Body J J, Dumon J C, Gineyts E, Delmas P D
Bone Metabolism Unit and Supportive Care Clinic, Service de Médecine et Laboratoire d'Investigation Clinique HJ Tagnon, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Br J Cancer. 1997;75(3):408-12. doi: 10.1038/bjc.1997.66.
The understanding of the pathophysiology and the monitoring of metastatic bone disease remains unsatisfactory. We compared several new markers of bone turnover in normocalcaemic patients with breast cancer-induced osteolysis before and after a single infusion of the bisphosphonate pamidronate. We studied 19 ambulatory patients with advanced breast cancer and extensive bone metastases who did not receive any systemic antineoplastic therapy. Pamidronate was administered at doses of 30, 60, 90 or 120 mg and the patients were followed weekly during a mean of 8 (range 4-10) weeks. Compared with healthy premenopausal women, the percentage of elevated values at baseline was 47% for fasting urinary calcium (uCa), 74% for hydroxyproline, 83% for CrossLaps (a new marker of type I collagen degradation) and 100% for the collagen cross-links (measured by high performance liquid chromatography), namely pyridinoline (Pyr) and deoxyPyr (D-Pyr). Pretreatment levels of uCa did not correlate significantly with any of the four markers of bone matrix resorption, whereas the correlations between these four markers were generally significant (r(s)=0.43-0.71). Alkaline phosphatase correlated significantly with markers of bone matrix resorption (r(s)=0.54-0.74). All parameters, except phosphaturia (uPi) and the bone formation markers (osteocalcin and alkaline phosphatase), fell significantly after pamidronate therapy, up to day 42 for hydroxyproline, D-Pyr and CrossLaps and day 56 for uCa. This longer lasting effect was probably due to the parathyroid hormone (PTH) surge following the decrease in serum calcium, implying that the decrease in uCa can overestimate the effects of bisphophonates on bone resorption. The decrease in bone turnover parameters was most marked for CrossLaps, indicating the potential of this new marker for monitoring therapy. Sequential determinations of markers of bone matrix resorption should be useful in delineating the optimal therapeutic schemes of bisphosphonates and for evaluating treatment effects on bone in cancer patients.
对转移性骨病的病理生理学的理解以及监测仍不尽人意。我们比较了正常血钙水平的乳腺癌诱导骨溶解患者在单次输注双膦酸盐帕米膦酸前后几种新的骨转换标志物。我们研究了19例晚期乳腺癌且有广泛骨转移的非卧床患者，这些患者未接受任何全身抗肿瘤治疗。帕米膦酸以30、60、90或120mg的剂量给药，患者在平均8周（范围4 - 10周）内每周接受随访。与健康的绝经前女性相比，基线时升高值的百分比分别为：空腹尿钙（uCa）47%、羟脯氨酸74%、CrossLaps（I型胶原降解的新标志物）83%以及胶原交联物（通过高效液相色谱法测量）100%，即吡啶啉（Pyr）和脱氧吡啶啉（D - Pyr）。uCa的治疗前水平与骨基质吸收的四个标志物中的任何一个均无显著相关性，而这四个标志物之间的相关性通常显著（r(s)=0.43 - 0.71）。碱性磷酸酶与骨基质吸收标志物显著相关（r(s)=0.54 - 0.74）。除了尿磷（uPi）和骨形成标志物（骨钙素和碱性磷酸酶）外，所有参数在帕米膦酸治疗后均显著下降，羟脯氨酸、D - Pyr和CrossLaps在第42天，uCa在第56天。这种持续时间更长的效应可能是由于血清钙降低后甲状旁腺激素（PTH）激增，这意味着uCa的降低可能高估了双膦酸盐对骨吸收的影响。骨转换参数的下降在CrossLaps方面最为明显，表明这种新标志物在监测治疗方面的潜力。骨基质吸收标志物的连续测定对于确定双膦酸盐的最佳治疗方案以及评估对癌症患者骨的治疗效果应该是有用的。
