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around £15 to the NHS (personal communication, St George’s NHS Trust 2011), and screening
has been recommended by the authors of a very balanced and comprehensive review3. Together
with the suggestion that even low doses might be sufficient in children (perhaps because started
earlier in their treatment history, though this has not been proven), and a recent study showing
that standard supplementation from the outset can prevent otherwise rapid falls on starting
AEDs92, my own practice has shifted in recent years towards checking vitamin D status early
on in treatment, recommending a standard supplementation (calcium and 400 IU vitamin D)
for those with levels below 30 nmol/L, and higher doses at least for short periods in those with
substantially low levels, with a subsequent recheck. Even in a centre with a local ‘champion’,
embedding in practice is difficult93,94, though including a prompt on electronic prescribing has
shown to improve compliance. Ideally this should be undertaken in the context of ongoing
audit/research, but this is currently precluded by resource limitations.

Treatment of identified cases

Other than ensuring adequate vitamin D, a broad range of treatment options are now available
for osteoporosis including hormone replacement therapy (oestrogen in postmenopausal
women, testosterone in men), bisphosphonates, recombinant PTH, oestrogen-receptor
modulators, monoclonal antibodies with effects on bone turnover, and calcitonin. No trials
have been powered to detect differences in the magnitude of fracture reduction between
treatments, and the vast majority have been undertaken in postmenopausal women, with little
evidence in younger age groups, and also less in men, though there is no evidence that skeletal
metabolism differences are fundamental between the sexes. Low-cost generic bisphosphonates
which have a broad spectrum of effects are usually first line in the absence of contraindications.
While previous guidelines recommended treatment of T scores below -2.5, current UK
guidance requires that age, T score and the number of additional clinical risk factors (including
presence of a fragility fracture or conditions ‘indicative’ of likely low BMD such as premature
menopause, or low BMI) are taken into account. Whether and how often to perform repeat
scans of patients with intermediate scores (-1 to -2.5) other than in patients on glucocorticoids
(usually recommended every 13 years) remains controversial, and patient management should
anyway be undertaken with local osteoporosis specialists. There has only been a single trial
reported in patients with epilepsy95: 80 male veterans (mean age 60 +/- 13 years) on older
AEDs for at least two years (many on high-dose phenytoin) all received calcium and vitamin
D supplements, and were randomised to risedronate or placebo and reassessed two years later.
All of the 53 who completed the study had improved BMD, lumbar BMD significantly so, and
fractures only occurred in the placebo group. However the study was underpowered to draw
conclusions.

Conclusions

There is accumulating evidence that patients on AEDs are at increased risk of metabolic bone
disease and fracture for several reasons. Most of the evidence relates to the older drugs, most
of which are enzyme inducers but including valproate, and there is really insufficient evidence
to draw any conclusions about the safety or not of newer AEDs in the context of bone health,
though levetiracetam and lamotrigine may prove preferable. That said, animal studies96 suggest
that multiple mechanisms are involved, many independent of enzyme inhibition, and that
newer drugs may be equally culpable. Clinical studies supporting that this is not just an ‘older’
AED problem are also now beginning to emerge97.

So what should we do? As a minimum, in line with population guidance, clinicians should be
actively thinking about bone health for patients with epilepsy and offering advice to all on
regular exercise, diet, smoking and alcohol, including intake of at least 1000 mg/day of dietary
calcium, and at least 400 IU/day of vitamin D. A standard supplement for all patients starting