Long-term administration of alendronate sodium caused an atypical femoral shaft fracture in a 36-year-old woman: a case report and literature review

Abstract

Long-term bisphosphonate therapy is associated with atypical or insufficiency fractures, particularly in the proximal femur. We observed a case of an atypical femoral shaft fracture in a patient with a long-term history of alendronate therapy. A 36-year-old woman was admitted with a complaint of pain in her right mid-thigh following low-energy trauma. She had been taking alendronate for more than 15 years. X-rays indicated a fracture of the right femoral shaft. The patient was treated with proximal femoral nail antirotation (PFNA) fixation. This case highlights concerns regarding long-term bisphosphonate therapy and its potential complications.

Introduction

Bisphosphonates (BPs) have been extensively developed and used as potent therapeutic agents for osteoporosis. BPs have bone-protective effects in both primary osteoporosis (OP), affecting both sexes, and secondary OP, such as glucocorticoid-induced OP. ¹ Evidence has demonstrated that the use of BPs effectively inhibits the bone remodeling process, leading to an increase in bone mineral density (BMD) and enhanced bone mechanical properties. Consequently, this translates to a reduced incidence of both vertebral and nonvertebral fractures.^2,3 Recently, there has been growing concern surrounding atypical femoral fractures (AFFs), which have emerged as a potential complication associated with prolonged BP therapy for the management of OP. ² In this study, we report a case of an atypical femoral shaft fracture in a 36-year-old female patient with a long-term history of alendronate use. Obvious microcracks were visible in radiographs of her unaffected femur, which could easily have been ignored.

Case report

A 36-year-old female patient presented with a complaint of pain in her right thigh and limited mobility after a fall at home. She had called emergency services and was brought to our hospital for evaluation. X-ray findings indicated a fracture of the right femoral shaft, and she was admitted to the Department of Trauma Orthopedics for treatment. Following the injury, her mental state was good, with clear consciousness, and she had no remarkable abnormalities regarding her appetite, sleep patterns, or bowel movements. A diagnosis of systemic lupus erythematosus (SLE) was made 10 years earlier. The patient disclosed regular use of the following medications: hydroxychloroquine sulfate tablets for 15 years, twice daily, 0.2 g per dose; methylprednisolone for 15 years, once daily, 7 mg per dose; leflunomide for 15 years, once daily, 20 mg per dose; calcitriol capsules for 15 years, once daily, 0.25 µg per dose; and alendronate sodium for 15 years, once per week, 70 mg per dose. She denied any other relevant medical history. On examination, her spine showed a normal physiological curvature, and marked swelling and deformity were observed at the right femoral shaft fracture site. There was tenderness on palpation and crepitus was felt upon movement of the limb. She was unable to cooperate with the mobility assessment, and no other abnormalities were found during physical examination of the limbs. Preliminary diagnosis: 1. right femoral shaft fracture, and 2. SLE. After discussing the patient’s femoral shaft fracture and performing a literature search, we found that the fracture was extremely rare and likely caused by the use of BPs. We immediately informed the patient of this situation and instructed her to stop taking alendronate sodium. Once her condition met the surgical requirements and a series of relevant examinations were completed, surgery was performed using closed reduction and internal fixation with proximal femoral nail antirotation (PFNA) fixation. We instructed the patient to return to the hospital 1, 5, and 10 months after surgery for radiographs to monitor fracture healing. Figure 1 shows the postoperative X-rays of the fracture at 1 month: Figure 1(a) shows the anteroposterior view, and Figure 1(b) is the lateral view. The postoperative X-rays at 6 months are shown in Figure 2, with Figure 2(a) showing the anteroposterior view and Figure 2(b) showing the lateral view. Figures 2(c) and 2(d) show the patient’s left femur, which had a high number of microcracks and fractures and localized periosteal thickening of the lateral cortex, which is also seen in Figure 3. We informed the patient of the need for treatment with teriparatide, but she declined this therapy owing to its high cost and her ability to walk normally. We discussed the need for regular X-rays to assess the condition of the left femur.

Figure 1.

Postoperative radiographs of the fracture at 1 month; (a) anteroposterior view and (b) lateral view, with the fracture outlined by the blue dashed line in each view.

Figure 2.

