ODP132 Efficacy of Romosozumab for Osteoporosis in a Patient with Hajdu-Cheney Syndrome: A Case Report

INTRODUCTION: Hajdu–Cheney syndrome (HCS) is a genetic disease with an autosomal-dominant pattern caused by mutations of NOTCH2. This rare disease primarily causes skeletal dysplasia, including craniofacial dysmorphology, dental anomalies, and short stature accompanied by radiographic abnormalities with acroosteolysis and generalized osteoporosis. Even if a definite diagnosis of HCS could be reached as techniques for genetic testing have been advanced, the more important problem is that there is no effective pharmacological treatment for this disease at present. In this study, we aimed to evaluate the efficacy of romosozumab for improving bone fragility in our osteoporotic HCS patient. CLINICAL CASE REPORT: A 43-year old woman was referred to our department to evaluate skeletal dysplasia. She underwent surgical correction of valvular disease when she was 11 years old. She did not have any fracture before she was 26-years old when she got an L1 compression fracture while carrying heavy stuff. She presented with persistent pain and progressive shortening of both fingers and toes since she was 29-years old. She also has hearing difficulty. Physical examination revealed coarse facial features such as micrognathia, low-set ears, elongated philtrum, bushy eyebrows, the wide nose and short digits showing pseudo-clubbing. There were no abnormalities in her biochemical results for liver and renal function, serum calcium, phosphate, alkaline phosphatase, thyroid-stimulating hormone, estradiol, parathyroid hormone, and 25-hydroxy vitamin D. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry showed T score of -4.2, -2.4, and -1.5 at the lumbar spine (LS), femur neck (FN), and total hip (TH), respectively. A skeletal survey revealed acro-osteolysis and deformity of all digits bilaterally and compression fracture at T8, T10, and L1. Her next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter amino acid in NOTCH2 gene annotated as pathogenic. Romosozumab treatment (210mg injected subcutaneously every month) with calcium and vitamin D supplements was started because she had already received bisphosphonate for 10 years without preventing progressive osteolytic lesions and repeated fractures. After one year of treatment with romosozumab, BMD increased by 15.4%, 6.3%, and 1.3% to T-score of -3.5, -2.1, and -1.4 at LS, FN, and TH, respectively. Overall, C-telopeptide was suppressed by 26.4%, 0.121 to 0. 089 ng/mL, and P1NP was increased by 18.7% from 25.2 to 29.9ng/mL with transient fluctuation during the follow-up period. Follow-up radiographs of the hand and feet showed no progressive acro-osteolysis. Clinical conclusion: This is the first treatment report of romosozumab for an osteoporotic HCS patient in Korea. One year of romosozumab treatment provided substantial gains in BMD and prevented progressive acroosteolysis, which represents a promising treatment option for the rare disease of HCS. Presentation: No date and time listed