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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Bisphosphonates in phenytoin-induced bone disorder.
Suruchi Khanna1, Krishna K Pillai, Divya Vohora
1Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Bone
|November 3, 2010
Summary
Phenytoin (PHT) causes bone loss, but alendronate (ALD) and risedronate (RSD) may prevent it. These bisphosphonates did not affect PHT
Area of Science:
- Pharmacology and Toxicology
- Bone Biology and Metabolism
Background:
- Chronic phenytoin (PHT) administration is linked to significant bone loss.
- PHT induces depletion of folic acid (FA), vitamin B6, and vitamin B12, leading to hyperhomocysteinemia.
- Elevated homocysteine (hcy) may indicate micronutrient-deficiency-related osteoporosis and oxidative stress.
Purpose of the Study:
- To evaluate the efficacy of bisphosphonates (alendronate, ibandronate, risedronate) in preventing or treating PHT-induced bone loss.
- To assess the impact of bisphosphonates on PHT's antiepileptic efficacy.
- To investigate the effects of PHT and bisphosphonates on homocysteine and antioxidant profiles.
Main Methods:
- Male mice received chronic oral administration of phenytoin (35 mg/kg) for 90 days to induce bone loss.
- Bisphosphonates (alendronate, risedronate, ibandronate) were administered orally for prevention and treatment of PHT-induced bone loss.
- Bone mineral density (BMD), bone turnover markers, serum homocysteine, folic acid, hydrogen peroxide, and total antioxidant capacity were analyzed.
Main Results:
- PHT administration significantly reduced BMD and altered bone turnover markers, confirming bone loss.
- Alendronate and risedronate significantly reversed PHT-induced bone loss and adverse effects.
- Ibandronate showed no significant protective effect on bone. All tested bisphosphonates did not interfere with PHT's antiepileptic efficacy and normalized homocysteine levels.
Conclusions:
- Alendronate and risedronate show promise in managing phenytoin-induced bone disease by mitigating bone loss.
- Ibandronate was ineffective in preventing PHT-induced bone loss in this model.
- Bisphosphonates tested did not exhibit pharmacodynamic interactions with phenytoin, suggesting potential co-administration viability pending clinical approval.
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