Standard radiographs are an insensitive tool for evaluating bone mineralization; an estimated decrease of 20–40 % must occur before reduced bone mass, or “osteopenia,” is detected [10]. While the term “osteopenia” is commonly used to describe an appearance suggestive of low bone mass on radiographs, it is not a recommended term for describing actual low bone mass by DXA in a pediatric population [7, 8]. The appearance of low bone mass may be an incidental finding on a chest or abdominal x-ray taken for nonskeletal indications or reported on a radiograph ordered due to bone pain or trauma. Such patients thought to have low bone mass on a standard radiograph should have subsequent DXA measures of bone density, especially if there are other identifiable risk factors for poor bone health.

Fractures occur in otherwise normal children. As many as half of all boys and one-third of girls will fracture by age 18, and one-fifth will sustain 2 or more fractures [11]. Most childhood fractures affect the forearm. Since peak bone growth precedes peak bone mineral accrual by 6–12 months, in early adolescence the skeleton may be relatively under-mineralized and more susceptible to fracture upon exposure to trauma. Several studies have compared the bone mineral density of “normal” children and adolescents who have sustained fractures to that of age-matched controls without fractures. Most [12–15], but not all [16, 17], studies have found the mean BMD to be significantly lower in children with forearm fractures than in controls. In a longitudinal study, Goulding et al. [13] found that 29 % of the subjects with a fracture at study entry had at least one subsequent fracture during the next 4 years as compared with only 8 % of control subjects. This being said, given the high prevalence of fractures among children it is not recommended that DXA measures be performed on all children who sustain a forearm fracture.

Recurrent fractures and those that occur in the setting of mild to moderate trauma warrant investigation with DXA. A detailed history of the nature of the injury is important, to assess the direction and magnitude of the force associated with the fracture [18]. For example, some fractures from a standing height, such as those that occur while is child is playing soccer or other vigorous sports, involve significant impact or torsion and may not qualify as mild trauma.

Vertebral compression fractures are far less common than extremity fractures during childhood. Spine fractures may indicate a marked deficit in bone quality, quantity, or both, particularly if other risk factors such as chronic glucocorticoid exposure are present. Recently, the ISCD noted that the presence of a compression (or crush) fracture in a child or adolescent constitutes a diagnosis of osteoporosis [8]. Bone densitometry is warranted in these patients to measure bone mass at nonvertebral sites and to establish a baseline DXA measure prior to treatment. However, bone mineral density may be increased in areas of compression as an artifact of the collapsed vertebrae. For this reason, areas of compression should be excluded when analyzing a DXA measure of the spine. With the availability of higher resolution bone densitometers, vertebral fracture assessments (VFA) by DXA has proven to be a useful tool for the diagnosis of moderate and severe vertebral fractures in children and adolescent, and radiation exposure is markedly less than with standard radiographs (see Chap. 10) [7, 19]. However, the “gold standard” for diagnosing vertebral fractures continues to be lateral spine x-rays.

Table 4.2 expands upon the genetic and acquired disorders that have been reported to be associated with low bone mass and fragility fractures in children and adolescents. Most of the conditions listed have been examined only in small convenience samples, many of which failed to consider delayed growth or maturity in interpreting the results. Because of these limitations, it is not possible to predict the risk of low bone mass or fractures in each condition with certainty. It is beyond the scope of this chapter to provide a detailed discussion for each of these disorders, but several are highlighted below, reviews are available in the literature [9], and additional disease-specific references are cited in Table 4.2.

Bone fragility in most of the heritable disorders results from defects in the bone matrix that can affect the entire skeleton [20–22]. Osteogenesis imperfecta, a primary bone disorder, exemplifies this point. With variable expressivity of the associated genetic defects, there is a wide range of skeletal effects and disease severity. Some patients show only asymptomatic low bone mass, whereas others progress to chronic bone pain, recurrent fractures, and progressive skeletal deformity. Others may have dentinogenesis imperfecta, hyperextensible joints, or other physical manifestations of the disorder. In patients with fibrous dysplasia, total bone mass is not diminished, but fragility fractures and pain occur at sites of lytic or cystic lesions. Idiopathic juvenile osteoporosis (IJO) is another primary bone disease process , highlighted in more depth below.

Myriad acquired diseases have been associated with a low bone mass, as noted in Table 4.2. In most of these diverse disorders, there is more than one threat to skeletal health. Malnutrition, vitamin D insufficiency, inadequate calcium intake or retention, immobility, deficiency of or resistance to sex steroids or growth hormone, and increased cytokines associated with these disorders can complicate the clinical picture [2]. Glucocorticoids, chemotherapeutic agents, and radiation therapy used to treat these disorders contribute to impaired bone health [9]. Therefore, severity of deficits in bone quantity and quality in chronic disease varies by diagnosis and disease course. For example, children with cystic fibrosis with marked disease severity and malnutrition may have markedly reduced bone mass and low-trauma fractures [23, 24]. By contrast, some, but not all, well-nourished children with mild cystic fibrosis have normal BMD for age [25]. Therefore, the decision to order DXA scans must be based upon clinical judgment regarding the presence of risk factors.

