Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures

Fatigue fractures in bones are common injuries with load-bearing activities, during which the remodeling aimed at removing microdamage has been suggested to play a role in increasing related fracture risk. Much attention has been given to the uncoupling between osteoclastic bone resorption and osteoblastic osteogenesis in fatigue fracture cases; however, the underlying pathophysiologic mechanisms of impaired fracture healing are yet unknown. Here we report multiple fatigue fractures in a physically active woman receiving contraceptive pills for years. Her fracture healing was remarkably slow, although she has been otherwise healthy. The patient underwent bone biopsy of the iliac crest that showed remarkable peritrabecular fibrosis with increased osteoclastic bone resorption combined with relatively low bone formation. Analysis of bone biochemical composition revealed a more complex picture: First, notable declines in bone mineral content-based parameters indicating abnormal mineralization were evident in both cancellous and cortical bone. Second, there was elevation in mineral crystal size, perfection, and collagen maturity in her bone tissues from different anatomical sites. To our knowledge, this is the first report showing generalized uncoupling in bone remodeling, increased peritrabecular fibrosis, and bone compositional changes associated with delayed healing of fatigue fractures. These results may explain delayed healing of fatigue and stress fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.