Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine.
A new immunoassay using an ELISA approach for measuring urinary excretion of cross-linked N-telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 early postmenopausal women who participated in a placebo-controlled trial of the aminobisphosphonate, alendronate sodium. Eight blood and urine samples were collected over a 9 month interval. Baseline cross-linked peptide excretion varied from 26 to 216 pmol BCE (bone collagen/mumol Cr. Within-subject variability (CV) for cross-linked peptide excretion was 20.2% over the 9 months in placebo-treated subjects, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respectively. Baseline cross-linked peptide excretion correlated significantly (p < 0.001) with baseline total urine lysylpyridinoline and serum osteocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral density at entry (r = -0.26, p < 0.05). Treatment for 6 weeks with alendronate produced a dose-dependent suppression of cross-linked peptide excretion (0 +/- 8, 29 +/- 6, 56 +/- 5, and 64 +/- 3% for 0, 5, 20, and 40 mg, respectively, p < 0.01 versus placebo for treatment effect), with a return toward pretreatment values during follow-up. Measurement of the urinary cross-linked N-telopeptides of type I collagen by this new ELISA approach appears promising as a simple and reliable method to assess overall bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Gertz
B J
BJ
Merck Research Laboratories, Rahway, New Jersey.
Shao
P
P
Hanson
D A
DA
Quan
H
H
Harris
S T
ST
Genant
H K
HK
Chesnut
C H
CH
Eyre
D R
DR
D019386:Alendronate; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy / Q000652:urine*; D002118:Calcium / Q000652:urine; D004164:Diphosphonates / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008159:Lumbar Vertebrae; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000652:urine*; D010446:Peptide Fragments / Q000652:urine*; D011347:Procollagen / Q000652:urine*; D015203:Reproducibility of Results
D000596:Amino Acids; D015415:Biomarkers; D004164:Diphosphonates; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; C036020:deoxypyridinoline; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate