doi:10.1111/j.1440-1754.2009.01506.

REVIEW

Assessing the skeleton in children and adolescents with disabilities: Avoiding pitfalls, maximising outcomes. A guide for the general paediatrician
Margaret Zacharin
Department of Endocrinology and Diabetes, Royal Childrens Hospital, Melbourne, Victoria, Australia

Abstract: Assessment of bone health of a young person with a severe disability is complex. Age of onset of disability, degree of physical limitation, nutritional status, calcium and vitamin D intake and pubertal progress all contribute to adult outcomes. Concomitant medical conditions may further adversely affect bone accrual.Bone quality, until growth is complete, must be interpreted in light of growth, height and puberty. For those children and adolescents who have disabilities where weight bearing is limited, satisfactory and reproducible measurements of bone density may be impossible to obtain. Fracture risk is dependent on the degree of immobilisation and on bone quality at any age. Meeting the goal of reducing extent and complications of adult osteoporosis is dependent upon an understanding of the nature and contribution of individual components of bone accrual, so that interventions can be appropriately targeted to optimise outcomes. Key words: bone health; disability; fracture risk reduction.

Introduction
Comprehensive care of a young person with a severe disability is multifaceted. Optimising bone health constitutes a major component of physical care, where chronic immobility exists. Unexpected or intercurrent illnesses, surgery or management changes all adversely impact bone health. This article is intended for practical information of and use by general paediatricians and those caring for children and adolescents with physical disabilities. Understanding the nature of bone growth during childhood and adolescence and interpretation of measurements of bone quality will help to implement management strategies appropriate to each individual, to maximise bone accrual.

Bone health
Overview
The concept that bone health in children and adolescents should be optimised, with the goal of reducing the extent and complications of adult osteoporosis in later life, has evolved over the past 20 years.1 This became possible with the advent of reproducible yardsticks for measurement of bone quality, such as bone densitometry, quantitative CT (QCT) and bone ultrasound. For several years, use of the new techniques outstripped comprehensive understanding of the nature of bone growth and development in childhood and adolescence, resulting in considerable confusion with interpretation of data. The older world literature is still replete with examples of erroneous conclusions being drawn, because of an early lack of understanding of the contribution of linear growth and bone size to parameters of bone mass. More recent publications have claried and addressed these issues.26 Understanding normal bone development is essential to appropriately assess pathologic states.

Key Points 1 Bone quality in childhood and adolescence must be interpreted in the context of height and pubertal status. 2 Fracture risk is dependent upon bone size, muscle mass, mechanical loading and pubertal status. 3 Maximising adult bone quality by optimising calcium, vitamin D and pubertal progress will reduce the extent and impact of adult osteoporosis.
Correspondence: Dr Margaret Zacharin, Department of Endocrinology and Diabetes, The Royal Childrens Hospital, Parkville, Vic. 3052, Australia. Fax: +61 3 9347 7763; email: margaret.zacharin@rch.org.au Accepted for publication 11 January 2009.

Structural aspects of bone

The axial skeleton is composed of thin bony envelopes, each containing a lattice work of trabeculae. These enlarge slowly with time but the amount of bone within the envelope remains constant until puberty7 when combined cortical thickening and trabecular mineralisation accompany an increase in both vertebral size and strength, under the inuence of sex hormone.8 The appendicular skeleton has a different bone structure, with a relatively thicker cortex and different trabecular organisation. In a weight-bearing bone, the lattice responds to imposed stresses, with resulting increase in strut formation, particularly

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in the hip, where weight bearing has a signicant positive impact on overall strength of hip bone. During puberty, the long bones behave differently in males and females.9 Under the inuence of testosterone, cortical bone apposition occurs, simultaneous with endocortical resorption, causing progressive expansion of long bone size. This happens in parallel with increased trabecular mineralisation. The net result is a broader, thicker bone, with signicantly less fracture risk than it would have had prior to puberty. The male bone continues to expand slowly throughout life, providing relative strength, compared with the adult female skeleton.10 The female skeleton, under the inuence of oestrogen, behaves differently. By contrast with the male long bone, inhibition of cortical apposition and simultaneous endocortical thickening, narrows the medullary cavity but maintains a slim bony contour. Trabecular mineralisation occurs in the same way for both sexes. At the end of puberty therefore, a girls bone is thicker than it was and less prone to injury than before puberty, but at no time in adult life does a female bone have the same strength as a male bone. Specic lifetime hazards of pregnancy, lactation and menopause all contribute to mineral losses and increased osteoporosis risk with time.

