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Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures
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Original article
Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures Umut Canbek ∗ , Ulas Akgun , Nevres Hurriyet Aydogan Mugla Sitki Kocman University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Mugla, Mentese, 48000, Turkey
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Article history: Received 20 January 2019 Accepted 9 July 2019 Available online xxx Keywords: Atypical Femoral fractures Fracture healing Insufficiency fractures
a b s t r a c t Background: Delayed unions are quite common in the treatment of atypical femur fractures, which are thought to result from the long-term use of bisphosphonates. The effects of interventions for sclerotic tissue on the fracture line in atypical femoral fractures are not fully known. For this reason, we compared the results of patients with atypical femoral fractures treated by closed intramedullary nailing to patients treated by open surgery accompanied with interventions for their sclerotic bone ends, aiming to answer: (1) In the treatment of atypical femoral fractures, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? (2) Do bone-end interventions influence complication rates in the treatment of atypical femoral fractures? Hypothesis: Bone-end interventions provide a faster and higher rate of union compared to closed intramedullary nailing and result in fewer complications in atypical femoral fractures. Patients and methods: A total of 32 patients who met the inclusion criteria and had atypical femoral fractures treated by intramedullary nailing between 01/01/2012 and 12/31/2016 were reviewed. Of these, 15 fractures were treated with intramedullary nailing (Group 1), and 17 were treated with open surgery and drilling of the bone ends followed by intramedullary nailing (Group 2). Demographic data, laboratory values, radiological union times, and complications were compared between the groups. Nonunion was defined as fractures with a persistent fracture line 12 months after surgery without any sign of union. Results: A similar rate of primary union was obtained in both groups (Group 1, 13/15 [87%]; Group 2, 16/17 [94%]; p = 0.471). The mean radiological consolidation period was shorter in Group 2 (Group 1, 6.8 ± 1.8 months; Group 2, 5.1 ± 1.3 months; p = 0.004). Nonunion rates were similar between the groups (Group 1, 1/15 [7%]; Group 2, 1/17 [6%]; p = 0.927). For 1 patient in Group 1, a femoral neck fracture occurred 10 months after surgery, and a revision was performed with a long femoral stem. Discussion: In the treatment of atypical femoral fractures with intramedullary nailing, we found that the patients who were treated with open intervention of the bone ends had similar union and complication rates to those treated with closed methods, but radiological union time was found to be shorter in the open-intervention group. Level of evidence: III, retrospective case-control study. © 2019 Elsevier Masson SAS. All rights reserved.
1. Introduction In recent years, orthopedic surgeons have encountered a growing number of atypical femur fractures (AFFs), which are thought to be associated with the long-term use of bisphosphonates [1]. Although the exact pathogenesis is not completely known, it is predicted that these drugs lead to AFFs by suppressing bone remodeling and causing the accumulation of microdamage in the bone [2]. According to the American Society of Bone and Mineral
∗ Corresponding author. E-mail address: [email protected] (U. Canbek).
Research’s (ASBMR’s) 2013 case definition, AFFs are noncomminuted, transverse-oriented fractures that originate from the lateral cortex of the femur; are caused by minimal or no trauma; and have localized periosteal or endosteal thickening of the lateral cortex at the fracture site. In addition, generalized cortical thickening, prodromal symptoms, bilateralism, and delayed recovery are also minor criteria for the definition of AFFs [3]. In the treatment of AFFs with intramedullary nailing, delayed union, nonunion, and implant failures are encountered more frequently in comparison with typical femoral fractures [4,5]. Both mechanical and histological factors are thought to have a role in the development of delayed unions in AFFs [6–8]. Somford et al. found increased osteoclastic activity near an atypical fracture site
https://doi.org/10.1016/j.otsr.2019.07.028 1877-0568/© 2019 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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with low static bone formation parameters [9]. Conversely, Kajino et al. did not observe multinucleated osteoclasts in either the fracture end or the newly formed bone, and the fractured cortex was found to be extremely hard and macroscopically sclerotic [10]. Schilcher et al. examined bone biopsies from AFFs and found no evidence of cellular activity in the gap region and no bone resorption on the fracture surface despite the presence of live osteoclasts and remodeling in the adjacent fracture site [6]. Bögl et al. reported that resecting the sclerotic lateral cortex in incomplete AFFs treated with prophylactic intramedullary nailing leads to new bone formation [7]. To our knowledge, there is no comparative study examining the effects of interventions for the sclerotic tissue at the fracture site on outcomes in the treatment of complete AFFs. For this reason, we compared the results of patients with AFFs treated by closed intramedullary nailing to patients treated by open surgery accompanied with interventions for the sclerotic bone ends. We aimed to answer:
• In the treatment of AFFs, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? • Do bone-end interventions influence complication rates in the treatment of AFFs?
