Penile Ossification in Peyronie's Disease: A Systematic Review of a Rare Pathologic Continuum From Fibrosis to Bone Formation

Peyronie’s disease (PD) is a localized fibroproliferative disorder of the tunica albuginea, causing plaque formation, penile curvature, pain, and variable erectile dysfunction. While calcification of PD plaques is common in advanced disease, true penile ossification, defined as the formation of mature bone within fibrotic plaques, is rare. This systematic review was conducted in accordance with PRISMA guidelines and examined clinical and mechanistic evidence linking PD to ossification. A structured search of PubMed, PubMed Central, Europe PMC, and Google Scholar identified eight eligible studies (six human and two experimental studies), including case reports, clinicopathological investigations, and experimental models. Data were extracted on clinical presentation, histopathology, molecular pathways, and therapeutic implications, and study quality was assessed using the CASP framework. Human studies indicate that ossified plaques most commonly occur in long-standing disease and are associated with severe deformity and poor response to treatment. Histopathology demonstrates organized lamellar bone, distinguishing true ossification from simple calcification. Experimental and tissue-based studies suggest mechanisms related to fibrosis and mineralization that may be relevant to ossification. Collectively, the evidence suggests a potential progression from inflammation and fibrosis to calcification, and in rare cases, ossification in PD. Although uncommon, penile ossification represents a late-stage manifestation, and understanding its mechanisms may improve disease staging, guide management, and inform future therapeutic strategies.