Collagen-related abnormalities, reduction in bone quality, and effects of menatetrenone in rats with a congenital ascorbic acid deficiency.

In this study, we focused on collagen metabolism as a factor involved in menatetrenone (MK-4)-related improvement in bone quality. Using rats with a congenital ascorbic acid (AA) deficiency, osteogenic disorder Shionogi (ODS) rats, we established a model in which abnormal collagen metabolism reduced bone mechanical properties, and investigated the effects of MK-4. We divided 13-week-old ODS rats into four groups: Pre, AA sufficiency (AA(+)), AA deficiency-control (AA(-)control), and AA deficiency+ MK-4-treated (AA(-)MK-4). MK-4 was given as a dietary supplement (30 mg/kg). At the beginning (pre) and after two, three, and four weeks, seven rats in each group were killed to measure plasma bone metabolism and femoral bone mass data and bone mechanical properties. In the rats killed after four weeks, histomorphometric data of the tibiae, the total amino acid level in bone collagen, and rates of proline and lysine hydroxylation were determined. In the AA(+)group, both the cortical bone mass data and bone mechanical properties were serially increased. However, in the AA(-)control group, the cortical bone mass data were similar for four weeks and the bone mechanical properties decreased after three to four weeks. After four weeks, the total level of amino acids in bone collagen and rates of proline and lysine hydroxylation were significantly lower in the AA(-)control group than in the AA(+)group. MK-4 increased bone mechanical properties after four weeks without influencing cortical bone mass. Simultaneously, it inhibited decreases in the total level of amino acids in collagen (P = 0.017). The rates of proline and lysine hydroxylation were higher in the AA(-)MK-4 group than in the AA(-)control group, but not significantly. These results suggest the level of collagen and abnormalities of hydroxylation are involved in the AA deficiency-related reduction in bone mechanical properties, and that MK-4 improves bone mechanical properties by restoring collagen metabolism.