According to the hypothesis of this study, bone-end interventions provide a faster and higher rate of union compared to closed intramedullary nailing, resulting in fewer complications in atypical femoral fractures.
2. Patients and methods 2.1. Patients 2.1.1. Study design This study was retrospectively designed and was performed in accordance with the Declaration of Helsinki. After receiving approval from an institutional review board committee, medical records, surgical notes, laboratory results, and radiographs of patients aged > 50 years who had been treated with internal fixation for femoral fractures between 01/01/2012 and 12/31/2016 were examined, and 217 of the fractures were found to be located at the diaphyseal region. A team of 2 orthopedic surgeons and a radiologist examined these fractures according to the 2013 ASBMR case definitions, and a consensus was reached on 41 fractures that showed atypical features. After excluding fractures from the study that did not meet the inclusion criteria, 32 fractures from 32 patients were considered eligible for the analysis. The fractures were divided into two groups: those treated with closed intramedullary nailing (Group 1, n = 15) and those treated by open surgery with interventions for the sclerotic bone ends (Group 2, n = 17). The flow diagram of the patient selection process is given in Fig. 1. Several characteristics were compared between the groups. These included the mean age, gender, duration of bisphosphonate treatment, duration of hospital stay, follow-up time, body mass index, femoral neck and lumbar spine T scores, laboratory results (serum calcium, 25-OH vitamin D, parathyroid hormone, and alkaline phosphatase levels), smoking status, the presence of diabetes mellitus and proton pump inhibitor use, the presence of radiological union within a six-month postoperative period, union time, and complications (infection and nonunion).
2.1.2. Inclusion and exclusion criteria Patients aged > 50 years who were diagnosed with AFFs treated with intramedullary nailing at our hospital were included in this study. Patients also had to be compatible with the standard followup program and were followed up with for at least 24 months. Patients met the exclusion criteria if they had a follow-up duration less than 24 months or inadequate follow-up data, subtrochanteric AFFs, a previous surgery on the femur, prophylactic intramedullary nailing for an incomplete AFF, fixation with plate and screws, varus malreduction or a > 1.5 cm lateral gap after fixation, use of long-term immunosuppressive therapy, or malignancy.
2.2. Surgical procedure and follow-up At our hospital, there are four orthopedic surgeons who deal with orthopedic trauma cases, and two of them perform routine open surgery and drill bone ends (n = 9 [53%] and n = 8 [47%], consecutively), whereas the other two prefer closed intramedullary nailing (n = 9 [60%] and n = 6 [40%], consecutively) in the treatment of AFF. One g of prophylactic cefazolin was preoperatively administered to all patients. All the closed nailing procedures were performed using a traction table, under fluoroscopy control, and by the anterograde route using ≥ 12 mm diameter standard intramedullary nails (n = 7 [47%]) or cephalomedullary nails (n = 8 [53%]) based on the surgeon’s preference. All the nails were statically locked in both groups. In Group 2 patients, a 4–6 cm long posterolateral approach was used to expose the fracture without interfering with the quadriceps muscle. The thickened sclerotic region of the fracture line was drilled with a 1.5 mm drill until bleeding from the bone ends and fresh bone tissue was observed (Fig. 2). Standard antegrade intramedullary nailing (n = 9 [53%]) or cephalomedullary nailing (n = 8 [47%]) were performed based on the surgeon’s preference, and a drain was placed. Bone grafts were not used in any patient who underwent open reduction. In Group 2 patients, the drains were removed 24 hours after surgery. Patients were mobilized on postoperative day 1, and as much weight-bearing as possible was encouraged. Low-molecularweight heparin was used for the prophylaxis of deep vein thrombosis for 3 weeks. Teriparatide was not used for any patient. Daily calcium and vitamin D support was provided. None of the patients underwent low-intensity ultrasound or extracorporeal shock wave therapy. Patients were followed up with monthly X-ray examinations until radiological consolidation was observed after surgery, and radiographs were also obtained from all patients in the study at the 12-, 18-, and 24-month follow-up examinations. After 24 months, annual examinations were performed.
