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  • 1
    Electronic Resource
    Electronic Resource
    Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3 (1994)
    Springer
    Calcified tissue international 55 (1994), S. 190-197 
    Details
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteoclast-like cell formation ; Bone Ca mobilization ; Intestinal Ca transport ; 24R,25-dihydroxy-26,27-dimethylvitamin D3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10-6 M and 24,25(OH)2(CH3)2D3 at 10-7 M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10-11 M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1α position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 α-hydroxylation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00425874
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  • 2
    Electronic Resource
    Electronic Resource
    Elongation of the side chain of analogs of 1α,25-dihydroxyvitamin D3 prevents osteopenia in a rat model (1995)
    Springer
    Calcified tissue international 56 (1995), S. 220-226 
    Details
    ISSN: 1432-0827
    Keywords: Bone density ; Dual energy X-ray absorptiometry ; Elongating side chain of analogs of 1α,25-dihydroxyvitanin D3 ; Prevention of osteopenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Five analogs of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] [1], 26,27-dimethyl-1α,25-dihydroxyvitamin D3 [1,25(OH)2(Me)2D3] [2], 26,27-dimethyl-1α,25-dihydroxyvitamin D3 [1,25(OH)2(Et)2D3] [3], 26,27-dipropyl-1α, 25-dihydroxyvitamin D3 [1,25(OH)2(Pr)2D3] [4], 26,27-dimethyl-24, 24-difluoro-1α,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3, and [5] 24a-homo-24,24-difluoro-1α,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3] were investigated to clarify the possibility that prevents osteopenia induced in rats by ovariectomy and sciatic neurotomy. The objective of our studies was to determine whether these analogs may be effective for treatment of subjects with osteoporosis. 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3 prevented decreases in bone mineral density (BMD) of the femur, as measured by dual energy X-ray absorptiometry (DXA). The potency of 1,25(OH)2(Me)2D3 in this test was higher than that of 1,25(OH)2D3. The potencies of 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3 were similar to that of 1,25(OH)2D3. On the other hand, though 1,25(OH)2(Et)2D3 and 1,25(OH)2(Pr)2D3 had a preventive effect on the decease in BMD, the potency of two analogs was lower than that of 1,25(OH)2D3. Decreases in cortical and trabecular bone areas of the femur were prevented by three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3. Serum calcium (Ca) concentration was elevated at the last administration of three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3. Decreases in the Ca concentration in untreated rats were noted a few days after the last administration. In light of these positive effects, we are continuing research on 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3 as putative treatment for osteoporosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00298614
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