## 2 Diagnosis  
As stated earlier, the ISCD definition of osteoporosis in children was not intended for children with significant risk factors for bone fragility due to chronic illness. Waiting for a second long bone fracture, a first vertebral fracture or a low BMD by DXA following low-trauma fractures unnecessarily delays the initiation of treatment in those with conditions known to be associated with an increased risk of bone fragility [8]. A vertebral fracture in children has been defined as \(>\)20% loss of vertebral height ratio according to the semi-quantitative Genant method [9]. The Genant method to define VF in children has been validated by showing that vertebral fractures defined in this way independently predict new (i.e., subsequent) vertebral and long bone fractures [8]. VFs are more common than long bone fractures in children with chronic illness treated with glucocorticoids: VFs occur in 32.5%, non-VFs in 23% of children with acute lymphoblastic leukemia [8], and VFs occur in 16.3% and non-VF fractures in 10.1% of children with rheumatic disorders treated with glucocorticoids [10]. Thirty-nine percent of children with VF in the group of children with acute lymphoblastic leukemia were asymptomatic [8]. For this reason, routine monitoring by lateral spine imaging (radiography or dual-energy x-ray absorptiometry) is required for their early detection [11]. Untreated VFs can lead to chronic back pain and spine deformity [8]. Therefore, screening for VF is so important that many clinicians are now using DXA-based Vertebral Fracture Assessment, for which there are guidelines in children put forward by the ISCD [12; 13]. This has the advantage of low radiation, lack of parallax, and showing the entire spine on one cassette (which minimizes errors in determining the affected vertebral level(s)) [12]. A child with a chronic illness associated with bone fragility with a size-adjusted BMD z-score \(<\)\(-\)2.0 but without a history of fractures is not classified as having osteoporosis per se but would be considered at-risk. The definition \"fractures without major trauma\" has been defined as fractures occurring outside of motor vehicle accidents or falling from 10 feet (3 m) or less [4]. With respect to falls in the at-risk, chronic illness setting, a more appropriate definition has been used: falling from a standing height or less or at no more than walking speed [8]. DXA-based BMD can be viewed as a clinical precursor to bone fragility, as it is considered a surrogate for bone strength. Because 90% of peak bone mass is acquired by the age of 18 years, chronic pediatric disease reduces BMD and thus increases fracture risk, not only in childhood and adolescence but also in adulthood [4; 14]. There is a strong correlation between BMD and fracture risk [15]. However, BMD can be normal in children with fractures due to secondary osteoporosis [8; 15]. DXA is the gold standard for the measurement of bone mass (bone mineral content, BMC) and bone mineral density (BMD) in children because of its precision, minimal radiation dose, reproducibility, availability of normative data, and correlation with prevalent and incident fractures in children [15; 16; 17]. Different DXA skeletal sites for BMD measurement have been described, with the lumbar spine (L1-L4) and hip (the latter, in children over 4-5 years of age) representing key skeletal sites [13; 16]. The main purpose thus of BMD is to provide additional evidence to justify an appropriate workup and therapeutic intervention. Follow-up of the BMD can be used as a predictor of bone fragility, with a loss of \(\geq\) 0.5 SD considered clinically significant [7; 11]. However, DXA has its limitations. DXA may be technically impossible to perform or interpret in children due to movement during measurement, metallic implants, contractures, and sometimes scoliosis [18]. Secondly, the z-scores are based on calendar age and not skeletal maturation. This may lead to inaccurate interpretation of measurements in those with delayed pubertal development [19; 20].