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Background <p>The incidence of atypical femoral fractures in breast cancer patients is theoretically expected to be significantly higher than in those with primary osteoporosis. This is due to the prolonged and higher dosages of bisphosphonates used for post-operative bone protection and secondary osteoporosis. However, there is a notable lack of literature addressing this issue. Diagnosing and managing atypical femoral fractures in breast cancer patients presents unique challenges that differ substantially from those encountered in osteoporosis patients.</p> Case presentation <p>We present a 58-year-old postmenopausal woman with a history of breast cancer who reported bilateral mid-thigh pain. From June 2015 to January 2017, she received zoledronic acid (4&#xa0;mg) intravenously every 3 months, totaling seven doses. From 2017 to 2021, her regimen changed to a 4&#xa0;mg infusion every 6 months, resulting in ten doses during this period. Overall, she underwent 17 zoledronic acid infusions over approximately 5.5&#xa0;years. After minor trauma, she suffered sequential bilateral femoral shaft fractures. Bone metastases were initially suspected but ruled out through histopathological examination of both fracture sites, which showed no malignancy. Following her last infusion in June 2024, a multidisciplinary team (MDT) discussion was held. Considering her prolonged bisphosphonate exposure, the fracture sites, and imaging consistent with the 2013 American Society for Bone and Mineral Research (ASBMR) criteria, she was diagnosed with bisphosphonate-related atypical bilateral femoral fractures. Zoledronic acid was discontinued, and teriparatide treatment began, leading to significant pain relief, improved mobility, and radiological evidence of fracture healing after 9 months. However, due to mildly elevated tumor markers (CA19-9 and neuron-specific enolase [NSE]), teriparatide was switched to denosumab, which led to a prompt recurrence of bilateral thigh pain.</p> Conclusion <p>This case underscores the critical importance of early and differential diagnosis of atypical femoral fractures in this patient population. The findings suggest that teriparatide can be effective in promoting atypical femoral fracture healing; however, its use in patients with a history of cancer remains controversial and requires individualized risk-benefit assessment under multidisciplinary guidance. Furthermore, switching to denosumab during active fracture healing may lead to symptomatic recurrence. This approach might also be relevant for patients with primary osteoporosis. Multidisciplinary management and long-term monitoring are crucial for managing such complex cases.</p>

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Case report and medication implications: bilateral atypical femoral fractures in a patient with long-term bisphosphonate use after breast cancer surgery

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Jiahui Liu,
  • Xi Zhu,
  • Zhenguo Liu,
  • Ruiyu Li

摘要

Background

The incidence of atypical femoral fractures in breast cancer patients is theoretically expected to be significantly higher than in those with primary osteoporosis. This is due to the prolonged and higher dosages of bisphosphonates used for post-operative bone protection and secondary osteoporosis. However, there is a notable lack of literature addressing this issue. Diagnosing and managing atypical femoral fractures in breast cancer patients presents unique challenges that differ substantially from those encountered in osteoporosis patients.

Case presentation

We present a 58-year-old postmenopausal woman with a history of breast cancer who reported bilateral mid-thigh pain. From June 2015 to January 2017, she received zoledronic acid (4 mg) intravenously every 3 months, totaling seven doses. From 2017 to 2021, her regimen changed to a 4 mg infusion every 6 months, resulting in ten doses during this period. Overall, she underwent 17 zoledronic acid infusions over approximately 5.5 years. After minor trauma, she suffered sequential bilateral femoral shaft fractures. Bone metastases were initially suspected but ruled out through histopathological examination of both fracture sites, which showed no malignancy. Following her last infusion in June 2024, a multidisciplinary team (MDT) discussion was held. Considering her prolonged bisphosphonate exposure, the fracture sites, and imaging consistent with the 2013 American Society for Bone and Mineral Research (ASBMR) criteria, she was diagnosed with bisphosphonate-related atypical bilateral femoral fractures. Zoledronic acid was discontinued, and teriparatide treatment began, leading to significant pain relief, improved mobility, and radiological evidence of fracture healing after 9 months. However, due to mildly elevated tumor markers (CA19-9 and neuron-specific enolase [NSE]), teriparatide was switched to denosumab, which led to a prompt recurrence of bilateral thigh pain.

Conclusion

This case underscores the critical importance of early and differential diagnosis of atypical femoral fractures in this patient population. The findings suggest that teriparatide can be effective in promoting atypical femoral fracture healing; however, its use in patients with a history of cancer remains controversial and requires individualized risk-benefit assessment under multidisciplinary guidance. Furthermore, switching to denosumab during active fracture healing may lead to symptomatic recurrence. This approach might also be relevant for patients with primary osteoporosis. Multidisciplinary management and long-term monitoring are crucial for managing such complex cases.