBHi or CD4+CD45RBLo T cells but had no effects on the gastrointestinal tract. Fc-OPG treatment of osteopenic mice with established IBD caused the normalisation of bone density. Osteopenia in CD4+CD45RBHi T cell recipients was accompanied by hypoparathyroidism that was partially normalised by treatment with Fc-OPG. CD4+CD45RBHi T cell recipients also had a bone marrow inflammatory cell infiltrate expressing tumour necrosis factor alpha which was unaffected by treatment with Fc-OPG.. CD4+CD45RBHi T cell transfer results in osteopenia in addition to colitis. Evidence suggests that this osteopenia was induced by inflammatory cell infiltration and not by malabsorption of calcium. Recombinant human osteoprotegerin effectively treated the osteopenia. OPG may be a useful therapeutic option for treating osteopenia in patients with IBD.

Topics: Animals; Bone Density; Bone Diseases, Metabolic; CD4-Positive T-Lymphocytes; Female; Glycoproteins; Inflammatory Bowel Diseases; Intestine, Large; Lymphocyte Transfusion; Mice; Mice, SCID; Osteoblasts; Osteoclasts; Osteoprotegerin; Parathyroid Hormone; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Serum Amyloid A Protein; T-Lymphocyte Subsets; Weight Loss

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation and activity and appears to be a critical regulator of bone mass and metabolism. In the current study, mice were challenged with various cytokines and hormones (interleukin-1beta, tumor necrosis factor-alpha, parathyroid hormone, parathyroid hormone-related protein, and 1alpha,25-dihydroxyvitamin D3) that are known to increase bone resorption and cause hypercalcemia and treated concurrently with either a recombinant chimeric Fc fusion form of human OPG, with enhanced biological activity (cOPG) (2.5 mg/kg/day) or vehicle. Mice receiving these bone-resorbing factors became hypercalcemic by day 3 after commencing treatment and had increased bone resorption as evidenced by elevated osteoclast numbers on day 5. Concurrent cOPG treatment prevented hypercalcemia (p < 0.05) and maintained osteoclast numbers in the normal range (p < 0.001). The demonstration that cOPG can inhibit bone resorption suggests that this molecule may be useful in the treatment of diseases including hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, and inflammatory bone disease, which are characterized, in part, by increases in osteoclastic bone resorption.

Topics: Animals; Bone and Bones; Bone Resorption; Calcitriol; Calcium; Cell Count; Glycoproteins; Humans; Hypercalcemia; Interleukin-1; Isomerism; Male; Mice; Osteoclasts; Osteoprotegerin; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Proteins; Radiography; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Weight Loss