Surgical management of bilateral hip fractures in a patient with fibrodysplasia ossificans progressiva treated with the RAR-γ agonist palovarotene: a case report
Open Access
- 3 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Musculoskeletal Disorders
- Vol. 21 (1), 1-8
- https://doi.org/10.1186/s12891-020-03240-2
Abstract
Background Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder marked by painful, recurrent flare-ups and heterotopic ossification (HO) in soft and connective tissues, which can be idiopathic or provoked by trauma, illness, inflammation, or surgery. There are currently no effective treatments for FOP, or for patients with FOP who must undergo surgery. Palovarotene, an investigational retinoic acid receptor-gamma agonist, offers a potential avenue to prevent HO formation. Case presentation The patient is a 32 year-old male, who at age 29 enrolled in a study evaluating palovarotene to prevent HO formation in FOP. One year after starting palovarotene, he fell resulting in a left intertrochanteric fracture. He underwent intramedullary nailing of the femur shaft with screw placement at the distal femur. After surgery, he received palovarotene at 20 mg/day for 4 weeks, then 10 mg/day for 8 weeks. Imaging 12 weeks after surgery showed new bridging HO at the site of intramedullary rod insertion and distal screw. Nine months after the left hip fracture, the patient had a second fall resulting in a subdural hematoma, left parietal bone fracture, and right intertrochanteric fracture. He underwent intramedullary nailing of the right hip, in a modified procedure which did not require distal screw placement. Palovarotene 20 mg/day was started at fracture occurrence and continued for 4 weeks, then reduced to 10 mg/day for 8 weeks. HO also formed near the insertion site of the intramedullary rod. No HO developed at the right distal intramedullary rod. After each fracture, the patient had prolonged recurrent flare-ups around the hips. Conclusion Surgery is only rarely considered in FOP due to the high risks of procedural complications and potential for inducing HO. This case emphasizes the risks of increased flare activity and HO formation from injury and surgery in patients with FOP. The efficacy of HO prevention by palovarotene could not be assessed; however, our observation that palovarotene can be administered in an individual with FOP following surgery with no negative impact on clinical fracture healing, osteointegration, or skin healing will help facilitate future trials testing the role of palovarotene as a therapy for HO.Funding Information
- National Institutes of Health (NIH R01AR073015, T32DK007418, F32HD91025, K08DE028946)
- Department of Medicine, University of California, San Francisco (REAC Summer Explore fellowship)
This publication has 26 references indexed in Scilit:
- Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome?Pediatric Rheumatology, 2019
- Non-steroidal anti-inflammatory drugs for heterotopic ossification prophylaxis after total hip arthroplastyThe Bone & Joint Journal, 2018
- The obligatory role of Activin A in the formation of heterotopic bone in Fibrodysplasia Ossificans ProgressivaBone, 2017
- The traumatic bone: trauma-induced heterotopic ossificationTranslational Research, 2017
- Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1R206H Fibrodysplasia Ossificans Progressiva (FOP) MutationJournal of Bone and Mineral Research, 2016
- In Brief: Classifications in Brief: Brooker Classification of Heterotopic Ossification After Total Hip ArthroplastyClinical Orthopaedics and Related Research, 2015
- Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptorEuropean Respiratory Journal, 2012
- Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonistsNature Medicine, 2011
- The biology of intramedullary reamingInjury, 2010
- Muscle Perfusion after Intramedullary Nailing of the Canine TibiaThe Journal of Trauma and Acute Care Surgery, 1998