2.3. Methods of assessment 2.3.1. Assessment of osseous consolidation Postoperative radiographs of the patients were evaluated by two independent orthopedic surgeons without any knowledge of the surgical procedure. Consolidation was defined as cortical bridging of at least three out of four cortices visible in X-rays. Representative radiographs from each group are presented in Figs. 3 and 4.
2.3.2. Assessment of complications Patients without any signs of bone union until postoperative month 12 were considered as having nonunions. Patients who underwent revision due to nonunions or peri-implant fractures were examined. All revisions were performed with closed exchange nailing.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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Fig. 1. Flow diagram of the patient selection process.
Fig. 2. Intraoperative photographs of the proximal fragment of a right atypical femoral fracture of a 75 years old female using alendronate for 7 years. The sclerotic area of lateral cortex (a) was drilled (b) until fresh bone is exposed (c).
2.4. Statistical analysis
3. Results
The statistical analysis was performed using SPSS for Windows 22.0 (IBM Corp., Armonk, NY, USA). Continuous data were reported as means, standard deviations, and ranges. Categorical variables between the two groups were compared using Pearson’s Chi2 test, and continuous data were compared using the Mann–Whitney U-test. A p-value < 0.05 was accepted as statistically significant.
3.1. Patient characteristics All 32 patients in the study were women, and none of them had a history of smoking. The mean age of the entire group was 74 ± 6 (range: 58–84) years. The mean duration of bisphosphonate treatment was 6.9 ± 1.4 (range: 5–11) years. The patient data and laboratory results of the two groups are presented in Table 1.
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Fig. 3. Demonstration of a 70 years old female patient using alendronate for 6 years, with a right atypical femoral fracture (a). She was treated with closed intramedullary nailing and standard statically locked nail is seen in immediate postoperative radiographs (b). Adequate cortical bridging is not present 5 months after surgery (c). Union was achieved after 7 months (d). Radiographs of the same patient 24 months after surgery (e).
Fig. 4. Demonstration of a 69 years old female patient using alendronate for 8 years, with a right atypical femoral fracture (a). She was treated with open intervention to bone ends followed by standard statically locked intramedullary nail (b). Onset of callus formation is seen in radiographs 3 months after surgery (c). Adequate cortical bridging is visible 5 months after surgery (d). Radiographs of the same patient 24 months after surgery (e).
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Table 1 Characteristics of patients. Variable
Age (years) (range) Gender Male Female Duration of BP Use (years) (range) BMI (range) DXA femoral neck (range) DXA lumbar spine (range) Calcium (mg/dL) (range) 25-OH vitamin D (ng/mL) (range) Parathyroid hormone (pg/mL) (range) Alkaline phosphatase (U/L) (range) Smoking Yes No Diabetes Yes No PPI use Yes No Nail type Cephalomedullary Standard Duration of hospital stay after surgery (days) (range) Follow-up time (months) (range)
Group
p-value
Closed IMN (n = 15)
Open Intervention IMN (n = 17)
72 ± 8 (58 to 83)
75 ± 4 (69 to 84)
0/15 (0%) 15/15 (100%) 6.7 ± 1.4 (5 to 10) 26 ± 2 (22 to 31) −2.3 ± 0.7 (−3.6 to −1.2) −2.9 ± 1 (−4.9 to −1.1) 8.5 ± 0.5 (7.5 to 9.7) 26 ± 6 (17 to 41) 52 ± 17 (30 to 89) 62 ± 13 (50 to 91)
0/17 (0%) 17/17 (100%) 7.2 ± 1.5 (5 to 11) 27 ± 2 (24 to 30) −2.5 ± 0.5 (−3.5 to −1.4) −3.2 ± 0.7 (−4.1 to −1.7) 8.4 ± 0.6 (7.3 to 9.3) 21 ± 10 (5 to 39) 48 ± 18 (23 to 79) 56 ± 12 (36 to 87)
0/15 (0%) 15/15 (100%)
0/17 (0%) 17/17 (100%)
3/15 (20%) 12/15 (80%)
6/17 (35%) 11/17 (65%)
5/15 (33%) 10/15 (67%)
10/17 (59%) 7/17 (41%)
8/15 (53%) 7/15 (47%) 2.7 ± 0.6 (2 to 4)
8/17 (47%) 9/17 (53%) 2.7 ± 0.7 (2 to 4)
41 ± 10 (24 to 54)
34 ± 8 (24 to 49)
0.39 a
0.202 0.941 0.71 0.123 0.655 0.132 0.455 0.35 a
0.337
0.149
0.723
0.941
0.058
BP: Bisphosphonate; IMN: Intramedullary nail; PPI: Proton pump inhibitor. a Because of the exact same distribution of variables, no statistics were computed.
