Thermal stability of cortical bone collagen in relation to age in normal individuals and in individuals with osteopetrosis

The thermal stability of cortical bone collagen was determined in iliac crest biopsies obtained from 41 normal individuals (21 women aged 20–96 years and 20 men aged 21–84 years) and 8 individuals with autosomal dominant osteopetrosis type I (4 women and 4 men aged 17–63 years). The cortical bone was decalcified and the bone matrix was cut into 80-μm-thick freeze sections parallel to the bone surface. Circular specimens punched out from the sections were used for determination of area shrinkage during gradual heating and shrinkage temperature, T s (representing the temperature for 50% of the area shrinkage). In normal men, T s was not found to decrease until the age of 60–65 years, but was markedly decreased in the elderly individuals. In normal women, T s varied considerably throughout the age range tested, without relationship to age. In contrast to agematched controls, T s decreased with age in men with osteopetrosis, whereas T s in affected women was neither related to age nor different from the highly variable values found in age-matched normal women. Previous findings in rats indicate that T s decreases with the chronological age of the bone collagen. The present results agree with these findings, which imply that a reduction in turnover rate of bone results in an increasing age and a reduced T s of the constituent collagen. Following this assumption, the turnover rate of bone seems to be more variable hi women than in men and reduced in osteopetrotic men. A T s gradient which was demonstrated through the cortical lamina in the osteopetrotic individuals may reflect the presence of older, unexchanged collagen, which is superimposed younger collagen. The present results demonstrate that the defective cortical bone resorption characteristic of osteopetrosis is accompanied by an accumulation with age of cortical bone collagen with reduced T s . The reduction in T s indicates that osteopetrosis implies an increasing proportion of abnormally aged cortical bone collagen.