## 3 Risk Factors for Developing Secondary Osteoporosis
### Drug-Induced Secondary Osteoporosis  
A myriad of drugs can lead to low BMD and secondary osteoporosis. The most well-known are glucocorticoids, anticonvulsants, and methotrexate [32]. Glucocorticids are often used for prolonged periods of time in (chronic) diseases in children like systemic inflammatory and autoimmune diseases, renal diseases, after organ transplantation,leukemia, and Duchenne muscular dystrophy. These diseases in themselves may also lead to fragility fractures because of reduced bone strength, for example, due to the effect of the increased cytokines (like IL1, IL6, and tumor necrosis factor-alpha) in case of systemic inflammatory and autoimmune diseases on bone metabolism [33]. Much is known about the adverse effects of glucocorticoids on bone strength [34]. Glucocorticoids cause decreased bone formation, with an additional early and transient increase in bone resorption. The final effect is increased bone turnover with early onset bone loss [35]. BMD rapidly decreases in the first 2 weeks after the start of glucocorticoids, leading to significant bone loss in the first 3-6 months of therapy [36]. This loss diminishes with time and is replaced by a chronic phase of decreased bone formation. The ultimate effect is a reduction of BMD and altered bone microarchitecture, with a predilection for the trabecular-rich spine [34]. This deleterious effect of glucocorticoids on bone strength can be seen in children with Duchenne muscular dystrophy. Glucocorticoids are used to delay loss of ambulation, improve or retain pulmonary function with reduced need for assisted ventilation and delay cardiomyopathy [37]. Before corticosteroids were used, vertebral fractures were rarely seen in children with Duchenne muscular dystrophy, and most fractures involved the lower extremities [28]. In boys living with Duchenne muscular dystrophy who are treated with glucocorticoids, the prevalence of vertebral fractures is \(>\)50%, with a cumulative incidence of 28% over a median follow-up of 4 years after starting with glucocorticoids [30; 38]. In Canada, an observational cohort study was performed to increase insight into glucocorticoid-induced osteoporosis in children [34]. The most important observations were that vertebral fractures are the hallmark of pediatric glucocorticoid-induced secondary osteoporosis, can occur in the first year of glucocorticoid treatment, and are frequently asymptomatic. However, some children have the growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is important to know since this may preclude the need for intravenous osteoporosis therapy [39]. Children with poor growth, older children (with less residual growth), and children with ongoing bone health threats have less potential for vertebral body reshaping, which can result in permanent vertebral deformity [8]. Therefore, timely intervention with intravenous osteoporosis therapy is paramount in children with vertebral fractures if they have persistent risk factors for ongoing spine collapse.  
Although preclinical models may help to understand the effects of glucocorticoids on bone metabolism and bone strength, up to now, there is no robust animal model to evaluate known and new interventions [40].