Interaction of dichloromethylene diphosphonate and vitamin D on bone of thyroparathyroidectomized rats.
Dichloromethylene diphosphonate (Cl2MDP) antagonized the action of vitamin D on bone in thyroparathyroidectomized rats by reducing the metabolic activity of osteoblasts and osteocytes and decreasing the number of osteoclasts. Ultrastructurally, osteoblasts in Cl2MDP-treated rats were interpreted to be less active in bone matrix synthesis. Osteocytes in Cl2MDP-treated rats were interpreted ultrastructurally to be inactive; there was no evidence of bone resorption when compared to osteocytes in rats given vitamin D alone. Abnormal osmiophilic densities in the pericellular bone matrix of rats given vitamin D alone were not present in rats given vitamin D and Cl2MDP. The ultrastructure of osteoclasts was unaltered by Cl2MDT. These cellular changes were associated with a decrease in serum calcium and increase in bone ash and magnesium concentration in rats given high levels (10 mg/kg) of Cl2MDP. Bone adenosine triphosphatase and alkaline phosphatase activities were not affected by Cl2MDP. These results suggest that Cl2MDP may limit the hypercalcemia of hypervitaminosis D by directly inhibiting bone cells in addition to its physicochemical action.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010011:Osteocytes / Q000187:drug effects; D010280:Parathyroid Glands / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000502:physiology; D013965:Thyroidectomy; D014807:Vitamin D / Q000037:antagonists & inhibitors*
D004164:Diphosphonates; D004002:Clodronic Acid; D014807:Vitamin D; D010758:Phosphorus; D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases; D002118:Calcium