MON-348 Surgical Management of Bilateral Hip Fracture in a Patient with Fibrodysplasia Ossificans Progressiva Treated with Palovarotene

Abstract Background: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder marked by painful, recurrent flare-ups and progressive heterotopic ossification (HO) in soft tissues. The bone formation can be idiopathic or provoked by trauma, illness, or inflammation. There are limited treatment options, with glucocorticoids and non-steroidal anti-inflammatory agents being used for palliative treatment. Palovarotene (PVO), an investigational retinoic acid receptor gamma agonist, offers a potential avenue to prevent HO development. Clinical Case: The patient was a 29 year-old male, diagnosed with FOP at age 9, who enrolled in a study evaluating chronic PVO (5mg/day) for the treatment of FOP. Major joints affected at enrollment were his spine, jaw, shoulders, right hip and ankles. One year after starting PVO, he had a fall that resulted in a left intertrochanteric fracture. He underwent intramedullary nailing of the femur shaft with screw placement at the distal femur. After surgery, he received flare-dosing PVO at 20 mg/day for 4 weeks, then 10 mg/day for 8 weeks. Post-surgical imaging 12 weeks after the surgery showed new bridging HO at the site of intramedullary rod insertion and around the distal screw. Nine months after the fracture the patient had a second fall resulting in a right intertrochanteric fracture. He underwent intramedullary nailing of the right hip, in a modified procedure which did not require distal screw placement. PVO was increased similarly to the above flare protocol, but, at the time of fracture occurrence rather than post-surgery. He had no skin or healing complications with either treatment regimen. After each fracture the patient had prolonged recurrent flare-ups at the injury sites, significantly increasing his number of flare-ups per year. After the fractures there was new Brooker class D HO at the left hip, originating at the insertion of the intramedullary rod, and new class B HO at the right greater trochanter, again near the insertion site of the intramedullary rod compared to his pre-surgery baseline. In contrast, there was no new HO at the right distal intramedullary rod whereas HO occurred around the screw placement site at the left distal rod. Conclusion: This case suggests that PVO in the dosing regimen received by this patient can be tolerated in an individual with FOP following major surgery. HO still occurred in this patient, particularly along the rod insertion track, suggesting that the PVO regimen may need to be optimized for surgical cases or that poly-trauma events may not be adequately blocked by the dosing regimen received by this patient. However, PVO did not negatively impact fracture healing or osteointegration, and no major skin healing effects were identified. Further investigation is needed to assess whether PVO can lead to a dose-dependent reduction in HO in the setting of trauma and surgery.