The influence of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on lysine hydroxylation and cross-link formation in rat bone, cartilage and skin collagen

Abstract

The effects in vivo of dichloromethanediphosphonate and 1-hydroxyethane 1,1-diphosphonate on collagen solubility, hydroxylation of lysine and proline and on the formation of collagen intermolecular cross-links were studied by using rat bone, cartilage and skin tissues. Dichloromethanediphosphonate decreased bone collagen solubility both in acetic acid and after pepsin treatment. Although none of the diphosphonates had any effect on the hydroxylation of proline, dichloromethane-diphosphonate, but not 1-hydroxyethane-1,1-diphosphonate, increased the number of hydroxylysine residues in the alpha-chains of bone, skin and cartilage collagen. The stimulatory effect was dose-dependent. The dichloromethanediphosphonate-mediated increase in hydroxylysine residues in bone and cartilage was manifested in an increase of dihydroxylysinonorleucine, the cross-link that is formed by the condensation of two hydroxylysine residues. The cross-link hydroxylysinonorleucine, a condensation product of hydroxylysine and lysine, on the other hand, was decreased. The total number of intermolecular cross-links was not changed by the diphosphonate.

Is a low skinfold thickness an indicator of osteoporosis?

“…The osteoporotic group was significantly older (P < 0.001) with a longer duration of time than the normal controls since the menopause (P < 0.0001) but linear regression of SFT against -chronological and menopausal age in normals (Figs 1 and 5 ) showed no correlation. This observation is contrary to previous reports (Hall et al, 1981;Hastie & Millard, 1983;Branchet et al, 1990;Chappard el al., 1991). However, no previous study has examined the relation between chronological age and SFT in a population of women with normal spinal and femoral BMD.…”

Bisphosphonates: mechanisms of action.

“…However, since the augmentation is small, it needs to be confirmed. This finding is also consistent with the observation that clodronate increases collagen synthesis by bone and cartilage cells in culture (14) and that alendronate increases mineralized nodule formation in bone marrow cultures (15).…”

Bisphosphonates: Mechanisms of Action

“…At the cellular level bisphosphonates have been shown to increase in vitro the proliferation of osteoblasts (119,120) and cartilage cells (121), as well as the biosynthesis of collagen and osteocalcin by bone cells (119,122,123) and proteoglycans by cartilage cells (124). The effect on collagen may be partially due to impaired intracellular collagenolysis (125).…”