Bone turnover in children with vitamin D deficiency rickets before and during treatment

Biochemical markers of bone formation [alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (PICP)] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and cross-linked N-telopeptides of type I collagen (NTX)] were measured in 14 children aged 8.5-10.5 mo with vitamin D deficiency rickets before and longitudinally during vitamin D treatment (3000-4000 IU/daily). Forty-four healthy children aged 8-10.5 mo were enrolled as sex- and age-matched controls. Before treatment, serum levels of alkaline phosphatase, PICP, and ICTP, and urinary excretion values of NTX were significantly higher, and serum osteocalcin levels significantly lower than controls (31.4 +/- 3.5 microkat/L and 9.8 +/- 2.9 microkat/L, p < 0.001; 1025 +/- 89 microg/L and 952 +/- 97.4 microg/L, p < 0.02; 15.6 +/- 2.6 microg/L and 14.2 +/- 1.3 microg/L, p < 0.01; 370.7 +/- 109.4 nmol BCE and 201.8 +/- 69.2 nmol BCE, p < 0.001: 17.6 +/- 9.1 microg/L and 22.5 +/- 7.6 microg/L, p < 0.05, respectively). During treatment, serum alkaline phosphatase levels progressively declined in association with the radiographic healing of the skeletal lesions. Serum levels of osteocalcin, PICP, and ICTP, and urinary excretion values of NTX showed a transient but significant (p < 0.05 to p < 0.001) increase in comparison with baseline values during the first 2-4 wk of treatment, and decreased slowly thereafter. They were within the mean +/- 2 SD of controls before the recovery of the skeletal lesions. CONCLUSIONS: These findings suggest that children with vitamin D deficiency rickets have increased bone turnover before and during the first weeks of treatment. Alkaline phosphatase is a more reliable marker than osteocalcin, PICP, ICTP and NTX for diagnosing and monitoring these patients.     

Adipokines as targets in musculoskeletal immune and inflammatory diseases

Adipokines are the principal mediators in adipose signaling. Nevertheless, besides their role in energy storage, these molecules can be produced by other cells, such as immune cells or chondrocytes. Given their pleiotropic effects, research over the past few years has also focused on musculoskeletal diseases, showing that these adipokines might have relevant roles in worsening the disease or improving the treatment response. In this review, we summarize recent advances in our understanding of adipokines and their role in the most prevalent musculoskeletal immune and inflammatory disorders.     

I型胶原吡啶交联终肽(ICTP)在骨肿瘤诊断中的临床研究

目的 检测良性骨肿瘤、恶性骨肿瘤患者及正常对照组血清中的I型胶原吡啶交联终肽(ICTP)活性，以评价ICTP在良恶性骨肿瘤诊断和鉴别诊断中的价值。方法 选取2005~2010年本院骨肿瘤科收治的78例恶性骨肿瘤患者，设为A组，其中49例为原发性恶性骨肿瘤、10例为继发性恶性骨肿瘤、19例为骨转移性肿瘤患者,另选43例良性骨肿瘤患者为B组，同时，设52例同龄正常人为C组，均采用酶免疫测定(EIA)方法测定他们血清中的ICTP活性。结果 B组患者血清ICTP活性为(6.75±3.34) μg/L，C组血清ICTP活性为(4.68±2.91) μg/L,A组患者血清ICTP活性为(14.84±8.49)μg/L，其中，原发性恶性骨肿瘤患者、继发性恶性骨肿瘤、骨转移性肿瘤患者的血清ICTP活性分别为(17.47±10.86)μg/L、(8.02±6.19) μg/L、(8.14±5.45) μg/L. A组中三类患者的血清ICTP活性与B组，C组相比差异均有统计学差异(P<0.05)，B组患者与C组相比差异无统计学差异(P>0.05)。而A组中原发性恶性骨肿瘤与继发性恶性骨肿瘤、骨转移性肿瘤组之间的差异也有统计学意义 (P<0.05)。结论 血清ICTP是反映骨肿瘤骨代谢的一个灵敏而简便的检测指标,并对良恶性骨肿瘤的诊断及鉴别诊断具有重要的临床意义。     

