Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease.
The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Paget's disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Paget's disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at 1 and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terminal propeptide (PINP), and C-terminal telopeptide 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 NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response 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 critical difference. Thus, ratio values of >1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced 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, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months 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.
Alvarez
L
L
Service of Clinical Biochemistry, Hospital Clinic, University of Barcelona, Barcelona, Spain. lalvarez@medicina.ub.es
Guañabens
N
N
Peris
P
P
Vidal
S
S
Ros
I
I
Monegal
A
A
Bedini
J L
JL
Deulofeu
R
R
Pons
F
F
Muñoz-Gomez
J
J
Ballesta
A M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers; D016723:Bone Remodeling / Q000502:physiology*; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000008:administration & dosage / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000097:blood* / Q000000981:diagnostic imaging* / Q000188:drug therapy; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000652:urine; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012680:Sensitivity and Specificity
D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C058651:tiludronic acid; D003094:Collagen; D000469:Alkaline Phosphatase