Tosi Patrizia, Zamagni Elena, Cellini Claudia, Parente Raffaele, Cangini Delia, Tacchetti Paola, Perrone Giulia, Ceccolini Michela, Boni Paola, Tura Sante, Baccarani Michele, Cavo Michele
Institute of Hematology and Medical Oncology L. e A. Seràgnoli Bologna University, Bologna, Italy.
Eur J Haematol. 2006 May;76(5):399-404. doi: 10.1111/j.0902-4441.2005.t01-1-EJH2520.x. Epub 2006 Feb 15.
Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism.
In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d).
At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (+/-SE) urinary NTX (52.7 +/-6.9 nmol/mmol creatinine +/-6.9 vs. 14 +/- 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 +/-945 pmol/L vs. 1414.9 +/- 173.8 pmol/L, P = 0.000) was observed in patients obtaining > or =partial response, at variance to what has been detected in patients showing <partial response.
Among all bone resorption markers, urinary NTX and serum crosslaps seem to be strictly related to the extent of bone involvement in MM. Combined thalidomide + dexamethasone and zoledronic acid seem to be highly effective in reducing bone resorption in sensitive patients, although the relative contribution of each drug cannot yet be determined.
在多发性骨髓瘤（MM）患者的诊断及疾病过程中，经常观察到骨骼受累情况。对骨转换生化标志物的评估能够动态评估特定治疗对骨代谢的影响。
在本研究中，对参与“博洛尼亚2002”临床试验的40例患者（23例男性，17例女性，中位年龄 = 53.5岁）在诊断时及诱导治疗后评估了骨吸收标志物[尿游离吡啶啉（PYD）、脱氧吡啶啉（DPYD）、I型胶原N端肽（NTX）和C端肽（血清交联C末端肽）]以及骨形成标志物[骨碱性磷酸酶（BAP）和骨钙素]。根据研究设计，所有患者接受4个月的沙利度胺（第1 - 2周100 mg/d，之后200 mg/d）、地塞米松（奇数周期第1 - 4天、9 - 12天、17 - 20天/28天给予40 mg/d，偶数周期第1 - 4天给予40 mg/d）和唑来膦酸（4 mg/28天）联合治疗。
诊断时，虽然超过40%的患者骨吸收标志物升高，但通过X线评估，仅NTX（P = 0.029）和交联C末端肽（P = 0.000）与骨骼病变程度显著相关。治疗4个月后，获得≥部分缓解的患者尿NTX均值（±标准误）显著降低（52.7±6.9 nmol/mmol肌酐±6.9 vs. 14±1.42 nmol/mmol肌酐，P = 0.000），血清交联C末端肽也显著降低（6242.4±945 pmol/L vs. 1414.9±173.8 pmol/L，P = 0.000），这与部分缓解未达标的患者情况不同。
在所有骨吸收标志物中，尿NTX和血清交联C末端肽似乎与MM患者的骨受累程度密切相关。沙利度胺 + 地塞米松和唑来膦酸联合治疗似乎对敏感患者降低骨吸收非常有效，尽管每种药物的相对贡献尚无法确定。
