The spectrum of skeletal changes associated with long-term administration of 13-cis-retinoic acid


The roentgenographic changes noted in 13 patients, who had been treated with long-term 13-cis-retinoic acid for inherited scaling disorders, are presented. These patients were aged 13–16 years and had received this therapy for 16–87 months (mean, 58 months). The most pronounced abnormality was osteophyte formation, particularly in the cervical spine. Other changes which were noted included ossification of the anterior longitudinal and atlanto-occipital ligaments, proliferative enthesopathies, diminished bone density, premature fusion of epiphyses, and modeling abnormalities. Six of the 13 patients were asymptomatic and the osseous manifestations of this therapy were identified only by roentgenographic evaluation.

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  1. 1.

    Abiteboul M, Arlet J (1985) Retinol-related hyperostosis (Letter to the editor). AJR 144:436

    Google Scholar 

  2. 2.

    Arlet J, Abiteboul M, Mazieres B, Laffont F, Dedieu-Snapir G, Fauvel JM (1983) Vitamine A et hyperostose vertebrale ankylosante (vitamin A and DISH). Rev Rhum Mal Osteoartic 50:63

    Google Scholar 

  3. 3.

    Boillat MA, Garcia J, Velebit L (1980) Radiological criteria of industrial fluorosis. Skeletal Radiol 5:161

    Google Scholar 

  4. 4.

    Caffey J (1946) Infantile cortical hyperostoses. J Pediatr 29:541

    Google Scholar 

  5. 5.

    Caffey J (1951) Chronic poisoning due to excess of vitamin A. AJR 65:12

    Google Scholar 

  6. 6.

    Gerber A, Raab AP, Sobel AE (1954) Vitamin A poisoning in adults. Am J Med 16:729

    Google Scholar 

  7. 7.

    Gerber LH, Helfgott RK, Gross EG, Hicks JE, Ellenberg SS, Peck GL (1984) Vertebral abnormalities associated with synthetic retinoid use. J Am Acad Dermatol 10:817

    Google Scholar 

  8. 8.

    Gerster JC, Lagier R, Nicod L (1985) Case report 311 (sternocostoclavicular hyperostosis). Skeletal Radiol 14:53

    Google Scholar 

  9. 9.

    Josephs HW (1944) Hypervitaminosis A and carotinemia. Am J Dis Child 67:33

    Google Scholar 

  10. 10.

    Karasick S, Karasick D (1982) Case Report 188 (sternocostoclavicular hyperostosis). Skeletal Radiol 8:74

    Google Scholar 

  11. 11.

    Largent EJ, Bovard PG, Heyroth FF (1951) Roentgenographic changes and urinary fluoride excretion amongst workmen engaged in the manufacture of inorganic fluorides. AJR 65:42

    Google Scholar 

  12. 12.

    Miller JH, Hayon II (1985) Bone scintigraphy in hypervitaminosis A. AJR 144:767

    Google Scholar 

  13. 13.

    Milstone LM, McGuire J, Ablow RC (1982) Premature epiphyseal closure in a child receiving oral 13-cis-retinoic acid. J Am Acad Dermatol 7:663

    Google Scholar 

  14. 14.

    McGuire J, Milstone LM, Lawson JP (1985) Isotretinoin administration alters juvenile and adult bone. In: Saurat JH (ed) Retinoids: new trends in research and therapy. Retinoid symposium, Geneva 1984. Karger, Basel, pp 419

    Google Scholar 

  15. 15.

    Ono M, Russell WJ, Kudo S, Kuroiwa Y, Takamori M, Motomura S, Murakami J (1982) Ossification of the thoracic posterior longitudinal ligament in a fixed population. Radiology 143:469

    Google Scholar 

  16. 16.

    Palmer AK, Louis DS (1977) Musculoskeletal abnormalities and ichthyosis. Clin Orthop 125:131

    Google Scholar 

  17. 17.

    Pease CN (1962) Focal retardation and arrestment of growth of bones due to vitamin A intoxication. JAMA 182:980

    Google Scholar 

  18. 18.

    Peck GL, Yoder FW (1976) Treatment of lamellar ichthyosis and other keratinizing disorders with an oral synthetic retinoid. Lancet ii:1172

    Google Scholar 

  19. 19.

    Pennes DR, Ellis CN, Madison KC, Voorhees JJ, Martel W (1984) Early skeletal hyperostoses secondary to 13-cis-retinoic acid. AJR 142:979

    Google Scholar 

  20. 20.

    Pennes DR, Martel W, Ellis CN (1985) Retinoid-induced ossification of the posterior longitudinal ligament. Skeletal Radiol 14:191

    Google Scholar 

  21. 21.

    Pittsley RA, Yoder FW (1983) Retinoid hyperostosis. Skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis. N Engl J Med 308:1012

    Google Scholar 

  22. 22.

    Resnick D, Shapiro R, Wiesner K, Niwayama G, Utsinger P, Shaul LS (1978) Diffuse idiopathic skeletal hyperostosis (DISH). Ankylosing hyperostosis of Forestier and Rotes-Querol. Semin Arthritis Rheum 7:153

    Google Scholar 

  23. 23.

    Seawright AA, English PB, Gartner RJW (1965) Hypervitaminosis A and hyperostosis of the cat. Nature 206:1171

    Google Scholar 

  24. 24.

    Wolbach SB (1947) Vitamin A deficiency and excess in relation to skeletal growth. J Bone Joint Surg 29:171

    Google Scholar 

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Correspondence to Jack P. Lawson M.B., F.R.C.R..

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Lawson, J.P., McGuire, J. The spectrum of skeletal changes associated with long-term administration of 13-cis-retinoic acid. Skeletal Radiol 16, 91–97 (1987).

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Key words

  • Retinoid therapy
  • Osteophytosis
  • Anterior longitudinal ligament ossification
  • Proliferative enthesopathy
  • Premature fusion of epiphyses
  • Osteopenia
  • Vitamin A toxicity
  • Retinoid toxicity