## 5 Prevention of Secondary Osteoporosis  
Numerous interventions may prevent or reduce bone fragility fractures [46]. This starts with recognizing the risk of bone fragility and osteoporosis, as discussed above. Children with a condition or risk factors known to be associated with low bone strength or secondary osteoporosis, such as wheelchair dependence, cytokine-release related disorders, or who are on certain drugs, have an increased risk of fragility fractures [23]. General osteoporosis prevention measures are effective treatment of the underlying condition and associatedorbidities, optimizing nutritional state and weight-bearing activities, and the diagnosis and treatment of endocrinopathies, including delayed puberty, growth hormone deficiency, and thyroid disorders. For children with chronic illnesses, adequate treatment of the illness is a sine qua non for osteoporosis prevention and treatment [39]. However, sometimes the disease cannot be causally treated (i.e., severe neurodevelopmental disorder), or the treatment induces bone loss and osteoporosis, such as glucocorticoids or chemotherapy. For this reason, whenever possible, treatments should be as steroid-sparing as possible. Nutritional state is an important factor. For example, a poor nutritional state (underweight or feeding difficulties) is associated with a lower BMD in children with cerebral palsy and chronic pancreatitis [26, 47, 48]. Other well-known risk factors for reduced bone strength are vitamin D deficiency and a shortage of dietary intake of calcium. Even in healthy children in Europe, the prevalence of vitamin deficiency is about one in every 4-5 children [49]. Children with chronic illnesses are at high risk due to a combination of limited sun exposure and often feeding problems. The recommended daily intake of vitamin D is 400-800 IU/day, depending on the 25-hydroxyvitamin D level. The optimal serum 25-hydroxyvitamin D threshold, however, remains controversial. From a practical perspective, a 25-hydroxyvitamin D level of 50 nmol/L [20 ng/mL] or more is recommended at the end of winter [39; 50]. Incidental studies report a positive result of this intervention. [PERSON] et al. [51] reported a significant increase in BMD in 65% of patients with Duchenne muscular dystrophy after two years of vitamin D treatment and adjustment of dietary calcium to the recommended daily dose. Calcium is an important nutrient for adequate skeletal mineralization. The recommended dietary allowance of calcium is 700 mg/day for children between 1-3 years, 1000 mg/day between 4-8 years, and 1300 mg/day for children between 9-18 years [52]. Optimal calcium intake can be achieved by an adequate diet whenever possible [39]. The role of standard calcium supplementation in healthy children has been investigated by a meta-analysis showing only a small effect on BMD, unlikely to alter fracture risk [53]; the situation in chronically ill children may be different since risk factors may \"stack\" towards an increased risk of bone fragility. For this reason, optimizing conservation measures to enhance bone health, such as calcium and vitamin D intake, are standard approaches in the chronic illness setting.  
Physical activities, including weight-bearing activities, have an anabolic effect on the growing skeleton. These physical activities increase bone mass in healthy children [54]. The evidence of the effect of physical or weight-bearing activities in children with chronic illnesses is still insufficient [55]. It is advised to encourage activities with a low risk of falling and bodily contact in ambulatory children with osteoporosis [39]. In non-ambulant children, modest increases in BMD have been reported following weight-bearing regimes and low amplitude, high-frequency vibration therapy [56; 57]. Moreover, it was shown that exercise might improve bone strength under conditions of adequate calcium intake, showing the importance of implementing these general measures in tandem [39; 58].