Peripheral quantitative CT (pQCT) as another tool to assess cancellous bone is of value but present evidence-based consensus is lacking as to measurement site, parameters for analysis and population reference data.11,12 pQCT allows for independent assessment of cortical and trabecular bone and may, for the rst time, provide a measure of appendicular bone strength.

Interpretation of Bone Growth and Bone Health in Children with Disabilities

BMD measurement, until growth is complete, must therefore be interpreted in the light of the stage of growth, height at time of assessment and pubertal development. For children and adolescents with disabilities, satisfactory and reproducible measurements of BMD may be impossible to obtain, as a result of severe bony deformity or with the inability of the child or adolescent to either lie still or to lie in the same position for each measurement. Limb contractures may prevent access for measurement. Conventional sites of lumbar spine and hip may not be able to be measured or interpreted at all. Internal metal xation, hip surgery, recurrent dislocations or hip dysplasia may render measurements meaningless or may make an area unt for assessment. Radial or lateral lower femoral BMD13 measurements may be the only reproducible sites available. Other techniques such as pQCT may provide useful data for these sites.14 Routine interpretation of bony density utilises population norms, assuming that it is possible to compare the subject with other children of similar age and gender (Z-score) but without regard to height or pubertal status. This results in inherent inaccuracies in conventional reporting of BMD. Children and adolescents with disabilities are often extremely different from age-matched peers in both height and pubertal status.15,16 Failure to account for variations in multiple contributors to bone size may result in an incorrect diagnosis of osteoporosis or of failure to accrue bone mass, causing anguish and anxiety for parents and medical practitioners alike. Often, for this group of individuals, the only value of a bone densitometry measurement during growth is as a baseline personalized reference for future reassessment, but improvement in data interpretation is now available, as outlined here. In the normal prepubertal child, aBMD increases by 25% per annum, simply because of bone growth. During puberty, an increase of 1015% per annum increase is seen, because of linear growth plus increased mineralisation of both cortex and trabeculae.17 Even if the measured aBMD is low, a rate of change that is similar to that of the rest of the population should be considered normal. Final outcome at the end of growth can then be assessed and compared with other, similar-sized adults. Several methods are now available to improve BMD evaluation and thus to estimate volumetric density (bone mineral apparent density (BMAD), Molgard18 calculations). These provide information as to bone size for height and for bone area. This information should be sought for all assessments of bone health in the growing child, particularly where comparison with a normal population is inappropriate. In the absence of availability of these methodologies, improvement in accuracy of data can be obtained by the simple expedient of using a height age or bone age Z-score for comparison, rather than a chronologic age Z-score.
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Techniques for Assessment of Bone Health

Plain radiograph
Where frequent assessment is needed, the lowest radiation exposure available should be considered. Bone densitometry and peripheral qualitative CT (pQCT) are preferred modalities for repeated assessment. X-ray is the most direct method of observing bone, providing accurate morphological data concerning fractures, altered vertebral alignment or shape and kyphoscoliosis. However, particularly in the axial skeleton, apparent reduction in density can be misleading as it is dependent not only on underlying bone structure but also on lm exposure, body weight and lung expansion. X-ray therefore cannot accurately assess bone density (BMD).

BMD
Conventional bone densitometry techniques utilise X-rays of two different energy levels, passed through the bone area of interest, to assess the amount of bone within that area. It is usually reported as areal bone density (aBMD) as g/cm2. This measurement can then be extrapolated, mathematically, to volume (gm/cm3). In making this calculation, bone size is of vital importance. If the area to be examined is large, the bone area will be larger and the volume measured will appear greater. Conversely, with small bones, the calculation of BMD will appear to be small. True volumetric density, however (i.e. the amount of bone contained within the small envelope), may be perfectly normal for bone size.7,10 Using this type of calculation without due regard to bone size, it is extremely easy to wrongly attribute a low bone density to a low bone mass rather than to a small bone size. In turn, bone size is dependent on many factors, including familial and genetic potential, growth at any time of life, timing of puberty and the pubertal growth spurt.

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Contributors to Bone Health

Fracture risk for a person with a physical disability varies considerably and is signicantly dependent on the degree of immobilisation and therefore on bone quality.19,20 During puberty, 4050% of total bone mass for life is accumulated and thus lifetime fracture risk decreases as bone strength increases.

