Serum OPG Levels Research Articles

SERUM OSTEOPROTEGERIN LEVEL IN CHRONIC HAEMODIALYSIS PATIENTS

Background: Osteoprotegerin is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the serum OPG level had been found significantly increased and associated to vascular calcification. Elevated OPG level was noted as a mortality predictor in HD patients. Objective: To assess mean serum osteoprotegerin level in HD patients and to approach the probably relationship between serum osteoprotegerin level and serum PTH, Creatinin, BUN levels in HD patients. Method: Cross – sectional study. Results: Mean serum osteoprotegerin level: 242.49 ± 115.65 pg/ ml. Mean serum BUN level: 58.12 ± 16.83 mg/dL. Mean serum Creatinin level: 6.80 ± 5.23 mg/dL. Mean serum PTH level: 148.52 ± 198.24 pmol/L, median at 66.8 pmol/L [9.2-1140] pmol/L High serum OPG levels were associated with older ages (r=0.464, p<0.001). High serum OPG levels were associated with high BUN (r=0.028, p=0.137) High serum OPG levels were associated with serum Creatinin levels.(r=-0.189, p=0.032). High serum OPG levels were associated with high serum PTH levels (r=0.045, p=0.611). Conclusions: Mean serum osteoprotegerin level in hemodialysis patient: 242.49 ± 115.65 pg/ml. High serum OPG levels were associated with high BUN (r=0.028, p=0.137), with serum Creatinin levels. (r=-0.189, p=0.032), with high serum PTH levels (r=0.045, p=0.611). Key words: End stage renal disease, maintenance haemodialysis, osteoprotegerin, vascular calcification

Elevated serum osteoprotegerin may predict peripheral arterial disease after kidney transplantation: a single-center prospective cross-sectional study in Taiwan.

BackgroundOsteoprotegerin (OPG) is a potential biomarker for severity and complications of cardiovascular diseases. Peripheral arterial disease (PAD) is associated with an increased risk of death in kidney transplantation (KT) patients. This prospective cross-sectional study evaluated the relationship between serum OPG and PAD in KT patients.MethodsSeventy-four KT patients were enrolled for this PAD study. Fasting blood samples were obtained to measure serum OPG levels by using enzyme-linked immunosorbent assay kits. The ankle-brachial index (ABI) of less than 0.9 was applied for PAD diagnosis.ResultsThirteen patients (17.6%) were diagnosed with PAD. Diabetes (P = 0.025), smoking (P = 0.010), and increased OPG levels (P = 0.001) were significantly more frequent in the PAD group. Multivariate logistic regression analysis showed that serum OPG (odds ratio [OR], 1.336; 95% CI [1.108–1.611]; P = 0.002) and diabetes (OR, 7.120; 95% CI [1.080–46.940]; P = 0.041) were independent predictors of PAD in KT patients. The area under the receiver operating characteristic (ROC) curve determined that the probability of a serum OPG level of 7.117 pg/L in predicting PAD in KT patients was 0.799 (95% CI [0.690–0.884]; P < 0.001).DiscussionExploration of reliable biomarkers for early identification of vascular risk is crucial for KT patients. Elevated serum OPG levels may predict PAD in KT patients with cutoff value of 7.117 pg/L.

Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus.

The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.

Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes.

The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (n = 93), impaired glucose regulation (IGR) (n = 90), and normal glucose regulation group (NGR) (n = 88), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) (p = 0.031) and T2DM group (183.20 ± 56.53 pg/mL) (p < 0.01), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009, p = 0.006) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.

MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway.

