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Mycophenolate mofetil: a promising new immunosuppressant that does not cause bone loss in the rat
I R Dissanayake1, G R Goodman, A R Bowman
1Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA.
Background:
Posttransplantation bone disease is a well-described phenomenon; among its etiology is immunosuppressant-induced bone disease. Mycophenolate mofetil (MMF) has emerged as a promising new immunosuppressant. Our study was designed to investigate the effect of MMF on in vivo bone mineral metabolism.
Methods:
Twenty-four 6-month-old male Sprague-Dawley rats were randomized into two groups to receive either MMF vehicle daily for 28 days or 30 mg/kg MMF daily for 28 days. The serum was assayed for osteocalcin and 1,25-dihydroxy vitamin D3. Subsequent to double-labeling, the right tibiae were removed on day 28 for histomorphometry.
Results:
MMF suppressed bone gla protein (osteocalcin) levels on days 14 and 28 (P < 0.05). Except for percentage osteoid perimeter, there was no difference in bone histomorphometry between the two groups.
Conclusion:
In this relatively short-term study, MMF did not cause osteopenia in the rat model, but the suppressed bone gla protein merits further study.
Insights
Mycophenolate mofetil (MMF) did not induce osteopenia in a rat model over 28 days. However, MMF suppressed bone gla protein, suggesting further investigation into its effects on bone metabolism is warranted.
Area of Science:
- Pharmacology
- Bone Metabolism
- Immunosuppression
Background:
- Posttransplantation bone disease is a significant clinical issue.
- Immunosuppressants are a known cause of bone disease.
- Mycophenolate mofetil (MMF) is a widely used immunosuppressant.
Purpose of the Study:
- To investigate the effects of MMF on bone mineral metabolism in vivo.
- To assess MMF's impact on osteocalcin and vitamin D levels.
- To evaluate MMF's influence on bone histomorphometry.
Main Methods:
- Adult male Sprague-Dawley rats received daily MMF or vehicle for 28 days.
- Serum osteocalcin and 1,25-dihydroxy vitamin D3 were measured.
- Tibial bone histomorphometry was performed after double labeling.
Main Results:
- MMF significantly suppressed serum osteocalcin levels at 14 and 28 days.
- No significant differences in bone histomorphometry were observed, except for percentage osteoid perimeter.
- MMF did not cause osteopenia in this short-term rat model.
Conclusions:
- Short-term MMF administration did not lead to osteopenia in rats.
- The suppression of bone gla protein (osteocalcin) by MMF requires further investigation.
- MMF's long-term effects on bone metabolism warrant continued research.