Breaking Bone: Vulnerability,Assessment,and Prevention

Abstract

Fragile Balance: Managing Bone Health in People with Intellectual Disability and Epilepsy, an English Multi-Site Study

Menon R, Young C, Dale M, Allen M, McCabe J, Badger S, Appleyard M, Mousailidis G, Newman R, Jory C, Hammett J, Swift A, Jones C, Sawhney I, Winterhalder R, Watkins L, Shankar R. Seizure. 2025;133:189-194. doi:10.1016/j.seizure.2025.10.018. Epub ahead of print. PMID: 41183451.

Background: People with intellectual disability (ID) experience poorer health outcomes than the general population, with epilepsy and polypharmacy contributing to further risks. Bone health is a neglected area, despite the established association between antiseizure medications (ASMs) (especially those cautioned by the UK Medicines and Healthcare products Regulatory Agency [MHRA]), and reduced bone mineral density. We aimed to evaluate prescribing practices, fracture risk, and bone health management in adults with ID and epilepsy attending specialist ID services. Methods: A cross-sectional study was conducted across 3 English specialist ID epilepsy services between August 2021 and August 2022. Data were collected from case-note review, including ASM prescribing, falls and fracture history, bone health monitoring, and protective treatments. Descriptive statistics, Chi-square, and Mann-Whitney U tests were conducted. Logistic regression was used to examine associations between ASM use and fracture risk. Results: Of 484 adults analyzed, almost all (97%) were prescribed ≥1 ASM, with 18% receiving 4 or more and 63% receiving at least one MHRA-cautioned ASM. Over 25% on MHRA-cautioned ASMs had a history of fractures, yet 38% received no bone-protective treatment. Patients with severe-profound ID were prescribed significantly more ASMs than those with mild-moderate ID. Each additional ASM increased fracture risk by 37%, and each additional MHRA-cautioned ASM by 43%. Conclusions: Adults with ID and epilepsy are frequently exposed to polypharmacy, including bone health–compromising ASMs, yet bone health monitoring and treatment remain suboptimal. Targeted strategies and ID-specific guidance are urgently required to reduce fracture risk and improve outcomes in this vulnerable group.

Commentary

People with epilepsy (PWE) and intellectual disability (ID) have poorer long-term health outcomes and higher mortality rates compared to those without ID, related to increased seizure frequency, polypharmacy, and drug–drug interactions. This group also portends a higher risk of bone disorder development related to poor ambulation or inactivity, reduced sunlight exposure/vitamin D, antiseizure medication (ASM) polypharmacy, and use of older inducing medications that are associated with increased risk of osteoporosis.^1,2 Multiple organizations, including the Medicines & Healthcare products Regulatory Agency (MHRA) and National Institute of Clinical Excellence in the UK, advise bone health assessment in people taking ASMs, particularly for those on long-term treatment with inducing medications, such as primidone, phenytoin, carbamazepine, phenobarbital, or sodium valproate. These organizations emphasize monitoring with DEXA scans and vitamin D levels and highlight primary prevention, especially with vitamin D supplementation. Winterhalder et al further emphasized the gap in care for these individuals by demonstrating that over 90% of their cohort (n = 92) of PWE and ID were either vitamin D insufficient (25-49 nmol/L) or deficient (<25 nmol/L), and, of the 76 patients who had a DEXA scan, 50 were in the osteopenic or osteoporotic range. ³ These findings, along with the lack of accepted guidelines regarding monitoring bone health in PWE, ⁴ highlight the epilepsy care deficiencies in PWE and emphasize the importance of proactive assessment and management of bone health.

