Hala M. Koura, Nagwa Abdallah Ismail, Ashraf F. Kamel, Azza M. Ahmed, Amal Saad-Hussein, Laila K. Effat Table V. Femoral and lumbar Z-scores of the baseline and follow-up study Negative ranks Positive ranks Ties Negative ranks Positive ranks Ties N 9 23 0 11 19 2 Wilcoxon signed ranks test Z test 2.656 1.45 Sig < 0.01 NS Positive ranks – improvement, negative rank – declined Z-score, Ties – no change Ranks FN_Z-score_2007 - FN_Z-score_2009 Z-score_L2_L4_2007 - Z-score_L2_L4_2009 had osteoporosis with BMD Z-score < –2.5. The current study was done on children and adolescents with PKU, while his study included adult PKU patients with a mean age of 25 ±5.3 years [13]. The difference may also be related to different geographical areas, as reported by Cowell (1995) [19], who evaluated 24 PKU patients (1-20 years) in his geographical area for osteopenia, but no abnormalities in lumbar BMD were found. Vitamin and trace element deficiency may contribute to osteopenia in PKU patients, although phe-free protein formulas are enriched with vitamins, minerals and trace elements; iron and B12 depletion as well as low zinc and selenium levels have been reported in PKU patients. Furthermore, calcium, folate, thiamine, niacin, and vitamin B6 intake may be up to 60% lower than the recommended amounts in this patient group [20], which was confirmed by our results where half of the osteopenic patients were on a strict low protein diet with adequate formula intake. The follow-up DEXA showed declined femoral and lumbar Z-scores in 28% and 34.4% of patients, respectively, almost equally to our three groups of diet compliance. These different patterns of compliance in relation to BMD proved, as found by other authors [21, 22], that diet control of PKU patients is difficult and hypomineralization in those patients needs to be clarified [13]. Furthermore, the numbers of patients who decide to stop dietary treatment increases gradually with age [23]. Half of the osteopenic patients were given oral calcium and vitamin D supplement and showed improvement of their BMD Z-score more than those who did not take the supplement. This was supported by Pérez-Due~nas (2002) [10], who found improvement of BMD of six PKU patients with a low dose of vitamin D. In addition, these patients were improved due to adequate sun exposure as the main source of vitamin D in Mediterranean countries is cutaneous synthesis from UV radiation [10]. Although the osteopenia was detected first in the femoral neck, we, like other authors [5], found a significant negative correlation of lumbar BMD Z-score with age, indicating that the lumbar spine is more prone to the development of osteopenia and/or osteoporosis with age. BMD measured by DEXA in the lumbar spine was the technique of choice for most authors because it has a high precision in vivo and permits monitoring of treatment in the lumbar spine, which is a very sensitive area for changes in BMD [2, 8, 12]. Data about the relation of BMD to diet are conflicting; as reported by other authors [10, 12], we found no correlation between BMD and dietary control, reflected either by blood phe concentrations or the duration of compliance; however, other investigators reported that lack of dietary compliance and phe level > 19.8 mg/dl were associated with a decrease in BMC [9]. Many patients in the present study showed variation in blood phe level; this was in keeping with Barat (2002), who suggested that this variation may contribute to osteopenia in PKU patients [6]. Zeman et al. (1999) suggested that mutations in the phenylalanine hydroxylase gene might inherently predispose PKU patients to osteoporosis although the potential mechanism for this is unknown [12], which was nearly in agreement with our study, in which we could not identify any specific causative factor for osteopenia. At the start of the study growth retardation was observed in our PKU patients in comparison with controls, like Dobbelaere (2003), who found his PKU patients shorter and lighter than the reference population [24]. European studies [25-29] found similar growth retardation during the first years of life followed by restoration of the normal growth curve from the second year or later, supporting our results that 65.6% of the patients were under 10 years of age and all of them showed a significant catch up of growth at the follow-up study. In agreement with other authors, we found no correlation between phe levels and growth [24, 25, 30, 31]. However, it is clear that the outcome of growth in PKU patients depends on the therapeutic approach, genetic background and novel alimentary substitutes. An international study comparing and evaluating these differences between centres would be extremely interesting [24]. 498 Arch Med Sci 3, June / 2011