Open AccessMeasurement of urinary excretion of nonisomerized and β‐isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget's disease
Author(s) -
Garnero Patrick,
Gineyts Evelyne,
Schaffer A. Victoria,
Seaman John,
Delmas Pierre D.
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199802)41:2<354::aid-art20>3.0.co;2-5
Subject(s) - n terminal telopeptide , type i collagen , medicine , endocrinology , bisphosphonate , excretion , urinary system , bone resorption , bone disease , bone remodeling , chemistry , alkaline phosphatase , osteoporosis , osteocalcin , biochemistry , enzyme
Objective: We have previously shown that the woven pagetic bone in patients with Paget's disease is characterized by an impaired degree of β‐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 (α) and β‐isomerized (β) CTX in patients with Paget's disease treated with a bisphosphonate. Methods 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), αCTX, and βCTX were measured at baseline and 5, 10, 30, and 60 days after injection. Results 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 αCTX (10‐fold) compared with PICP (2.2‐fold), free D‐Pyr (2.5‐fold), and βCTX (3‐fold). The ratio of αCTX to βCTX 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 µg), 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, αCTX (‐55% after 10 days), and βCTX (‐42% after 10 days) than for free D‐Pyr (‐25% after 30 days). After the initial decrease, the urinary excretion of βCTX increased between days 10 and 30 and returned to pretreatment levels after 2 months, in contrast to the sustained decrease in αCTX and NTX that was maintained up to 60 days. The urinary ratio of αCTX to βCTX 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 β‐isomerization of type I collagen, as previously documented by histology. Conclusion The determination of the urinary ratio of αCTX to βCTX could be useful for monitoring the effect of bisphosphonate treatment in restoring bone quality in patients with Paget's disease.