Atypical femoral fracture in a multiple myeloma patient undergoing treatment with denosumab: A case report and literature review

Abstract

Introduction and importance: Denosumab is a new standard treatment for bone disease caused by multiple myeloma. There are a few reports of atypical femoral fracture in patients with multiple myeloma, all of which were associated with long-term use of bisphosphonate. Here, we report the first case of denosumab-induced atypical femoral fracture in a patient with multiple myeloma.

Case presentation: A 71-year-old woman with multiple myeloma developed dull pain in her right thigh 8 months after restarting high-dose denosumab following its initial administration for 4 months and subsequent withdrawal for 2 years. Fourteen months later, complete atypical femoral fracture occurred. Osteosynthesis was achieved using an intramedullary nail and she was switched to oral bisphosphonate 7 months after cessation of denosumab. There was no exacerbation of the multiple myeloma. Bone union was achieved and she recovered to her pre-injury level of activities. The oncological outcome was alive with disease at 2 years after surgery.

Clinical discussion: Prodromal symptoms such as thigh pain and radiographical finding of thickening of the lateral cortex in the subtrochanteric region of the femur were attributed to denosumab-induced atypical femoral fracture in the case. A unique aspect of this case worth highlighting is that the fracture occurred after short-term denosumab use. This may be associated with multiple myeloma or other medication including dexamethasone and cyclophosphamide.

Conclusion: Atypical femoral fracture may occur in patients with multiple myeloma who receive denosumab, even for a short period. Attending physicians should be cognizant of the early symptoms and signs of this fracture.

Keywords: Atypical femoral fracture; Denosumab; Multiple myeloma.

Graphical abstract

Fig. 1

(a) Anteroposterior radiographs of the right femur 8 months after restarting denosumab showing localized thickening of the lateral cortex in the subtrochanteric region (white arrow). (b) A bone scintigraphy scan showing uptake of ^99mTc in the subtrochanteric region of the right femur (black arrow). (c) Fifteen months after restarting denosumab, localized thickening of the lateral cortex is expanding (white arrow). (d) Antero-posterior radiographs of the right femur after low-energy trauma showing a short oblique fracture and medial spike in the subtrochanteric region.

Fig. 2

(a) Anteroposterior radiographs of the right femur after internal fixation of the fracture with an antegrade long intramedullary nail. (b) Pathological examinationof femoral intramedullary tissue detected some viable myeloma cells (hematoxylin-eosin staining). (c) Bone union achieved 7 months after surgery. (d) Plain radiograph at final follow-up, 2 years after surgery.

Fig. 3

Computed tomography images of the right femur during denosumab withdrawal indicating no findings of localized thickening of the lateral cortex.