Direct analysis of bone turnover in experimental arthritis

Chronic arthritis usually leads to loss of periarticular bone. Inflammatory bone loss results from an imbalance between bone formation and bone resorption. Recent research has focused on the role of osteoclast formation and bone resorption in arthritis. However, bone resorption cannot be seen isolated since it is closely linked to bone formation and changes in bone formation may also affect inflammatory bone loss.

To assess bone resorption and bone formation simultaneously, we developed a histological technique that allowed visualization of osteoblast function by in situ hybridization for osteocalcin and osteoclast function by histochemistry for tartrate-resistant acid phosphatase simultaneously on the same section. Paw sections from human tumor necrosis factor transgenic mice, which develop erosive arthritis, were analyzed at three different sites: subchondral bone erosions, adjacent Haversian bone channels and endosteal regions distant from bone erosions.

In subchondral bone erosions, resorption sites were far more common than formation sites. Thus, both the areas covered by osteoclasts as well as numbers of osteoclasts showed a fivefold increase compared with the area covered by osteoblasts and osteoblast numbers, respectively. In contrast, adjacent Haversian channels showed a completely different bone turnover, with functional osteoblasts significantly more frequent than osteoclasts. Bone turnover in Haversian channels was even higher (50% bone surface covered by osteoclasts or osteoblasts) than in subchondral bone erosions (30%). At endosteal sites distant from bone erosions, bone turnover was far lower (6%) and again bone formation exceeded bone resorption.

These data indicate that bone resorption dominates at skeletal sites close to synovial inflammatory tissue, whereas more distant sites such as the Haversian channels attempt to counterregulate this process by increased bone formation.