REDUCED CONCENTRATIONS OF COLLAGEN CROSS-LINKS ARE ASSOCIATED WITH REDUCED STRENGTH OF BONE

The known cross-links of bone collagen are derived from lysine and hyd roxylysine. The first step in the enzymatic cross-linking process is a deamination by lysyl oxidase producing an aldehyde which then may con dense with a lysyl or hydroxylysyl residue of a neighbouring collagen molecule. Some of the resulting divalent aldimine and oxo-imine cross- links may later on be incorporated in trivalent hydroxylysyl-pyridinol ine and lysyl-pyridinoline crosslinks. In bone collagen prepared from the cancellous bone of vertebral bodies of osteoporotic individuals we found a reduced stability towards acetic acid and pepsin, and a subst antial reduction in the concentration of the divalent collagen cross-l inks compared with sex- and age-matched controls. To what extent do th e collagen cross-links influence the mechanical properties of bone? be ta-amino-propionitrile (BAPN) irreversibly inhibits the enzyme lysyl o xidase and therefore, the formation of cross-links between the collage n molecules. In the present study female rats, 70 days old, injected s ubcutaneously two times daily with BAPN (333 mg/kg/day) for 1 month an d saline injected control rats were studied. The concentration of the hydroxypyridinium cross-links of femoral mid-diaphyseal cortical bone was determined by HPLC with fluorescence detection and the mechanical properties of the rat femoral diaphyses were analyzed by a materials t esting machine. The BAPN injections resulted in a 45% reduction in the concentration of the hydroxypyridinium crosslinks and a 31% decrease in the stability of the bone collagen towards acetic acid and pepsin c ompared with the control rats. No changes were found in ash or collage n concentrations of the cortical bone. The mid-diaphyseal deflection u ntil breaking, bending stress and elastic stiffness (Young's modulus) of the BAPN injected rats were decreased by 21%, 26% and 30%, respecti vely, compared with the control rats. The present study shows that col lagen cross-links are essential for bone to possess a sufficient defle ction capacity, bending strength and stiffness.