Mobility and weight bearing the muscle-bone unit27,28

Structural bone integrity is altered by weight bearing and muscle pull on bones. In a non-weight bearing situation, long bone cortices are relatively thinner with less trabecular strut formation.29 The use of weight-bearing exercises on a daily basis, even for relatively short periods, has been reported to increase BMD,29,30 which in turn, may result in signicant reduction in fracture risk. Dedicated involvement of family members, ancillary and school staff is needed, to aid with both active weight bearing and with the use of the more passive mechanism of a standing frame, in order to make a signicant difference to bone health. Acute, severe immobilisation, such as may be experienced at a time of surgery, further decreases already attenuated muscle bulk, mechanical loading and cortical quality. Furthermore, a lack of the cushion effect of a low muscle bulk increases exposure of bone to any external minimal trauma. Either limb contractures or physical, neurological or intellectual disability, all reduce capacity to respond rapidly and appropriately to an impending fall, with consequent increased injury risk compared with an able-bodied person, whose reexes reduce the impact of injury. Cumulative fracture risk assessment therefore must include mechanical factors as well as BMD and mass accrual.31.32

Calcium and vitamin D

Pregnancy, birth and the neonatal period
Calcium is required for normal mineralised bone matrix. True calcium deciency is relatively rare unless a diet is totally decient in dairy products and no calcium supplement is used. For a young child with a disability that results in low bone turnover and a chronically deplete skeleton, contribution to skeletal fragility from past early metabolic bone disease, particularly difculty with provision of adequate early phosphate needs, may be a component that continues to adversely contribute to overall bone mass.21

The early years of life

Decision making for percutaneous gastrostomy that may take months or years to be resolved. This can be agonising for families. Slow oral feeding may result in barely adequate or inadequate nutrition. Calcium, magnesium and vitamin D deciencies are common under these circumstances and further adversely affect skeletal accrual.22 Suitable calcium containing formulations may sometimes be difcult to nd where oral tolerability is a factor. There is also no consensus as to exact daily calcium requirement for individuals of different size and mobility, at different times of growth. Vitamin D is made by the action of sunlight on skin, with only a low contribution (525%) from oral intake.23,24 Its actions are complex and include calcium absorption and deposition in bone and effects on immune and cardiac function.24 Indoor lifestyle and limited skin exposure, where poor temperature control and mobility require extra clothing, contribute to vitamin D deciency risk. Older anticonvulsants may interfere with hepatic vitamin D metabolism. In addition, many newer preparations have direct adverse effects on bone.25 Most gastrostomy feeding formulations contain adequate vitamin D but regular monitoring of vitamin D status in those who have solely oral feeding is still not performed routinely. Ketogenic diet, utilising a high protein, low fat intake, when used for control of epilepsy may further adversely affect vitamin D metabolism.26 Corticosteroid use may be required in any acutely or chronically ill child or adolescent. The multiple adverse effects of steroids on bone include reduced IGF-1 action, resulting in lowered growth hormone effect and thus smaller bones with reduced endocortical accretion, inhibition of gonadotrophins and adrenal androgens, and lowered vitamin D action on intestinal and renal absorption of calcium. This in turn leads to results in secondary hyperparathyroidism, less chondrocyte differentiation, bone mineralisation and resorption.
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Management strategies to reduce skeletal fragility

See care plan for bone health in Figure 1.

Acute immobilisation
Acute immobilisation results in a sudden increase in bone turnover whereas chronic immobilisation is followed by a change in balance between bone formation and resorption, with slowing resorption.33,34 Bisphosphonates act primarily as osteoclast inhibitors, with reduced bone turnover resulting in net gain of bone. In situations of acute immobilisation such as fracture or surgery, fracture at the lower end of cast application is common, especially in the prepubertal child who has a smaller bone. With rapid bone turnover, short-term use of bisphosphonate may help reduce the impact of immobility, whereas it has less effect in lower bone turnover states. Reported outcomes of this type of intervention have been variable.35,36 With better understanding of the relative contributions of a small bone, low muscle mass, nutritional and pubertal status to the overall lifetime fracture risk in the presence of disability, it is not surprising that past reported outcomes have varied. At present, guidelines are lacking as to the most appropriate circumstances for such treatment, which may need to be decided on individual need37 until outcomes of large clinical trials are reported. In general, specialist consideration for bisphosphonate use should be sought when an affected child or adolescent has suffered one or more long bone fractures in the apparent absence of trauma appropriate to the injury. Decisions will be predicated by bone size, likelihood that the fracture occurred with little or no trauma, bone pain and timing of the event. As sex hormones increase both cortical thickness and

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Height Weight Fracture history Nutritional assessment Calcium intake ? Vitamin D use ? Anticonvulsants ?