3.2. In the treatment of AFFs, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? Although there was no statistically significant difference between the union rates of patients who were treated with open surgery and closed intramedullary nailing (p = 0.471), patients treated with open surgery had shorter union times (p = 0.004), and their union rate was higher in the first 6 months (p = 0.028). The data on unions are shown in Table 2. 3.3. Do bone-end interventions influence complication rates in the treatment of AFFs? No postoperative infections were encountered in any patients. Twelve months after surgical intervention, primary union did not occur in one patient in Group 1 (7%) and one patient in Group 2 (6%). Both patients had oligotrophic nonunions after being treated with standard intramedullary nails. Both nonunions were revised with closed exchange nailing using cephalomedullary nails 12 months after index surgery. After revision, unions were observed in both Group 1 and Group 2 patients (after 6 months and after 5 months, respectively). Further, 1 patient in Group 1 (7%) showed a delayed union that presented with a femoral neck fracture 10 months after the initial surgery and received a revision with a long femoral stem and peri-prosthetic fixation implants. Fracture union had not
yet occurred 16 months after the second surgery, and another surgical intervention could not be performed due to the refusal of the patient. There were no differences in the infection rates (because none of the patients were infected, no statistics were computed), nonunion rates (p = 0.927), and peri-implant fracture rates (p = 0.279) between the two groups. 4. Discussion Recent studies have shown that similar union rates can be obtained in atypical fractures as in typical fractures with intramedullary nailing, but complications, such as delayed union and reoperation, are more frequent in AFFs [5,8,11,12]. Based on the hypothesis of our study, we predicted that an intervention on the sclerotic surfaces may contribute to union by stimulating the fracture-repair process. Therefore, we aimed to compare the outcomes of patients treated using open surgery and drilling of the bone ends with patients treated using closed intramedullary nailing. To the best of our knowledge, there is no comparative study in the literature about this topic. Both mechanical and histological factors are thought to have an effect in the pathophysiology of delayed unions in AFFs [6–8]. In their study, Lim et al. examined 109 atypical fractures and found that the long-term use of bisphosphonates, supra-isthmic fracture localization, ≥ 10◦ femoral bowing in the coronal plane, ≥ 1.4 lateral/medial cortical thickness ratio, cortical perforation
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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Primary union Yes No Union within 6 months Yes No Union time (months)(range)
Group
p-value
Closed IMN (n = 15)
Open Intervention IMN (n = 17)
13/15 (87%) 2/15 (13%)
16/17 (94%) 1/17 (6%)
8/15 (53%) 7/15 (47%) 6.8 ± 1.8 (4 to 11)
15/17 (88%) 2/17 (12%) 5.1 ± 1.3 (4 to 9)
0.471
0.028a
0.004a
IMN: Intramedullary nailing. a Indicates significant influences.
