Regulation of bone metabolism in immunosuppressant (FK506)-treated rats

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• 作者：Shiho Kirino ; Jyoji Fukunaga ; Shuji Ikegami ; Hiroshi Tsuboi ; Masataka Kimata ; Naoki Nakata ; Makoto Nakano ; Takaaki Ueno ; Nobuyoshi Mizukawa and Toshio Sugahara
• 关键词：osteoporosis ; bone metabolism marker ; immunosuppressant
• 刊名：Journal of Bone and Mineral Metabolism
• 出版年：2004
• 出版时间：November 2004
• 年：2004
• 卷：22
• 期：6
• 页码：554-560
• 全文大小：239 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Metabolic Diseases
  Orthopedics
  Internal Medicine
  
• 出版者：Springer Japan
• ISSN：1435-5604

文摘

After organ transplantation, severe osteoporosis is occasionally seen, and the use of immunosuppressants is thought to be one of the causes of such osteoporosis. In the present study, we investigated the effects of FK506 monotherapy on bones and determined the mechanism of onset of osteoporosis, both by assessing chronological changes in bone metabolism and by identifying factors that facilitate bone resorption. In 8-week-old male Sprague-Dawley rats, FK506 (1mg/kg) was injected intraperitoneally every day for 5 weeks (FK506-treated group), and for comparison, physiological saline was administered in the same manner in a control group of rats. Serum and urine samples were collected at weeks 0, 1, 3, and 5 of administration. The femur and tibia were collected within 24h of the final administration. When compared to the control group, findings on three-dimensional micro-computed tomography of the femur for the FK506-treated group showed a significant decrease in trabecular bone volume. The level of serum osteocalcin in the FK506-treated group at week 1 of administration was significantly higher than the control. Throughout the administration period, the sum of urinary pyridinoline (PYD) and deoxypyridinoline (Dpd) was significantly higher in the FK506-treated group. Of the various bone resorption factors tested, the level of serum parathyroid hormone (PTH) in the FK506-treated group was significantly higher than the control at week 3 of administration. The results of the present study confirmed that FK506 monotherapy in rats induced high-turnover osteoporosis. Soon after the start of FK506 administration, bone formation and resorption were elevated, and PTH appeared to have been involved in the maintenance of the elevated bone resorption.