Nature communicationsDec 30, 2025

Chemotherapy causes fat-related cell aging that leads to bone loss

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Chemotherapy-induced senescence in bone marrow adipo-lineage cells may drive RANKL-mediated bone loss.

Evidence

This preclinical mechanistic study found senescence in CAR cells and bone marrow adipocytes, with p38MAPK-MK2 inhibition or dasatinib plus quercetin preventing chemotherapy-induced bone loss.

Caveat

The abstract presents mechanistic preclinical evidence and does not report clinical outcomes in chemotherapy-treated patients.

Simplified

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to significant bone loss. Notably, we find that inhibition of the p38MAPK-MK2 pathway suppresses the senescence-associated secretory phenotype (SASP), including RANKL production abrogating bone loss. Furthermore, treatment with the senolytic combination dasatinib and quercetin (D + Q) selectively eliminates senescent CAR cells and BMAds, effectively preventing chemotherapy-induced bone loss. Given that nearly all chemotherapy treated patients experience bone loss and associated fracture risk, our findings offer a promising therapeutic avenue to preserve bone integrity and improve quality of life for cancer patients.