Stability of bonds made to superficial vs. deep dentin,before and after thermocycling

ObjectivesBonding stability of resinous adhesives to dentin is still problematic and may involve regional variations in dentin composition. This study is to evaluate the effect of dentin depth on the stability of resin-dentin bonds under thermocycling challenge.MethodsDentin slabs with two flat surfaces parallel to the tooth axis were obtained from extracted human third molars. The slabs were randomized into eight groups according to the location of dentin [deep dentin (DD) or superficial dentin (SD)], the adhesive treatment (Single Bond 2 or Clearfil S³ Bond), and the storage treatment (thermocycling for 5000 times vs. no). After the adhesive treatment and composite buildup on the dentin slabs, the micro-shear bond strength (μSBS) of each group was detected. The concentrations of cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were also evaluated using an immunoassay to detect the degree of collagen degradation in each group.ResultsDentin depth, adhesive treatment and storage treatment all showed significant effects on both the μSBSs and the ICTP values (P < 0.05). Regardless of the adhesive type, thermocycling decreased the μSBSs and increased the ICTP values (P < 0.05). The DD groups showed significantly lower μSBSs and higher ICTP values than SD groups after thermocycling aging (P < 0.05). The treatment with Single Bond 2 significantly increased the ICTP values (P < 0.05), whereas Clearfil S³ Bond showed no effect on the ICTP values (P > 0.05).SignificanceDeep dentin showed significantly more bond degradation after thermocycling than did superficial dentin.     

Clinical usefulness of serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen for diagnosis of bone metastases in patients with primary lung cancer

OBJECTIVE: Recently, various blood and urine markers of bone metabolism have been developed and applied to the diagnosis of bone metastases. However, the cut-off values for each parameter have not yet been completely defined. In this study, the usefulness of serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (I CTP) was assessed for detecting bone metastases from primary lung cancer and the most efficient cut-off value for I CTP based on the receiver operating characteristic curve was calculated. METHODOLOGY: Over a 1-year period, serum I CTP and serum alkaline phosphatase (ALP) were assayed for 87 primary lung cancer patients, including 21 bone metastases-positive cases at Nagoya Ekisaikai Hospital, Nagoya, Japan. RESULTS: I CTP was significantly higher in patients with bone metastases than in the group without bone metastases. In contrast, there was no significant difference in serum ALP between the two groups. The most efficient cut-off value for I CTP computed in this study was 6.4 ng/mL. This was higher than the recommended value (4.5 ng/mL) based on the data from the summated values obtained for lung cancer, breast cancer and prostate cancer, as well as the maximum value for healthy controls (4.9 ng/mL). CONCLUSION: These results suggest that measurement of serum I CTP is a useful test for diagnosing bone metastases from lung cancer. Each type of cancer has a different pattern of bone turnover at the site of bone metastases. Considering that lung cancer mainly metastasizes to bone in an osteolytic pattern, it is proposed to set a higher cut-off value for lung cancer patients than the currently recommended value.     

