EHDP‐induced rachitic syndrome in rats is not reversed by vitamin D metabolites

To examine whether either of the two known active vitamin D metabolites 1,25(OH)₂D₃ or 24,25(OH)₂D₃ could reverse the mineralization defect induced by 1‐hydroxyethylidene‐1,1‐bis phosphonate (EHDP), a model of EHDP‐induced rickets was used. Rats at the age of 31 days were injected for 10 consecutive days with EHDP (10 mg/kg). Other littermates were treated with a combination of EHDP and either 1,25(OH)₂D₃ or 24,25(OH)₂D₃ or were treated following 10 days of EHDP, with either of the vitamin D metabolites for an additional 72 hr. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscope studies of growth plate cartilage and bone. EHDP‐treated rats revealed signs of typical rickets, manifested by widened growth plates and impaired bone mineralization. Transmission electron microscope (TEM) examination revealed matrix vesicles distributed throughout the growth plate; however, there appeared to be an arrest of the spread of the crystals at the provisional zone of calcification. Treatment with either 1,25(OH)₂D₃ or 24,25(OH)₂D₃ failed to reverse the rachitic condition of the animals. Serum calcium blood levels were elevated in the 1,25(OH)₂D₃ and EHDP‐treated group. 1,25(OH)₂D₃ and 24,25(OH)₂D₃ further increased the already elevated serum alkaline phosphatase levels observed in EHDP rats, although the increase observed with 1,25(OH)₂D₃ was not statistically significant. In contrast to this, 24,25(OH)₂D₃ lowered the Cfl levels of alkaline phosphatase to the normal range despite the absence of apparent morpholoogical healing of the EHDP rachitic condition. It therefore appears that in our animal model pharmacological doses of vitamin D metabolites do not reverse the EHDP‐induced mineralization defect.