Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

甲状腺功能亢进患者骨代谢指标和甲状腺激素水平变化及其临床意义

为探讨甲状腺功能亢进(甲亢)患者骨代谢指标与甲状腺激素水平的变化, 本文对70例甲亢患者及60名健康对照者采用放射免疫分析法(RIA)测定了Ⅰ型胶原羧基末端肽(ICTP), 全自动微粒子化学发光分析法测定了骨碱性磷酸酶(BAP)及甲状腺激素(T3、T4、FT3、FT4)水平, 同时用二维骨密度仪测定骨密度(BMD).结果表明: 甲亢患者血清BAP、ICTP与甲状腺激素水平均明显高于健康对照组(P均小于0.01), 骨密度(BMD)则显著低于健康对照组(P＜0.01).相关分析显示, 甲亢患者血清BAP、ICTP水平与BMD呈明显负相关(r分别为-0.298和-0.276, P＜0.05), 与T3呈正相关(r分别为0.452和0.531,P＜0.01), 与T4亦呈正相关(r分别为0.419和0.398, P＜0.01).提示甲亢患者骨转换增强, 并以骨吸收增加更为显著, 与甲亢时甲状腺激素分泌过多有关. 定量检测血清BAP、ICTP水平对于甲亢代谢性骨病的诊断、病情研究均有重要的临床价值.     

Pamidronate is superior to ibandronate in decreasing bone resorption,interleukin-6 and beta 2-microglobulin in multiple myeloma

OBJECTIVES: Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients. METHODS: Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radiotherapy were analysed. Bone resorption markers [N-terminal cross-linking telopeptide of type-I collagen (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b)], bone formation markers (bone alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, beta 2-microglobulin), and interleukin-6 (IL-6) were also studied. RESULTS: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and beta 2-microglobulin from the second month of treatment, having no effect on bone formation. TRACP-5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL-6, and beta 2-microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP-5b, starting at the fourth month (P = 0.014), that being continued throughout the 10-month follow-up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP-5b, IL-6, and beta 2-microglobulin from the second month for patients of both groups. CONCLUSIONS: These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL-6, and possibly tumour burden in MM. TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM.     

Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium,cartilage, and bone in the LITHE study

Objective

We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.

Methods

The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early response was evaluated at week 16 as ±20% improvement in swollen/tender joint counts; and ACR50 was evaluated at week 52. Biomarkers (tissue inflammation: C3M, CRPM, and VICM; cartilage degradation: C2M; and bone turnover: CTx and osteocalcin) were tested in serum from baseline, week 4, 16, 24, and 52, and dose-dependent effect was investigated. Patients were divided into the following three groups: early non-responders (ENR), ACR50 responders, and non-responders; their biomarker profiles were compared.

Results

At week 52, CRP was inhibited to 4% and 40% of baseline by TCZ8 and TCZ4, respectively. CRPM (63%), C2M (84%), C3M (69%), and VICM (42%) were significantly (p < 0.05) reduced by TCZ8, but not by TCZ4. MMP3 and osteocalcin changed to <58% and >111%, respectively, in response to TCZ. CTx was not changed significantly. ENRs had significantly less inhibition of CRPM (p < 0.05), C2M (p < 0.01), and C3M (p < 0.01) compared to early responders. There was a significant difference in the C2M, C3M, and CRPM profiles of the ENRs, non-responders, and responders. ACR50 responders had significantly inhibited levels (p < 0.001), irrespective of dose.

Conclusions

TCZ8 strongly inhibited the biomarkers of joint tissue remodeling suggesting that TCZ actively suppresses key pathobiological processes at the site of inflammation in RA patients. The differences in biomarkers' profiles of responders and non-responders indicate that specific responder profiles exist.     

维生素D缺乏性佝偻病患儿破骨细胞活性的研究

目的 探讨维生素D缺乏性佝偻病患儿破骨细胞功能状态,了解其与性别和年龄的关系。方法 选取符合维生素D缺乏性佝偻病诊断标准患儿有68例列入佝偻病组,健康婴幼儿66例列入对照组,检测血清25-(OH)D、抗酒石酸酸性磷酸酶5b(tartrate-resistant acid phosphatase isoform 5b,TRACP5b)、I型胶原交联羧基端肽(carboxyterminal cross-linking telopeptide,CTX),对所得结果采用SPSS 20.0软件进行数据分析处理。结果 维生素D缺乏性佝偻病组较对照组血清25-(OH)D、TRACP5b、CTX水平均低,有显著统计学差异,两组血清25-(OH)D水平婴儿较幼儿均低,两组血清TRACP5b、CTX水平婴儿较幼儿均高,差异有显著统计学意义。两组血清25-(OH)D、TRACP5b、CTX水平男女之间差异均无统计学意义。维生素D缺乏性佝偻病组血清TRACP5b、CTX与25-(OH)D水平呈负相关关系,血清TRACP5b与CTX水平呈正相关关系。结论 维生素D缺乏性佝偻病患儿破骨细胞活性明显活跃。婴儿破骨细胞活性较幼儿明显活跃,同年龄组不同性别之间破骨细胞活性无明显差异。TRACP5b和CTX是评价骨吸收的良好指标。破骨细胞分子标志物可作为维生素D缺乏性佝偻病的评价指标。