Underlying conditions which adversely affect skeletal strength are one of the most common reasons for consultations in pediatric bone health clinics. The diseases most frequently linked to fragility fractures include leukemia and other cancers, inflammatory disorders, neuromuscular disease, and those treated with osteotoxic drugs (particularly glucocorticoids). The decision to treat a child with secondary osteoporosis is challenged by the fact that fractures are frequent in childhood, even in the absence of risk factors. Furthermore, some children have the potential for medication-unassisted recovery from osteoporosis, obviating the need for bisphosphonate therapy.
Over the last decade, there have been important advances in our understanding of the skeletal phenotypes, fracture frequencies, and risk factors for bone fragility in children with underlying disorders. With improved knowledge about the importance of fracture characteristics in at-risk children, there has been a shift away from a bone mineral density (BMD)-centric definition of osteoporosis in childhood, to a fracture-focused approach. As a result, attention is now drawn to the early identification of fragility fractures, which includes asymptomatic vertebral collapse. Furthermore, even a single, long bone fracture can represent a major osteoporotic event in an at-risk child. Fundamental biological principles of bone strength development, and the ways in which these go awry in chronic illnesses, form the basis for monitoring and diagnosis of osteoporosis in children with underlying conditions. Overall, the goal of monitoring is to identify early, rather than late, signs of osteoporosis in children with limited potential to undergo medication-unassisted recovery. These are the children who should undergo bisphosphonate therapy, as discussed in part 1 (monitoring and diagnosis) and part 2 (recovery and the decision to treat) of this review.

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