Atypical femur fractures associated with chronic bisphosphonates use: A case series with 66 patients^[*]

Abstract

Objective The present study aims to describe outcomes from a series of surgically treated patients with atypical femoral fracture due to bisphosphonates use, in addition to correlate the time of previous medication use with fracture consolidation time, and to compare the consolidation time of complete and incomplete fractures.

Methods This is an observational, retrospective study with 66 patients diagnosed with atypical femur fractures associated with chronic bisphosphonates use. The patients underwent orthopedic surgical treatment at a referral hospital from January 2018 to March 2020.

Results All patients were females, with two bilateral cases. Fracture consolidation occurred in all cases, with an average time of 2.3 months and a follow-up time of 5.8 months. The average time of bisphosphonates use was 7.8 years. There was no correlation between the time of previous bisphosphonates use and the time for fracture consolidation. Consolidation time differed in complete and incomplete fractures.

Conclusion Surgical treatment with a long cephalomedullary nail resulted in consolidation in all patients. The consolidation time was longer in complete fractures when compared with incomplete lesions, and there was no correlation between the time of previous bisphosphonates use and the consolidation time .

Level of evidence Level IV, case series

 

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Keywords

femoral fractures - bisphosphonate - osteoporosis

Introduction

Osteoporosis is defined as gradual, progressive reduction of bone mass. The main risk factors for osteoporosis include a sedentary lifestyle, alcoholism, smoking, prolonged use of corticosteroids, and a reduced calcium and vitamin D bioavailability.[1] Hip, spinal, distal radial, and proximal humeral fractures are the most associated with osteoporosis.[2] Medical treatment of osteoporosis is recommended as primary prevention for these fractures, with bisphosphonates as first-line drugs.[3]

Prolonged bisphosphonates use can result in a progressive loss of bone elastic properties,[4] representing a risk factor for atypical femoral fractures. These injuries are defined as both incomplete (affecting the lateral cortex alone) and complete (in a transverse pattern) fractures occurring between the lesser trochanter and the supracondylar region of the femur (subtrochanteric or diaphyseal fracture) after minimal trauma.[5] [6] [7] [8]

The risk for atypical fracture increases in people using oral bisphosphonates for > 3 years (average treatment, 7 years). The absolute risk in females is three times higher when compared with males, and alendronate is associated with the highest risk for atypical fractures.[5]

The literature describes good outcomes from the treatment of these fractures using intramedullary nails.[9] However, the consolidation time is often quite prolonged, potentially because bisphosphonates acts on the soft callus to suppress its remodeling.[10]

The present study aims to describe outcomes from a series of surgically treated patients with atypical femoral fractures due to bisphosphonates use, to correlate the time of previous medication use with fracture consolidation time, and to compare the consolidation time in complete and incomplete fractures.

 

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Material and Methods

This is an observational, retrospective study with 66 patients (2 bilateral cases), totaling 68 atypical femur fractures associated with chronic bisphosphonates use. The patients underwent orthopedic surgical treatment at a referral hospital from January 2018 to March 2020.

Inclusion and exclusion criteria

The following inclusion criteria were applied: 1) symptomatic complete and incomplete atypical femur fractures; 2) chronic (> 5 years) bisphosphonates use; 3) age > 60 years old.

The following exclusion criteria were applied: 1) previous or current ipsilateral osteoarticular hip infection; 2) typical femoral osteoporotic fractures (femoral neck, transtrochanteric, subtrochanteric injuries); 3) pathological fractures associated with primary or metastatic tumors and other bone conditions (for example, Paget disease or fibrous dysplasia).

 

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Data Collection, Radiographic Evaluation, and Surgical Technique

Data were collected directly from the electronic medical records of the hospital after approval by the ethics committee. Variables included gender, age, body mass index (BMI), and time of previous continuous bisphosphonates use.

Radiographic images were obtained in a standardized manner on a digital device with a predefined 100% magnification. Images were analyzed digitally with the Centricity Universal Viewer Zero Footprint software (GE Healthcare, Barrington, IL, USA). Consolidation was defined by the formation of bridge calluses in at least three cortical layers in two radiographic views (anteroposterior and lateral views), using the reliability of the radiographic union scale in tibial fractures (RUST) score expanded for femoral fracture consolidation.[11]

The lack of radiographic signs of consolidation after ≥ 6 months postoperatively was defined as pseudoarthrosis. All radiographic evaluations were performed independently by 2 orthopedists with > 5 years of experience. If there was no consensus among the evaluators, the final decision was taken by the senior researcher of the study.

All patients were submitted to surgical treatment with closed reduction on an orthopedic table, using a long cephalomedullary nail, a cephalic screw with an antirotating device and a distal locking screw ([Figure 1]).

Fig. 1 (A) Preoperative radiographic image of an atypical bilateral fracture. (B) Radiographic image 7 months after surgery.

The postoperative procedures were standardized. Partial load with a walker was allowed as tolerated starting at the 1^st postoperative day. The patients continued on motor physical therapy until fracture consolidation. Bisphosphonate therapy was suspended after fracture, and teriparatide, 20 mcg per day subcutaneously for 2 years, was indicated according to the institutional protocol. Follow-up was carried out at the outpatient clinic specialized in bone metabolism.

