We report on the clinical and biochemical outcomes in a 20-year-old male suffering from active craniofacial monostotic fibrous dysplasia (MFD) treated with the RANK-L inhibitor, Denosumab, following unsatisfactory responses to prior long-term bisphosphonates therapy. The patient had been treated over 9 years with pamidronate (cumulative dose of 81 mg), but experienced only mild reductions in pain scores. Following initiation of Denosumab 60 mg subcutaneously, bone pain and bone turnover markers (osteocalcin, total and bone alkaline phosphatase and β-crosslaps) were monitored over a period of 14 months. Following the first administration, the patient demonstrated a promptly and pronounced clinical and biochemical response: within few hours the patient reported pain disappearance and after 4 weeks bone turnover markers fell to levels within the normal range. Three months after initiation of Denosumab the patient reported an acute pain reactivation that required a second administration. As previously, after few hours the pain disappeared. Later Denosumab was administered according to pain reappearance and the injections were always followed by complete pain relief. However, a gradual shortening of the pain-free interval between administrations was observed, ranging from 90 days after the first one to 75 days after the fifth one. Treatment with Denosumab was always well tolerated. The monitoring of bone turnover showed that all markers stayed in the lower half of the normal range, even at the moment of pain reappearance, suggesting that the effect of Denosumab on pain depends on mechanisms other than bone resorption suppression.
In conclusion, Denosumab appears to be effective in reducing bone turnover and bone pain in adult patients with active MFD and could represent a good alternative to bisphosphonates, allowing to avoid elevate cumulative doses of these agents. Further studies are required to clarify the efficacy, safety and mechanisms of long-term therapeutic RANK-L inhibition in MFD.