L. Alvarez et al., Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease, BONE, 29(5), 2001, pp. 447-452
The aim of this study was to investigate the usefulness of biochemical mark
ers of bone turnover for monitoring treatment efficacy of Paget's disease o
f bone, and also to evaluate the utility of biological variation data in ch
oosing the best markers for assessment of biochemical response to therapy.
Thirty-eight patients with Paget's disease were included in a prospective s
tudy. All received 400 mg/day of oral tiludronate for 3 months. In 31 patie
nts that completed treatment, biochemical markers were measured at baseline
and at I and 6 months after treatment ended. In serum we determined the le
vels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP),
procollagen type I N-terininal propeptide (PINP), and C-terminal telopeptid
e of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline
(Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and N
Tx, respectively). Quantitative bone scintigraphy was performed at baseline
and at 6 months after discontinuation of therapy. A ratio for monitoring r
esponse to treatment was obtained for each marker. This ratio reflected the
size of treatment response of the marker in relation to the value of its c
ritical difference. Thus, ratio values of > 1 indicated a significant decre
ase of the marker after therapy. In addition, response to therapy was evalu
ated according to disease activity. Mean values of all markers of bone turn
over decreased significantly after therapy. Serum bAP and PINP and urinary
NTx showed the highest percentage reduction (between 58% and 68%). Furtherm
ore, serum bAP and PINP showed the highest ratios for monitoring changes in
duced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary
CTx as well as Hyp showed mean ratios for monitoring changes of < 1, indic
ating a low sensitivity for monitoring treatment. Patients with polyostotic
disease showed a continuous decrease in mean values for all markers at 6 m
onths from the end of therapy, whereas, in monostotic patients, there was a
trend toward increased levels at this timepoint. In conclusion, serum bAP
and PINP were the most sensitive markers for monitoring treatment efficacy
in Paget's disease, although serum tAP and urinary NTx were also sensitive
markers for monitoring changes. Data on biological variation are useful for
assessing actual changes induced by treatment. (C) 2001 by Elsevier Scienc
e Inc. All rights reserved.