Antiepilepsy drugs increase rate of bone loss

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Rheumawire

June 8, 2004 Zosia Chustecka

Antiepilepsy drugs increase rate of bone loss

Minneapolis, MN - Antiepileptic drugs increase the rate of bone loss in

elderly women, a new study has found. Women over 65 years of age taking

these drugs were losing bone mass at nearly twice the rate of women not

on the medications, researchers from the University of Minnesota report

in the June 2004 issue of Neurology [1].

" Older women taking epilepsy drugs should be screened for osteoporosis

and counseled about the importance of getting enough calcium and taking

vitamin-D supplements, " says lead author Dr e Ensrud (VA Medical

Center, Minneapolis, MN).

Like osteoporosis, epilepsy becomes more common as people age, Ensrud

comments. An estimated 1.5% of people aged 65 and over have epilepsy,

which is about twice the rate of younger adults. In addition,

antiepileptic drugs are also used for neuropsychiatric conditions other

than seizures, and this use has nearly doubled since 1991, she noted.

The prevalence of osteoporosis in community-dwelling women aged 50 or

older has been estimated at between 13% and 15%.

The study involved elderly community-dwelling women participating in the

Study of Osteoporotic Fractures (SOF) and involved bone-mineral density

(BMD) measurement at the heel and at the hip. Both sites were tested

because previous researchers had hypothesized that antiepileptic drugs

affect only cortical bone, which is prevalent in the hip but makes up

only a fraction of the heel bone (which consists of at least 90%

trabecular bone). " This study shows that the drugs affect both types of

bone, " Ensrud said.

The heel cohort consisted of 6044 women, with measurements taken at the

beginning of the study and again an average of 5.7 years later. At

baseline, 41 women (0.7%) reported continuous use of antiepileptic

drugs, and this rose to 61 women (1%) as the study progressed. The drugs

included phenytoin, phenobarbital, carbamazepine, and primidone.

The hip cohort involved 4202 women, who had the first hip BMD

measurement taken at the same time as the second heel measurement (an

average of 5.7 years into the study) and the second hip measurement

taken an average 4.4 years later. At baseline, 40 women (1%) were using

antiepileptic drugs, and this rose to 68 women (1.6%) as the study

progressed.

Women who were taking antiepileptic drugs had a 1.8 greater average rate

of bone loss at the heel and a 1.7 greater average rate of loss at the

hip than women not taking these drugs. These results did not change even

after adjusting for other risk factors, such as age, estrogen use, poor

health status, inactivity, smoking, and a lower calcium intake. After

adjustment for confounders, the average rate of decline in total hip BMD

steadily increased from -0.70% per year in nonusers to -0.87% per year

in partial users to -1.16% per year in continuous users of antiepileptic

drugs (p value for trend=0.015).

" If unabated, the rate of hip bone loss among the older women with

continuous use of antiepileptic drugs in our cohort was sufficient to

increase the risk of hip fracture by 29% in 5 years, " say the

researchers.

It's not clear why or how antiepileptic drugs affect bone loss. " It's

possible that the drugs damage the body's ability to metabolize vitamin

D or absorb calcium, " Ensrud speculates. " Irrespective of the mechanism

. . our findings have important implications for clinical practice, "

she says. " Older women taking antiepileptic drugs should be targeted for

osteoporosis screening, including assessment of clinical risk factors

for fracture, counseling regarding calcium intake and vitamin-D

supplementation, and consideration of bone-density testing and

laboratory evaluation for evidence of vitamin-D deficiency. "

The American Academy of Neurology has a " patient page " about bone health

on its website, in which it explains that certain antiepileptic drugs

can adversely affect bone and increase fracture risk [2]. It states that

phenytoin, primidone, and phenobarbital are known to affect bone, while

the data for carbamazepine and valproate are not as clear, although they

have also been implicated in some studies. It also notes that there are

no definite data for the effect of newer medications, including

gabapentin, tiagabine, lamotrigine, topiramate, oxcarbazepine,

zonisamide, and levetiracetam.

Sources

Ensrud KE, Walczak TS, Blackwell T, et al.

Anti-epileptic drug use increases rates of bone loss in older women; a

prospective study. Neurology 2004; 62:2051-2057.

Gross RA, Gidal BE, and Pack AM. Antiseizure drugs and

reduced bone density. Neurology 2004 :[E24-E25]. Available at:

http://http:www.neurology.org

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org