ACS患者血清OPG、sRANKL表达水平与Gensini评分相关性研究

目的：探讨急性冠脉综合征（ACS）患者血清OPG及sRANKL表达水平变化及其与Gensini评分的相关性。方法：25例ACS患者作为研究组,25例健康体检者作为对照组,采用Elisa法检测两组血清OPG、sRANKL表达水平差异,对研究组进行Gensini评分,分析OPG、sRANKL表达水平与Gensini评分的关系。结果：研究组血清OPG表达水平高于对照组、sRNAKL表达水平低于对照组（均P〈0.05）。相关性检验显示OPG表达水平与Gensini成正相关（r=0.369,P〈0.01）。血清sRANKL表达水平与Gensini评分成负相关（r=-0.317,P〈0.01）。结论：ACS患者血清OPG、sRANKL高表达,对其进行检测能够反映冠脉病变的严重程度。     

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.     

RANKL/RANK/OPG system and bone status in females with anorexia nervosa

Minimal data exist concerning the relationship between osteokines of the RANKL/RANK/OPG system, especially RANKL, and bone status in females with anorexia nervosa (AN). For this reason we investigated the relationship between bone metabolism (as assessed based on serum levels of OC and CTx), and OPG and sRANKL concentrations in females with AN. Ninety-one female patients with AN and 29 healthy female subjects aged 13 to 18 years of age participated in the study. Serum OC, CTx, OPG and sRANKL were measured by ELISA. The female patients with AN demonstrated an essential suppression of OC and CTx, increased OPG and sRANKL levels, and a reduced OPG/sRANKL ratio. OC, CTx and the OPG/sRANKL ratio correlated positively with body mass and BMI in these patients, whereas in the case of OPG and sRANKL the relationship was negative. A significant positive correlation was observed between OPG and sRANKL and also between bone markers and the OPG/sRANKL ratio, and negative between CTx and sRANKL. In female patients with AN, the OPG/RANKL ratio was a significant and independent predictor of osteocalcin, a bone formation marker — OC (R² = 0.065, p = 0.012) whereas the OPG/sRANKL ratio and BMI were significant and independent predictors of a bone resorption marker — CTx (R² = 0.095; p = 0.012). In conclusion, the body mass, BMI values, and bone markers suppression observed in female patients with AN might be associated with an increase in OPG and sRANKL levels and a significant decrease of the OPG/sRANKL ratio. Although higher OPG levels may compensate for excessive bone resorption in female patients with AN, the lower OPG/sRANKL ratio seems to indicate that some inadequacies exist regarding this compensation effect, which might contribute to low bone density in these patients. The OPG/sRANKL ratio might prove a more relevant marker to predict bone metabolism in female patients with AN than sRANKL and/or OPG alone.     

Bone formation following lenalidomide-dexamethasone combination therapy in cases of multiple myeloma refractory to high-dose chemotherapy with bortezomib and autologous peripheral blood stem cell transplantation: report of a case and review of the literature

A 41-year-old man presented with the chief complaint of right hip pain that had persisted for 6 months. F18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showed FDG accumulation in the right pubic bone. A bone biopsy specimen from the site revealed findings suggestive of a plasma cell tumor. Bone marrow examination and serum and urine immunofixation tests showed no abnormalities. Based on these findings, the patient was diagnosed as having non-secretory multiple myeloma. FDG accumulation in the right pubic bone diminished following four cycles of weekly bortezomib and concomitant dexamethasone therapy. Tandem autologous peripheral blood stem cell transplantation was performed, followed by monthly bortezomib/dexamethasone maintenance therapy. A further FDG-PET/CT scan 9 months after the start of therapy indicated that FDG accumulation in the right pubic bone had worsened. Consequently, the therapy was switched to twice-weekly bortezomib/dexamethasone as remission re-induction therapy. New FDG uptake in the right hip bone was noted after six cycles of the therapy, and plain X-ray examination revealed osteolytic changes. The patient was then administered eight cycles of combined lenalidomide-dexamethasone therapy, which resulted in a marked decrease of the FDG accumulation in the right pubic bone and disappearance of uptake in the right hip bone. There was radiographic evidence of bone formation at these sites. This is only the second reported case in which treatment with the immunomodulatory drug lenalidomide and concomitant dexamethasone has been found to induce bone formation.     