全膝关节磁共振成像积分对膝骨关节炎诊断价值的探讨

目的:探讨全膝关节磁共振成像积分(WORMS)对膝骨关节炎(KOA)患者的诊断价值。方法:回顾性分析2009年11月至2011年1月门诊及住院KOA伴膝关节积液患者70例,男12例,女58例;年龄46～75岁,平均(59.66±9.93)岁。用WOMAC量表进行临床症状评估,用K-L分级及全膝关节磁共振成像积分(WORMS)进行放射学评估,同时应用ELISA法检测患者关节液中COMP及CTX-Ⅱ的浓度。并对上述指标进行相关性分析及多重线性回归分析。结果:WOMAC评分及WORMS分别为(57.50±8.20)和(64.54±16.45)分,CTX-Ⅱ及COMP含量分别为2.42ng/ml和4.56ng/ml。选择WORMS四分位数中轻和严重2组,比较2组COMP差异有统计学意义(Z=2.04,P=0.039),而CTX-Ⅱ差异则无统计学意义(Z=0.79,P=0.427)。相关性分析发现WORMS与WOMAC评分、K-L分级呈正相关(r=0.777,P<0.01;r=0.716,P<0.01),K-L分级与WOMAC评分也呈正相关(r=0.692,P<0.01)。WORMS中关节软骨积分、骨赘积分、滑膜炎积分分别与WOMAC评分、K-L分级及COMP亦呈正相关(r=0.771,P<0.01;r=0.509,P<0.01;r=0.917,P<0.01)。以WOMAC评分为应变量,年龄、性别、K-L分级、WORMS、COMP和CTX-Ⅱ为自变量进行逐步回归(F=20.327,P<0.01),KOA病情主要受WORMS、K-L分级影响(P=0.015,P=0.025)。结论:WORMS对膝骨关节炎的诊断有较高的参考价值。WORMS高时,关节液中COMP含量升高。膝骨关节炎的临床症状主要受WORMS、K-L分级影响。     

应用定量CT检测骨密度评估抗骨质疏松治疗效果#br#

［摘要］ 目的探讨应用定量CT检测骨密度评估抗骨质疏松治疗效果的可行性。 方法选择绝经后骨质疏松患者,均给予双膦酸盐类抗骨吸收药物治疗。于治疗前和治疗6个月后检测血清β胶原降解产物（β-C-terminal telopeptide of type Ⅰ collagen,β-CTX）、双能X线骨密度及定量CT骨密度,依照血清β-CTX变化情况分为治疗有效组和治疗无效组,比较2组骨密度变化情况。 结果共纳入患者220例。血清β-CTX含量下降超过50%患者211例为治疗有效组,血清β-CTX含量下降未达到50%患者9例为治疗无效组。口服双膦酸盐类药物治疗6个月后,治疗有效组及治疗无效组双能X线吸收测定法骨密度检测均无明显变化,治疗有效组定量CT骨密度检测提示骨密度升高,治疗无效组则无明显变化。 结论血清β-CTX检测与定量CT骨密度检测可以对绝经后骨质疏松患者抗骨吸收治疗效果进行评估,且2种检测方式互为补充,为绝经后骨质疏松治疗提供指导。     

Regulation of osteoclast function via Rho-Pkn3-c-Src pathways

BackgroundWnt signaling pathways are largely divided into the β-catenin-dependent canonical pathway and β-catenin-independent non-canonical pathways. The roles of Wnt signaling in bone metabolism have been extensively investigated.We previously attempted to clarify the roles of Wnt-non-canonical signaling in bone resorption and demonstrated that Wnt5a-receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling promoted osteoclast differentiation by enhancing RANK expression in osteoclast precursor cells. However, the roles of Wnt5a-Ror2 signaling in osteoclast function remain unclear.HighlightTrabecular bone mass was significantly greater in osteoclast-specific Ror2-deficient (Ror2^ΔOCL/ΔOCL) mice than in control mice due to the decreased bone-resorbing activity of osteoclasts. Wnt5a-Ror2 signaling activated Rho in osteoclasts via dishevelled-associated activator of morphogenesis 2 (Daam2). The expression of protein kinase N3 (Pkn3), a Rho effector, increased during osteoclast differentiation. Trabecular bone mass was significantly greater in Pkn3-deficient mice than in wild-type mice due to the decreased bone-resorbing activity of osteoclasts. Pkn3 bound to c-Src and Pyk2 in a Wnt5a-Ror2 signaling-dependent manner, thereby enhancing the kinase activity of c-Src in osteoclasts. The binding of Pkn3 to c-Src was essential for the bone-resorbing activity of osteoclasts.ConclusionWnt5a-Ror2 signaling promotes the bone-resorbing activity of osteoclasts by activating the Daam2-Rho-Pkn3-c-Src pathways. Pkn3 inhibitors, therefore, have potential as therapeutic agents for osteoporosis and bone destruction in inflammatory diseases.