Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture - A NOREPOS Population-Based Cohort Study.

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variation in immune responses affect fracture-risk on a population-level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involve some of the immune pathways that also drive bone loss. During 1963-1975 the vast majority of the Norwegian adult population were examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940-1960 and aged 14-30 years at examination) who had all received BCG vaccination following a negative TST at least one year prior, and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244 607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway during 1994-2013. There were 3 517 incident hip fractures during follow-up. Using a predefined Cox model we found that men with a positive or a strong positive TST result had a 20% (HR 1.20, 95% CI 1.01-1.44) and 24% (HR 1.24, 95% CI 1.03-1.49) increased risk of hip fracture, respectively, compared to men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample, and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response following vaccination is associated with an increased risk of hip fracture decades later among men, possibly due to increased immune-mediated bone loss. This article is protected by copyright. All rights reserved.