Exercise increases pyridinoline cross-linking and counters the mechanical effects of concurrent lathyrogenic treatment

BAPN treatment significantly reduced lysylpyridinoline, pyrrole, hydroxylysinorleucine, and total mature collagen cross-linking, resulting in decreased bone elastic modulus and increased yield strain despite a marginal increase in TMD. Exercise caused a shift toward pyridinoline cross-linking, with increased hydroxylysylpyridinoline and decreased pyrrole cross-linking resulting in total mature cross-linking and estimated tissue level mechanical properties matching sedentary control levels. Exercise superimposed on BAPN treatment increased total mature cross-linking from BAPN to control levels, but did so by increasing pyridinoline, not pyrrole, cross-links. Exercise also counteracted the BAPN effects on modulus and strain, without a change in TMD. Pyrrole cross-linking was the strongest correlate of modulus (r = 0.470, p < 0.01) and yield strain (r = − 0.467, p < 0.01). Cross-links with similar levels of telopeptide lysine hydroxylation to pyrrole (lysylpyridinoline and hydroxylysinorleucine) also correlated with modulus and strain to a lesser extent. In conclusion, exercise in growing mice promotes pyridinoline collagen cross-linking in bone, the resulting increase in total mature cross-linking is sufficient to counteract the mechanical effects of concurrent cross-link inhibition, and this responsiveness to loading is a potential means by which exercise might improve bone quality in diseased or otherwise compromised bone.