Abstracts

Rationale: Ketogenic Diet Therapy (KDT) is increasingly utilized as effective treatment for refractory epilepsy in adults. Known adverse effects of KDT in children, including potentially deleterious effect on bone health, merit further exploration in adult populations. This study aims to investigate whether adults on KDT are at risk for low bone density (LBD), and which clinical factors may increase that risk.

Methods: This is a retrospective cohort analysis of adults treated with KDT for refractory epilepsy who had dual energy X-ray absorptiometry (DXA) assessment. Risk factors assessed include sex, age at seizure onset, antiseizure medication (ASM) history, fracture history, vitamin D status, use of corticosteroids, age at KDT initiation, and duration of KDT use. Data from DXA scans were collected including bone mineral density T-scores and Z-scores, from which the lowest clinically appropriate standard score was established, hereafter referred to as DXA score. Patients were categorized to normal or LBD groups using clinical criteria defined by the International Society for Clinical Densitometry. Bone health was analyzed as a categorical variable (normal vs LBD) and as a continuous variable (DXA score).

Results: Data were collected from the medical charts of 58 adults (37 females), with seizure onset between infancy to 61 years (mean=15.9 years), age at KDT initiation between 3 to 70 years (mean=32.5 years), and duration of diet exposure at time of DXA ranging from 9 days to 29 years (mean=3.8 years). A higher relative risk of LBD was seen in patients with prior exposure to enzyme-inducing anti-seizure medications (EI-ASM; RR=2.98, p=0.021), as well as those with a history of fracture (RR=2.16, p=0.003). Seizure onset at a younger age was associated with lower DXA scores (r=0.263, p=0.046). Amongst patients exposed to EI-ASMs, no association was found between duration of KDT use and DXA scores. However, in patients who had not been exposed to EI-ASMs, younger age at diet initiation (p=0.048) and longer duration of diet use (p=0.011) were correlated with lower DXA scores. There was a trend toward lower DXA scores in patients who started KDT at a younger age (r=0.234, p=0.077); specifically, patients who started the diet before age 47 were more likely to have LBD than those who started the diet after that age (73% vs 36%, p=0.042).

Conclusions: These data suggest that adults on KDT may be at risk for LBD, providing neurologists with associated clinical risk factors to consider including history of fracture and EI-ASM exposure. While patients with prior EI-ASM use were more likely to have poor bone health overall, it was actually those who were not exposed to EI-ASMs for whom age at KDT initiation and duration of diet most impacted bone health. Further investigation is needed to determine mechanisms by which prior EI-ASM use (or lack thereof) drives the effect of KDT on bone density, as well as the implications of KDT on bone metabolism changes throughout the lifetime. Appropriate monitoring of bone health should be incorporated into routine KDT management in adults.

Funding: Please list any funding that was received in support of this abstract.: None.