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Age-related differences in phosphonoformate-induced bone toxicity in cats
C L Swenson1, S E Weisbrode, L A Nagode
1Department of Veterinary Pathobiology, Ohio State University, Columbus.
Calcified Tissue International
|May 1, 1991
Summary
Phosphonoformate (PFA) caused bone abnormalities in cats, including rickets-like lesions in young cats and osteomalacia in adults. This suggests monitoring patients receiving PFA for metabolic bone disease.
Area of Science:
- Veterinary Pathology
- Pharmacology
- Bone Biology
Background:
- Phosphonoformate (PFA) is a pyrophosphate analog.
- PFA is undergoing Phase I trials for AIDS treatment.
- Understanding PFA's effects on bone is crucial for patient safety.
Purpose of the Study:
- To investigate the effects of PFA on plasma biochemistry and bone histomorphology in cats.
- To assess potential metabolic bone disease induced by PFA.
Main Methods:
- Cats (young and adult) received continuous intravenous PFA (1,000 mg/kg/day) for 14 days.
- Plasma biochemical parameters (calcium, phosphorus, alkaline phosphatase, calcitriol) were analyzed.
- Bone histomorphology was examined, including growth plate, osteoid, mineralization, and resorption indices.
Main Results:
- Young cats showed increased plasma calcium, decreased phosphorus, alkaline phosphatase, and calcitriol, with rickets-like lesions.
- Adult cats exhibited decreased plasma alkaline phosphatase, with osteomalacia and increased resorption indices.
- PFA inhibited bone mineralization in both age groups, similar to bisphosphonates.
Conclusions:
- PFA induces significant plasma biochemical and bone abnormalities in cats.
- The findings suggest a risk of metabolic bone disease in patients treated with PFA.
- Clinical evaluation for bone disease is recommended for individuals receiving PFA therapy.