MON-517 Treatment of Gorham-Stout Disease with Combination Sirolimus and Denosumab

Abstract

Background: Gorham-Stout Disease (GSD), or vanishing bone disease, is a rare condition characterized by lymphatic vessel proliferation associated with progressive, sometimes massive bone resorption. The underlying mechanism of osteolysis in this condition remains unclear; prevailing theories suggest that the disease is driven by lymphovascular growth factors, increased osteoclastic activity, and absence of osteoblast repair. Clinical Case: A 44-year-old Caucasian male was found to have an absent right scapula and multiple right rib fractures on an x-ray performed to evaluate chest discomfort. Notably, 3 years prior, a right shoulder MRI showed normal anatomy. He has no family history of bone disease. Physical exam showed soft tissue swelling in the area of the right scapula and limited range of motion of the right arm to 60 degrees in all directions. Serum calcium, phosphorous, and iPTH were normal. Bone resorption marker C-Telopeptide (CTx) was elevated to 722 pg/mL (93-630 pg/mL) while bone formation marker Procollagen I intact N-terminal (P1NP) was within normal limits. CT and MRI confirmed the absence of the body of his right scapula and identified posterior right rib lesions with overlying fractures. The remnant scapula and rib foci showed abnormally elevated activity on 18F-sodium fluoride (18F-NaF) PET/CT scan. Given his clinical and imaging findings, he was diagnosed with GSD. Treatment included two years of monthly denosumab (120 mg) and sirolimus (trough goal 7-13 mcg/L), followed by zoledronic acid infusion every 2 months for 3 doses to prevent the rebound bone resorption associated with denosumab cessation. After therapy, CTx was suppressed to 70 pg/mL and P1NP to 15 mcg/L (22-87 mcg/L). Serial imaging showed one new posterior right rib lesion noted after 6 months of treatment, but no further bone loss. He noted no pain or new weakness. Adverse events included worsening hypertriglyceridemia due to sirolimus as well as denosumab-induced hypocalcemia and hypophosphatemia. Discussion: There is no consensus on the optimal treatment of GSD. Medical therapy usually includes an antiproliferative agent (usually sirolimus or interferon 2b) and an antiresorptive agent (usually a bisphosphonate). The RANK-ligand inhibitor denosumab, the most potent osteoclast inhibitor, may be a more effective agent in preventing bone resorption in GSD. This case demonstrates the effective use of sirolimus and denosumab in GSD, but further study and careful monitoring for mineral metabolism side effects and rebound are needed.