ObjectiveTo investigate the role of microRNA-145 (miR-145) in steroid-induced necrosis of the femoral head (SINFH) by evaluating its effects on the OPG/RANK/RANKL signaling pathway.MethodsA rat model of SINFH was constructed via injection of the lentiviral vector pLV-shRNA-miR-145. Pathological observation was performed via tartrate-resistant acid phosphatase (TRAP) staining, and serum OPG levels were detected by ELISA. The mRNA expression levels of miR-145, OPG, RANK and RANKL in THP-1 cells were assessed by RT-PCR, and the protein expression levels of OPG, RANK and RANKL were assessed by western blotting.ResultsThe expression of miR-145 in the lentivirus-mediated miR-145 group was significantly up-regulated compared with that in the control and normal groups (both P < 0.01). Serum OPG levels were decreased in SINFH rats compared with control and normal rats. The mRNA and protein expression levels of OPG in THP-1 cells decreased after transfection (all P < 0.05). By contrast, the mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection (all P < 0.05). After transfection of 293T cells with an miR-145 overexpression vector, miR-145 expression in 293T cells increased significantly, while OPG mRNA and protein expression decreased significantly (all P < 0.05).ConclusionMiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.

Inverse Association Between Serum Osteoprotegerin and Bone Mineral Density in Renal Transplant Recipients

BackgroundOsteoprotegerin (OPG) has pleiotropic effects on bone metabolism as well as endocrine function. Our aim was to evaluate the relationship between bone mineral density (BMD) and serum OPG concentration in renal transplant recipients. MethodsFasting blood samples were obtained from 69 renal transplant recipients. BMD was measured in lumbar vertebrae (L2–L4) by dual-energy X-ray absorptiometry. Eight patients (11.6%) had BMD values indicative of osteoporosis, 28 patients (40.6%) had BMD values indicative of osteopenia, and 33 patients had normal BMD values. Increased serum OPG levels (P < .001), decreased body mass index (BMI) (P = .033), and decreased body weight (P = .010) were significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis). ResultsWomen had significantly lower lumbar BMD values than men (P = .013). Menopause (P = .005), use of tacrolimus (P = .020), and use of cyclosporine (P = .046) were associated with lower lumbar BMD in renal transplant recipients. Univariate linear regression analysis revealed that lumbar BMD was positively correlated with height (P = .016), body weight (P = .001), and BMI (P = .015) and negatively correlated with age (P = .039) and log-OPG (P = .001). Multivariate linear regression analysis revealed that log-OPG (β: −0.275, R2 change = 0.154, P = .014), body weight (β: 0.334, R2 change = 0.073, P = .004), and age (β: −0.285, R2 change = 0.079, P = .008) were independent predictors of lumbar BMD values in renal transplant recipients. ConclusionsSerum OPG concentration correlated negatively with lumbar BMD values in renal transplant recipients.

Osteoclastogenesis-related cytokines and peri-prosthetic osteolysis in revision metal-on-metal total hip replacements.

Peri-prosthetic osteolysis is a major cause for revision hip arthroplasty; various cytokines including those in the osteoclastogenesis pathway have been identified as potentially key in the osteolysis process. Adverse reactions to metal debris in metal-on-metal total hip replacements have led to an increase in revision procedures. This study examines the levels of osteoclastogenesis-related cytokines in serum and synovial fluid samples obtained from patients at the time of revision metal-on-metal total hip replacement and compares between patients with and without radiographic evidence of peri-prosthetic osteolysis. Sandwich ELISA techniques were used to detect IL-6, IL-18, M-CSF, sRANKL and OPG in the samples. Results were analysed with linear regression, Fisher's tests and t-tests; p<0.05 considered significant. Samples from 36 patients (18 with osteolysis, 18 without osteolysis) were analysed. There was wide variation in the detectable levels of cytokines. No significant differences were found between patients with and without osteolysis in mean synovial fluid levels of IL-6 (p = 0.863), IL-18 (p = 0.324), M-CSF (p = 0.508), sRANKL (p = 0.884), OPG (p = 0.776) or mean serum levels of OPG (p = 0.993) or sRANKL (p = 0.565) (insufficient detection of IL-6, IL-18 or M-CSF in serum samples). A correlation was found between synovial fluid levels of IL-6 and OPG in patients without osteolysis (r2 = 0.618, p<0.001) but not with osteolysis (r2 = 0.0004). These results indicate that the process of peri-prosthetic osteolysis is complex and multifactorial; there may also be an influence of metallosis. Further research is needed to increase understanding of peri-prosthetic osteolysis and influence clinical practice.

