Increased serum OPG in atrophic nonunion shaft fractures

Background Bone repair alteration is hypothesized for nonunion fracture pathogenesis. Since it is involved in osteoclast regulation, the RANK/RANKL/OPG system (receptor activator of nuclear factor kB/its ligand/osteoprotegerin) may play a role. Materials and methods Serum OPG, free RANKL, bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined in 16 male patients (20\u201339 years) with long bone atrophic nonunion fractures. Serum markers were also measured in 18 agematched male controls who healed from the same type of fractures within six months, and in 14 age-matched male controls who were healing from the same fractures one month after injury. One-way ANOVA and Bonferroni\u2019s test were used for statistical analysis. Results Only OPG was significantly higher (0.56 sd 0.11 ng/ml) in the patients compared to healed (0.26 sd 0.04 ng/ml; P\0.001) and healing (0.29 sd 0.09 ng/ml; P\0.001) controls. The patients\u2019 DPD levels were normal. No correlations were found between bone markers and the characteristics of the subjects in all groups. Conclusions A normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. The reason for the inability of the patients\u2019 OPG to inhibit osteoclastic activity is unknown. Osteoblast activity also appears normal, so another cellular source of OPG can be hypothesized

From bone to breast and back - the bone cytokine RANKL and breast cancer

Receptor activator of nuclear factor-κB ligand (RANKL) plays a pivotal role in regulating bone homeostasis. Osteoporosis and malignant bone disease secondary to breast cancer are characterized by enhanced RANKL production and increased bone turnover. Thus, denosumab, a monoclonal antibody to RANKL, has been developed and is now approved for various bone loss conditions. Recent results indicate that RANKL may also promote the development and osseous migration of breast cancer

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG

No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year

<p>Abstract</p> <p>Background</p> <p>In meta-analyses supplementation with vitamin D appears to reduce incidence of fractures, and in cross-sectional studies there is a positive association between serum 25-hydroxyvitamin D (25(OH)D) levels and bone mineral density (BMD). However, the effect of supplementation with high doses of vitamin D on BMD is more uncertain and could in theory have both positive and negative effects.</p> <p>Methods</p> <p>The study was a one year, double blind placebo-controlled intervention trial performed at the University Hospital of North Norway. 421 subjects, 21 - 70 years old, were included and 312 completed the study. The subjects were randomized to vitamin D₃40.000 IU per week (DD group), vitamin D₃20.000 IU per week (DP group), or placebo (PP group). All subjects were given 500 mg calcium daily. Serum 25(OH)D, osteoprotegrin (OPG), receptoractivator of nuclear factor-kappaB ligand (RANKL), and BMD at the lumbar spine and the hip were measured before and at the end of the study.</p> <p>Results</p> <p>At baseline the mean serum 25(OH)D levels were 58 nmol/L (all subjects) and increased to 141 and 100 nmol/L in the DD and DP groups, respectively. After one year, no significant differences were found between the three groups regarding change in BMD, serum OPG or RANKL.</p> <p>Conclusions</p> <p>Supplementation with high doses of vitamin D for one year does not appear to have a negative effect on BMD in healthy subjects. In order to disclose a positive effect, subjects with low BMD and/or low serum 25(OH)D levels need to be studied.</p> <p>Trial registration</p> <p>The trial was registered at ClinicalTrials.gov (NCT00243256).</p

RANK, RANKL and osteoprotegerin in bone biology and disease

Upon the discovery of RANK, RANKL and OPG in the late 1990s, their importance in the maintenance of the skeletal structure and their dramatic role in bone disease were largely unexpected. In recent years the understanding of these proteins, in particular their regulation, has greatly increased. This review aims to bring the interested reader up to date with the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions

Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis

Osteoprotegerin (OPG), receptor activator of nuclear factor-?B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change?=?1.79, p?=?0.013 and 2.07, p?=?0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change?=?0.50, p?=?0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change?=?1.46, p?=?0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p?=?0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL

Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study

To evaluate the incidence of new and/or progressive vertebral deformities and changes in bone mineral density, we re-examined 66 patients with sarcoidosis after a follow-up period of four years. In 17 subjects (26%) new and/or progressive vertebral deformities were found, though BMD did not change significantly. INTRODUCTION: Previous studies from our group have shown that morphometric vertebral deformities suggestive of fractures can be found in 20% of patients with sarcoidosis, despite a normal bone mineral density (BMD). The aim of this study was to determine the incidence of new and/or progressive vertebral deformities and the evolution of BMD during the course of this disease. METHODS: BMD of the hip (DXA) and vertebral fracture assessment (VFA) with lateral single energy densitometry was performed at baseline and after 45 months in 66 patients with sarcoidosis. Potential predictors of new/ progressive vertebral deformities were assessed using logistic regression analysis. RESULTS: The BMD of the total group was unchanged after follow-up. The prevalence of vertebral deformities increased from 20 to 32% (p < 0.05); in 17 subjects (26%) new or progressive vertebral deformities were diagnosed. A lower T-score of the femoral neck [(OR = 2.5 (CI: 1.0-5.9), p < 0.05)] and mother with a hip fracture [(OR = 14.1 (CI: 1.4-142.6), p < 0.05)] were independent predictors of new/progressive deformities. CONCLUSIONS: In subjects with sarcoidosis the number of vertebral deformities increases in the course of this disease, despite unchanged BMD. The combination of low normal BMD and family history of fragility fractures confers an increased risk of the incidence of these deformities