The natural history of osteogenesis imperfecta: a systematic review.

Abstract

Osteogenesis imperfecta (OI) is a rare, heritable condition characterised by bone fragility, varied manifestations, and phenotypic heterogeneity. Understanding its natural history is essential for anticipating clinical needs. This systematic review collated literature on OI's natural history, focussing on diagnosis, signs, symptoms, and events (SSEs), and mortality. MEDLINE, Embase, and Embase Conference Abstracts were searched on March 24, 2024. Longitudinal (≥5 years follow-up) and cross-sectional studies which analysed outcomes by age were included, irrespective of interventions, due to treatment variability in OI. Sixty-six studies were included. Age of diagnosis varied widely; severe OI was typically diagnosed in early childhood, whereas milder types showed greater variability. SSEs manifest across ages. Some SSEs progress rapidly in childhood (e.g. scoliosis and bone deformities), whereas others (e.g. cardiac, ocular, auditory, and joint issues) emerge in adulthood, often earlier and more commonly than in the general population. Severe phenotypes may be associated with earlier onset and greater symptom severity than milder types. Fractures may be most frequent during childhood and adolescence but continue into adulthood, with limb fractures most reported. Aging, pregnancy, and menopause may increase the risk of hip, spine, and femur fractures. Life expectancy appears reduced by an average 9.5 years in men and 7.1 in women versus the general population. Leading causes of mortality include OI-related complications, cardiovascular and respiratory issues, and fracture-related trauma. The heterogeneous, progressive nature of SSEs supports the need for tailored, multidisciplinary long-term care. However, substantial evidence gaps and methodological inconsistencies limit comparability, highlighting the need for further evidence.