Regulation of bone metabolism in immunosuppressant (FK506)-treated rats.
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 (1 mg/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 24 h 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.
Kirino
Shiho
S
Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, Japan. gmd13130@cc.okayama-u.ac.jp.
Fukunaga
Jyoji
J
Ikegami
Shuji
S
Tsuboi
Hiroshi
H
Kimata
Masataka
M
Nakata
Naoki
N
Nakano
Makoto
M
Ueno
Takaaki
T
Mizukawa
Nobuyoshi
N
Sugahara
Toshio
T
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood* / Q000139:chemically induced / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
D000596:Amino Acids; D007166:Immunosuppressive Agents; D015675:Osteocalcin; C015484:pyridinoline; C036020:deoxypyridinoline; D016559:Tacrolimus