Effect of $1{\alpha},\;25\;Dihydroxyvitamin\;D_3$ on Osteoporosis in Rats

$1{\alpha},\;25\;Dihydroxyvitamin\;D_3$이 랫드 골다공증에 미치는 영향

  • Bae, Chun-Sik (College of Veterinary Medicine, Chonnam National University) ;
  • Choi, Seok-Hwa (College of Veterinary Medicine, Chungbuk National University)
  • Published : 2002.09.01

Abstract

Vitamin D is one of important factors involved in the regulation of bone metabolism. In osteoporosis, the therapeutic effect of vitamin D on the healing process has still been controversial. To confirm the effects of $1{\alpha},\;25\;Dihydroxyvitamin\;D_3$ on the osteoporosis, the change of bone mineral density and the histologic changes of osteoporotic femur were examined comparatively in normal control group (positive control), CFA control group (negative control), CFA+$1{\alpha}$, 25 dihydroxyvitamin $D_{3}\;0.01{\mu}g/kg$ group (Vit $D_{3}L$) and CFA+$1{\alpha}$, 25 dihydroxyvitamin $D_{3}\;0.1{\mu}g/kg$ group (Vit $D_{3}H$) after osteoporosis was induced by single injection of complete Freund's adjuvant (CFA) in rats. The value of bone mineral density and bone mineral content of femur was increased in both Vit $D_{3}L$ and Vit $D_{3}H$ than CFA control, and the increase rate of that was higher in Vit $D_{3}H$ than Vit $D_{3}L$. In CFA control, the size of the bone marrow cavities significantly increased and the width from the bone marrow cavity and cortex significantly decreased than normal control. In Vit $D_{3}H$ and Vit $D_{3}L$, the increase rate of the size of bone marrow cavity and the decrease rate of the width from the bone marrow cavity and cortex was depressed than CFA control. These results suggest that $1{\alpha},\;25\;Dihydroxyvitamin\;D_3$ has therapeutic effect on adjuvant-induced osteoporosis in rats.

Sprague-Dawley rat에 complete Freund's adjuvant (CFA)를 투여하여 유발한 골다공증에 미치는 $1{\alpha}$, 25 dihydroxyvitamin $D_3\;(Vit\;D_3)$의 효과를 알아보기 위하여 실험동물을 정상 대조군, CFA 투여 대조군, CFA 투여후 $1{\alpha}$, 25 dihydroxyvitamin $D_3\;0.01{\mu}g/kg$ 투여군 (Vit $D_{3}L$) 및 $0.1{\mu}g/kg$ 투여군(Vit $D_{3}H$)으로 분류하여 경구로 3주간 투여하였다. 골다공증의 억제 효과를 알아보기 위하여 골밀도와 골함유량의 변화 및 주사전자현미경적 소견을 관찰한 결과 다음과 같은 결론을 얻었다. 골밀도와 골함유량은 $1{\alpha}$, 25 dihydroxyvitamin $D_3$ 투여용량과 부위에 따라 차이가 있었는데 Vit $D_3$ 투여군이 CFA 투여 대조군과 비교하여 골밀도와 골함유량이 증가하였으며 Vit $D_{3}H$군이 Vit $D_{3}L$군보다 좀 더 효과적이었다. 대퇴골의 주사전자현미경적 소견은 Vit $D_3$ 투여군의 골피질과 골소주의 손상이 CFA 투여 대조군보다 억제되었음을 볼 수 있었으며 Vit $D_{3}H$ 투여군이 Vit $D_{3}L$ 투여군보다 좀 더 효과적이었다. 이상의 결과를 종합해 보면 $1{\alpha}$, 25 dihydroxyvitamin $D_3$의 투여는 CFA에 의해 유발된 rat의 골다공증 모델에서 골다공증의 진행을 억제하였고 Vit $D_{3}H$ 투여군이 Vit $D_{3}L$ 투여군보다 좀 더 효과적이었다.

