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 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 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 enzymeinducing 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 significant changes in calcium and vitamin D metabolism within few weeks of the initiation of AED treatment The Neurology India | Mar-Apr 2010 | Vol 58 | Issue possible confounding effect of low dietary calcium intake and vitamin deficiency, 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 deficient 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 deficiency and dual-energy X-ray absorptiometry is likely 175 Murthy: Antiepileptic drugs and bone health beneficial.[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 coadministration 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 fortified with calcium or vitamin D in India and also most of the Indian diets are not rich in calcium 10 11 12 13 14 15 References 176 Valsamis HA, Arora SK, Labban B, McFarlane SI Antiepileptic drugs and bone metabolism Nutr Metab (Lond) 2006;3:36-46 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 Seth RD Metabolic concerns associated with antiepileptic medication Neurology 2004;63:S24-9 Pack AM, Gidal B, Vazquez B Bone disease associated with antiepileptic drugs Cleve Clin J Med 2004;71:S42-8 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 Sheth RD, Wesolowski CA, Jacob JC, Penney S, Hobbs GR, Riggs JE, et al Effect of carbamazepine and valproate on bone mineral density J Pediatr 1995;127:256-62 Sato Y, Kondo I, Ishida S, Motooka H, Takayama K, Tomita Y, et al Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy Neurology 2001;57:445-9 Pack AM, Morrell MJ, Marcus R, Holloway L, Flaster E, Doñe S, et al Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy Ann Neurol 2005;57:252-7 16 17 18 19 20 21 22 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 Rajeswari J, Balasubramanian K, Bhatia V, Sharma VP, Agarwal AK Aetiology and clinical profile of osteomalacia in adolescent girls in northern India Natl Med J India 2003;16:139-42 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 Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, et al High prevalence of low dietary calcium high phytate consumption and vitamin D deficiency in health south Indians Am J Clin Nutr 2007;85:1062-7 Bhatia V Dietary calcium intake – a critical appraisal Indian J Med Res 2008;127:269-73 Food composition table In: Gopalan C, Sastri BV, Balasubramanyam SC, editors Nutritive value of Indian foods Hyderabad: India: National Institute of Nutrition ICMR; 1996: Appendix p.92-4 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] Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC, et al Vitamin D and bone mineral density status of healthy school children in northern India Am J Clin Nutr 2005;82:477-82 Marwaha RK, Sripathy G Vitamin D and bone mineral density of healthy school children in north India Indian J Med Res 2008;127:239-44 Harinarayan CV Prevalence of vitamin D insufficiency in postmenopausal south Indian women Osteoporos Int 2005;16:397-402 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 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 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 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 Neurology India | Mar-Apr 2010 | Vol 58 | Issue Copyright of Neurology India is the property of Medknow Publications & Media Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use ... 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...Murthy: Antiepileptic drugs and bone health beneficial.[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. .. intakes of calcium, vitamin D, phytates and protein on bone health in patients with epilepsy on AEDs Milk is not fortified with calcium or vitamin D in India and also most of the Indian diets are