Association Between Herpes Zoster and Risk of Incident Fragility Fractures in US Veterans: A Matched Cohort Study.

Background: Herpes zoster (HZ) and fragility fractures typically affect older adults and present major burdens to healthcare systems. While HZ is associated with an increased risk of neurological, ocular, skin, and visceral complications, it is unclear whether it affects long-term bone health. Therefore, we aimed to compare the risk of fragility fractures in Veterans with HZ relative to matched Veterans without HZ in the United States.

Methods: We used routinely collected data from the Veterans Aging Cohort Study (VACS-National) from 01/01/2008 to 31/12/2023. Veterans with incident HZ diagnoses aged 40+ were matched on age, sex, race, ethnicity, site of care, and calendar time with up to five Veterans without HZ. The association between HZ and subsequent fragility fractures (defined as hip/femoral, shoulder/upper arm, vertebral, and wrist/forearm fractures) overall and by site was assessed using a Cox model stratified by matched set adjusting for sociodemographic, lifestyle, and clinical confounders. Age, frailty, and receipt of antivirals (AVT) within 7 days of exposure were investigated as potential effect modifiers for the relationship.

Results: We included 229,992 Veterans with HZ matched to 1,134,519 Veterans without HZ. Both groups were comparable in median age (67.8 vs. 67.7 years), percentage males (93.5% vs. 93.7%), and median follow-up time (5.9 vs. 5.4 years). Veterans with HZ had a 15% higher risk of incident fragility fracture (aHR = 1.15, 95% CI: 1.13, 1.18) compared to Veterans without HZ. The increased risk was observed for each fracture site. There was evidence of interaction by age, frailty, and receipt of AVT, as older, frailer, and AVT-treated Veterans had a higher risk of fragility fracture.

Conclusions: Veterans with HZ were at a higher risk of fragility fractures relative to Veterans without HZ, highlighting the need for improved fracture prevention among those diagnosed with HZ. Further research in non-Veteran and female populations will improve generalizability.