The use of denosumab in rare bone diseases in adults: a systematic review from the ECTS Rare Bone Disease Action Group.

contextRare bone diseases (RBDs) may display a disrupted RANKL-RANK-osteoprotegerin pathway causing increased osteoclastogenesis and enhanced bone resorption. Although bisphosphonates are commonly used, they often fall short of desired outcomes. Denosumab, an anti-RANKL antibody, provides a promising alternative by swiftly and strongly suppressing bone turnover (faster and more potent suppression of bone resorption than bisphosphonates), though its effects are reversible on discontinuation. The use of denosumab has been highlighted, especially in pediatric cases, but not substantially in adults. EVIDENCE ACQUISITION: A targeted evidence search was conducted to retrieve studies reporting denosumab use in RBDs in adults. EVIDENCE SYNTHESIS: Denosumab administration may lead to pain reduction, lesion reduction, or bone formation. Treatment dosage, schedules, and duration varied, however, a dose of 120 mg dosed monthly or every 3 months for almost 1 year reached the desired treatment effect in most patients. Denosumab is generally well tolerated in adults, with mild common side effects such as (asymptomatic) hypocalcemia and hypophosphatemia. Serious adverse effects such as osteonecrosis of the jaw or atypical femoral fractures are rarely reported. Main concerns regard rebound effect after denosumab discontinuation, with disease recurrence in some cases. Zoledronic acid after discontinuation of denosumab might be advisable, but is seldom reported.

conclusionDenosumab is a feasible treatment in adults with RBDs when managed by multidisciplinary teams with knowledge of both the underlying disease and potential surgeries as well as the medical site of treatment. Denosumab discontinuation management is paramount to prevent recurrence and severe complications. The paucity of data supports the need for data collection through rare disease registries for future pertinent evidence-based recommendations.