BAPN dose dependence of mature crosslinking in bone matrix collagen of rabbit compact bone: corresponding variation of sonic velocity and equatorial diffraction spacing.

Crosslinking density in demineralized bone matrix collagen was found to depend on the beta-aminopropionitrile (BAPN) dose level for compact bone from rabbit femurs. The dependence was demonstrated for the hydroxypyridinium (HP) concentration, a mature crosslink. A more consistent dependence on BAPN dosage was observed for the fraction of the demineralized bone matrix insoluble in 0.5 M acetic acid (AIF) corresponding to the remaining crosslinked collagen. The average HP concentration in 21 week old controls was 0.24 moles HP/mole collagen which decreased to 0.13 +/- 0.04 for the same age rabbits dosed with 1 gm BAPN/kg/day for 13 wks. The comparable mean AIF values were 0.91 for controls and 0.75 for maximum dose level. Most of the effect of BAPN on crosslinking was observed at the lower dosages below 0.2 g/kg/day. On the other hand, overt osteolathyritic symptoms are seen only for BAPN dosages greater than 0.2 g/kg/day. The mean sonic plesio-velocity was previously found to decrease from 3.4 to 3.03 km/sec as the BAPN dosage was increased. A similar close relationship was discovered for the equatorial diffraction spacing in fully mineralized bone which increased from 1.235 for normal rabbit bone to 1.28 nm for maximum dose. Most of the effect on these physical properties is exhibited at the highest BAPN dosage after much of the decrease in mature crosslinking density has been observed and when the further decrease in mature crosslinking density proceeds very slowly with increased drug dosage. These observations suggest that osteolathyrism does not become manifest until practically all mature crosslinking that can be affected has been inhibited. The mineralization process apparently can be maintained in the newly laid collagen even in the presence of severe osteolathyritic conditions. Intermolecular crosslinking in bone collagen appears to play an important role in the development of bone properties whether by direct or indirect processes. Much of the effects on bone properties occur at the higher BAPN dosages where overt osteolathyrism is observed and where there seem to be only small changes in crosslinking density.