Prognostic Value of Osteoprotegerin in Acute Heart Failure

BackgroundOsteoprotegerin (OPG) is promising as a predictor of adverse prognosis in patients with acute coronary syndromes and chronic heart failure. Its prognostic value in acute heart failure (AHF) is unknown. The aim of this study was to assess the prognostic value provided by serum OPG levels at discharge after an admission for AHF. MethodsIn a prospective study, we enrolled 338 patients consecutively admitted with AHF to the internal medicine department of a tertiary care university hospital in Porto, Portugal between March 2009 and December 2010. OPG was measured using a commercial enzyme-linked immunosorbent assay and was both analyzed as a continuous variable and categorized by quartiles. Patients were followed for up to 6 months after discharge to ascertain the occurrence of all-cause death or hospital readmission resulting from AHF. ResultsDuring follow-up, 119 patients died or were readmitted for AHF. A graded increase in the risk of the combined end point was observed across quartiles of OPG. At 6 months, the cumulative risk of the end point was 25% for the first quartile and 50% for the fourth quartile. The multivariable adjusted risk of death or hospitalization for AHF increased progressively across categories of OPG up to a statistically significant 2.44-fold increase in risk in the highest category (P for linear trend = 0.002, ie, by 5% per 10 pg/mL increase in OPG). ConclusionsSerum OPG was directly associated with a higher probability of death or readmission for AHF within 6 months, irrespective of other known prognostic markers. This was true both when the ejection fraction was preserved and when it was reduced.

Association of serum Dkk-1 levels with β-catenin in patients with postmenopausal osteoporosis.

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group (P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin (r=-0.161, P=0.003) and OPG (r=-0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin (β=-0.165, P=0.009) and BMD (β=-0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX (β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.

Correlations between osteoprotegerin serum levels and body composition parameters in patients with sleep apnea syndrome and the possible influence on cardiovascular risk

IntroductionOsteoprotegerin (OPG) is a member of the tumor necrosis factor family and a key regulator in bone turnover; it plays a role in the development of many cardiovascular diseases and may be treated as a marker of vascular damage. Bioelectrical impedance analysis (BIA) is a reliable, non-invasive and effective technique for measuring body composition.The aim of the study was to evaluate correlations between osteoprotegerin serum levels and body composition parameters in sleep apnea patients and their influence on cardiovascular risk. Material and methodsA total of 125 patients with newly diagnosed OSA were enrolled in the study (including 34 females). The mean age was 54.48±8.81 years, mean AHI 33.16±20.44/h and mean BMI 33.76±7.18. A control group comprised 59 healthy subjects with mean age of 51.27±12.97 years and mean BMI 29.47±5.42.All subjects underwent a nocturnal respiratory polygraphy and body composition measurements were taken with bioelectrical impedance analysis. OPG serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. ResultsIn OSA patients OPG correlated negatively with muscle mass percentage (MM%), phase angle, fat free mass percentage (FFM%) and body cell mass percentage (BCM%), while there was a positive correlation between osteoprotegerin and fat mass percentage (FM%). We demonstrated higher OPG serum levels in OSA patients with cardiovascular diseases than in those without comorbidities (4.01 vs 3.46pmol/l, p<0.05). ConclusionOur findings, combined with previous observations in other diseases, suggest that elevated OPG serum levels together with selected body composition parameters may be helpful in identifying OSA patients with increased cardiovascular risk.

Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

Assessment of OPG and RANKL serum levels after treatment with hormonal replacement therapy and tibolone in patients after menopause with osteopenia or postmenopausal osteoporosis

Assessment of OPG and RANKL serum levels after treatment with hormonal replacement therapy and tibolone in patients after menopause with osteopenia or postmenopausal osteoporosis

Abstract W MP82: Role of OPG/RANKL/RANK System in Ischemic Brain in Mice

Background &amp; Purpose: Although recent clinical studies showed that the high serum osteoprotegerin (OPG, decoy receptor for RANKL) level was associated with unfavorable outcome in ischemic stroke, its mechanism is unknown. Since OPG/ RANKL (receptor activator of nuclear factor-β ligand)/ RANK (receptor for RANKL) system has critical roles in immune systems as well as osteoclast biology, we hypothesized the OPG/RANKL/RANK system might play roles in post-ischemic inflammation and immune response. To explore the possibility, we examined their expressions and functions in mice. Methods: The expression and the functional analysis of OPG/RANKL/RANK system were examined in 70 min-transient cerebral artery occlusion model in C57BL6/J (WT) mice or OPG -/- mice, whose serum RANKL level is higher than that in WT mice. The effects of RANKL/RANK signaling were also examined in mixed glial-neuron cultures stimulated by lipopolysaccharide (LPS). Results: RANK mRNA was increased from 4 hrs after ischemia, whereas OPG and RANKL mRNA were up-regulated from 5 hrs after ischemia. The RANKL and RANK were expressed in activated macrophage/microglia and OPG was partly expressed in activated macrophage/microglia. OPG -/- mice showed reduced infarct volume 72 hrs after ischemia, whereas the infarct volume was not reduced in OPG -/- mice treated with RANK/Fc chimera. Also, RANKL-treated wild type mice showed the reduction in infarct volume. The expression of IL-6, TNF-α, and IL-1β was less in OPG -/- mice and RANKL-treated mice. Additionally, the LPS-stimulated neuron-glia mixed culture showed less neuronal death in the group of RANKL-treatment cultures through inhibition of inflammatory cytokines production. Conclusions: These data indicate that RANKL/RANK signaling might work as anti-inflammation in the ischemic brain through inhibiting TLR signaling pathways. High serum OPG level in clinical situations might inhibit RANKL/RANK signaling and exacerbate the post-ischemic inflammation, resulting in poor outcomes. Further studies on the OPG/RANKL/RANK system might shed light on the clarification of molecular mechanisms in post-ischemic inflammation.

Osteoclastogenic Potential of Peripheral Blood Mononuclear Cells in Cleidocranial Dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by hypoplastic or aplastic clavicles, dental abnormalities, and delayed closure of the cranial sutures. In addition, mid-face hypoplasia, short stature, skeletal anomalies and osteoporosis are common. We aimed to evaluate osteoclastogenesis in a child (4 years old), who presented with clinical signs of CCD and who have been diagnosed as affected by deletion of RUNX2, master gene in osteoblast differentiation, but also affecting T cell development and indirectly osteoclastogenesis. The results of this study may help to understand whether in this disease is present an alteration in the bone-resorptive cells, the osteoclasts (OCs). Unfractionated and T cell-depleted Peripheral Blood Mononuclear Cells (PBMCs) from patient were cultured in presence/absence of recombinant human M-CSF and RANKL. At the end of the culture period, OCs only developed following the addition of M-CSF and RANKL. Moreover, real-time PCR experiment showed that freshly isolated T cells expressed the osteoclastogenic cytokines (RANKL and TNFα) at very low level, as in controls. This is in accordance with results arising from flow cytometry experiments demonstrating an high percentage of circulating CD4+CD28+ and CD4+CD27+ T cells, not able to produce osteoclastogenic cytokines. Also RANKL, OPG and CTX serum levels in CCD patient are similar to controls, whereas QUS measurements showed an osteoporotic status (BTT-Z score -3.09) in the patient. In conclusions, our findings suggest that the heterozygous deletion of RUNX2 in this CCD patient did not alter the osteoclastogenic potential of PBMCs in vitro.

