Osteoporosis is a skeletal disorder with enhanced bone fragility, usually affecting the elderly. It is very rare in children and young adults and the definition is not only based on a low BMD (a Z-score < - 2.0 in growing children and a Z-score ≤ - 2.0 or a T-score ≤ - 2.5 in young adults) but also on the occurrence of fragility fractures and/or the existence of underlying
chronic diseases or secondary factors such as use of
glucocorticoids. In the absence of a known
chronic disease, fragility fractures and low BMD should prompt extensive screening for secondary causes, which can be found in up to 90% of cases. When fragility fractures occur in childhood or young adulthood without an evident secondary cause, investigations should explore the possibility of an underlying monogenetic
bone disease, where bone fragility is caused by a single variant in a gene that has a major role in the skeleton. Several monogenic forms relate to
type I collagen, but other forms also exist. Loss-of-function variants in LRP5 and WNT1 may lead to early-onset
osteoporosis. The X-chromosomal
osteoporosis caused by PLS3 gene mutations affects especially males. Another recently discovered form relates to disturbed
sphingolipid metabolism due to SGMS2 mutations, underscoring the complexity of molecular pathology in monogenic early-onset
osteoporosis. Management of young patients consists of treatment of secondary factors, optimizing lifestyle factors including
calcium and
vitamin D and physical exercise. Treatment with bone-active medication should be discussed on a personalized basis, considering the severity of
osteoporosis and underlying disease versus the absence of evidence on anti-fracture efficacy and potential harmful effects in pregnancy.