Community Dent Oral Epidemiol 1999; 27: 48–56 Copyright C Munksgaard 1999 Printed in Denmark . All rights reserved ISSN 0301-5661 Amid I. Ismail 1 and Rajesh R. Bandekar 2 Fluoride supplements and 1 Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan and fluorosis: a meta-analysis 2 Consortium for Health Outcomes, Innovations and Cost-Effectiveness Studies, University of Michigan, Ann Arbor, Michigan, USA Ismail AI, Bandekar RR: Fluoride supplements and fluorosis: a meta-analysis. Community Dent Oral Epidemiol 1999; 27: 48–56. C Munksgaard, 1999 Abstract – This paper presents a systematic review of the dental literature that was carried out to investigate whether the regular use of fluoride supplements in non-fluoridated communities during the period of tooth development increases the risk of dental fluorosis. A MEDLINE search was organized for all documents published, in English, between January 1966 and September 1997 using the following key words: fluorosis, dental, fluoride, fluoride supplement or supple- ments, drop or drops, and tablet or tablets. Twenty-four studies that assessed the development of dental fluorosis in children who had used fluoride supplements earlier in their life were included in this review. Of the 24 studies, 10 were cross- sectional/case control studies and four were follow-up studies. These studies had data that allowed a quantitative estimation of the risk of developing dental fluo- rosis in users of fluoride supplements. The other 10 studies were excluded because they either did not present enough data or had other methodological problems. Key words: fluoride supplements; fluorosis; meta-analysis A qualitative review of the studies found a consistent and strong association be- tween the use of fluoride supplements and dental fluorosis. The meta-analyses Amid I. Ismail, Department of Cariology, Restorative Sciences, and Endodontics, of the cross-sectional/case-control studies estimated that the odds ratio of dental School of Dentistry, The University of fluorosis in users of fluoride supplements compared with non-users ranged be- Michigan, 1011 N. University, D2347, tween 2.4 and 2.6. The meta-analyses of the follow-up studies estimated that the Ann Arbor, Michigan 48109–1078, USA relative risk in long-term users was between 5.5 and 12.2. This review confirmed Tel: π1 734 647 9190. Fax: π1 734 936 1597 E-mail: ismailai/umich.edu that in non-fluoridated communities the use of fluoride supplements during the first 6 years of life is associated with a significant increase in the risk of develop- Accepted without peer review 9 November ing dental fluorosis. 1998 The objective of this paper is to present a systemat- ic review of the dental literature to answer the following question: does the regular use of fluoride supplements in non-fluoridated communities dur- ing the period of tooth development increase the risk of dental fluorosis? In the absence of direct evidence from random- ized clinical trials, harm from interventions, such as fluoride products, should be determined following the criteria described by Lilienfeld & Stolley (1). Specifically, fluoride supplements are considered a risk factor of dental fluorosis if the association be- tween the use of supplements and fluorosis is strong, consistent, and specific; has the correct tem- 48 poral sequence of an exposure preceding the occur- rence of disease; is dose-response dependent; and is biologically plausible. To assess the strength of the association between the use of fluoride supplements and dental fluoro- sis, measures such as relative risk (RR) or odds ra- tios (OR) are used (1). The magnitude of these two measures determines the strength of an association between fluoride supplements and fluorosis. For instance, if the value of RR is at least 2.0 (the prob- ability of disease in the exposed group is two times higher than the probability of disease in the unex- posed group), then there is a possibility that the association may be causal if the other criteria are