title: Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency.
abstract: Recent findings have shown that bisphosphonates had different effects on the urinary excretion of free and peptide-bound cross-links. Because of this discrepancy, we investigated the effects of another antiresorptive therapy, i.e. vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g elemental calcium daily for 6 months) in elderly women (n = 21, age: 83.5 +/- 1.5 yr) with vitD insufficiency and secondary hyperparathyroidism (mean level 25 hydroxy vitamin D = 3.17 +/- 1.2 ng/mL, mean level of intact parathormone = 45.3 +/- 22.7 pg/mL) on the urinary excretion of free and peptide-bound cross-links. A group of free-living, healthy elderly women (n = 25, age: 76.6 +/- 3.1 yr) with a normal vitD status (mean level of 25 OH D = 23.4 +/- 8.9 ng/mL, intact parathormone = 30.2 +/- 11.2 pg/mL) was simultaneously studied. Bone resorption was assessed by total (T), free (F), peptidyl (P) hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) measured with high performance liquid chromatography, by F-LP determined with enzyme linked immunosorbent assay (iF-LP) and by the N- and C-terminal telopeptides of type I collagen (NTX and Cross-laps) before and after (3 and 6 months) therapy. Comparison of the two groups of elderly women at baseline showed that the urinary excretion of pyridinoline cross-links (T, F, and peptide-bound forms) and of telopeptide fragment of type I collagen were all increased in patients with a low vitD status. Highly significant differences were seen principally for T-HP, F-HP, and F-LP (P < 0.001). Correlation studies between each marker showed that the values of pyridinoline cross-links (T and peptide-bound forms) and of the telopeptide fragments of type I collagen correlated well, but the correlation was slightly less pronounced between free pyridinolines and the other markers. After treatment, the response to therapy was greatest for peptide-bound cross-links assessed by high performance liquid chromatography and for telopeptide fragments of type I collagen (percent change at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0.05, -31% for NTX P < 0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F-HP and F-LP) assessed by high performance liquid chromatography as well as by immunoassay remained unchanged at 3 and 6 months. Because marked and significant changes were seen with peptide-bound cross-links only and not with free forms, we conclude that vitD and Ca therapy has the same effects as bisphosphonates on the urinary excretion of free and peptide-bound cross-links. So far, no rational mechanism can be given to explain this discrepancy, and further studies are needed before routine application of these bone collagen degradation products as bone resorption markers.
authors.affiliation: Laboratoire de Pharmacie Clinique, Faculté de Pharmacie, Amiens, France.
authors.forename: S
authors.initials: S
authors.lastname: Kamel
authors.forename: M
authors.initials: M
authors.lastname: Brazier
authors.forename: J C
authors.initials: JC
authors.lastname: Rogez
authors.forename: O
authors.initials: O
authors.lastname: Vincent
authors.forename: M
authors.initials: M
authors.lastname: Maamer
authors.forename: G
authors.initials: G
authors.lastname: Desmet
authors.forename: J L
authors.initials: JL
authors.lastname: Sebert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000652:urine*; D015415:Biomarkers; D001862:Bone Resorption / Q000652:urine; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000008:administration & dosage / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000652:urine*; D024042:Collagen Type I; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000652:urine*; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000652:urine
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D002762:Cholecalciferol; C015484:pyridinoline; D003094:Collagen; D002112:Calcifediol; D002118:Calcium