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.