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-dihydroxyvitamin D(3), in combination with bone sparing products such as bisphosphonates allow immune modulation in vivo without affecting bone.
Van Etten
E
E
Laboratory of Experimental Medicine and Endocrinology, Catholic University of Leuven, Herestraat 49, Belgium.
Branisteanu
D D
DD
Overbergh
L
L
Bouillon
R
R
Verstuyf
A
A
Mathieu
C
C
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D005269:Femur / Q000187:drug effects; D051379:Mice; D015675:Osteocalcin / Q000097:blood; D000077268:Pamidronate; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D016207:Cytokines; D004164:Diphosphonates; D015675:Osteocalcin; D014807:Vitamin D; D000077268:Pamidronate; D002118:Calcium