Tibial Stress Reaction Presenting As Bilateral Shin Pain in a Man Taking Denosumab for Giant Cell Tumor of the Bone

Prolonged bisphosphonate use has been associated with increased risk of atypical femoral fractures. Very few cases of atypical femoral fractures have been reported with denosumab. We report a case of bilateral tibial stress reactions in a 60-year-old man with no history of osteoporosis who was on prolonged high-dose denosumab for the treatment of giant cell tumor of bone. He presented with a 3-month history of pain in his bilateral shins worsening with activity and improving with rest. Although initial radiographs were unremarkable, he was found to have changes consistent with a stress reaction on magnetic resonance imaging of the distal tibia. To our knowledge, bilateral tibial stress reactions have not been previously reported with anti-resorptive therapies (neither bisphosphonates nor denosumab). Our case is intriguing in terms of the development of stress reactions as a precursor to stress fractures which may also relate to atypical fractures. Our case suggests a possible association between denosumab use and stress reactions. Of note the indication for denosumab in our case was for the treatment of giant cell tumor of bone where the Food and Drug Administration (FDA) approved dose is substantially higher than the FDA approved dose for osteoporosis treatment. Although rare, clinicians should consider the possibility of stress fractures in patients on anti-resorptive medications such as denosumab, especially when a patient presents with new onset thigh pain, hip pain or pain over an area affecting the long bones. Evaluation by imaging of affected areas should be pursued to enable early detection and intervention, as well as prevention of morbidity and associated ongoing risk to the patient.