Effect of the combinatory mixture of Rubus coreanus Miquel and Astragalus membranaceus Bunge extracts on ovariectomy-induced osteoporosis in mice and anti-RANK signaling effect

Ethnopharmacological relevancePostmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus and Astragalus membranaceus have been used for their various pharmacological properties in Asia as a traditional medicine. The present study evaluated the anti-osteoporotic effects of the optimal combination of Rubus coreanus and Astragalus membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX) mice by investigating bone biomechanical properties and the serum levels of TNF-α, osteocalcin, RANKL, OPG, and RANK–RANKL signal-related osteoclast differentiation markers. Materials and methodsA total of 36 mature female outbred ICR (Institute of cancer research) strain mice (7 weeks) were divided into 6 groups with 7 mice in each group as follows: (1) Sham-operated control mice (Sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through gavage. (2) OVX mice received a daily oral gavage of PBS (OVX). (3) OVX mice were treated daily with 50mg/kgb.w./day of RAM (4) with 100mg/kgb.w./day of RAM or (5) with 200mg/kgb.w./day of RAM via oral gavage. (6) OVX mice received i.p. injections of 17β-estradiol (E2) (0.1mg/kgb.w./day) three times per week for 12 weeks. ResultsMicro-CT images showed that oral administration of RAM to OVX mice prevented tibial bone loss, preserved trabecular bone microarchitecture, and improved bone biomechanical properties. RAM administration also showed recovery effects on the levels of TNF-α, OPG and RANKL concentration in OVX-states. Additionally, we found that the mechanism by which RAM elicited anti-osteoporotic effects was by down-regulating the expression of TRAF6 and NFATc1 in RANKL-RANK pathway, a route of osteoclast differentiation, followed by reducing the production of osteoclast differentiation factors, calcitonin receptors and cathepsin K. ConclusionsOur research strongly suggests that RAM can be clinically used in the prevention and treatment of postmenopausal osteoporosis.

Lanthanum carbonate prevents accelerated medial calcification in uremic rats: role of osteoclast-like activity

BackgroundArterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing.MethodsDetailed time-course studies were conducted of Sprague–Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa’s and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit.ResultsSerum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 ± 0.73 mmol/L vs CRF Group 3.48 ± 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found.ConclusionsAbnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased phosphate retention and cross-talk between osteoblast and osteoclast-like cell, both of which can be the therapeutic target for uremia associated with AMC.

OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Women's Health Initiative Observational Study

PurposeThe osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture. MethodsA nested case–control study was conducted among postmenopausal, Caucasian women aged 50–79 at baseline (1993–1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors. ResultsSerum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45–3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15–3.04; p for linear trend=0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed. ConclusionSerum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women.

FRI0108 Serum osteoprotegerin levels, aortic stiffness and carotid intima-media thickness as cardiovascular risk factors in patients with rheumatoid arthritis

BackgroundOsteoprotegerin (OPG) is implicated in the pathogenesis of atherosclerosis. Recent studies have shown that arterial stiffness, carotid intima-media thickness (CIMT) and OPG are independent risk factors of cardiovascular (CV) disease....

FRI0489 Haemophilic artropathy: from sonographic scoring to histopathological modifications

BackgroundHaemophilic arthropathy (HA) may involve mainly the larger joints (target joint) presenting a spontaneous bleeding, haemarthrosis. Repeated bleeding episodes lead to synovitis implying synovial changes, cartilage and bone damages resulting...

Relationship between Serum Levels of OPG and TGF-βwith Decreasing Rate of BMD in Native Chinese Women

The objective of this study was to investigate the relationship between serum levels of OPG, TGF-β1, and TGF-β2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35–80 years. Serum levels of OPG, TGF-β1, and TGF-β2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r = −0.122 to –0.230, all P = 0.007–0.000) and TGF-β2 (r = −0.100 to –0.173, all P = 0.029–0.000) and a positive correlation between BDR and serum TGF-β1 (r = 0.245 − 0.365, all P = 0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF-β2 and BDR. However, statistically significant correlations between serum TGF-β1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4–3.7% of BDR variation. Serum TGF-β1 was a positive determinant of BDR and could explain 5.3–13.3% of BDR variation.