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Urinary calcium and bone resorption markers during 3 years of denosumab treatment in pediatric osteogenesis imperfecta

Year: 2025
Type: article
Abstract: . Denosumab, a monoclonal antibody targeting RANKL, inhibits osteoclast differentiation and activation, thereby preventing bone resorption. Despite its efficacy as an anti-resorptive therapy, concerns of rebound hypercalcemia limit its clinical use. This investigation was part of the multicenter trial NCT02352753, which was terminated early due to calcium-related adverse events. We implemented a sub-study to investigate dynamics of bone resorption markers and calcium, and the precise timepoint of rebound during denosumab therapy in OI patients. About 40 participants between 2 and 16 yr received subcutaneous denosumab (1 mg/kgBW) every 6 mo for 3 yr. Calcium supplementation was started on the day of denosumab injection. Spot urine samples were collected at weeks 2, 8, 12, 16, 18, 20, and 22 post-injection in every treatment cycle to measure urinary bone resorption markers (n-terminal telopeptide [NTX] and deoxypyridinoline [DPD]), calcium and creatinine. Calcium supplementation was ended when urinary Ca/Creatinine ratios reached age-specific thresholds. Denosumab effectively suppressed bone resorption within the first 2 mo post-injection. However, after 8 wk, uNTX and DPD levels re-increased again, reaching baseline levels after 3 mo, followed by a mild rebound after 4 mo. Average duration of Ca supplementation was 10 wk, two patients developed mild nephrocalcinosis. In conclusion, we saw that rebound of bone resorption emerges as early as 4 mo after denosumab injection. Continuous monitoring of calcium levels and careful handling of calcium supplementation is mandatory during therapy, but Ca-related side effects can still occur.
Source: JBMR Plus
DOI: 10.1093/jbmrpl/ziaf140
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,888
OpenAlex ID: W4413875102
FWCI: 1.898
Cites: 35
Cited by: 2
Related to: 10