This disorder of unknown etiology presents in pre-pubertal children as bone pain and fragility fractures of spine and long bones; low bone mass is found when densitometry is performed [26, 27]. The diagnosis of IJO is made when other potential causes for bone fragility have been excluded. The etiology of IJO remains elusive. On radiographs, absence of callus at fracture sites and radiolucent bands in metaphyseal regions (i.e., neo-osseus osteoporosis) are characteristic of IJO, whereas callus formation is normal at fracture sites in osteogenesis imperfecta. Many patients with IJO exhibit dramatic “catch-up” bone accrual during puberty. However, for patients who sustain vertebral compression fractures and/or have an extremely low BMD Z-score, pamidronate therapy may be prescribed. This therapy has been shown to be effective in raising lumbar spine BMD and reducing fracture risk over 3 years, and DXA can be a helpful tool to monitor effects of therapy when it is initiated [28].

Deficiencies or excesses of certain hormones can limit bone mineral accrual and can contribute to skeletal losses. In Type 1 diabetes mellitus, bone mass is lower in children with this disease compared to healthy controls [29]. With poorly controlled diabetes or associated celiac disease bone mass is notably lower [30, 31]. Of enormous clinical concern is the skeletal effects of long term systemic glucocorticoids prescribed for chronic disease, malignancy, or posttransplantation. The dose, route of administration, specific agent, and duration of glucocorticoid therapy may influence the severity of the skeletal deficits. However, factors such as nutrition, activity, inflammation, and genetic variables appear to modify the skeletal response to chronic glucocorticoid excess, as well [4, 32, 33].

Appropriate treatment to correct endocrine deficits (such as sex steroid replacement therapy for ovarian insufficiency [34]) may be sufficient to prevent or restore deficits in bone mineral density. In other cases, such as with anorexia nervosa, the complexity of the hormonal imbalance that is impairing bone health complicates the therapeutic effort [35, 36].

Mechanical loading of bone is a key determinant of bone strength. For children who are immobilized due to cerebral palsy, neuromuscular disorders, or congenital or posttraumatic spinal injury, inadequate accrual and increased loss of bone are inevitable [37–40]. In many of these conditions, the adverse effects of immobilization may be compounded by coexisting deficiencies of calories, protein, calcium, or vitamin D intake and by the use of anticonvulsant therapies. Low bone mass and fragility fractures, particularly of the hip and lower extremities, are common in these disorders.

Muscle mass is often impaired in children and adolescents with limited mobility and may also contribute to skeletal losses or inadequate accrual. Research shows that muscle development plays an important role in bone mineral accrual ; referred to as the “muscle-bone unit .” [41] Modern DXA technology affords reliable assessments of body composition which may inform clinical management in the future, but more research is needed [42].

Increased use of DXA for pediatric clinical research has led to an extensive list of conditions associated with low bone mass or fractures in childhood (Table 4.2). However, without systematic screening of large numbers of children with the same diagnosis, the prevalence and severity of low bone density and fractures cannot be established. Little is known about the frequency of fragility fractures in these conditions since cohort sizes are often too small to determine whether fractures exceed the expected incidence for age. Until further research is available, recommendations regarding whom to screen by DXA and how frequently to repeat these studies represent expert opinion rather than evidence-based indications [8].

For a few disorders, subspecialty panels have developed recommendations for DXA examinations based upon analysis of the available literature by assembled experts. For example, in cystic fibrosis the European Cystic Fibrosis Mineralization Guidelines recommended DXA screening no later than at ages 8–10 years and then subsequent DXA measures at designated time intervals depending on the BMD Z-score at baseline [43]. Table 4.3 summarizes the published guidelines for several chronic disorders.

For disorders in which specific recommendations have not been established, the decision to perform DXA assessments should be based upon clinical judgment of risk. Routine DXA screening for the conditions listed in Table 4.2 are not mandated. The decision to perform DXA screening in an individual patient is influenced by disease severity, immobility, bone pain, skeletal deformity, malnutrition, and/or use of medications known to affect bone adversely. As with any test used in clinical practice, bone density testing should be carried out only when it is likely to influence patient management. For example, DXA measures would be indicated if results modify the decision to initiate therapy. If treatment is initiated, DXA screening is appropriate to establish a baseline measurement for monitoring the response to therapy over time.