Bone formation is not coupled to bone resorption in site‐specific manner in adult rats

Abstract
The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. It has been clearly shown that in adult man the coupling of formation and resorption involves a site‐specific sequence of events, in which bone resorption is normally followed, at the same site, by bone formation. Whether the coupled processes of bone resorption and formation also occur at the same site in the rat is controversial. To elucidate the spatial relationship between bone formation and resorption in the rat, we compared the percentage of crenated and non‐crenated cement lines with the percentage of crenated and non‐crenated bone surfaces in the proximal tibia of adult rats aged 16 weeks to 2 years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16‐week‐old and 7‐month‐old rats exhibited a low percentage (7–11%) of crenated cement lines, which is opposite to the proportion (88%) we observed in human trabecular bone. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone (rat 1.1–1.4% vs. 5% in humans). In older (2 years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to 45%. These results imply that the major proportion of bone formation in the trabecular bone of growing rats occurs on non‐resorbed surfaces. Thus, although there is substantial evidence that bone formation is coupled to resorption in the rat, such that increased resorption is associated with increased formation, and suppression of resorption suppresses bone formation, bone formation does not necessarily occur on a previously resorbed site. This suggests that in the rat, the processes are not coupled by local release of cytokines or local cell interactions but by some other signal, such as mechanical stimulation. Since site‐specificity appears not to be crucial to the coupling of formation to resorption, the greater site‐specificity of coupling in man, and in older rats, may be attributable to a more static skeleton, which engenders a closer spatial correlation between bone formation and the resorption that induced it.