Keywords

References

  1. Bae CS: Therapeutic effects of 1$\alpha$, 25 dihydroxycholecalciferol on osteoporotic fracture in a rat model. Korean J Vet Res 39(5): 974 985,1999, (Korean)
  2. Bae CS, Park CH, Chang BJ, Kim HY, Cho IH, Uhm CS: Effects of safflower (Carthamus tinctorius L.) seed powder on bone resorption in ovariectomized rats, Korean J. Electron Microscopy 31(2): 109 116, 2001, (Korean)
  3. Baumgartner WA, Beck FWJ, Whitehouse MW: Adjuvant disease in rats : biochemical criteria for distinguishing several phases of inflammation and arthritis, Proc Soc exp BioI Med 145: 625 630, 1974 https://doi.org/10.3181/00379727-145-37863
  4. Binderup L: Decreased T suppressor cell activity in rats with adjuvant arthritis, Ann Rhewn Dis 42: 693 698,1983 https://doi.org/10.1136/ard.42.6.693
  5. Brandi ML: New treatment strategies: ipriflavone, strontium, vitamin D metabolites and analogs, Am J Med 95(suppl 5A): 69 74, 1993 https://doi.org/10.1016/0002-9343(93)90386-4
  6. Christiansen C, Christiansen MS, R$\phi$dbro P, Hagen C, Transb$\phi$l I: Effect of 1,25 dihydroxyvitam in $D_3$, in itself or combined with hormone treatment in preventing postmenopausal osteoporosis, Eur J Clin Invest 11(4): 305 309, 1981 https://doi.org/10.1111/j.1365-2362.1981.tb02121.x
  7. Endo K, Katsumata K, Hirata M, Ikeda K, Ogata E: 1,25 dihydroxyvitamin $D_3$, as well as its analogue OCT lower blood calcium through inhibition of bone resortion in hypercalcemic rats with continuous parathyroid hormone related peptide infusion, J Bone and Mineral Research 15(1): 175 181, 2000 https://doi.org/10.1359/jbmr.2000.15.1.175
  8. Erben RG, Bromm S, gtsngassinger M: Short term prophylaxis against estrogen depletion induced bone loss with calcitriol does not provide long term beneficial effects on cancellous bone mass or structure in ovariectomized rats, Osteoporos Int 8: 82 91, 1998a https://doi.org/10.1007/s001980050052
  9. Erben RG, Bromm S, Stsngassinger M: Therapeutic efficacy of 1$\alpha$, 25 dihydroxyvitam in $D_3$, and calcium in osteopenic ovariectomized rats: evidence for a direct anabolic effects of 1$\alpha$, 25 dihydroxyvitamin $D_3$, on bone, Endocrinology 139(10):4319 4328, 1998b https://doi.org/10.1210/en.139.10.4319
  10. Erben RG, Weiser H, Zucker H: Vitamin D metabolites prevent vertebral osteopenia in ovariectomized rats, Calcif Tissue Int 50(3): 228 236, 1992 https://doi.org/10.1007/BF00296287
  11. Falch JA, $\phi$degaard OR, FinnangerAM, Matheson I: Postmenopausal osteoporosis: no effect of three years treatment with 1,25 dihydroxycholecalciferol. Acta Med Scand 221(2)',199 204,1987 https://doi.org/10.1111/j.0954-6820.1987.tb01267.x
  12. Gallagher JC, Jerpbak CM, Riggs BL: 1,25 dihydroxyvitamin $D_3$,: Short and long term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis, Proc Natl Acad Sci USA 79 (10): 3325 3329, 1982 https://doi.org/10.1073/pnas.79.10.3325
  13. Gallagher JC, Riggs BL: Action of 1,25 dihydroxyvitamin $D_3$, on calcium balance and bone turnover and its effect on vertebral fracture rate, Metabolism 39(4 Suppl 1): 30 34, 1990
  14. Gallagher JC, Riggs BL: Calcitriol for postmenopausal osteoporosis, Ann Intern Med 111(7): 621, 1989