Calcium, ALP, PTH 25 OH Vit D aBMD BMAD If low

Calcium 31200 mg/day total Vitamin D 4002000 IU/day Increase dose if on anticonvulsant Optimize nutrition

If puberty late >14

If puberty not late or not appropriate to induce

Induce puberty with short course of oestrogen / androgen

Consider bisphosphonate

Observe for continuing progress

Fig. 1 Assessment and care plan for bone health in children with disabilities. aBMD, areal bone density; ALP; alkaline phsphatase; BMAD, bone mineral apparent density; HRT; Hormone replacement treatment; PTH, Parathyroid hormone.

If no progress Take through puberty over 2.5 years then reassess off HRT

trabecular mineralisation and thus reduce fracture risk, it may be more appropriate to intervene in this area, rather than use a pharmaceutical mineralising agent. Bisphosphonate use in adults for non-malignant osteoporosis has been associated with a small but signicant risk of osteonecrosis jaw.38 Thus far, this disorder has not been seen in childhood bisphosphonate users but continued surveillance is needed.39 Prior to instrumentation for kyphoscoliosis, advice is frequently sought by orthopaedic surgeons as to use of bisphosphonates for low bone density. This complex question can only be resolved in the light of the many aspects of bone health pertaining to growth and pubertal status of the individual being assessed.40 Attention to calcium and vitamin D intake, together with prediction of timing of puberty or treatment to induce puberty, may help decisions as to timing of surgery. Occasionally, specic treatments to increase bone mass may be required prior to surgical procedures.35,36

Contribution of physical activity

Weight-bearing exercise and mechanical vibration treatments have both been assessed as possible methods for increasing bone

mass accumulation for children and adolescents with disabilities. Reported outcomes of treatment have not always taken body size, puberty or rate of change of these events into account. Vibration studies, using a whole body vibration plate, are reporting encouraging improvements.41 Improvement in tibial BMD has been reported with the same technique.42 Care with interpretation of existing study reports and further controlled studies are required before these methods can be properly evaluated. Fracture risk in the context of disability is thus seen as complex and changing with time. Any fracture assessment must therefore evaluate contributions of a small, light gracile bone exposed to trauma in the absence of protective cushion effect of normal muscle. Calcium, vitamin D and anticonvulsant use must be considered together with timing of and progress through puberty, leading to cumulative reduction in lifetime fracture risk. Investigation for possible occult fracture will always be dependent on clinical suspicion where the appendicular skeleton is involved, that is, where swelling, new lack of movement or unusual distress on movement of a limb are perceived by carers. For immobilised children, the axial skeleton tends not to fracture spontaneously and is less at risk. Fracture risk reduction is signicant after puberty. Where puberty is
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delayed, consideration should be given to possible pubertal induction, to achieve adult bone mass and reduce lifetime risk. Puberty is responsible for 4050% of total bone mass for life in males and females. If puberty occurs early for children who have disabilities, it may cause parental angst, in terms of coping with loss of childhood and with practical management strategies, but it has side benets of increased cortical accrual and trabecular mineralisation. On the contrary, particularly if body mass index (BMI) is low, puberty is often extremely delayed, thus exposing the affected child to extra years of a small, gracile bone, undermodelled by lack of muscle and absence of weight bearing. Judicious induction of puberty may be advantageous, to reduce the burden of skeletal fragility. This is without adverse effect if managed carefully by an appropriate physician.43,44 Management of pubertal induction or longer-term hormone replacement, where needed, is beyond the scope of this paper but is addressed in a recent related article. This includes the important area of menstrual control in adolescents who have severe multiple disabilities.45

Conclusions
Children and adolescents who have physical disabilities have special risks to their skeletal and hormonal health. Bone health can only be adequately addressed by improved understanding of the growing skeleton and the components that are altered in situations of immobility and reduced weight bearing. Interventions to reduce the impact of adverse circumstances will contribute to meeting goals of reducing extent and complications of adult osteoporosis.

Acknowledgement
The author wishes to thank A/Prof Dinah Reddihough for her review and helpful advice in formulating the paper for a general audience.

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