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Trials should co-primary mechanistic change (e.g., Prx cycling, 2-OH-E by DHE-HPLC, LIP de-quench) and clinical improvement, with biomarker gates for entry and adaptive dosing to respect where, when, how much. Pre-specified normalization (per protein/cell, oxygenation, m for mito-probes) and orthogonal controls (SOD/catalase, chelators, genetics) should be mandatory (Katerji et al

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58 Earlier studies found that iron overload in mice increases oxidative stress in bone, leading to changes in bone microstructure and mineral deposition properties, resulting in osteoporosis