  15. Gurlek A, Bayraktar M, Gedik O: Comparison of calcitriol treatment with etidronate calcitriol and calcitonin calcitriol combinations in Turkish women with postmenopausal osteoporosis: a prospective study, Calcif Tissue Int 61(1): 39 43, 1997 https://doi.org/10.1007/s002239900291
  16. Haneji T, Kurihara N, Ikeda K, Kumegawa M: 1$\alpha$, 25 dihydroxyvitamin $D_3$, induce alkaline phosphatase activity in osteoblastic cells derived from newborn mouse calvaria. J Biochem (Tokyo) 94(4): 1127 1132, 1983 https://doi.org/10.1093/oxfordjournals.jbchem.a134456
  17. Hauselmann HJ, Kramer E, Michel BA: Physical therapy in prevention and treatment of osteoporosis. Ther Umsch 55 (11):724 730, 1998
  18. Holick MF: Vitamin D and bone health. J Nutr 126(SuppI4): 1159 1164,1996 https://doi.org/10.1093/jn/126.suppl_4.1159S
  19. Ilich JZ, Badenhop NE, Nagode LA, Markovic V: Calcitriol and bone mass accumulation in females during puberty. Calcif Tissue Int 61(2): 104 109, 1997 https://doi.org/10.1007/s002239900304
  20. Jensen GF, Meinecke B, Boesen J, Transbol I: Does 1,25 $(OH)_2D_3$, accelerate spinal bone loss? A controlled therapeutic trial in 70 year old women, Clin Orthop 192: 215 221, 1985
  21. Lane JM, Nydick M: Osteoporosis: current modes of prevention and treatment. J Am Acad Orthop Surg 7 (1): 19 31, 1999 https://doi.org/10.5435/00124635-199901000-00003
  22. Lindgren JU, Narechania RG, Lange TA, Deluca HF: Effects of 1,25 dihydroxyvitamin $D_3$, and calcitonin on fracture healing in adult rats, Clinical Orthopedics and Related Res 160:304 308, 1981
  23. Masud T, Mulcahy B, Keen RW, Doyle DV, Spector TO: Effects of cyclical etidronate combined with calcitrio l versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women, Annals of the Rheumatic Diseases 57 (6) : 346 349, 1998 https://doi.org/10.1136/ard.57.6.346
  24. Melton LJ, Atkinson EJ, O'Fallon WM, Riggs BL: Bone density and fracture risk in man, J Bone Miner Res 13(12) : 1915 1923, 1998 https://doi.org/10.1359/jbmr.1998.13.12.1915
  25. Morgan SL: Calcium and vitamin D in osteoporosis, Rheumatic Diseases Clinics of North America 27(1): 101 130, 2001 https://doi.org/10.1016/S0889-857X(05)70189-7
  26. O'Brien KO: Combined calcium and vitamin D supplementation reduces bone loss and fracture incidence in older men and women, Nutr Rev 56(5 Pt 1): 148 150, 1998 https://doi.org/10.1111/j.1753-4887.1998.tb01740.x
  27. Rosenthale ME, Capetola RJ: Adjuvant arthritis: immunopathological and hyperalgesic features, Fed Proc 41: 2577 2582, 1982
  28. Shiraki M, Ito H, Orimo H: The effect of 1,25 $(OH)_2D_3$, on bone mineral content in senile osteoporosis A dose finding study, Nippon Naibunpi Gakkai Zasshi 65 (11): 1253 1263, 1989
  29. Takagi T, Tsao PW, Totsuka R, Takata I: Changes in bone mineral density in rat adjuvant arthritis, Clinical Immuno l and Immunopathol 85(2) : 166 170, 1997 https://doi.org/10.1006/clin.1997.4417
  30. Vukicevic S, Stavljenic A, Bagi C, Winter I: 1,25 dihydroxyvitamin $D_3$, stimulates alkaline phosphatase activity and inhibits soft tissue proliferation in implants of bone matrix, Clin Orthop 196 : 285 291, 1985
  31. Ziegler R: Drug treatment of osteoporosis, Ther Umsch 55(11): 696 701,1998