Pathological Mechanisms of Bone Disease

Much clinical and experimental experience has been obtained about the manifestation of bone diseases, especially in renal patients. Many patients with Al-induced bone disease remain asymptomatic. There are two distinct forms of Al bone disease. The most severe form is osteomalacia, with recurrent fractures and resistance to vitamin D therapy. This disease is characterized by an increase of osteoid due to a mineralization defect induced by Al that is localized at a critical site in the bone, i.e., the osteoid calcification front [250]. The adynamic bone disease is another form of Al-related bone disease, characterized by a reduced bone turnover [97]. Al can have a direct negative effect on the bone by deposition at the mineralization front, causing a defective calcification. This is due to the influence of Al on calcium-phosphorus precipitation, crystal formation and crystal growth [251]. There might also be a toxic effect on the proliferation of osteoblasts and on mature osteoblasts with a time- and dose-dependent effect on osteoblast growth and function [143]. 

Al also suppresses PTH secretion and maybe as well as PTH synthesis, which results in reduced bone formation and increases Al accumulation in the bone [252]. Other studies have found that  

These in vitro findings allow us to suggest that transferrin receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaC03 intake, play a role in the development of hypoparathyroidism associated with Al bone disease. The exact mechanism by which Al-transferrin suppresses iPTH secretion remains to be elucidated [253]. Hyperparathyroidism may afford the bone some protection against the toxic effects of Al [17]. 

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