The Effect of Clodronate (Dichloromethylene Diphosphonate) on the Mineral Concentration of Dental Enamel and Bone of the Miniature Swine

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Abstract
Diphosphonates are compounds which prevent the crystallisation of calcium phosphates from solution. Our aim was to study the effects of clodronate (dicloromethylene diphosphonate), one of the diphosphonates, on the mineral concentrations of dental enamel and bone. In a subchronic experiment the effects of this compound were investigated. The drug was administered orally in three doses (100, 300, 1000 mg/kg) per day to 32 Gottingen miniature swines for six months. From the acid etch biopsy of enamel the amount of dissolved hydroxyapatite, and the concentrations of fluoride and magnesium were measured. The calcium, phosphorus, fluoride, magnesium carbonate and citrate concentrations were determined from the cancellous bone sample. All values were calculated for dry bone. Calcium/phosphorus and calcium/magnesium ratios were calculated for both enamel and bone. In tooth enamel the magnesium concentration showed a significant dose dependent decrease and calcium/magnesium ratio a significant dose dependent rise. Calcium phosphorus/ratio exhibited a dose dependent increase in surface enamel. Bone fluoride concentration showed a highly significant and calcium/magnesium ratio a significant dose dependent rise. Clodronate seems to interfere with the remineralisation process of tooth enamel, through its effect on magnesium. Incorporation of the drug also appears to exhibit a marked action on the fluoride metabolism of bone. This may require attention in certain long term treatment situations with clodronate in high fluoride areas.