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Age-related differences in phosphonoformate-induced bone toxicity in cats

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Summary

Phosphonoformate (PFA), a monophosphonate pyrophosphate analog, caused plasma biochemical and bone histomorphologic abnormalities in cats given 1,000 mg/kg/day as a continuous intravenous infusion for 14 days. Plasma biochemical alterations observed in young cats (10 weeks old) treated with PFA included increased calcium and decreased phosphorus, alkaline phosphatase, and calcitriol. Young cats treated with PFA developed rickets-like lesions characterized by widened growth plates, increased osteoid, and failure of mineralization. In addition, area of mineralized trabecular bone was decreased. Osteoclast size was increased whereas osteoclast perimeter and number were unaffected in young PFA-treated cats. Plasma alkaline phosphatase was decreased in adult cats (≥1 year old) treated with PFA but changes in calcium, calcitriol, and immunoreactive parathyroid hormone were highly variable and not significantly different. Adult cats treated with PFA exhibited osteomalacia characterized by increased osteoid area, perimeter, and width with failure of mineralization. In addition, static resorption indices were increased in PFA-treated adult cats but area of mineralized trabecular bone was not decreased. The monophosphonate PFA inhibited bone mineralization in young and adult cats similar to bisphosphonate treatment in other species. Because PFA is currently in phase I trials for use in AIDS, results of this study suggest a need to evaluate patients treated with PFA for metabolic bone disease.

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Author notes

  1. Cheryl L. Swenson

    Present address: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI

Authors and Affiliations

  1. Department of Veterinary Pathobiology, The Ohio State University, Columbus, OH, USA

    Cheryl L. Swenson, Steven E. Weisbrode, Larry A. Nagode, Kathleen A. Hayes, Carol L. Steinmeyer & Lawrence E. Mathes

  2. Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA

    Lawrence E. Mathes

  3. The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Lawrence E. Mathes

Authors
  1. Cheryl L. Swenson
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  2. Steven E. Weisbrode
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  4. Kathleen A. Hayes
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  5. Carol L. Steinmeyer
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  6. Lawrence E. Mathes
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Swenson, C.L., Weisbrode, S.E., Nagode, L.A. et al. Age-related differences in phosphonoformate-induced bone toxicity in cats. Calcif Tissue Int 48, 353–361 (1991). https://doi.org/10.1007/BF02556155

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  • DOI: https://doi.org/10.1007/BF02556155

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