X-linked osteoporosis with fractures

X-linked osteoporosis with fractures (Orphanet code 391330) is a rare genetic bone disorder characterized by reduced bone mineral density (osteoporosis) and an increased susceptibility to fractures, inherited in an X-linked pattern. This condition primarily affects males, though carrier females may occasionally show milder manifestations. The disease impacts the skeletal system, leading to fragile bones that are prone to fractures from minimal or no trauma. Affected individuals may experience fractures in the vertebrae (spine), long bones, and other skeletal sites. Reduced bone density can be detected on dual-energy X-ray absorptiometry (DXA) scanning. The condition has been associated with loss-of-function variants in the PLS3 gene (plastin 3), located on the X chromosome, which plays a role in bone formation and the regulation of osteoblast and osteocyte function. Clinical features typically manifest in childhood or adolescence, with recurrent fractures being the hallmark presentation. Some patients may also develop vertebral compression fractures leading to back pain and reduced height. Unlike some other forms of hereditary osteoporosis, affected individuals generally do not exhibit blue sclerae, dentinogenesis imperfecta, or significant joint hypermobility, which helps distinguish this condition from osteogenesis imperfecta. Management is primarily supportive and aimed at reducing fracture risk. Treatment strategies may include bisphosphonates or other anti-resorptive therapies to improve bone mineral density, calcium and vitamin D supplementation, physical therapy, and fracture prevention measures. There is currently no cure, and long-term management requires monitoring of bone density and skeletal health throughout life.

Common questions about X-linked osteoporosis with fractures