The effect of aluminum on the bone inductive properties of implanted bone matrix was studied in rats. After decalcification femur sections were placed in either 0.1 or 0.01 M AlCl3 or a solution of similar pH without Al for 24 hours. Following 28 days of implantation in subcutaneous pouches the aluminum content was 3232 ± 1020 and 51 ± 6 mg/kg in the matrix pretreated with 0.1 and 0.01 M AlCl3. At the same time period following implantation the matrix calcium content was 794 ± 539 and 3038 ± 692 mmol/kg in the 0.1 and 0.01 M AlCl3 pretreated groups versus 4252 ± 579 mmol/kg in the control group (P<0.01). In the control group bone histology showed extensive osteoblastic and osteoclastic remodelling, tetracycline labeling and bone formation. In contrast all of these histological features were virtually absent in aluminium treated matrix. Aluminum-induced resistance of bone matrix to collagenase degradation and restoration of bone inductive properties with chelation suggests that aluminum forms intermolecular cross links between collagen fibrils. Aluminum-induced cross links of collagen fibrils and/or its effects on bone inductive proteins present in bone matrix could explain the mechanism by which aluminium induces osteomalacia.
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Zhu, J. M., Huffer, W., & Alfrey, A. C. (1990). Effect of aluminum on bone matrix inductive properties. Kidney International, 38(6), 1141–1145. https://doi.org/10.1038/ki.1990.324