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ARTICLES: G. Farhat, B. Yamout, M. A. Mikati, S. Demirjian, R. Sawaya, and G. El-Hajj Fuleihan Effect of antiepileptic drugs on bone density in ambulatory patients Neurology 2002; 58: 1348-1353 [Abstract] [Full text] [PDF]

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The use of an american control group for reseach in BMD in Lebanon is Inappropriate?

Dougall J.P. McCorry MRCP.MBChB   (26 July 2003)

Reply to McCorry

Ghada El-Hajj Fuleihan, MD, MPH   (26 July 2003)

The use of an american control group for reseach in BMD in Lebanon is Inappropriate? 26 July 2003
Dougall J.P. McCorry MRCP.MBChB, Specialist Registrar in Neurology Saint James University Hospital Ward 17, Department of Neurology, SJUH, Leeds UK Send Correspondence to journal: Re: The use of an american control group for reseach in BMD in Lebanon is Inappropriate? dougallmccorry{at}yahoo.com Dougall J.P. McCorry MRCP.MBChB	This article by Farhat et al [1] poses the question: Do antiepileptic drugs and in particular chronicity of use gave rise to an altered bone mineral density? The use of the American database as a control group may flaw this study and invaladate the implication set out in the conclusion; that the differences found are due to antiepileptic medication. The population in Beirut is very different to the Database and without firstly validating the database in Beirut we should be very cautious as to suggest differences found relate to epilepsy or antiepileptic drugs. Secondly you found a significant correlation between duration years of AED's and BMD. Was this corrected for age?, if not this alone could account for the difference. References 1). Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients Neurology 2002; 58: 1348-1353.
Reply to McCorry 26 July 2003
Ghada El-Hajj Fuleihan, MD, MPH, American University of Beirut Medical Center Send Correspondence to journal: Re: Reply to McCorry gf01{at}aub.edu.lb Ghada El-Hajj Fuleihan, MD, MPH	One of the primary end-points chosen in our study is bone mineral density (BMD), because it is a very powerful predictor of fracture risk as demonstrated in many cross-sectional and longitudinal studies from the US and Europe. Although we have demonstrated in a population-based study that peak BMD is slightly lower in Lebanese compared to American subjects, we have warned against the use of the local database until validated. [1] It is for those reasons that we avoided the use of a local database in our study. [2] Firstly, the WHO definition of osteoporosis using bone mineral density (BMD) derived T-scores only applies to Western Caucasian BMD databases [3], the database in which the WHO T-score cut-offs were established, and the population in whom the BMD-fracture relationship is validated. No such validation is yet available in our population, and although we are in the process of conducting such study, until its results are available, the use of local databases would be flawed. Indeed, it is for these reasons that the International Osteoporosis Foundation (IOF) recommends the use of established universal databases. [4] Secondly, it is reasonable to expect the BMD-fracture relationship is the same in Caucasians whether they are American, European or Lebanese. In fact, the IOF recommends the American NHANES III database as an international reference for hip T-score calculation and fracture risk estimates. [4] Furthermore, we have demonstrated mean BMD in Lebanese and American patients with hip fractures to be very similar. [5] Thirdly, let us consider applying the approach suggested by McCorry to the cholesterol-coronary artery disease analogy in our population. Lebanese subjects have higher mean cholesterol level than western counterparts. The argument presented by McCorry would imply that we should adjust the universally recognized NCEP cholesterol thresholds for intervention upwards taking into local “normative databases”. This would be an unwarranted. Contrary to what McCorry suggested, the inverse relationship in adults between BMD at the total body, total hip and trochanter and duration of anti-epileptic drug therapy is not due to age. The R values we reported between these variables varied between –0.38—0.45 and exceeded those known to correlate BMD and age, in the age range studied. In our study, the correlation between age and BMD was weaker and only significant at the trochanter. Finally, linear regression analyses revealed that duration of anti-epileptic drug use, and not age, was a significant correlate of BMD at the three skeletal sites. The results and conclusions presented in our study are indeed solid and justified. However, as we discussed, the ultimate evidence for understanding the impact of epilepsy and antiepileptic drugs on skeletal health would only be attained by conducting randomized trials. [2] References 1. El-Hajj Fuleihan G, Baddoura R, Awada H, Salam N, Salamoun M, Rizk P. Low peak bone mineral density in healthy Lebanese subjects. Bone 2002; 31:520-8. 2. Farhat G, Yamout B, Mikati MA, Demirjian S, Saway R, El-Hajj Fuleihan G. Effect of antiepilectic drugs on bone density in ambulatory patients. Neurology 2002;58: 1348-1353. 3. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis Report of a WHO study group. WHO technical report series 1994; 843:1-129. 4. Kanis JA, Gluer CC for the Committee of Scientific Advisors, International Osteoporosis Foundation. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int 2000; 11: 192-202. 5. El-Hajj Fuleihan G, Badra M, Tayim A, Makari M, Salamoun M, Afeiche N, Baddoura O, Boulos S, Haidar R, Lakkis S, Musharrafieh R, Nsouli A, Taha A. Lebanese patients with hip fractures are relatively young, but have osteoporosis. J Bone Miner Res 2001; Suppl 1: Abstract M 337.