Garnero P, Gineyts E, Schaffer A V, Seaman J, Delmas P D
INSERM, Lyon, France.
Arthritis Rheum. 1998 Feb;41(2):354-60. doi: 10.1002/1529-0131(199802)41:2<354::AID-ART20>3.0.CO;2-5.
We have previously shown that the woven pagetic bone in patients with Paget's disease is characterized by an impaired degree of beta-isomerization of C-telopeptides of type I collagen molecules, which results in a preferential urinary excretion of nonisomerized type I collagen C-telopeptide breakdown products (CTX). The aim of this study was to measure the urinary excretion of nonisomerized (alpha) and beta-isomerized (beta) CTX in patients with Paget's disease treated with a bisphosphonate.
We studied 28 patients with active Paget's disease of bone who were a part of a randomized, double-blind, placebo-controlled study comparing the effects of several doses of a single injection of zoledronate, a new potent bisphosphonate. Serum bone alkaline phosphatase (BAP) and type I collagen C-terminal extension propeptide (PICP) and urinary excretion of free deoxypyridinoline (free D-Pyr), N-telopeptide breakdown products (NTX), alphaCTX, and betaCTX were measured at baseline and 5, 10, 30, and 60 days after injection.
At baseline, all markers were significantly increased in the patients compared with a group of 97 sex- and age-matched controls, with a greater increase in BAP (12-fold), NTX (19-fold), and alphaCTX (10-fold) compared with PICP (2.2-fold), free D-Pyr (2.5-fold), and betaCTX (3-fold). The ratio of alphaCTX to betaCTX was about 3-fold higher than in controls (2.1 versus 0.76; P < 0.001). After a single intravenous injection of zoledronate (200 or 400 microg), all markers decreased within 5 days, except for BAP and free D-Pyr, which decreased on day 10. The maximum decrease was greater and occurred faster for NTX, alphaCTX (-55% after 10 days), and betaCTX (-42% after 10 days) than for free D-Pyr (-25% after 30 days). After the initial decrease, the urinary excretion of betaCTX increased between days 10 and 30 and returned to pretreatment levels after 2 months, in contrast to the sustained decrease in alphaCTX and NTX that was maintained up to 60 days. The urinary ratio of alphaCTX to betaCTX decreased significantly between days 10 and 60, and returned to within the normal range in most patients after 2 months of treatment, probably reflecting the progressive replacement of woven bone by a lamellar bone with a higher and normal degree of beta-isomerization of type I collagen, as previously documented by histology.
The determination of the urinary ratio of alphaCTX to betaCTX could be useful for monitoring the effect of bisphosphonate treatment in restoring bone quality in patients with Paget's disease.
我们之前已经表明，佩吉特病患者的编织状畸形骨以I型胶原分子C端肽段的β-异构化程度受损为特征，这导致非异构化的I型胶原C端肽段分解产物（CTX）优先经尿液排泄。本研究的目的是测量接受双膦酸盐治疗的佩吉特病患者尿液中非异构化（α）和β-异构化（β）CTX的排泄情况。
我们研究了28例活动性骨佩吉特病患者，他们参与了一项随机、双盲、安慰剂对照研究，该研究比较了几种剂量的单次注射唑来膦酸（一种新型强效双膦酸盐）的效果。在基线以及注射后5、10、30和60天测量血清骨碱性磷酸酶（BAP）、I型胶原C端延长前肽（PICP）以及游离脱氧吡啶啉（游离D-Pyr）、N端肽段分解产物（NTX）、αCTX和βCTX的尿液排泄量。
在基线时，与97名年龄和性别匹配的对照组相比，患者的所有标志物均显著升高，与PICP（2.2倍）、游离D-Pyr（2.5倍）和βCTX（3倍）相比，BAP（12倍）、NTX（19倍）和αCTX（10倍）升高幅度更大。αCTX与βCTX的比值比对照组高约3倍（2.1对0.76；P<0.001）。单次静脉注射唑来膦酸（200或400μg）后，除BAP和游离D-Pyr在第10天下降外，所有标志物在5天内均下降。NTX、αCTX（10天后下降55%）和βCTX（10天后下降42%）的最大降幅比游离D-Pyr（30天后下降25%）更大且发生得更快。在最初下降后，βCTX的尿液排泄量在第10天至30天之间增加，并在2个月后恢复到治疗前水平，与之形成对比的是，αCTX和NTX持续下降直至60天。αCTX与βCTX的尿液比值在第10天至60天之间显著下降，并且在大多数患者治疗2个月后恢复到正常范围内，这可能反映了编织骨逐渐被板层骨替代，I型胶原的β-异构化程度更高且正常，这一点先前已通过组织学得到证实。
测定尿液中αCTX与βCTX的比值可能有助于监测双膦酸盐治疗对恢复佩吉特病患者骨质的效果。
