Effect of calcium, vitamins K 1 and D 3 on bone in galactosemia Bianca Panis a,b , Cees Vermeer c , Marinus J.P.G. van Kroonenburgh d , Fred H.M. Nieman e , Paul P.C.A. Menheere f , Leo J. Spaapen b , M. Estela Rubio-Gozalbo a,b, ⁎ a Dept. of Pediatrics, University Hospital Maastricht, Maastricht, The Netherlands b Dept. of Laboratory Genetic Metabolic Diseases, University Hospital Maastricht, Maastricht, The Netherlands c Dept. of Biochemistry, University Hospital Maastricht, Maastricht, The Netherlands d Dept. of Nuclear Medicine, University Hospital Maastricht, Maastricht, The Netherlands e Dept. of Clinical Epidemiology and Medical Technology Assessment (KEMTA), University Hospital Maastricht, Maastricht, The Netherlands f Dept. of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands Received 23 November 2005; revised 11 April 2006; accepted 3 May 2006 Available online 19 June 2006 Abstract Classical galactosemia is an inherited disorder of galactose metabolism. Recently, diminished bone mineral content (BMC) in children and adolescents has been found. The aim of this study was to evaluate the effect of calcium, vitamins K 1 and D 3 supplementation on bone in children with galactosemia. A 2-year randomized, double-blind, placebo-controlled clinical trial was undertaken in which 40 children with classical galactosemia (13 males and 27 females, aged 3–17 years) were included to receive daily either 750 mg calcium, 1.0 mg vitamin K 1 and 10.0 μg vitamin D 3 or placebo. BMC of femoral neck, lumbar spine and total body and body composition data were determined by dual energy X-ray absorptiometry (DXA) at baseline and after 1 and 2 years. Diet was assessed using a food frequency questionnaire and a 3-day food diary. Biochemical measurements were determined at baseline and after 1 and 2 years. In the children receiving treatment, carboxylated osteocalcin (cOC) concentration significantly increased (P < 0.001) and undercarboxylated osteocalcin (ucOC) concentration significantly decreased (P = 0.001) when compared to the children receiving placebo. Furthermore, there was a statistically significant increase in BMC of lumbar spine (P = 0.001), lean tissue mass (LTM: P = 0.016) and fat mass (FM: P = 0.014) in the treatment group when compared to the placebo group. The significant increase in cOC and decrease in ucOC concentration in the treatment group were present in prepubertal (P < 0.001 and P = 0.006 respectively) and pubertal children (P = 0.004 and P = 0.042 respectively). The significant increase in BMC of lumbar spine in the treatment group was present only in the prepubertal children (P = 0.015). Supplementation of calcium, vitamins K 1 and D 3 given in this dose (750 mg, 1.0 mg and 10.0 μg respectively) is likely to have a role in the treatment of BMC abnormalities in galactosemia. © 2006 Elsevier Inc. All rights reserved. Keywords: Galactosemia; Bone mineral content (BMC); Calcium; Vitamin K 1 ; Vitamin D 3 Introduction Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism, caused by deficiency of galactose-1-phosphate-uridyltransferase (GALT). Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as learning and motor disabilities, speech deficits and ovarian failure [1,2]. Recently, another long-term complication, a diminished bone mineral content (BMC), has been recognized. Although a diminished BMC in adult female patients is a well-known complication due to ovarian insufficiency, the fact that bone mass is already decreased in young children was reported by Kaufman et al. in 1993 and by our group in 2002 and 2004 [3–5]. Eighty to ninety percent of peak bone mass is acquired between birth and adolescence [6]. A maximal peak bone mass at skeletal maturity is considered the best protection against age- related bone loss and fracture risk. The bone mass of treated Bone 39 (2006) 1123 – 1129 www.elsevier.com/locate/bone ⁎ Corresponding author. University Hospital Maastricht, Dept. of Pediatrics and Laboratory Genetic Metabolic Diseases, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands; Fax: +31 43 387 5246. E-mail address: mrub@paed.azm.nl (M.E. Rubio-Gozalbo). 8756-3282/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bone.2006.05.002