Isotretinoin-Associated Musculoskeletal Adverse Effects: Mechanisms, Clinical Manifestations, Risk Factors, and Monitoring Strategies – A Narrative Review.

Abstract

Background: Oral isotretinoin is highly effective for severe and treatment-resistant acne, but its musculoskeletal safety profile remains incompletely defined.                                        

Aim: This narrative review aimed to summarize current evidence regarding the relationship between isotretinoin therapy and musculoskeletal adverse effects, with particular emphasis on pathophysiological mechanisms, the role of exercise, clinical manifestations, and monitoring strategies.                                                                                                             

Methods: PubMed and Google Scholar were searched for English-language articles published from January 2010 to March 2026. Observational studies, case reports, case series, reviews, and guidelines on musculoskeletal outcomes were included.                

Results: Isotretinoin-associated musculoskeletal manifestations include low back pain, myalgia, arthralgia, tendinopathy, sacroiliitis, fatigue, asymptomatic creatine kinase elevation, and rare rhabdomyolysis. Most abnormalities appear mild or reversible, but severe muscle injury has been reported, particularly after strenuous exercise. Proposed mechanisms include retinoid-related apoptotic signaling, oxidative stress, mitochondrial vulnerability, and exercise-induced muscle membrane injury, although direct mechanistic evidence remains limited. Creatine kinase elevation is nonspecific and should be interpreted together with symptoms, recent exercise, renal function, hydration status, and aminotransferase patterns.

Conclusions: Although severe muscle complications during isotretinoin therapy are uncommon, clinicians should be aware of potential muscle toxicity, particularly in physically active patients. Individualized monitoring, patient education, and further prospective studies are needed to improve the safety of isotretinoin treatment.