The relationship between lean body mass and bone mineral content in paediatric health and disease
Introduction
The interpretation of bone mineral density (BMD) in children is generating a great deal of interest amongst paediatricians across many disciplines. The main area of contention is the misdiagnosis of osteopenia in children when using traditional age-matched areal BMD (g/cm2) results [1]. Problems arise particularly when assessing children with abnormal growth or skeletal maturation.
The child's skeleton is an ever-changing organ in both size and composition. As the child's skeleton grows, it is continually modelling and remodelling itself to produce a competent mechanical structure optimally designed to provide protection, locomotion and support. Bone growth occurs both by increasing size and by accruing bone mineral [2], [3]. These processes are dissociated in time in children; however, by adulthood, the skeleton has reached both its maximum size and peak bone mass [4], [5], [6].
Data on bone growth are well documented [7], [8]. However, it is important to be able to assess when either growth or bone accrual is altered in a way which puts the child at increased risk of fragility fractures, either during childhood or later on in life. To detect problems with bone accrual, appropriate reference data need to be established.
Several publications have reported manufacturer, skeletal region and geographically specific reference data for bone mineral density as measured by dual-energy X-ray absorptiometry (DXA) [9], [10], [11], [12], [13], [14], [15]. Initially, these data were reported with reference to chronological age. Whilst this may be suitable for evaluating the child who is following average growth patterns, it is unsuitable in cases of abnormal growth or skeletal maturation. This is due to both technical issues regarding areal BMD [16], [17], [18] and mechanical issues relating to growth [19]. Small children will have lower than average bone mass for their age purely due to their size, irrespective of any disease factors. This has led researchers to consider establishing body size normative data [20], [21], [22], [23], [24], [25]. To date, the methods of normalisation have concentrated on the individual aspects of the problem, either making an adjustment for the bone size or adjusting mineralisation to body size.
In a recent publication, Schonau et al. [26] presented a functional approach using peripheral quantitative computed tomography (pQCT). This approach is based on the hypothesis that bone strength is regulated by the mechanical loads on bone and that such loads arise from muscle forces rather than body weight [27], [28], [29], [30], [31], [32], [33]. They investigated a two-stage algorithm to establish whether bone strength was normally adapted to these mechanical loads and whether these loads were normally adapted for their body size. This technique was further developed for use in DXA evaluating the relationship in a group of healthy Australian children and children with growth hormone deficiency (GHD) and anorexia nervosa. The authors used a 4-stage algorithm, evaluating their bone mineral content for age; height for age; lean tissue mass for height and the ratio of BMC/LBM for height, to evaluate whether a recorded low BMC was a result of short stature, or a primary, secondary or mixed bone defect [34].
The aims of this study were to generate British DXA reference data and evaluate whether using an alternative normalization technique based on lean body mass and bone mineral content could identify and discriminate between children with either a chronic bone or muscle defect.
Section snippets
Subjects
Two groups of children were studied, a group of healthy controls and a group of children with chronic diseases. The control data consisted of 646 white children aged 5–18 years, recruited from two cities within the UK (Birmingham and Middlesbrough). Children were excluded if they suffered from a chronic disease, a metabolic bone disorder or were taking any medication known to affect bone. An exception was made for those suffering from asthma using inhaled corticosteroids as they made up 13% of
Control data
Preliminary analysis of variance demonstrated that there were no significant differences in the age adjusted, anthropomorphic or basic bone parameters (height, weight, LBM, LSBMC and TBBMC) between healthy controls and those who suffer from asthma. (P > 0.05). Additionally, there were no significant differences between children taking inhaled corticosteroids and those using only bronchodilators to control their asthma (data not shown). Consequently, all children were grouped together to form a
Discussion
The control data demonstrated that the strongest significant predictor of bone mineral content (BMC) was lean body mass (LBM) and as such deviations from this close relationship could identify children with either chronic bone, muscle or mixed defects.
The most striking observation was the difference in the relationship between males and females. From approximately 30 kg LBM, girls had significantly more bone per unit of lean body mass than their male counterparts. This relationship was still
Acknowledgements
We thank the children and parents who participated in this study and Gail Couser and Joanne Venables for their tireless efforts in recruitment. We also thank D. Chapman, J. Dudley and J. Bates for DXA scanning. This study was supported in part by the National Osteoporosis Society (UK).
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