around the fracture, and ≥ 0.2 gap/lateral cortical thickness ratio after reduction were factors associated with problematic healing [8]. Considering the possible impacts on union, patients with subtrochanteric fractures, patients with varus malreduction, and patients with > 1.5 cm gap at the fracture site after reduction were excluded from the study. Thus, we aimed to evaluate the efficacy of bone-end interventions on healing in AFFs by ensuring that the mechanical properties of the groups were as similar as possible. Lee et al. [11] investigated 46 AFFs in patients treated with closed intramedullary nails and found that 96% of patients had primary unions; further, 63% of these patients had unions within 6 months, and the mean union time was 6.5 months. In the study by Lim et al. [8], the primary union rate in AFFs treated with closed intramedullary nailing was 94%, and 70% of the patients showed unions within 6 months. In our study, unions occurred within the first 6 months in 53% of the patients treated with closed intramedullary nailing. The rate of primary union was 87%, and the mean union time was 6.8 months. Although these results are slightly lower than the aforementioned studies, we believe that our results are consistent with the literature. In the group whose bone ends were drilled, unions were achieved in 88% of the patients within 6 months, the rate of primary union was 94%, and the mean union time was 5.1 months. Although there was no significant difference between two groups related to primary union rates, it was found that the union rate obtained in AFFs by intervening with the sclerotic region in the lateral cortex was slightly higher compared to closed nailing. We think that, the low power of this study to reveal a significant difference may have caused these results. However, primary unions occurred significantly faster with bone-end intervention technique than closed intramedullary nailing, and the number of patients with unions within 6 months was significantly higher in bone-end intervention group. These results partially confirm our main hypothesis. Closed intramedullary nailing is the gold-standard treatment for typical femoral fractures, as it provides more biological fixation with minimal damage to the bone [13]. However, the biology of the bone is impaired in AFFs, and the remodeling potential is suppressed [14]. Although we did not have any clear data, during the follow-up, we observed that a fracture line was still visible at the lateral cortex in some patients in the closed nailing group despite the presence of bridging in the other three cortices (Fig. 5). We believe that the lack of bridging at the lateral cortex in these patients was due to the weakness of biological activity in this region. Although the bone-end intervention with open surgery is a more invasive technique and causes much more fracture hematoma loss compared to closed IM nailing, we think that faster union times was achieved as a result of induction of fracture healing process with this method. Cephalomedullary nailing is recommended for the fixation of AFFs [8,15]. It has been reported that femoral neck fractures may occur in the future when standard intramedullary nails are used
Fig. 5. Radiographs of a patient with a left atypical femoral fracture treated with closed intramedullary nailing 24 months after surgery. A fracture line is present at the lateral cortex, despite bridging of other 3 cortices.
[4,8]. In our study, standard intramedullary nails were used in 47% of the closed group and 53% of the second group. To increase the number of patients in our study, patients treated with both types of nails were included in the study. A femoral neck fracture occurred in one (7%) patient in the closed group before union, and this was revised with a long-stem prosthesis. Considering the risk of a future femoral neck fracture, we also recommend that cephalomedullary fixation should be preferred for the treatment of AFFs. In our study, no infections occurred in either group. In each group, oligotrophic nonunion occurred in one patient. Although some authors recommend dynamization for treating AFF nonunions, many authors consider exchange nailing, with or without grafting, as a reliable method [12,16–18]. Both of our patients with oligotrophic nonunions were initially treated with standard intramedullary nails. Due to the risk of a femoral neck fracture, revisions for these patients were performed with closed exchange nailing with cephalomedullary nails, and no bone grafts were used. Unions were obtained in both patients. According to these results, it was concluded that treating AFFs through open or closed means does not have any effect on complications.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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The limitations of the present study are that it was retrospective, the operations were performed by different surgeons and some important variables such as operative time, postoperative pain levels and wound problems were not investigated. Furthermore, another limitation is that only the radiological unions of the patients were evaluated, and the functional results were not investigated. Although the distribution of intramedullary nail types used for femoral fixation and the number of patients with diabetes mellitus and smoking history between the groups was similar, there was no randomization of the methods applied, the numbers of patients in the groups were small, and the group size required to demonstrate a significant difference was not calculated. 5. Conclusions In the treatment of atypical femoral fractures with intramedullary nails, we found that patients who were treated with open interventions for the bone ends had a similar union rate and complication rate to those treated with a closed method, but the radiological union time was found to be shorter in the open-intervention group. Based on this research, we conclude that interventions for the sclerotic tissue at the bone ends of AFFs is a reasonable alternative method that should be considered in the treatment of selected patients. Ethics approval Before commencement of the study approval was received from the local institutional ethics committee and the study was performed in concordance with the Declaration of Helsinki. Disclosure of interest The authors declare that they have no competing interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Contribution of authors Umut Canbek: conception and design of the study, experimentation, acquisition of data, analysis and interpretation of data, drafting the article, final approval of the version to be submitted. Ulas Akgun: conception and design of the study, analysis and interpretation of data, drafting the article, statistics, final approval of the version to be submitted.
