Revised: 4 September 2025

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Systemic retinoids and diffuse idiopathic skeletal hyperostosis (DISH)

Published: 4 September 2025
Prescriber Update 46(3): 45–46
September 2025

The New Zealand Pharmacovigilance database recently received a case report of diffuse idiopathic skeletal hyperostosis (DISH) in a person taking isotretinoin (NZ-Medsafe-159059). This article provides an overview of the condition and medicines associated with it.

Diffuse idiopathic skeletal hyperostosis

DISH is a non-inflammatory, systemic condition characterised by the calcification and ossification of ligaments and entheses (the regions where tendons and ligaments attach to bone). It primarily affects the spine, although the pelvis, knee, heels and shoulders may also be affected.¹

Most patients with DISH are asymptomatic and the condition is generally an incidental find on imaging. However, in advanced disease, new bone formation can cause patients to experience musculoskeletal symptoms such as pain, morning stiffness and reduced range of motion.¹ Rarely, compression of the oesophagus and spinal cord can cause dysphagia and motor and sensory disturbances, respectively.²

DISH is more common in men and its prevalence increases with age.³

The cause of DISH remains unclear. Genetic, metabolic, mechanical and environmental factors may be associated with its development.³

Systemic retinoid exposure and DISH

Cases of DISH have been reported with the use of systemic retinoids, such as isotretinoin and acitretin, usually after long-term use and/or at high doses.^4-8 Retinoids may cause stem cell proliferation and differentiation, leading to osteoblast formation and ossification.⁴

Abnormal bone formation (hyperostosis) may be detectable on imaging as soon as 6 months after starting retinoid treatment. More extensive hyperostosis can appear 3 to 5 years after continuous long-term therapy. However, patients with hyperostosis usually remain asymptomatic, unless the condition becomes advanced.⁵

Disease progression does not appear to continue after stopping retinoid therapy. Management of DISH is generally symptomatic.⁹

References

1. Stovall R, Murakami AM and Dubreuil M. 2018. Case report: Acne drug leads patient to retinoid hyperostosis. The Rheumatologist: November 2018. URL: www.the-rheumatologist.org/article/case-report-acne-drug-leads-patient-to-retinoid-hyperostosis/3/?singlepage=1 (accessed 2 July 2025).
2. Helfgott SM. 2025. Diffuse idiopathic skeletal hyperostosis (DISH). In UpToDate 11 November 2024. URL: www.uptodate.com/contents/diffuse-idiopathic-skeletal-hyperostosis-dish (accessed 1 July 2025).
3. Mader R, Verlaan JJ and Buskila D. 2013. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nature Reviews Rheumatology 9(12): 741-50. DOI: 10.1038/nrrheum.2013.165 (accessed 1 July 2025).
4. Zhao S and Goodson NJ. 2015. Diffuse idiopathic skeletal hyperostosis and isotretinoin in cystic acne. BMJ Case Reports 2015. DOI:10.1136/bcr-2015-209775 (accessed 1 July 2025).
5. Graf SW and Whittle SL. 2014. Isotretinoin-induced skeletal hyperostosis. Springerplus 3: 698. DOI: 10.1186/2193-1801-3-698 (accessed 1 July 2025).
6. Gour-Provençal G, Newman NM, Boudier-Revéret M, et al. 2020. Severe acitretin-induced diffuse idiopathic skeletal hyperostosis: a case report. Journal of International Medical Research 48(10): 300060520966896. DOI: 10.1177/0300060520966896 (accessed 1 July 2025).
7. Douglas Pharmaceuticals Ltd. 2024. Oratane New Zealand Data Sheet 10 December 2024. URL: www.medsafe.govt.nz/profs/Datasheet/o/oratanecap.pdf (accessed 29 July 2025).
8. Douglas Pharmaceuticals Ltd. 2024. Novatretin New Zealand Data Sheet 15 November 2024. URL: www.medsafe.govt.nz/profs/Datasheet/n/novatretincap.pdf (accessed 29 July 2025).
9. Doolan BJ, Paolino A, Greenblatt DT, et al. 2022. Retinoid-induced skeletal hyperostosis in disorders of keratinization. Clinical and Experimental Dermatology 47(12): 2273–6. DOI: 10.1111/ced.15382 (accessed 1 July 2025).