Heterotopic bone formation (HBF), also known as heterotopic ossification (HO), is the abnormal development of mature, lamellar bone tissue in soft tissues where bone typically does not exist, such as muscles, tendons, or fascia. This unexpected growth differs from normal skeletal development. HBF can range from small, clinically insignificant fragments to larger deposits that may lead to pain and restricted movement.
Understanding Heterotopic Bone Formation
This newly formed bone is structurally similar to normal bone, but its presence in an atypical location disrupts normal tissue function. The underlying cellular processes involve mesenchymal stem cells, found throughout the body, differentiating into osteoblasts, the cells responsible for bone formation.
This differentiation is often triggered by an inflammatory response and the creation of a suitable environment within the damaged tissue. Bone morphogenetic proteins (BMPs), particularly BMP-2, play a role in initiating inflammation by releasing neuroinflammatory factors from sensory nerves, which then recruit immune cells like mast cells and neutrophils. These immune cells contribute to the remodeling of local peripheral nerves, which can activate sympathetic signaling. Ultimately, these processes can lead to the migration and expansion of progenitor cells from nerves to the site of new bone formation.
Causes and Risk Factors
HBF often arises after specific events that cause tissue damage or inflammation. A common trigger is traumatic injury, including severe fractures, dislocations, or crush injuries. Surgery, particularly total hip arthroplasty (hip replacement), is another significant factor, with some studies indicating that between 28% and 61% of individuals undergoing hip replacements may develop some form of HBF.
Neurological conditions also pose a considerable risk, with spinal cord injury (SCI) and traumatic brain injury (TBI) being prominent examples; HBF can affect 20-29% of SCI patients and 5-20% of TBI patients. Severe burn injuries are another recognized cause. Rare genetic conditions like Fibrodysplasia Ossificans Progressiva (FOP) also cause HBF, where injured tissues are progressively replaced by abnormal bone, leading to chronic pain and severe immobilization over time.
Common Locations and Symptoms
HBF commonly develops around major joints, frequently at the site of a prior injury or surgical intervention. The hip is the most common location for HBF, especially following spinal cord injuries, but it can also occur around the elbows, shoulders, and knees.
Symptoms typically appear within 3 to 12 weeks following an inciting event. Individuals may experience localized pain and tenderness, often accompanied by swelling and warmth in the affected area. As the abnormal bone grows, it can restrict movement in the adjacent joint, leading to stiffness or a noticeable, firm lump under the skin. If the bone growth presses on nearby nerves, symptoms of nerve compression, such as numbness or tingling, may also occur. Diagnosis of HBF often involves imaging techniques like X-rays, which can reveal the abnormal bone formation, although it may take 3 to 8 weeks for the bone to become visible. A triple-phase bone scan is considered highly sensitive for detecting early lesions, sometimes as early as 2.5 weeks after injury, while CT scans can provide detailed views for surgical planning.
Treatment Approaches
Managing HBF involves both preventive strategies and treatments for established bone growth. For prevention, non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin are often used after injury or surgery to reduce the risk of HBF, typically at a dose of 75 to 100 mg per day for 7 to 14 days post-operatively in hip arthroplasty patients. Radiation therapy, involving low-dose external beam radiation (e.g., a single dose of 7 Gy to 8 Gy), is another preventive measure, often administered within 72 hours of surgery, particularly after total joint arthroplasty.
Once HBF has developed, conservative management is often the initial approach. Physical therapy helps maintain joint mobility and reduce stiffness. Pain management strategies also alleviate discomfort. If the HBF significantly impairs function or causes persistent pain, surgical excision of the abnormal bone may be considered.
Surgery is typically performed only after the heterotopic bone has fully matured, a process that can take 6 to 18 months. This waiting period helps reduce the risk of recurrence, which remains a consideration after surgical removal. While less common, certain bisphosphonates like etidronate may be prescribed to prevent progression of HBF, typically at a dose of 20 mg/kg per day for 2 weeks followed by 10 mg/kg per day for 10 weeks in spinal cord injury-associated cases. Researchers are also exploring new therapeutic avenues, such as targeting specific pathways like TGF-β signaling, to hinder HBF progression.