A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes.

Anne Daly,Wolfgang Högler,Anita Macdonald,Alex Pinto,Boyd J Strauss,Jonathan C Y Tang,Júlio C Rocha,Gisela Wilcox,Sharon Evans,Catherine Ashmore,William D Fraser,Richard Jackson,Nick Shaw,Nicola Crabtree

doi:10.3390/nu13062075

Abstract

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.

Highlights

Optimal bone mass is key to preventing the risk of fractures later in life, and many factors influence peak bone mass accretion including genetics, physical activity, body composition, and quality of diet
Has been associated with improved bone mass in PKU animal models [19], but CGMP compared with Amino acids (AAs) and their influence on bone mass, density, and geometry has not been studied in children with PKU. In this longitudinal prospective controlled study over 36 months, we investigated the efficacy of CGMP-AA as compared with L-AA protein substitutes on bone mass, density, geometry, and turnover markers in children with PKU
Forty-seven children were of European origin and three children were of Asian origin

Summary

Introduction

Optimal bone mass is key to preventing the risk of fractures later in life, and many factors influence peak bone mass accretion including genetics, physical activity, body composition, and quality of diet. Severe dietary restriction may be problematic in conditions such as phenylketonuria (PKU) which require rigorous exclusion of many natural foods [1]. In children with classical PKU, the majority of protein is provided by a low phenylalanine, semisynthetic protein (protein substitute), with some limited dietary phenylalanine given from natural foods according to individual metabolic tolerance and disorder severity. Protein substitutes, are traditionally derived from essential and non-essential amino acids and are usually supplemented with added vitamins, minerals, and trace minerals aimed at achieving optimal growth, bone mass, and body composition. Amino acids (AAs) contribute to the structural components of bone in addition to those of growth and tissue maintenance [2,6,7]

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