Quadriplegic CP is the most prevalent pediatric condition with severe osteopenia. The prevalence of CP is 2 to 3 per 1000 live births, and 20% are involved to the extent that they are unable to ambulate.(21
) Other pediatric disorders are also associated with severe motor impairment, including the muscular dystrophies, myelodysplasia (spina bifida), spinal cord injuries, cerebellar (Friedrich) ataxia, spinal muscular atrophy, Rett syndrome, and severe traumatic brain injury. Despite the wide variation in pathophysiologies, these conditions have in common skeletal fragility.
Undoubtedly, diminished ambulation is a major factor, but it is important to recognize that the etiology of skeletal fragility in these children is complex, resulting from the interplay of potentially multiple factors. For examples, BMD in the proximal femur but not the lumbar spine is severely diminished in boys with Duchenne MD early in the course of the disease before ambulation is significantly affected.(7
) In persons with acute spinal cord injury, BMD is truly lost, but in children with CP, generally BMD increases over time despite declining BMD Z
); skeletal fragility in CP is part of a more complex growth disorder.(22
) Nutritional factors and medications such as steroids and anticonvulsants can contribute to poor bone health in children with these conditions. Short-term immobilization for surgeries or fractures, diminished sunlight exposure, feeding difficulties, and altered pubertal progression also may be important factors in children with assorted physical disabilities.
Not only is the etiology of skeletal fragility complex in these children, so too is the assessment. Joint contractures, hip dysplasia, and metallic implants usually prevent reliable measures of BMD in the proximal femur; less commonly, scoliosis and spinal fusion instrumentation prevent DXA measures in the lumbar spine. It is critical to note in children with physical impairments that measures of BMD in the lumbar spine may not accurately reflect BMD in the femur. In this study, the correlation between BMD Z
-scores in the lumbar spine and region 1 of the distal femur was only 0.37 compared with a correlation of 0.61 reported in normal children.(18
) Other reports confirm the often large differences between BMD Z
-scores in the femur and spine of children with low BMD.(7
) In clinical practice with these children, one should not be falsely reassured by a lumbar spine BMD Z
-score that is only mildly to moderately low; BMD Z
-score in the femur is likely to be at least 1.0 lower, and in this series, one-third were at least 3.0 lower.
Technical difficulties are generally apparent when attempting to obtain an assessment of BMD. However, the more subtle issue routinely overlooked is whether the BMD assessment in a child with a particular condition is at all relevant to the clinical problem of fractures in that specific population. In children with physical impairments, the femur is the most common site of fracture,(7
) and very rarely do they sustain spinal compression fractures. This, coupled with the weak correlation between BMD Z
-scores in the femur and spine, likely explains the finding in a previous longitudinal study that BMD Z
-scores in the lumbar spine did not predict fracture risk in a small series of 43 children and adolescents with CP and little or no ability to ambulate.(11
) In this much larger study, the simple cross-sectional data (see ) suggest that lumbar spine BMD Z
-scores likely do correlate with fracture risk. However, the sophisticated survivorship analysis necessary to account for age could not be applied successfully to the lumbar spine data owing to an inadequate sample size. Thus the relationship between lumbar spine DXA measures and fractures in this population is currently best characterized as “unproven.”
Another complexity in the assessment of pediatric bone “density” relates to the fact that DXA provides measures of aBMD (g/cm2) rather than measures of true volumetric density (g/cm3). As a result, differences in bone size can significantly affect the measured aBMD independent of any differences in true volumetric density. This difference between aBMD and volumetric measures has resulted in the widespread practice of “correcting” or “adjusting” for size of pediatric subjects when interpreting DXA aBMD measurements. Typically, such adjustments are based on height of the child, but in nonambulatory children it is difficult to obtain an accurate measure of height owing to contractures, scoliosis, and the inability to stand erect. As a result, height measures were not consistently available for subjects in this series. However, it was found that simple age- and gender-normalized Z-scores for BMD in the distal femur, without consideration of subject size, correlated strongly with fracture. The issue of whether or not some sort of adjustment for size of the subject would strengthen the relationship between distal femur DXA measures and fracture warrants further investigation.
One of the limitations of this study was that the primary outcome (history of fracture) sometimes was based on self-report and not consistently confirmed by review of medical records or X-rays. Potentially, a past event may be erroneously recalled as a fracture when it was not, thus overreporting the outcome with false-positive results.(24
) It is expected that the likelihood of this error would be independent of BMD Z
-scores and thus not significantly affect the observed relationship between BMD Z
-scores and fracture.
Recall self-report of fractures also may result in false-negative results with underreporting of fractures.(24
) A fracture may have been recognized when it occurred but was simply forgotten when fracture history was later obtained. Further, several factors make it possible for fragility fractures in these children sometimes to go undiagnosed: (1) Such fractures may occur without significant or recognized trauma, (2) the child may be unable to effectively communicate, and (3) in osteopenic bone, a fracture that is minimally displaced or angulated can be difficult to identify on radiographs or clinical examination. For these reasons, it has been recommended that a bone scan be obtained in the evaluation of profoundly involved children who appear to be in pain of uncertain etiology, which is not a rare clinical dilemma in this population.(25
) In that report, a bone scan identified a fragility fracture in 10 of 45 such children. These factors contributing to the underreporting of fractures are weighted toward those children with the lowest BMD Z
-scores. Therefore, this bias would tend to diminish the observed relationship between distal femur BMD Z
-scores and fracture.
This study in children with disabilities carries with it the same significant limitations as many of the early similar studies on osteoporotic fractures in postmenopausal women, and those studies have been critically reviewed.(26
) One finding of that review was that the magnitude of the relationship varied more among cross-sectional studies than among prospective, longitudinal studies. The potential causes for this were bias in subject selection and/or postfracture bone loss and led the authors to recommend placing greater emphasis on prospective studies. Another recommendation from this review was to minimize subject selection bias by ensuring that nonfracture subjects indeed come from the same pool as fracture subjects. Fracture history was not a potential selection bias with roughly half of our subjects for whom BMD measures were obtained as part of broader clinical research projects focused on growth and nutrition in children with moderate to severe CP. Indeed, prospective studies of fractures and BMD in children with disabilities are warranted.
The technique of using DXA to assess BMD in the distal femur of children with severe motor impairment was developed to accomplish both technical feasibility and clinical relevance to fractures. This multicenter cross-sectional study supports our hypothesis that this technique provides measures that are clinically relevant in this population, with risk ratios of 1.06 to 1.15 for the different subregions of the distal femur. These findings, the technical feasibility of obtaining a reliable assessment of BMD in the distal femur, and the recent publication of more robust normal reference data(18
) establish distal femur DXA as the clear technique of choice for assessment of BMD in children and adolescents with significantly impaired mobility. However, being the technique of choice is due far more to the lack of any more feasible, more available, or better validated alternatives than on the state of development of the distal femur technique. Prospective longitudinal studies are necessary to truly establish the predictive value of these measures, and the potential impact of bone and body size issues on the relationship to fracture risk warrants study. This study was limited to subjects up to 18 years of age, in keeping with the upper limit of the available normal reference data. Application of the technique to adults with disabilities and broadening of the normal reference age range are additional important future steps.