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Nevres Hurriyet Aydogan: conception and design of the study, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be submitted. References [1] Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res 2012;27:2544–50. [2] Stepan JJ, Burr DB, Pavo I, Sipos A, Michalska D, Li J, et al. Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosis. Bone 2007;41:378–85. [3] Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014;29:1–23. [4] Koh A, Guerado E, Giannoudis P. Atypical femoral fractures related to bisphosphonate treatment: issues and controversies related to their surgical management. Bone Joint J 2017;99:295–302. [5] Schilcher J. High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures. Injury 2015;46:2468–73. [6] Schilcher J, Sandberg O, Isaksson H, Aspenberg P. Histology of 8 atypical femoral fractures: remodeling but no healing. Acta Orthop 2014;85:280–6. [7] Bögl H, Aspenberg P, Schilcher J. Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series. Osteoporos Int 2017;28:2439–44. [8] Lim H-S, Kim C-K, Park Y-S, Moon Y-W, Lim S-J, Kim S-M. Factors associated with increased healing time in complete femoral fractures after long-term bisphosphonate therapy. J Bone Joint Surg Am 2016;98:1978–87. [9] Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res 2009;24:1736–40. [10] Kajino Y, Kabata T, Watanabe K, Tsuchiya H. Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy. J Orthop Sci 2012;17:313–8. [11] Lee K-J, Yoo JJ, Oh K-J, Yoo J-H, Rhyu KH, Nam KW, et al. Surgical outcome of intramedullary nailing in patients with complete atypical femoral fracture: a multicenter retrospective study. Injury 2017;48:941–5. [12] Bogdan Y, Tornetta III P, Einhorn TA, Guy P, Leveille L, Robinson J, et al. Healing time and complications in operatively treated atypical femur fractures associated with bisphosphonate use: a multicenter retrospective cohort. J Orthop Trauma 2016;30:177–81. [13] Ricci WM, Gallagher B, Haidukewych GJ. Intramedullary nailing of femoral shaft fractures: current concepts. J Am Acad Orthop Surg 2009;17:296–305. [14] Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000;15:613–20. [15] Larsen MS, Schmal H. The enigma of atypical femoral fractures: a summary of current knowledge. EFORT Open Rev 2018;3:494–500. [16] Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma 2011;71:186–90. [17] Teo BJ, Koh JS, Goh SK, Png MA, Chua DT, Howe TS. Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J 2014;96–b:658–64. [18] Githens M, Garner MR, Firoozabadi R. Surgical management of atypical femur fractures associated with bisphosphonate therapy. J Am Acad Orthop Surg 2018;26:864–71.
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Original article
Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures Umut Canbek ∗ , Ulas Akgun , Nevres Hurriyet Aydogan Mugla Sitki Kocman University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Mugla, Mentese, 48000, Turkey
a r t i c l e
i n f o
Article history: Received 20 January 2019 Accepted 9 July 2019 Available online xxx Keywords: Atypical Femoral fractures Fracture healing Insufficiency fractures
a b s t r a c t Background: Delayed unions are quite common in the treatment of atypical femur fractures, which are thought to result from the long-term use of bisphosphonates. The effects of interventions for sclerotic tissue on the fracture line in atypical femoral fractures are not fully known. For this reason, we compared the results of patients with atypical femoral fractures treated by closed intramedullary nailing to patients treated by open surgery accompanied with interventions for their sclerotic bone ends, aiming to answer: (1) In the treatment of atypical femoral fractures, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? (2) Do bone-end interventions influence complication rates in the treatment of atypical femoral fractures? Hypothesis: Bone-end interventions provide a faster and higher rate of union compared to closed intramedullary nailing and result in fewer complications in atypical femoral fractures. Patients and methods: A total of 32 patients who met the inclusion criteria and had atypical femoral fractures treated by intramedullary nailing between 01/01/2012 and 12/31/2016 were reviewed. Of these, 15 fractures were treated with intramedullary nailing (Group 1), and 17 were treated with open surgery and drilling of the bone ends followed by intramedullary nailing (Group 2). Demographic data, laboratory values, radiological union times, and complications were compared between the groups. Nonunion was defined as fractures with a persistent fracture line 12 months after surgery without any sign of union. Results: A similar rate of primary union was obtained in both groups (Group 1, 13/15 [87%]; Group 2, 16/17 [94%]; p = 0.471). The mean radiological consolidation period was shorter in Group 2 (Group 1, 6.8 ± 1.8 months; Group 2, 5.1 ± 1.3 months; p = 0.004). Nonunion rates were similar between the groups (Group 1, 1/15 [7%]; Group 2, 1/17 [6%]; p = 0.927). For 1 patient in Group 1, a femoral neck fracture occurred 10 months after surgery, and a revision was performed with a long femoral stem. Discussion: In the treatment of atypical femoral fractures with intramedullary nailing, we found that the patients who were treated with open intervention of the bone ends had similar union and complication rates to those treated with closed methods, but radiological union time was found to be shorter in the open-intervention group. Level of evidence: III, retrospective case-control study. © 2019 Elsevier Masson SAS. All rights reserved.
