Fractures

It is well documented that the rate of fractures for people with epilepsy is higher than for the population as a whole.30 While this is partly due to falls occurring during seizures, other mechanisms also exist. In particular, attention has focused on the impact of anticonvulsants on bone mineral density and the development of osteoporosis. In addition, a further impact may be the sedatory effects of anticonvulsants, which may increase the risk of falls.31

Patients with ID and coexisting epilepsy share the increased risk of fractures. Jancar and Jancar reported an incident fracture rate of 26% for patients with ID and with epilepsy compared with 15% in those without.32 Of 68 fractures occurring in those patients with epilepsy, 17 (25%) occurred as a result of a seizure. In the UK, the admission rate for fractures to accident and emergency units was almost three times greater for patients with ID and with coexisting epilepsy compared with those without.6

A study based in the United States in a long-term care institution revealed an odds ratio for fracture of 1.9 for patients with epilepsy compared to those without.33 Interestingly, the same study found no association between risk of fracture and severity of ID, although this may be due to the bidirectional nature of the relationship in that while severity of ID is associated with increased frequency of seizures, it is also associated with reduced mobility.

One case control study considering nontraumatic appendicular fractures among an institutionalized population reported an annual prevalence rate of 7.3%, sevenfold that expected in the general population.34 There was an increased risk in those patients who were prescribed antiepileptic medication. Of cases who had a history of fracture, 83% were prescribed antiepileptic medication compared with 52% of controls. A South African based case-control study of patients with cerebral palsy also demonstrated a significant association between use of antiepileptic medication and number of fractures occurring.35

In the prospective observational Norwegian study by Nakken and colleagues 15 (see above) based on an observed cohort of 62 patients, nine fractures resulted from a total of 2,714 seizure-related falls over a 13-month period. Of these five were considered to be serious: two fractured legs, one mandibular fracture, one fractured neck of the femur, and one fractured skull.

In addition to the likelihood of fractures resulting from falls occurring during seizure, it is well documented that anticonvulsants are associated with low bone mineral density36 and that duration of exposure to anticonvulsants is an important factor.37

Several potential mechanisms have been suggested to explain this association, including failure to synthesize or absorb vitamin D, calcium, vitamin K, and phosphorus.38 Phenytoin, primidone, and phenobarbitone have all been shown to lead to osteomalacia.39

The prevalence of low bone mineral density and osteoporosis is significantly exceeded in patients with ID in general^04 The extent of this, however, may be exaggerated, as many of the studies supporting this finding were conducted within institutions, and the two suggested mechanisms -- osteopenia and osteomalacia -are associated with institutionalization. Osteopenia can occur as a result of immobility, which may be due to motor problems associated with the ID, which may also be increased due to institutional regimens. Osteomalacia is the softening of bone mass resulting from deficiency or inadequate metabolism of vitamin D. In institutionalized patients this may be due to insufficient exposure to sunlight. In addition, there is evidence of other medication for psychiatric and behavior disorders impacting on bone loss.

A further factor which should be noted is that risk of falls and fracture are predicted by the presence of generalized seizure,42 43 and despite potential problems with diagnosis of seizure type it has been shown that patients with ID have an increased likelihood of generalized seizures compared with patients with epilepsy as a whole.44 ,45

To summarize, patients with ID and epilepsy may be have an inflated risk of fracture due to factors associated with both individual conditions. For all patients on anticonvulsants, osteoporosis should be considered as a potential comorbidity. Monitoring of bone density should be considered, and osteoporosis in these patients should be minimized by ensuring adequate nutrition, including supplements to provide optimal levels of calcium and vitamin D. Simple measures such as increasing exposure to sunlight for institutionalized patients might prove simple to implement and effective.

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