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Summary Extended survival in breast cancer marks a major therapeutic success, but the persistence of late-onset bone metastasis remains an unresolved clinical issue. The driver of this latency is not merely the loss of bone mineral density, but rather a fundamental metabolic reprogramming within the aging osteoporotic marrow. Distinct from a simple structural decline, the osteoporotic niche evolves into a "metabolic sanctuary" which is defined as a privileged microenvironmental state that provides disseminated tumor cells with dedicated bioenergetic fuel while simultaneously shielding them from systemic immune and therapeutic pressures. Fueled by marrow adipogenesis, immunosenescence, and disrupted mechanotransduction, this degraded microenvironment actively coaxes dormant tumor cells into reactivation. This mechanistic distinction may offer a plausible hypothesis for the divergent outcomes seen in the D-CARE and ABCSG-18 trials. Pharmacologically preserving bone density alone may prove insufficient if the host's underlying metabolic dysregulation is left unaddressed. Preventing late recurrence implies a need for a paradigm shift: It requires not simple anti-resorptive approaches, but strategies targeting the metabolic crosstalk that disrupts the bone marrow niche.
Duan et al. (Mon,) studied this question.