Changes in the ratio of non-calcified collagen to calcified collagen in human vertebrae with advancing age.

Bone loss associated with aging is associated primarily with a decline in bone formation. To try and further understand the nature of this process we have used a biochemical approach which relies on the fact that osteoid is susceptible to enzymatic degradation whereas calcified collagen is protected by the mineral phase against proteolytic digestion. Our findings show a statistically significant inverse relationship between osteoid and age (r = 0.70 female, r = 0.47 male). A closer relationship was observed when age was related to the ratio of osteoid to bone (r = 0.73 female, r = 0.56 male). In both cases, the observed linear decline begins at an early age and becomes marked with advancing age. Histologic observations illustrate these findings showing decreased osteoid and osteoblasts in the older vertebral specimens compared to the younger ones. Even though the mechanism for osteoid calcification seems to remain unimpaired, the decline of a calcifiable matrix in the presence of normal bone turnover could lead to bone loss.

Inhibition of ectopic calcification of glutaraldehyde crosslinked collagen and collagenous tissues by a covalently bound diphosphonate (APD).

Calcification of collagen-derived prosthesis, such as glutaraldehyde crosslinked porcine heart valves or heart valves assembled out of bovine pericardium, presents a major clinical problem. Their subcutaneous implantation into young rats provides us with a reproducible method of assessing this form of ectopic calcification. Long-term implantation is essential, since some materials which do not calcify within the first month frequently exhibit a delayed calcific response. Crosslinked pericardium is much more likely to calcify than crosslinked tendon or reconstituted crosslinked pepsin extracted bovine type I collagen. The covalent binding of a diphosphonate to collagen and collagen-rich tissues can prevent calcification. The binding of this diphosphonate and its ability to inhibit calcification can be enhanced by increasing the number of amino groups on the collagen molecule. The degree of calcification is inversely related to the number of diphosphonate molecules covalently bound to collagen. Under standard conditions, chemical modifications appear to occur primarily on the surface of the collagen fibrils, as evidenced by the relationship between the number of molecules of APD bound and fibril diameter. The bound diphosphonate seems to interfere with crystal growth and prevent the formation of highly insoluble hydroxyapatite on the surface and interstices of the collagen fibrils.