Background:​ Adults with epilepsy have an increased risk of fragility fractures, which contributes to an accelerated rate of premature morbidity and mortality. In the general population, osteoporosis treatment has shown improvements in health and survival, possibly through improving skeletal robustness;​ however, the effect of osteoporosis medication on survival among adults with epilepsy has not been investigated. The purpose of this propensity score-matched, observational cohort study was to determine if osteoporosis medication was associated with mortality risk among adults with epilepsy. An exploratory analysis then examined the association between the type of osteoporosis medication with mortality.

Methods:​ Data from 01/01/2012–09/30/2017 was extracted from Optum Clinformatics® Data Mart. Adults ≥50 years of age with epilepsy that were treatment naïve for and initiated osteoporosis medication (EP new users) were the primary group of interest, and were compared to adults with epilepsy that were not prescribed osteoporosis medication (EP no users) and adults without epilepsy that were treatment naïve for and initiated osteoporosis medication (w/o EP new users). Comparison groups were matched 1:​4 to EP new users (n = 733;​ comparison groups, n = 2932) for demographics, glucocorticoid and antiseizure medication, prior 12-month fracture, and the Elixhauser comorbidity index. Crude incidence rate (IR) and IR ratio (IRR and 95% confidence intervals [CI]) was estimated for mortality for up to 3 years of follow-up. For new users, the association between type of osteoporosis medication (bisphosphonates vs. others) and mortality was explored using Cox proportional hazards regression after adjusting for all covariates.

Results:​ For new users, the majority of the prescribed osteoporosis medications were bisphosphonates (~83%). The incidence of mortality for EP new users was lower compared to EP no users (IRR = 0.69;​ 95%CI = 0.52–0.93), but elevated compared to w/o EP new users (IRR = 1.42;​ 95%CI = 1.04–1.94). Comparing bisphosphonates to other medications for new users (P for EP group interaction = 0.089), EP new users showed a lower fully adjusted hazard ratio for mortality (HR = 0.56;​ 95%CI = 0.30–1.04), but was marginally insignificant (P = 0.066), while w/o EP new users showed no evidence of an association (HR = 1.09;​ 95%CI = 0.72–1.65).

Conclusions:​ Osteoporosis medication initiation was associated with a lower 3-year risk of mortality among adults with epilepsy. The exploratory analysis revealed potential evidence of a unique protective effect of bisphosphonates as compared to other osteoporosis medications on 3-year mortality for adults with epilepsy.