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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 &lt; 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 &lt; 0.05, -26% for P-LP P &lt; 0.05, -31% for NTX P &lt; 0.01, and -51% for CLaps P &lt; 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.

Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency.