Different effects of bisphosphonate and estrogen therapy on free and peptide-bound bone cross-links excretion.
We have measured the free and peptide-bound type I collagen cross-link excretions in normal women and in patients with metabolic bone disease using the HPLC technique and immunoassays recognizing specifically the free or peptide-bound forms of pyridinoline (Pyr). After menopause, free deoxypyridinoline (free D-Pyr) excretion measured by HPLC without urine hydrolysis and expressed as a fraction of the total excretion was lower than in premenopausal women (45 +/- 15% vs. 59 +/- 12%, p < 0.005), whereas the fraction of free Pyr was not changed. In normal pre- and postmenopausal women (n = 43), the fraction of free D-Pyr was negatively correlated with bone turnover rate as assessed by the total urinary excretion of Pyr (r = -0.64, p < 0.001). In patients with a variety of metabolic bone diseases characterized by increased bone turnover (osteoporosis, Paget's disease, and hyperthyroidism), the fractions of free Pyr and free D-Pyr were significantly lower than in premenopausal controls (p < 0.001 for all diseases). After 3 days of intravenous (iv) treatment with the bisphosphonate pamidronate in patients with Paget's disease and osteoporosis, the urinary excretion of cross-linked peptides measured by high performance liquid chromatography (HPLC) or enzyme-linked immunoassay (ELISA) (NTX and CrossLaps) was markedly decreased (-52% and -85% for NTX, -71% and -93% for CrossLaps in Paget's disease and osteoporosis, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Garnero
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P
Inserm Unit 403, Hôpital E. Herriot, Lyon, France.
Gineyts
E
E
Arbault
P
P
Christiansen
C
C
Delmas
P D
PD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000652:urine; D001846:Bone Development / Q000187:drug effects; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D006868:Hydrolysis; D006980:Hyperthyroidism / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000077268:Pamidronate; D017698:Postmenopause; D017697:Premenopause
D000596:Amino Acids; D004164:Diphosphonates; C015484:pyridinoline; C036020:deoxypyridinoline; D000077268:Pamidronate