J Clin Endocrinol Metab. 2026 Apr 7:dgag154. doi: 10.1210/clinem/dgag154. Online ahead of print.
ABSTRACT
CONTEXT: Rare bone diseases 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 upon 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 rare bone diseases 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 3 monthly for almost one 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.
CONCLUSIONS: Denosumab is a feasible treatment in adults with rare bone diseases 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.
PMID:41955566 | DOI:10.1210/clinem/dgag154
