Treatment of Polyostotic Fibrous Dysplasia With Intravenous Ibandronate

Abstract

Introduction: Fibrous Dysplasia (FD) is proliferation of fibrous tissue within the bone marrow causing osteolytic lesions and pathologic fractures. Polyostotic FD in combination with a thigh myxoma is consistent with Mazabraud syndrome (MS). Bisphosphonates have shown promise in treatment and prevention of progression of FD. Clinical Case: A 34-year-old male with an unremarkable family history developed left thigh pain shortly after Whipple’s procedure for pancreatic cancer in 2017. Imaging revealed a 9cm left thigh mass and multiple femoral and pelvic intramedullary lesions compatible with FD. The thigh mass was removed and final pathology revealed an intramuscular myxoma with +GNAS mutation. Given clinical picture, genetics raised concern for MS and recommended endocrinology consultation. Patient reported chronic pain in chest, abdomen, back and multiple joints requiring spinal stimulator placement. Labs displayed subclinical hyperthyroidism and thyroid uptake scan revealed a right toxic MNG. Hence ablation was performed. Labs also displayed elevated alkaline phosphatase (ALP) bone isoenzyme of 103 IU/L (RR 0–72). Thoracic X-ray revealed chronic endplate vertebral compression fracture with no history of trauma and normal DEXA scan. NM bone scan was consistent with FD in skull, humerus, scapula, ribs, pelvis, femur and tibia. Given chronic pain at multiple sites and compression fractures, therapy with IV Zoledronic acid was given after Vitamin D was repleted. Within several hours, patient developed acute phase reaction (APR) with severe bone pain requiring hospitalization. ALP levels normalized within 1 year of therapy. 1.5 years post therapy, patient experienced a grand mal seizure. MRI brain revealed multifocal abnormal bone marrow within the calvarium, facial bones and skull base. Labs again displayed elevated ALP but new hypophosphatemia and an elevated serum FGF23. Given progression of skeletal disease as indicated by elevated FGF23, additional off-label injectable treatment options were reviewed and patient agreed to Ibandronate. Discussion: Majority of evidence for bisphosphanate treatment in FD is derived from observational studies, which report variable symptomatic improvement despite improvement of bone turnover markers. Oral anti-resorptives are commonly used but were not an option for our patient given history of Barrett’s esophagus and Whipple’s surgery. Pamidronate was first used in the treatment of FD with variable success rates. Denosumab is also being considered as a therapeutic option in FD however there are insufficient case reports to outline safety profile. Zoledronic acid is commonly used however our patient developed APR to the first dose and refused retrial. Given progression of disease, treatment was recommended. Therefore a milder anti-resorptive such as Ibandronate was considered which warrants further investigation in the treatment of FD.