DIFFERENT RESPONSES OF BIOCHEMICAL MARKERS OF BONE-RESORPTION TO BISPHOSPHONATE THERAPY IN PAGET DISEASE

We examined the response of different biochemical markers of bone reso rption to bisphosphonate therapy (400 mg of etidronate daily for 6 mon ths) in mild Paget disease (n = 14). Urinary markers included hydroxyp roline (OHP), total (T) and free (F) pyridinolines (Pyds) determined b y HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-t erminal telopeptides of type I collagen (NTx, CL), Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-termina l telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minim al response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 /- 3.4, respectively), The response was greatest for urinary telopepti des (NTx and Ct; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectivel y). The response was somewhat greater for TPyds than for FPyds. We con clude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therap y than do FPyds and may be more sensitive indicators of bone resorptio n; and (c) as yet no evidence suggests that these markers are substant ially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and t he clinical utility of these measurements remains uncertain.