antiepileptic drugs and bone health dietary calcium and vitamin d the confounding factors

Although women are at particular risk, bone loss associated with AED use happens at all ages in both sexes.[1] However, the awareness of the effects of AEDs on bone health among the p

175 Neurology India | Mar-Apr 2010 | Vol 58 | Issue 2

Editorial

Antiepileptic drugs and bone health:

Dietary calcium and vitamin D the

confounding factors

J M K Murthy

Chief of Neurology, The Institute of Neurological Sciences, CARE Hospital, Hyderabad, India

There is a mounting body of evidence linking a variety of

biochemical, metabolic and radiological abnormalities in

bone to the use of antiepileptic drugs (AEDs) Although

women are at particular risk, bone loss associated

with AED use happens at all ages in both sexes.[1]

However, the awareness of the effects of AEDs on bone

health among the physicians dealing with patients

with epilepsy is quite low.[2] Often the low bone mass

associated with AED treatment is largely unrecognized,

undetected, and untreated.[3,4] Though the adverse effects

on bone health are mostly seen with the use of

enzyme-inducing AEDs,[1] these effects have also been shown

with the use of non-enzyme-inducing AEDs including

valproate[1] and newer AEDs.[5] Enzyme-inducing AEDs

accelerate the metabolism of vitamin D3, resulting in

inactive metabolites, leading to decreased fractional

calcium absorption, secondary hyperparathyroidism

with greater bone resorption, and higher rates of bone

loss.[1] Valproate, a hepatic enzyme inhibitor, is thought

to act by stimulating osteoclast activity.[6] Studies of

valproate and calcium levels are contradictory.[7,8] The

possible mechanisms for the higher rates of bone loss

with the use of non-enzyme-inducing newer AEDs have

not yet been elucidated

The study by Krishanmurthy and colleagues[9] documents

that monotherapy with pheyntoin and valproate in

Indian adult patients with epilepsy results in signifi cant

changes in calcium and vitamin D metabolism within

few weeks of the initiation of AED treatment The

possible confounding effect of low dietary calcium intake and vitamin defi ciency, for these early effects, needs consideration in patients with epilepsy on AEDs

in India Adequate nutrient intakes of calcium, vitamin

D, and protein are of critical importance for bone health and help to maintain bone mineral mass attained at the end of growth period The daily dietary calcium intake by the population in India[10-13] is below that of the recommended daily allowance (RDA) suggested

by the Indian Council of Medical Research (ICMR)[14]

which is far lower than the Western data.[15] In a study in south India, the 25-hydroxyvitamin D levels of both the urban and rural children were low.[12] High prevalence

of clinical and biochemical hypovitaminosis D has been documented in apparently healthy school children from north India,[16,17] Studies form the Indian subcontinent also suggest low dietary calcium and 25-hydroxyvitamin

D status in postmenopausal women[18-20] and pregnant women.[21] The study by Menon and colleagues[22] in this issue, documents that the dietary consumption of calcium is far below the RDA suggested by the ICMR in all the age groups of patients with epilepsy on AEDs This study also shows that women aged between 15–45 years, the reproductive age group, and postmenopausal women are grossly defi cient in their dietary calcium intake There are currently no evidence-based guidelines for diagnosis or treatment of bone disease associated with AED use Periodic screening for vitamin D defi ciency and dual-energy X-ray absorptiometry is likely

Address for correspondence:

Dr J M K Murthy

Chief of Neurology,

The Institute of Neurological Sciences,

CARE Hospital, Hyderabad, India

E-mail: jmkmurthy@satyam.net.in

PMID: 20508330

DOI: 10.4103/0028-3886.63773

176 Neurology India | Mar-Apr 2010 | Vol 58 | Issue 2

benefi cial.[1] In India there is a strong case for prophylactic

supplementation with vitamin D and calcium for all

patients on AEDs as the intake of dietary calcium is

suboptimal and far below the recommended RDA

dosage Higher dose vitamin D therapy may be required

in the presence of osteomalacia and rickets In addition

adequate sunlight exposure and physical activity

are to be encouraged The study by Krishnamurthy

and colleagues also suggests that simultaneous

co-administration of calcium and 25-OHD in RDA dosage

is beneficial in limiting the changes in calcium and

vitamin D metabolism in these patients Thus there is an

urgent need for nationwide well-designed prospective

longitudinal studies to evaluate the effects of nutrient

intakes of calcium, vitamin D, phytates and protein on

bone health in patients with epilepsy on AEDs Milk is

not fortifi ed with calcium or vitamin D in India and also

most of the Indian diets are not rich in calcium

References

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and bone metabolism Nutr Metab (Lond) 2006;3:36-46

2 Valmadrid C, Voorhees C, Litt B, Schneyer CR Practice patterns of

neurologists regarding bone and mneral effects of antiepileptic drug

theapy Arch Neurol 2001;58:1369-74

3 Seth RD Metabolic concerns associated with antiepileptic medication

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4 Pack AM, Gidal B, Vazquez B Bone disease associated with antiepileptic

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5 Ensrud KE, Walczak TS, Blackwell TL, Ensrud ER, Barrett-Connor

E, Orwoll ES, et al Antiepileptic drug use and rates of hip bone loss in

older men: a prospective study Neurology 2008;71:723-30

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9 Krishnamurthy G, Nair R, Sundar U, Kini P, Shrivastava M Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dasage: A prospective study Neurol India 2010;58:213-9

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AK Aetiology and clinical profile of osteomalacia in adolescent girls in northern India Natl Med J India 2003;16:139-42

11 Mathew JT, Seshadri MS, Thomas K, Krishnaswami H, Cherian AM Osteomalacia—Fifty five patients seen in a teaching institution over a 4-year period J Assoc Physicians India 1994;42:692-4

12 Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao

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14 Food composition table In: Gopalan C, Sastri BV, Balasubramanyam

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15 Report of the Joint FAO/WHO Expert Consultation on vitamin and mineral requirement in human nutrition: Bangkok 1998 2nd

ed FAO Rome, 2004 Available from: http://whqlibdoc.who.int/ publications/2004/9241546123.pdf [last cited on 2004]

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of healthy school children in north India Indian J Med Res 2008;127:239-44

18 Harinarayan CV Prevalence of vitamin D insufficiency in postmenopausal south Indian women Osteoporos Int 2005;16:397-402

19 Harinarayan CV, Ramalakshmi T, Venkataprasad U High prevalence of low dietary calcium and low vitamin D status in healthy south Indians Asia Pac J Clin Nutr 2004;13:359-65

20 Shatrugna V, Kulkarni B, Kumar PA, Rani KU, Balakrishna N Bone status of Indian women from low income group and its relationship to the nutritional status Osteoporos Int 2005;16:1827-35

21 Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V High prevalence of vitamin D deficiency among pregnant women and their new borns in north India Am J Clin Nutr 2005;81:1060-4

22 Menon B, Hrinarayan CV, Raj N, Swapna V, Himabindu G, Afsana T Prevalence of low dietary calcium intake in patients with epilepsy: a study from south India Neurol India 2010;58:209-12

Murthy: Antiepileptic drugs and bone health

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