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Causes of Delays in Fracture Healing

A White Paper by Sonogen Medical, Inc.

Intro

Bone fractures typically undergo a well-orchestrated healing process involving inflammation, repair, and  remodeling. However, in certain instances, this process is disrupted, leading to delayed union or  nonunion of the fracture. Delayed union refers to a slower-than-expected healing trajectory, while  nonunion denotes the cessation of all reparative processes without achieving bone continuity. Various  medical conditions can predispose individuals to these complications, influencing both the duration and  success of fracture healing. This paper explores the primary medical conditions associated with delayed  and nonunion fractures, supplemented by statistical insights into their prevalence across different  fracture types. 

Contributing Factors 

Overall, more than half a million fractures the United States progress to nonunion annually, with an  overall nonunion rate ranging as high as 10%, depending on various factors such as fracture type and  patient health. The likelihood of delayed union or nonunion varies depending on the fracture's  anatomical location and the nature of the injury. High-energy fractures, comminuted fractures (i.e.,  fractures in multiple pieces), and injuries with significant soft tissue damage are at an increased risk. 

Incidence by Injury 

The incidence of nonunion fractures varies across different bones, influenced by factors such as blood  supply, mechanical stress, and patient demographics. The following table presents the approximate  nonunion rates for the six major long bones, as well as the wrist and ankle: 

The Importance of Vascularity 

Vascularity also plays a crucial role in fracture healing, as an adequate blood supply is essential for  delivering oxygen, nutrients, and essential signaling molecules to the injury site. Following a fracture,  the healing process relies on a robust vascular response to facilitate inflammation, cellular proliferation,  and tissue regeneration. Blood vessels help transport osteoprogenitor cells, which differentiate into  osteoblasts responsible for new bone formation. Additionally, angiogenesis—the formation of new blood vessels—is a key component of the reparative phase, ensuring that the developing bone tissue  receives sufficient metabolic support. Impaired vascularity due to a number of comorbidities can also  lead to delayed healing, nonunion, or compromised bone strength, including: 

  • Diabetes Mellitus
    Diabetes mellitus, particularly when poorly controlled, has been identified as a significant risk  factor for impaired fracture healing. Hyperglycemia can adversely affect osteoblast function,  reduce collagen production, and impair angiogenesis, all of which are crucial for bone repair.  Studies have demonstrated that individuals with diabetes experience higher rates of delayed union and nonunion compared to non-diabetic populations. For instance, a comprehensive  review highlighted that diabetes is consistently associated with an increased risk of fracture healing complications, regardless of the fracture site.
  • Osteoporosis
    Osteoporosis, characterized by decreased bone mass and microarchitectural deterioration,  inherently increases fracture risk. The compromised quality of osteoporotic bone can also  impede the healing process. Fragility fractures, common in osteoporotic patients, often occur in  the vertebrae, femoral neck, and distal radius. The weakened bone structure in osteoporosis not  only predisposes individuals to fractures but also challenges the healing process, potentially  leading to delayed union or nonunion.
  • Infection
    Infections, particularly osteomyelitis, can severely disrupt bone healing. The presence of  pathogenic organisms at the fracture site can lead to inflammation, necrosis, and sequestration  of bone tissue. Open fractures are especially susceptible to infections due to direct exposure to  the environment. The development of osteomyelitis in such scenarios can hinder the normal  healing cascade, increasing the likelihood of nonunion.
  • Smoking and Nicotine Use
    Tobacco use has been extensively studied concerning bone health. Nicotine and other  constituents of tobacco can constrict blood vessels, reducing perfusion to the healing bone. This  diminished blood flow can lead to hypoxia at the fracture site, adversely affecting osteogenesis.  Clinical data indicate that smokers have a higher incidence of delayed union and nonunion  compared to non-smokers.
  • Advanced Age
    Aging is associated with a natural decline in bone density and regenerative capacity. Elderly  individuals often exhibit delayed fracture healing due to reduced osteoblastic activity and slower  cellular responses. Additionally, age-related comorbidities, such as vascular insufficiencies and  nutritional deficiencies, can further compromise bone repair mechanisms. 
  • Hormonal Issues
    Thyroid hormones play a pivotal role in bone metabolism, influencing both resorption and  formation. Hypothyroidism, characterized by deficient thyroid hormone levels, can lead to a  decrease in bone turnover. This hormonal imbalance can result in delayed fracture healing, as  the reduced metabolic activity slows down the reparative processes necessary for bone union. 

Conclusion 

Delayed and nonunion fractures present significant challenges in orthopedic care, often resulting from a  complex interplay of patient-specific factors and the nature of the fracture. Medical conditions such as  diabetes mellitus, osteoporosis, infections, smoking, advanced age, and hypothyroidism have been  identified as prominent risk factors that can impede the normal bone healing process. Understanding  these associations is crucial for clinicians to develop tailored treatment strategies, optimize patient  outcomes, and mitigate the risk of impaired fracture healing. 

References

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About Sonogen

Sonogen Medical is a medical devices manufacturer, specializing in developing cutting-edge therapeutic and diagnostic ultrasound equipment. Sonogen’s products are designed to help protect, detect, and treat patients through the unique application of advanced ultrasound procedures and techniques. Sonogen’s bone fracture healing device, built on shear wave acoustics, is the first of its kind in the world.

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