Effects of etidronate-mediated suppression of bone remodeling on aluminum-induced de novo bone formation.
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.
Quarles
L D
LD
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Drezner
M K
MK
D000535:Aluminum / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002452:Cell Count; D002712:Chlorides / Q000494:pharmacology*; D004285:Dogs; D012968:Etidronic Acid / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010018:Osteomalacia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D000535:Aluminum; D012968:Etidronic Acid