To examine the impact of Multiple Sclerosis on bone health and explore mechanisms for this association.

People with MS (PwMS) have an increased risk of osteoporosis and fractures; this is thought to be related to shared risk factors, although has not been confirmed. 

Using  well described exposures, we investigated associations with heel Bone Mineral Densitometry (BMD) and fractures in PwMS in UK Biobank. We used heel BMD from 960 people with MS and 278,138 controls, and 47,466 fractures in 502,583 individuals. 

Multivariate linear (heel BMD) or logistic (fracture) regression adjusting for age, sex, ethnicity and current deprivation status was performed. Likelihood ratio test was used to assess model fit. 

Demographic characteristics were representative of the MS population (F:M ratio 2.58:1, mean age 55.2 SD 7.6). 234/1781 PwMS in UK Biobank (13.1%) reported fractures Heel BMD T-scores were lower among PwMS (mean -0.649+/-1.3 vs -0.336+/-1.24). 

Lower heel BMD was associated with smoking (beta -0.1), alcohol consumption (beta -0.03), later menarche (beta -0.03), post-menopausal status (beta -0.18), epilepsy (beta -0.28,), and vitamin D supplementation (beta -0.1). 

In a model incorporating all individually-significant predictors, the effect of MS on BMD attenuated slightly (beta -0.11, 95%CI -0.19 to -0.02) while the effect of MS on fracture risk reversed (OR 0.81, 95% CI 0.69-0.95). To determine which exposure explained this association, we built models for each significant predictor and MS status. After adjustment for falls, the effect of MS on fracture attenuated (OR 0.90, 95% CI 0.78 to 1.04). No other exposures altered this association. 

These results confirm in a large cohort that MS is associated with lower BMD and higher risk of bone fractures. No single factor studied appears to explain the reduced BMD in MS; however increased rates of fracture appear to be driven by both decreased BMD and increased frequency of falls.