biostudies-literatureJoseph GJVanderbilt University Medical Center Department of MedicineNIDDK NIH HHSVanderbilt-Ingram Cancer Center P3 Catalyst AwardDoD Breakthrough AwardVanderbilt University Medical Center Department of Orthopedic SurgeryNCI NIH HHSNIH Transition AwardMicroenvironment Influences in Cancer Training Program950-964https://www.ebi.ac.uk/biostudies/studies/S-EPMC12340981biostudies-literatureUnknown40(8)Immune checkpoint inhibitors (ICIs) block immunoregulatory receptor-ligand interactions and robustly increase survival of cancer patients but frequently result in immune-related adverse events (irAEs). While rheumatologic toxicities are commonly reported as irAEs, the effect of immune checkpoint blockade on the underlying mechanisms of ICI-induced fractures and bone loss is controversial, with reports of both positive and negative effects on bone mass in preclinical models. However, no previous reports have investigated the impact of ICIs on females or aged mice, or on fracture risk in either sex. We report that global deletion of programmed cell death protein 1 (PD-1) broadly results in bone loss in skeletally mature male and female PD-1-/- mice, with a sexually divergent phenotype in adoJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral ResearchProgrammed cell death protein 1 (PD-1) blockade regulates skeletal remodeling in a sex- and age-dependent manner.PMC123409815T32CA009592-33F99CA294171P30 CA068485P30CA068485P30 DK058404T32 CA009592F99 CA294171W81XWH-18-1-0029Tanaka HKell DJohnson RWHill PWeivoda MMSearcy MBUppuganti SRosenthal ELNyman JSVecchi Iii LAChen WKane JFDurdan MJoseph GJHarrison DGMcAdoo AGfalseProgrammed cell death protein 1 (PD-1) blockade regulates skeletal remodeling in a sex- and age-dependent manner.Immune checkpoint inhibitors (ICIs) block immunoregulatory receptor-ligand interactions and robustly increase survival of cancer patients but frequently result in immune-related adverse events (irAEs). While rheumatologic toxicities are commonly reported as irAEs, the effect of immune checkpoint blockade on the underlying mechanisms of ICI-induced fractures and bone loss is controversial, with reports of both positive and negative effects on bone mass in preclinical models. However, no previous reports have investigated the impact of ICIs on females or aged mice, or on fracture risk in either sex. We report that global deletion of programmed cell death protein 1 (PD-1) broadly results in bone loss in skeletally mature male and female PD-1-/- mice, with a sexually divergent phenotype in ado2025-01-01T00:00:00Z2025 Jul2026-05-04T21:57:54.147Z2026-04-07T21:00:43.244ZS-EPMC123409814031822210.1093/jbmr/zjaf055