Does hemophilia cause pathologic fractures?

Does Hemophilia Cause Pathological Fractures?

No, hemophilia does not cause pathological fractures in the traditional sense, but it does significantly increase the risk of fragility fractures due to secondary osteoporosis and bone loss from the disease process itself.

Understanding the Distinction

Pathological fractures classically refer to fractures through abnormal bone weakened by tumors, infections, or metabolic bone diseases like Paget's disease 1. Hemophilia does not create pathological fractures through these mechanisms. However, people with hemophilia (PWH) develop osteoporosis-related fragility fractures through distinct hemophilia-specific pathways 2, 3.

Mechanisms of Bone Loss in Hemophilia

The bone fragility in hemophilia is multifactorial and includes several direct and indirect mechanisms:

Direct Factor Deficiency Effects

• Factor VIII and IX deficiency directly affects bone metabolism by interfering with the RANK/RANKL/OPG pathway, which regulates osteoblast and osteoclast activity 3
• Thrombin deficiency alters cytokine profiles that affect both osteoblast and osteoclast function 3

Indirect Mechanisms

• Recurrent joint bleeding (hemarthroses) leads to hemophilic arthropathy, causing prolonged immobilization and reduced mechanical loading on bones 2, 3, 4
• Reduced physical activity from joint damage and disability decreases weight-bearing exercise, further accelerating bone loss 2, 4
• Nutritional deficiencies, particularly vitamin D deficiency, compound the problem 2

Clinical Evidence of Increased Fracture Risk

Bone Density Studies

• PWH demonstrate significantly lower bone mineral density (BMD) compared to healthy controls: lumbar spine BMD 0.825 vs. 0.939 g/cm² (P < 0.0001) and hip BMD 0.725 vs. 0.938 g/cm² (P < 0.0001) 4
• The incidence of osteoporosis (T-score ≤ -2.5) is significantly higher in hemophiliacs compared to age-matched controls 4

Fracture Incidence

• Fracture incidence in adult PWH is significantly elevated at 12% compared to 0% in controls 4
• These fractures typically occur after trivial trauma due to underlying bone fragility, not from the bleeding disorder itself 4
• There is a statistically significant correlation between joint evaluation scores and hip BMD, indicating that worse arthropathy predicts lower bone density 4

Important Clinical Distinctions

What Hemophilia Does NOT Cause

• Spontaneous pathological fractures through diseased bone (as seen with metastatic cancer or primary bone tumors) 1
• Fractures from the bleeding itself—the fractures result from weakened bone structure, not hemorrhage 2, 3

What Hemophilia DOES Cause

• Secondary osteoporosis with increased susceptibility to fragility fractures 2, 3, 4
• Normal fracture healing when adequate factor replacement is provided—the primary disease does not essentially influence healing if early and sufficient substitution of missing coagulation factors is administered 5

Management Implications

Fracture Treatment in PWH

• Fractures heal normally in PWH with appropriate factor replacement therapy 5
• Both conservative and surgical management are viable options depending on fracture characteristics and severity of arthropathy 5
• Correct pretreatment with plasma or coagulation factors is essential before any intervention 5

Osteoporosis Prevention and Treatment

• Pharmacological options include antiresorptive agents, anabolic drugs, and dual-action medications 2, 3
• Weight-bearing exercise and fall prevention are critical non-pharmacological interventions 3
• Prophylactic coagulation factor replacement therapy helps maintain joint health and mobility, indirectly protecting bone density 3
• Early assessment of bone density and administration of anti-osteoporotic therapy is recommended for all PWH 4

Common Pitfalls to Avoid

• Do not assume fractures in PWH are "pathological" in the classic sense—they are fragility fractures from secondary osteoporosis 2, 3, 4
• Do not delay fracture treatment waiting for complex hematologic workup—ensure adequate factor replacement and proceed with standard orthopedic management 5
• Do not overlook bone health screening in PWH, especially those with severe arthropathy and limited mobility 4
• Do not attribute all skeletal complications to bleeding alone—the coagulation factor deficiency itself directly affects bone metabolism 3