The article highlighted in this commentary examined bone health management in adults with epilepsy and ID. ⁵ Data from 3 English secondary care services for PWE and ID were analyzed to characterize ASM prescribing patterns, fall and fracture prevalence, bone health monitoring, and the use of bone-protective therapies (vitamin D, calcium, and bisphosphonates). The cohort included adults with a diagnosis of mild to profound ID and epilepsy. Data collected on the number and type of prescribed ASMs, use of an antidepressant and/or antipsychotic, history of falls and fractures, and prescription of bone-protective treatments. Bone health monitoring was assessed by identifying serum measures of bone health (alkaline phosphatase, calcium, and vitamin D) within the past 12 months and documented prior DEXA scans. The association between the total ASM burden and the odds of experiencing a fracture was examined. A secondary model replaced total ASM count with the number of ASMs cautioned by the MHRA due to the associated risk of osteoporosis. The median age of patients was 35 (range 18-78 years), and the majority of the sample was male (285/484, 59%). Generalized epilepsy was present in 67%, focal epilepsy in 31%, and 2% had both. Twenty percent were wheelchair-bound. The median number of ASMs prescribed per patient was 2, and the maximum was 7; 18% were prescribed 4 or more ASMs, and 63% were prescribed at least one MHRA-cautioned ASM. Among the 303 patients prescribed at least one MHRA-cautioned ASM, 29% had a history of falls, and 26% had a history of fractures. Clinically relevant monitoring (either on a bone profile or vitamin D level) was found in 61%. In regard to treatment, 62% were receiving primary or secondary bone protective therapy (ie, vitamin D, calcium, or combination therapy). The remaining 38% prescribed at least one MHRA-cautioned ASM were not receiving any bone protective treatment. Among patients with a history of falls, fractures occurred in 56% of those on an MHRA-cautioned ASM compared to 38% of those not prescribed one. After adjusting for age, sex, and fall history, each additional ASM was associated with a 37% increase in fracture risk, and each MHRA-cautioned ASM with a 43% increase. In both models, older age and a history of falls were also independently associated with increased fracture risk.

This study identified a marked association between the number of MHRA-cautioned ASMs prescribed and fracture occurrence. Notably, more than one-third of patients with a fracture history were not receiving bone-protective therapies. Despite the high prevalence of bone health risk factors in this population, only 58% (n = 279) were receiving any form of bone protective therapy. These findings highlight the need for clearer guidance on bone health screening and management in populations with increased vulnerability, such as those at higher risk ASMs, to adverse bone health outcomes.

Major study limitations include modest sample size, retrospective design, and barriers to assessing bone health and implementing treatment in clinical practice, such as inability to tolerate blood tests or DEXA scans. There was also significant reporting variability in bone health measures and treatment implementation. Information on ASM dosage and duration was unavailable, limiting analyses to the number of ASMs prescribed rather than daily cumulative dose. Lack of specific seizure types may have confounded results, as certain seizure types, such as generalized seizures, may increase the risk of injury independent of bone health. Additionally, because the known mechanism of injury could not be reliably determined from radiographic findings, the authors were unable to examine the prevalence of fractures not related to trauma. Lifetime fracture history likely included fractures linked to significant trauma rather than poor bone health, which may have overestimated the burden of bone health–related fracture risk. Lastly, the authors mention 20% of the population was wheelchair-bound, but do not comment on how weight-bearing status may have further impacted bone health.

This publication highlights significant gaps in bone health management among PWE, and more specifically in those with ID and epilepsy, a population already at heightened risk due to polypharmacy, limited mobility, and increased rates of falls and fractures. Despite frequent exposure to ASMs, which are cautioned by the MHRA for their adverse effects on bone density, many individuals did not receive adequate bone health monitoring or protective treatments. With the lack of formalized guidelines for bone health management in PWE, there is a need for the development of proactive and systematic assessment of bone health, ultimately establishing practice guidelines for assessment and management as part of routine care for these populations. Further research is needed to clarify causal relationships, identify monitoring and implementation barriers, develop risk assessment and validated tools, and evaluate prevention treatment strategies. This publication identified a clear unmet need and reinforced the importance of improving bone health management in high-risk populations to ultimately reduce the risk of fractures and other epilepsy-related complications and improve quality of life.