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Modulation of bone turnover by alfacalcidol and/or alendronate does not prevent glucocorticoid-induced osteoporosis in growing minipigs.

Abstract
The study was performed to clarify the effects of active vitamin D (alfacalcidol) and/or alendronate (ALN) on bone tissue turnover in glucocorticoid (GC)-treated growing minipigs. Göttingen minipigs aged 8 months were divided into six groups (n = 5 each): group BC, killed for baseline control; group GC, injected subcutaneously with prednisolone (0.5 mg/kg body weight [BW] per day, 5 days/week for 24 weeks); group VC, treated with vehicle alone; group alf, treated with oral alfacalcidol at 0.1 microm/kg BW per day, 5 days/week; group ALN, treated with alendronate 1 mg/kg BW per day; and group alf* ALN, treated with both alf and ALN as above. Biochemical examinations dual-energy X-ray absorptiometry, micro-computed tomography, peripheral quantitative computed tomography, and histomorphometry were performed. In group GC, all bone chemical markers were lower than in group VC. GC treatment reduced the age-dependent augmentation of bone mass and structure by reducing the bone formation rate (BFR) and activation frequency (Ac.f) relative to VC in lumbar bone and femoral cortex. Trabecular and osteonal wall thickness values did not change by GC. Treatments with alf, ALN, and alf* ALN did not have substantial effects on bone mass or structure. Alf treatment maintained lumbar BFR and Ac.f, while ALN reduced osteoclasts. Femoral cortical Ac.f values were not affected by these treatments. GC caused reduced bone formation, leading to low tissue turnover and imbalance of bone formation and resorption. Modulation of bone tissue turnover by alfacalcidol and/or alendronate failed to maintain the growth-dependent increases in mass and structure in GC-treated young minipigs.
AuthorsShojiro Akahoshi, Akinori Sakai, Shinobu Arita, Satoshi Ikeda, Yoshiomi Morishita, Hideki Tsutsumi, Masako Ito, Ayako Shiraishi, Toshitaka Nakamura
JournalJournal of bone and mineral metabolism (J Bone Miner Metab) Vol. 23 Issue 5 Pg. 341-50 ( 2005) ISSN: 0914-8779 [Print] Japan
PMID16133683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adjuvants, Immunologic
  • Glucocorticoids
  • Hydroxycholecalciferols
  • Prednisolone
  • alfacalcidol
  • Alendronate
Topics
  • Absorptiometry, Photon (methods)
  • Adjuvants, Immunologic (pharmacology)
  • Alendronate (pharmacology)
  • Animals
  • Body Weight
  • Bone Density (drug effects)
  • Bone Regeneration
  • Bone Resorption
  • Bone and Bones (drug effects, metabolism)
  • Femur (pathology)
  • Glucocorticoids (metabolism)
  • Hydroxycholecalciferols (pharmacology)
  • Lumbar Vertebrae (metabolism)
  • Osteoporosis (metabolism)
  • Prednisolone (pharmacology)
  • Swine
  • Swine, Miniature
  • Time Factors
  • Tomography, X-Ray Computed (methods)

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