A Case of Chronic Bone Pain in Mc-CuneAlbright Syndrome

Introduction: McCune-Albright syndrome (MAS) is a rare genetic disorder that effects the endocrine, skin and bone systems and caused by a somatic mutation in the G protein activating adenylyl cyclase resulting in abnormal osteoblast differentiation and development of fibrous dysplasia (FD). We describe a patient with extensive fibrous dysplasia and severe bone pain in the setting of MAS. Case: A 56-year-old female with a history of MAS was evaluated in the osteoporosis clinic for chronic bone pain. She was diagnosed with MAS at the age of two when she presented with precocious puberty and treated with hormonal blockade. She had multiple orthopedic issues including chronic left hip and lower back pain with impending fracture and pelvic microfractures treated with prophylactic rodding and cement osteoplasty at age 46 and 51 respectively. She was taking Tramadol as needed. The patient reported an inch of height loss, and imaging revealed T4 compression fracture. She was treated with zoledronic acid 4 mg IV on a monthly basis for 1 year without any improvement in bone density or pain symptoms She reached menarche at age 12, and is currently menopausal. Her calcium intake was limited but vitamin D intake was adequate. The patient was quite active performing intense cardio exercises several times a week. Physical exam was remarkable for café-au-lait spots on her left trunk and abdomen not crossing the mid-line. Bone density showed spine DJD, right femoral neck and forearm T scores of -1.1 and -1.6 respectively. Recent CT scan demonstrated multiple lucent lesions in the thoracic spine, bilateral ribs and sternum consistent with fibrous dysplasia. Biochemical evaluation showed high bone turnover; urine NTX of 74 nM BCE/mM creatinine (26–124 nM BCE/mM) and bone specific alkaline phosphatase 80.7 U/L (14.2–42.7) Calcium and vitamin D levels were within limits. The patient initiated denosumab 60mg every 6 months to determine if significant reduction in bone turnover and bone pain would follow. Discussion: As patients with MAS and FD have elevated RANKL levels and increased bone resorption, treatments that reduce bone turnover markers (BTMs) have been studied. Bisphosphonates have demonstrated decline in BTMs but with mixed results regarding improvement of clinical symptoms (1). In a recent study, denosumab, a monoclonal antibody to RANK-L was given at either 3- or 6-month intervals. Patients who received 3-month interval injections demonstrated a sustained suppression of BTM and improvement of pain (2). Thus, denosumab is a promising and well-tolerated agent that may be effective in FD, especially when response to bisphosphonates is inadequate. References: 1. Boyce et al, A randomized, double blind placebo-controlled trial of Alendronate treatment for fibrous dysplasia of the bone 2. Bas C.J Majoor Outcome of Long-term Bisphosphonate therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia.