0145-6008/96/2007-1305$03.00/0 zyxwvutsrqpo ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH Vol. 20, No. 7 October 1996 Effect of Maternal Ethanol Consumption on Maternal and Fetal Calcium Metabolism zy K. Keiver, L. Herbert, and J. Weinberg Alcohol consumption can have deleterious effects on both adult and developing bone. The mechanism(s) by which alcohol affects bone, however, is unknown. This study investigated the possibility that alcohol affects bone by alterations in calcium (Ca) metabolism. Fe- male rats were fed lab chow ad libitum (C, Control) or a liquid diet with (E, Ethanol) or without (PF, Pair-Fed) ethanol. After zyxwvut 2 weeks on their respective diets, the rats were bred and the experimental diets continued throughout gestation. Blood (dams only) and tissue were collected on day 21 of gestation. The Ca content of maternal bone showed a trend toward a decrease in E and PF compared with C dams. Ionic Ca (iCa) levels were decreased in the blood of the E compared with PF and C dams. Serum parathyroid hormone levels were elevated in the E compared with C dams, consistent with the low iCa levels. Serum levels of 1 ,25(OH),D, however, were elevated only in the PF dams. Mean fetal body weight and fetal skeletal ossi- fication were reduced in the E compared with PF and C groups, but no group differences were found in fetal Ca content. These results indicate that maternalethanol consumption compromisedthe ability of the dam to regulate her blood iCa levels, possibly partly due to a failure to increase 1,25(OH),D levels. The delays in skeletal develop- ment observed in the ethanol exposed fetuses, however, do not ap- pear to result from impaired placental Ca transfer. Key Words: Alcohol, Fetal Alcohol Exposure, Calcium, Bone, Hor- mones. HRONIC ALCOHOL consumption or chronic expo- C sure to high doses of alcohol adversely affects the bone of developing',* and a d ~ l t ~ - ~ animals. Fetal alcohol exposure commonly results in reduced body length, re- duced length of individual bones and delayed ossification of bones.lT2 The effect of prenatal alcohol exposure on body length does not appear to resolve after birth and has been shown to persist until at least 3 years of age in humans6 and until weaning in rats.' It is unknown whether the effects on body length persist into adulthood. In human adults, osteo- porosis is often a consequence of high chronic alcohol cons~mption.~~~ The mechanisms by which alcohol affects bone, however, are not well understood. Alcohol directly inhibits bone formation in vitro' and, at least in adult and juvenile animals, appears to have this zyxwvu From the Department zyxwvutsrqpo of Anatomy, University of British Columbia, Van- Received zyxwvutsrqp for publication January 24, 1996; accepted June 14, 1996 This research was supported by a Postdoctoral Fellowship zyxwvutsrq from the Med- ical Research Council of Canada (KK) and by National Institute on Alcohol Abuse and Alcoholism grant AA07789 (J. E). Reprint requests: K Keiver, Ph.D., Department of Anatomy, 21 77 Wes- brook Mall, University of British Columbia, Vancouver, Britkh Columbia V6T I Z3, Canada. couver, British Columbia, Canada. Copyright 0 1996 by The Research Society on Alcoholism. Alcohol Clin Erp Res, Vol20, No 7, 1996: pp 1305-1312 effect in vivo as well.1o3" Chronic alcohol ingestion is often associated with low levels of the metabolites of vitamin D12-15 and high levels of parathyroid hormone (PTH).13,16 Vitamin D and PTH are both hormones involved in cal- cium (Ca) regulation and bone metabolism, and low blood levels of ionic Ca (ica) have been found in both hu- man~~~-~~ and rats2' consuming alcohol. In addition, alco- hol has been shown to decrease intestinal Ca absorption in the rat.21 Whether or not the effects of alcohol on Ca metabolism and the Ca-regulating hormones contribute significantly to alcohol-induced osteoporosis in the adult is unknown. The mechanisms by which prenatal alcohol exposure affects skeletal development are also unknown. Alcohol crosses the placenta2' and so may affect fetal bone forma- tion directly, or indirectly through alterations in fetal hor- mones required for bone development. It is also possible that alcohol affects the placental transfer of essential nu- trients, such as Ca, directly, by reducing placental blood or indirectly, via effects on maternal and/or fetal hormones. The present study investigated the hypothesis that ma- ternal alcohol consumption affects fetal bone development via disturbances in maternal and/or fetal Ca metabolism in the rat. Specifically, we examined the possibilities that al- cohol affects bone by: (1) altering maternal Ca metabolism through effects on the Ca-regulating hormones (the vita- min D metabolites 25-OH-D and 1,25(OH),D, PTH, and calcitonin) and (2) inhibiting placental Ca transfer to the fetuses directly or via effects on the Ca-regulating hor- mones. MATERIALS AND METHODS Virgin female Sprague Dawley rats (Canadian Breeding Farms, St. Constant, Quebec) were weighed (initial body weights = 225-305 g) and divided into three weight-matched groups: Ethanol (E, n = 11), which received a liquid diet ad libitum containing 36% ethanol derived calories; Pair-Fed (PF, n = 15), which received an isocaloric liquid diet (with the ethanol calories replaced by maltose-dextrin) in amounts equivalent to that consumed by the weight-matched rats in the E group; and Control (C, n = 18), which received rodent lab chow and water ad libitum. Liquid diets were supplied by BioServ Inc. (Frenchtown, NJ). The Ca and phosphorus (P) contents, on a dry weight basis, were E = 0.9% Ca, 0.7% P; PF = 0.8% Ca, 0.6% P; and C = 1.0% Ca, 0.6% P. The Ca and P contents of the E and PF diets were identical on a wet weight basis; therefore, the total intakes of the minerals were similar between rats on these diets. The Ca and P contents of the diets exceeded the National Research Council requirements for pregnant rats.24 Rats were maintained in a temperature 1305