Information on the diagnosis

of MG patients was therefore limited. For this reason, we determined fracture risk not only among all patients with a MG recording in either GPRD or HES, but also among more probable MG patients with more than one recording of MG only. We could only use variables recorded in the GPRD to assign disease severity and classification of severity of disease could have been improved, if we would have had access to tertiary care data such as plasmapheresis. We did not have data on femoral bone mineral density JAK2 inhibitors clinical trials and no data on history of hip fracture among the parents of patients. Only small numbers of incident MG patients were present in the subgroup analyses. For this reason, these data should be interpreted with care. Moreover, no data were present about

vitamin D plasma levels, degree of exercise or longitudinal data on body weight. This could have confounded Trichostatin A chemical structure the observed increased fracture risks in patients using CNS medication. We showed an absence of fracture risk among MG patients using oral glucocorticoids compared to unexposed MG patients and a lower risk compared to control patients using oral glucocorticosteroids, but we were unable to determine any significant difference. This issue warrants further research. In theory, high-dose prednisolone might exacerbate MG, which could have interfered with the analyses. However, glucocorticoid treatment is regularly started with a low dose, which is gradually increased Mirabegron [14, 15]. This minimizes the risk of an exacerbation. In conclusion, this study showed that MG was not associated with a statistically significant increased fracture risk, not even among MG patients who received high-dose oral glucocorticoids. This suggests that there is no need to alter current management of MG. In contrast, fracture risk was increased among patients using CNS medication. Therefore, fracture risk assessment may be indicated among patients with MG who have recently used CNS medication. Further investigation should be performed to address the underlying mechanism for the observed absence of an increased fracture

risk among MG patients exposed to high-dose oral glucocorticoids. Acknowledgements This work was funded in part by The European Calcified Tissue Society and the NIHR, Biomedical Research Unit in Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford. Conflicts of interest The Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, employing authors Sander Pouwels, Anthonius de Boer, Hubertus G Leufkens and Frank de Vries, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, private–public funded Top Institute Pharma (www.​MK-8776 cost tipharma.​nl and includes cofunding from universities, government, and industry), the Dutch Medicines Evaluation Board and the Dutch Ministry of Health.