00 1 00   1 00 1 00    Oral glucocorticoid use 0 88 (0 52–1 47) 1

00 1.00   1.00 1.00    Oral glucocorticoid use 0.88 (0.52–1.47) 1.50 (1.02–2.20) 0.217 0.75 (0.38–1.50) 1.86 (1.23–2.83) 0.065  No antidepressant use 1.00 1.00   1.00 1.00    Antidepressant use 2.15 (1.22–3.79) 1.50 (1.15–1.96) 0.608 3.27 (1.63–6.55) 1.63 (1.18–2.27) 0.260  No anxiolytic use 1.00 1.00   1.00 1.00    Anxiolytic use 1.80 (0.97–3.34) 1.14 (0.82–1.59) 0.101 2.18 (1.04–4.57) 1.17 (0.79–1.73)

0.044  No anticonvulsant BV-6 use 1.00 1.00   1.00 1.00    Anticonvulsant use 5.36 (2.76–10.39) 0.96 (0.53–1.76) 0.000 6.88 (2.91–16.27) 1.19 (0.61–2.33) 0.002 aAdjusted for the same confounders as described below Table 2 for any and osteoporotic fracture, but the confounder is not added to the model if it is similar to

the drug being investigated bThe interaction term (MG × drug use in the previous 6 months) was investigated within the GANT61 cohort of MG patients and controls Conversely, within the group of incident MG patients risk of fracture was twofold higher in those with a recent use of antidepressants (AHR 2.15 [95 % CI 1.22–3.79]), twofold higher for anxiolytics (AHR 1.80 [95 % CI 0.97–3.34]) and fivefold increased with recent use of anticonvulsants (AHR 5.36 [95 % CI 2.76–10.39]). Typical osteoporotic fracture risk was threefold higher within incident MG patients with recent use of antidepressants BIX 1294 mouse (AHR 3.27 [95 % CI 1.63–6.55]), twofold higher with recent use of anxiolytics (AHR 2.18 [95 % CI 1.04–4.57]) and sevenfold higher with recent use of anticonvulsants (AHR 6.88 [95 % CI 2.91–16.27]). Finally, within the complete cohort with both incident MG patients and control patients, the interaction CYTH4 term between MG and anxiolytics showed statistical significance for osteoporotic fracture (p value < 0.05). The interaction term between MG and anticonvulsants showed statistical significance for both osteoporotic and any fracture (p value < 0.05). To further investigate whether a true association between MG and fracture

risk had been averaged out by a fluctuating hazard function, we showed that MG duration was not related to fracture risk: 1-year risk of any fracture yielded an AHR of 1.15 (95 % CI 0.88–1.52) in patients with MG versus population-based controls, while 5-year risk (AHRs of 0.97 [95 % CI 0.74–1.28]) and 10-year risk (AHR 0.94 [95 % CI 0.71–1.23]) were not different. The Kaplan–Meier curve as presented in Fig. 1 showed similar results with a non-significant log-rank test (p value > 0.05) when MG patients were compared with control patients. In addition, the severity of MG was not related to increased risk of fracture (Table 5). Finally, using MG patients only from the GPRD (without HES data) did not alter the findings.

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