Combination of a 1,25-dihydroxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone

The vitamin D analog TX527 (19-nor-14,20-bis epi-23-yne-1,25(OH)(2)D-3), decreased disease severity (P < 0.001) and postponed disease onset (P < 0.0001) in SJL mice in which experimental autoimmune encephalomyelitis was induced. Levels of IFN-gamma and IL-2 mRNA were decreased in spinal cord and spleen in the analog-treated mice, suggesting a Th-1-targeted effect. Adding the bisphosphonate pamidronate did not affect analog-protective efficacy, but completely prevented TX527-caused acceleration of bone turnover and increased total bone mineral content as well as femoral mineral and calcium content (P < 0.01). Less calcemic analogs of 1,25-dibydroxyvitamin D-3, in combination with bone sparing products such as bisphosphonates allow immune modulation in vivo without affecting bone. (C) 2003 Elsevier Science (USA). All rights reserved.