Metaphyseal band fractures in pediatric patients treated with denosumab
Bibliographic record
Abstract
OBJECTIVE: Denosumab, a potent antiresorptive agent targeting receptor activator of nuclear factor kappa-B ligand (RANKL), is increasingly used off-label in RANKL-mediated pediatric bone disorders, but concerns remain regarding rebound hypercalcemia and altered bone modeling and remodeling. This study describes clinical, biochemical, and radiological features of metaphyseal sclerotic band fractures in children on denosumab and assesses risk factors with focus on timing and occurrence of rebound hypercalcemia. DESIGN AND METHODS: We conducted a retrospective multicenter study. Clinical, biochemical, and X-ray data were reviewed. High-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis were performed in 1 case to assess bone microarchitecture. RESULTS: Five pediatric patients (aged 7-18 years) were included: 4 received denosumab for RANKL-mediated bone lesions, and 1 for secondary osteoporosis. Fractures occurred 1.5-7.7 years after starting denosumab, involving the distal radius, ulna, femur, clavicle, and rib. All followed low- or moderate-impact trauma and involved zones of metaphyseal sclerosis. Rebound hypercalcemia occurred in all patients (1 to >16 episodes); in 4 cases, it preceded the fracture by 0-4 months, while 1 case first developed hypercalcemia 3 weeks postfracture. HR-pQCT in a single patient revealed markedly increased trabecular volumetric bone mineral density and stiffness within the sclerotic band plus reduced estimated failure load. Bisphosphonates were used, albeit variably, for prevention or treatment of hypercalcemia. CONCLUSIONS AND RELEVANCE: Fractures through sclerotic metaphyseal bands may represent a distinct complication of denosumab therapy in children. Rebound hypercalcemia and fractures can co-occur, underscoring the need for close monitoring and management by pediatric bone specialists throughout treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".