 

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Statistical Analysis

Categorical variables were shown as proportions, and continuous variables as mean and standard deviation (SD) values. The Wilcoxon test compared continuous nonparametric variables after distribution assessment using the Shapiro test. All statistical evaluations were performed with the open-source Stats package from the R software (R Foundation, Vienna, Austria).[12] Variables were correlated using the Pearson test.

 

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Results

All patients were females, and two cases were bilateral. The patients were followed-up on an outpatient basis until fracture consolidation, which occurred in all subjects. The average follow-up time was 5.8 months. The mean age was 78.4 years old, with a an SD value of 6.5. Most fractures occurred on the left side (56.5%). The mean BMI was 26.6, with an SD value of 2.4.

Regarding fracture location, 65% were diaphyseal injuries and 45% occurred at the subtrochanteric region of the femur. Regarding the anatomical type of fracture, there were 55 cases of atypical complete fractures (81%), mostly transverse, followed by oblique fractures and 1 case of a simple wedge fracture. There were 13 cases of atypical incomplete fractures, representing ∼ 19%.

According to the radiographic analysis using the RUST score, fracture consolidation occurred in an average period of 2.3 months, with an SD value of 1.6. Incomplete fractures consolidated on an average period of 1.4 months, while complete fractures consolidated within 2.5 months; this difference was statistically significant (p <0.05), as shown in [Figure 2].

Fig. 2 Consolidation time (in months) in complete or incomplete fractures.

There was no evidence of a correlation between the time of previous bisphosphonate use and consolidation time, since the Pearson test revealed a correlation index of 0.05 and p = 0.63.

Cortical thickening was identified in all cases. The most common bisphosphonate was alendronate (84.0%), followed by risendronate (8.7%), ibandronate (4.3%), and pamidronate and denosumab (1.5% each).

The trauma mechanism was fall from own height in most cases (82.6%); there was no history of trauma in the remaining cases. Only 26% of the patients included in the study reported pain prior to the fracture. The mean time of bisphosphonates use was 7.8 years, with an SD value of 5.7 years.

 

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Discussion

The main finding of the present study is the lack of correlation between the time of previous bisphosphonate use and the fracture consolidation time after treatment with a long cephalomedullary nail. There was a statistically significant difference in the consolidation time when complete and incomplete fractures were compared.

Intramedullary fixation has biomechanical and biological advantages over plate osteosynthesis in atypical fractures.[13] In a study, the plate failure rate was higher in atypical fractures (30%) when compared with typical fractures (0%). Patients treated with intramedullary nail presented a 98% consolidation rate, as in our study, with a long consolidation time (8.3 months).

Weil et al.[14] showed that 7 (46%) of the 17 fractures treated with a long milled intramedullary nail required a revision surgery. The high failure rate was attributed to impaired bone healing related to the prolonged bisphosphonate therapy, not to the surgical technique. In addition, these authors observed differences in consolidation time between atypical femoral fractures submitted to anatomical and nonanatomical reduction; anatomically reduced fractures healed an average of 3.7 months faster than those fixed in a varus position.

Incomplete atypical femoral fractures represent a diagnostic challenge, as patients may only experience discomfort in the thigh when walking. Thus, diagnosis is often made only in the context of a complete fracture with major associated functional limitation. A plain radiograph of the contralateral femur is recommended in patients with complete fracture.[15] [16] [17] As a result, prophylactic fixation is recommended to patients with persistent pain.

However, the decision to proceed with prophylactic surgery for an incomplete fracture is based on several factors, including the presence of a bilateral incomplete fracture, persistent pain, and a complete fracture on the opposite side. Prophylactic surgery may not be warranted in an asymptomatic patient.[18] In the present study, incomplete fractures in symptomatic patients were surgically fixed.

The literature lacks definitive evidence regarding the consolidation time in surgically treated complete and incomplete fractures. Some studies report a longer consolidation time both in conservatively treated incomplete fractures and surgically treated complete fractures. Authors attribute these findings to the biological effect of bisphosphonate and to a reduction leaving a small diastasis at the fracture focus in some cases.[17] [19] [20]

The average age described in the literature for patients with atypical femur fractures is ∼ 75 years old,[6] as in our study. Nevertheless, despite affecting elderly patients, atypical femur fractures are not associated with an increased mortality.[7]

Bisphosphonate treatment must be discontinued in patients with atypical femoral fractures.[4] [5] [15] [21] In addition, there is evidence that antiosteoporotic agents with potent bone-forming effects, such as strontium ranelate and especially teriparatide, can improve bone turnover and microarchitecture.[22] [23] After diagnosis, all patients in the present study stopped using bisphosphonate and were prescribed teriparatide.

Our study has some limitations. As it is retrospective, it suggests a potential information bias regarding data collection from medical records. In addition, the methodology employed in a single group does not allow a statistical verification of risk factors related to this type of fracture. For the future, the authors plan to assess risk factors in a case-control design and to establish a protocol for the prospective follow-up of patients with atypical fractures.

 

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Conclusion

All patients presented consolidation after surgical treatment with a long cephalomedullary nail. The consolidation time was longer for complete fractures when compared with incomplete injuries. There was no correlation between the time of previous bisphosphonate use and the consolidation time for atypical femoral fractures.

 

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Conflito de interesses

Os autores declaram não haver conflito de interesses.

^* Study developed at the Department of Orthopedics and Traumatology, Instituto Prevent Senior, São Paulo, SP, Brazil.

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Publication History

Received: 16 September 2020

Accepted: 01 December 2020

Article published online:
31 March 2021