Postoperative radiographs at 5 months; (a) anteroposterior view, (b) lateral view, with the fracture outlined by the blue dashed line in each view; (c) and (d) show the patient’s left femur with localized periosteal thickening of the lateral cortex.

Figure 3.

Postoperative radiographs at 10 months; (a) anteroposterior view, (b) lateral view showing that the fracture in the right femur is gradually healing (areas outlined by the blue dashed lines). Panels (c) and (d) show the patient’s left femur, with clear localized periosteal thickening of the lateral cortex (within the areas outlined by the blue dashed lines).

Discussion

BPs are the current gold standard therapy for OP. ⁴ Despite their ubiquitous prescription, numerous questions continue to linger, especially regarding the most efficacious approaches to patient care. Additionally, the potential adverse consequences of prolonged BP intake, notably atypical femoral fractures, have sparked numerous debates. ⁵ Nonetheless, the research examining the connection between BP use and pelvic insufficiency fractures remains scarce. It is plausible that existing studies lack the statistical power necessary to discern an association between these atypical fractures and BPs, given that the incidence of atypical fractures is relatively low compared with the vast number of patients using the medication.^6,7

In this study, we reported the case of an atypical right femoral shaft fracture in a 36-year-old woman with a 15-year history of alendronate consumption, with microfractures in her left femur that could easily have been ignored. Clinically, it is easy for doctors to ignore similar findings. As a result, the patient was not aware of the condition and was not checked regularly to assess the left femur. We also reviewed the relevant literature and found no articles that provided clear radiographs of a patient’s bilateral femurs, in patients with atypical femoral fractures.

BP therapy has been associated with an increased rate of delayed union in up to 56% of people taking these drugs compared with no BP therapy.^8,9 There is also a significantly higher incidence in patients who receive long-term therapy and a higher incidence of non-union that necessitates additional surgery (25% vs 13% of patients; short- vs long-term therapy, respectively).^8,9 However, in this study, gradual healing of the fracture after PFNA fixation in this young patient suggests that fractures in young patients can also heal without the use of teriparatide. Studies by Zhang, ² and Peake and Trompeter ¹⁰ also confirm this hypothesis. Febrian Kunta Adjie et al. reported a rare case of a blocked intramedullary femoral canal found during surgery in an 85-year-old Indian woman with an atypical femoral shaft fracture associated with 5-year alendronate therapy. ¹¹ Niikura et al. reported a rare case of an atypical femoral fracture that occurred at the stem tip of a total hip arthroplasty that fulfilled the major criteria defined by the second American Society for Bone and Mineral Research Task Force report for an atypical femoral fracture and that was associated with prolonged BP use. ¹² Thompson et al. reported a case of an atypical femoral fracture in a female patient who had been treated with denosumab, highlighting that caution is needed before prescribing denosumab in patients with previous long-term BP therapy. ¹³ Righetti et al. reported the case of a 67-year-old woman with OP treated with alendronate for 10 years who developed bilateral femoral fractures. ¹⁴ To accelerate bone healing, teriparatide was introduced, and after 1 year of therapy, her pain and functional difficulty decreased, and alkaline phosphatase levels normalized. ¹⁴ This indicates that teriparatide may be a treatment option in adult patients with hypophosphatasia. Huang et al.’s research confirms this hypothesis. ¹⁵ However, teriparatide is expensive, which prevents many patients from receiving this drug. The risk of atypical femoral fractures increases with every additional year of use of BPs. ¹⁶ Given the potential risks associated with BP therapy, it is crucial to exercise caution in both the duration and indications for treatment. Healthcare professionals must remain vigilant and be aware of the likelihood of the uncommon adverse effects resulting from prolonged BP use. Until comprehensive long-term safety data are available, a re-evaluation of extended treatment durations should be undertaken.

Conclusion

When young patients experience atypical femoral shaft fractures, it is imperative that their unaffected femur is not overlooked. Notably, these fractures in young individuals can also heal naturally without the administration of teriparatide. Hence, healthcare professionals must maintain awareness and be vigilant about the potential for these rare adverse reactions to prolonged BP use. Until definitive long-term safety data are established, the continuation of extended BP therapy should be reconsidered.

Ethics approval was obtained from the Medical Ethics Committee of The First Affiliated Hospital of BaoTao Medical College, Inner Mongolia University of Science and Technology for the publication of this study. Verbal consent was obtained from the patient for the publication of this case report and accompanying images.