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Objectives: To describe peripheral long bone material and structural differences in youth at risk of secondary osteoporosis across disease-specific profiles., Methods: Upper- and lower limbs of children and adolescents were scanned at 4% distal and 66% mid-shaft sites using peripheral Quantitative Computed Tomography sub-categorised as (1) increased risk of secondary osteoporosis (neuromuscular disorders; chronic diseases; endocrine diseases; inborn errors of metabolism; iatrogenic conditions), (2) low motor competence and (3) non-affected controls., Results: Children with disease-specific profiles showed a range of bone deficits compared to the control group with these predominantly indicated for neuromuscular disorders, chronic diseases and low motor competence. Deficits between upper arm and lower leg long bone parameters were different for disease-specific profiles compared to the control group. Endocortical radius, muscle area, and mid-cortical ring density were not significantly different for any disease-specific profile compared to the control group for any bone sites., Conclusions: Neuromuscular disorders, chronic diseases and low motor competence have a strong correlation to bone health for appendicular bone parameters in youth, suggesting a critical mechanical loading influence which may differ specific to disease profile. As mechanical loading effects are observed in regional bone analyses, targeted exercise interventions to improve bone strength should be implemented to examine if this is effective in reducing the risk of secondary osteoporosis in youth., Competing Interests: The authors have no conflict of interest.