Fractures at virtually all sites are associated with adverse outcomes: an observational study

The FRAX model defines fractures occurring at the hip, vertebrae, humerus, and forearm as major osteoporotic fractures (MOF), leading to the misconception that fractures at other sites (NonMOF) are unimportant. We aimed to compare MOF and NonMOF to 1) assess their contribution to subsequent fracture and mortality risks and 2) the differences in subsequent fracture and mortality risks between MOF and NonMOF as well as 3) assess these contributions using an anatomical classification of hip, vertebral, proximal and distal fractures. Data from 7568 women and 3366 men aged 60+ were utilised from two Longitudinal cohorts (the Canadian Multicentre Osteoporosis Study and Dubbo Osteoporosis Epidemiology Study) to assess subsequent fracture and mortality following initial fractures. Initial fractures were classified as MOF or NonMOF for aim 1 and 2, and as hip, vertebral, proximal, or distal for aim 3. There were 1998 initial fractures (38% NonMOF) in women and 484 (48% NonMOF) in men. During 9551 person-years (py), women experienced 605 subsequent fractures (38% post-NonMOF) and during 2230 py, men had 97 subsequent fractures (48% post-NonMOF). Following the initial fracture, 556 women died (29% post-NonMOF) over 12065 py and 196 men died (38% post-NonMOF) over 2773 py. NonMOF were associated with 69% higher subsequent fracture risk in women (HR: 1.69; 95% CI: 1.47-1.95) and two-fold in men (2.06; 1.52-2.80), compared to initial fracture, comparable to MOF (women: 1.76; 1.56-1.98 and men: 2.09; 1.53-2.85. NonMOF imparted >30% excess mortality (women: 1.37; 1.16-1.60 and men: 1.33; 1.03-1.72), compared to fracture-free population, lower than MOF (women: 1.75; 1.54-1.99 and men: 2.26; 1.81-2.81) but still substantial. All anatomical fracture sites were associated with subsequent fracture risk, and the risk of mortality increased incrementally from distal to proximal, vertebral and hip. MOF and NonMOF showed comparable risks of subsequent fracture and mortality. All sites are associated with adverse outcomes and should be addressed in clinical care guidelines.