DIFFERENT RESPONSES OF FREE AND PEPTIDE-BOUND CROSS-LINKS TO VITAMIN-D AND CALCIUM SUPPLEMENTATION IN ELDERLY WOMEN WITH VITAMIN-D INSUFFICIENCY

Recent findings have shown that bisphosphonates had different effects on the urinary excretion of free and peptide-bound cross-links. Becaus e of this discrepancy, we investigated the effects of another antireso rptive therapy, i.e. vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g elemental calcium daily for 6 months) in elder ly women (n = 21, age: 83.5 +/- 1.5 yr) with vitD insufficiency and se condary 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 grou p 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 studie d. Bone resorption was assessed by total (T), free (F), peptidyl (P) h ydroxylysylpyridinoline (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 telop eptides of type I collagen (NTX and Cross-laps) before and after (3 an d 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. Highl y significant differences were seen principally for T-HP, F-HP, and F- LP (P < 0.001). Correlation studies between each marker showed that th e values of pyridinoline cross-links (T and peptide-bound forms) and o f the telopeptide fragments of type I collagen correlated well, but th e correlation was slightly less pronounced between free pyridinolines and the other markers. After treatment, the response to therapy was gr eatest for peptide-bound cross-links assessed by high performance liqu id chromatography and for telopeptide fragments of type I collagen (pe rcent change at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0. 05, -31% for NTXP < 0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F-HP and F-LP) assessed by high performa nce liquid chromatography as well as by immunoassay remained unchanged at 3 and 6 months. Because marked and significant changes were seen w ith peptide-bound crosslinks only and not with free forms, we conclude that vitD and Ca therapy has the same effects as bisphosphonates on t he urinary excretion of free and peptide-bound cross-links. So far, no rational mechanism can be given to explain this discrepancy, and furt her studies are needed before routine application of these bone collag en degradation products as bone resorption markers.