Effect of abatacept treatment on serum osteoclast-related biomarkers in patients with rheumatoid arthritis (RA): A multicenter RA ultrasound prospective cohort in Japan

We evaluated the effect of abatacept treatment on osteoclast-related biomarkers and explored whether the biomarkers are associated with the therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.We enrolled 44 RA patients treated with abatacept from a multicenter prospective ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug therapy. We evaluated the disease activity score (DAS) 28-CRP (C-reactive protein), musculoskeletal ultrasound scores including the total grayscale score (GS)/power Doppler (PD) score and the serum concentrations of isoform 5b of tartrate-resistant acid phosphate (TRACP-5b) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) at baseline and at 3 and 6 months of treatment. “PD responder” was defined as a patient whose Δtotal PD score over 6 months was greater than the median change of that.Abatacept significantly improved DAS28-CRP as well as the total GS/PD score over 6 months. Serum TRACP-5b was significantly elevated and serum sRANKL was significantly decreased at 6 months (P < .0001 and P < .01, respectively). At 6 months, serum sRANKL was significantly decreased in the patients who achieved DAS28-CRP remission and the PD responders but not in those who did not. However, serum TRACP-5b rose regardless of the therapeutic response.Among RA patients treated with abatacept, serum sRANKL decreased in the patients with a good therapeutic response, but serum TRACP-5b elevated paradoxically regardless of the therapeutic response.     

The Concentrations of Markers of Bone Turnover in Normal Pregnancy and Preeclampsia

Background. The purpose of our study was to investigate the concentrations of markers of bone turnover in normal pregnancy and preeclampsia. Material and Methods. Forty-five pregnant patients with preeclampsia, 78 healthy pregnant women (26 in first, 26 in the second, and 26 in third trimester of pregnancy), and 20 nonpregnant women were included in the study. Serum concentrations of osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps—degradation products of type I collagen, were determined using the ELISA method. Statistical analysis was performed using Mann–Whitney U-test. Results. The concentrations of sRANKL and OPG were significantly higher in the second trimester of normal pregnancy when compared to the first and the third trimesters and to nonpregnant controls. The concentrations of osteocalcin were significantly higher in the first trimester of physiological pregnancy in comparison with nonpregnant women and with second and third trimesters of pregnancy. The concentrations of CrossLaps were significantly higher in the second trimester of normal pregnancy when compared to the first and third trimester. In preeclampsia, the sera concentrations of osteocalcin and CrossLaps were significantly higher when compared to the third trimester of normal pregnancy. Conclusion. The results suggest that the bone formation is increased in the first trimester, whereas the bone resorption is increased in the second trimester of normal pregnancy. Furthermore, the results suggest that the bone turnover is increased in patients with preeclampsia when compared to healthy normotensive pregnant women.     

维生素D_3抑制电离辐射引起的小鼠破骨细胞激活

目的研究维生素D3(VD3)对电离辐射引起破骨细胞代谢改变的保护作用。方法 24只雄性C57BL/6小鼠随机分为对照组、γ射线辐照组和1000IU VD3注射处理的γ射线辐照组。酶联免疫吸附双抗体夹心法测定小鼠血清中小鼠肿瘤坏死因子α(TNF-α)、小鼠抗酒石酸酸性磷酸酶5b(TRAP-5b)、小鼠可溶性核因子-κB受体活化因子配体(sRANKL)、小鼠Ⅰ型胶原C端肽(CTX-1);采用甲基百里香酚蓝比色法测定血清中钙离子浓度。抗酒石酸酸性磷酸酶(TRAP)染色骨病理石蜡切片观察破骨细胞形态变化。用SPSS12.0统计软件分析数据。结果与对照组比,γ射线辐照组小鼠血清中TRAP-5b、CTX-1、sRANKL和TNF-α含量分别升高了37.30%、47.14%、19.55%和17.67%(P<0.05)。VD3注射处理的γ射线辐照组血清中TRAP-5b、CTX-1和sRANKL升高不明显(P>0.05)。VD3的保护率分别为42.06%、69.80%和68.12%,而TNF-α升高明显(P<0.05)。镜下γ射线辐照组小鼠骨内破骨细胞形态呈代谢增强改变;而VD3注射处理则明显改善γ射线辐照引起的破骨细胞的形态变化。结论 VD3通过降低破骨细胞活性关键因子sRANKL可以有效地减轻电离辐射引起的小鼠破骨细胞代谢增强。使用VD3是减轻放疗患者受电离辐射损害的一种潜在有效方法。     

Serum osteoprotegerin and receptor activator of nuclear factor-κB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?

Purpose: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-κB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss. Methods: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids – with or without pamidronate – prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls. Results: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls; in the two patient groups it increased by 26–27% at 6 months post-SCT (p=0.002–0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p<0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. Conclusion: Serum sRANKL concentrations may be modulated by bisphosphonates.