The mechanism by which
aluminum chloride stimulates de novo bone formation is unknown. To evaluate the role of bone remodeling and mature osteoblastic function in
aluminum-induced neoosteogenesis, we compared the osteogenic effects of
aluminum in normal beagles to those in animals with low turnover
osteomalacia induced by treatment with
etidronate [1-hydroxyethane-1,1-
diphosphoric acid (HEBP)]. As assessed by quantitative bone histomorphology, beagles treated with HEBP developed low turnover
osteomalacia characterized by a 78% reduction in osteoblast number, a 5.5-fold increase in osteoid volume, complete absence of active mineralization, and diminished resorption surfaces compared to untreated controls. The iv administration of
aluminum chloride to normal dogs generated new trabecular structures in the marrow cavity consistent with induction of de novo bone formation. This response consisted of increased trabecular bone volume and number, accumulation of woven osteoid, and increased number of bone-forming cells. The concomitant administration of HEBP failed to prevent induction of de novo bone formation by
aluminum. Instead, the neoosteogenic process was superimposed on low turnover
osteomalacia in HEBP-treated dogs. Serum
aluminum concentrations were increased 2-fold, whereas bone
aluminum accumulation was reduced by 58% in HEBP- and
aluminum-treated dogs compared to that in
aluminum-treated controls. These findings indicate that
aluminum stimulation of neoosteogenesis in beagles is independent of mature osteoblast function, normal bone remodeling, and total bone
aluminum accumulation. Rather,
aluminum-induced de novo bone formation appears to result from stimulation of mesenchymal precursors to form a primitive type of bone which is distinct from coupled bone formation.