Bone mineral and matrix maturation in chronically uremic, nonacidotic rats were investigated after 25-hydroxcholecalciferol (25OHD) and/or dichloromethylene diphosphonate (C12MDP) therapy utilizing bromoform-toluene density gradient fractionation and X-ray diffraction analyses. The bromoform-toluene density gradient analyses demonstrated that the progressive accumulation of less dense, more immature bone characteristic of progressive uremia was reversed by 25OHD and/or C12MDP therapy for a 2-wk period, and that after 4 wk of therapy the maturational profile of bones from chronically uremic animals treated with 250HD and/or C12MDP was comparable to that from nonuremic littermates. X-ray diffraction analysis revealed that by the 4th wk of therapy with 25OHD and C12MDP both the degree of crystallinity and the crystal size/perfection parameters in the uremic bones were comparable to those of nonuremic, pair-fed control littermates. Treatment for 4 wk with 25OHD resulted in enlarged and/or more perfect apatite crystallites, while C12MDP alone slightly inhibited crystal growth and/or perfection after 2 wk of treatment. Soft tissue calcification was diminished in uremic animals treated for 4 wk with C12MDP or a combined C2MDP/25OHD regimen, the latter being much more effective in this regard. The accumulated data in this study support the premise that the attendant accelerated bone resorption, soft tissue calcification, and abnormal mineralization and maturation of the skeletal tissue, well documented to characterize experimental ranal insufficiency, may be alleviated with therapeutic dosages of 25OHD and/or C12MDP.
J E Russell, J D Termine, L V Avioli