1. Introduction In recent years, orthopedic surgeons have encountered a growing number of atypical femur fractures (AFFs), which are thought to be associated with the long-term use of bisphosphonates [1]. Although the exact pathogenesis is not completely known, it is predicted that these drugs lead to AFFs by suppressing bone remodeling and causing the accumulation of microdamage in the bone [2]. According to the American Society of Bone and Mineral
∗ Corresponding author. E-mail address: [email protected] (U. Canbek).
Research’s (ASBMR’s) 2013 case definition, AFFs are noncomminuted, transverse-oriented fractures that originate from the lateral cortex of the femur; are caused by minimal or no trauma; and have localized periosteal or endosteal thickening of the lateral cortex at the fracture site. In addition, generalized cortical thickening, prodromal symptoms, bilateralism, and delayed recovery are also minor criteria for the definition of AFFs [3]. In the treatment of AFFs with intramedullary nailing, delayed union, nonunion, and implant failures are encountered more frequently in comparison with typical femoral fractures [4,5]. Both mechanical and histological factors are thought to have a role in the development of delayed unions in AFFs [6–8]. Somford et al. found increased osteoclastic activity near an atypical fracture site
https://doi.org/10.1016/j.otsr.2019.07.028 1877-0568/© 2019 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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with low static bone formation parameters [9]. Conversely, Kajino et al. did not observe multinucleated osteoclasts in either the fracture end or the newly formed bone, and the fractured cortex was found to be extremely hard and macroscopically sclerotic [10]. Schilcher et al. examined bone biopsies from AFFs and found no evidence of cellular activity in the gap region and no bone resorption on the fracture surface despite the presence of live osteoclasts and remodeling in the adjacent fracture site [6]. Bögl et al. reported that resecting the sclerotic lateral cortex in incomplete AFFs treated with prophylactic intramedullary nailing leads to new bone formation [7]. To our knowledge, there is no comparative study examining the effects of interventions for the sclerotic tissue at the fracture site on outcomes in the treatment of complete AFFs. For this reason, we compared the results of patients with AFFs treated by closed intramedullary nailing to patients treated by open surgery accompanied with interventions for the sclerotic bone ends. We aimed to answer:
• In the treatment of AFFs, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? • Do bone-end interventions influence complication rates in the treatment of AFFs?
According to the hypothesis of this study, bone-end interventions provide a faster and higher rate of union compared to closed intramedullary nailing, resulting in fewer complications in atypical femoral fractures.
2. Patients and methods 2.1. Patients 2.1.1. Study design This study was retrospectively designed and was performed in accordance with the Declaration of Helsinki. After receiving approval from an institutional review board committee, medical records, surgical notes, laboratory results, and radiographs of patients aged > 50 years who had been treated with internal fixation for femoral fractures between 01/01/2012 and 12/31/2016 were examined, and 217 of the fractures were found to be located at the diaphyseal region. A team of 2 orthopedic surgeons and a radiologist examined these fractures according to the 2013 ASBMR case definitions, and a consensus was reached on 41 fractures that showed atypical features. After excluding fractures from the study that did not meet the inclusion criteria, 32 fractures from 32 patients were considered eligible for the analysis. The fractures were divided into two groups: those treated with closed intramedullary nailing (Group 1, n = 15) and those treated by open surgery with interventions for the sclerotic bone ends (Group 2, n = 17). The flow diagram of the patient selection process is given in Fig. 1. Several characteristics were compared between the groups. These included the mean age, gender, duration of bisphosphonate treatment, duration of hospital stay, follow-up time, body mass index, femoral neck and lumbar spine T scores, laboratory results (serum calcium, 25-OH vitamin D, parathyroid hormone, and alkaline phosphatase levels), smoking status, the presence of diabetes mellitus and proton pump inhibitor use, the presence of radiological union within a six-month postoperative period, union time, and complications (infection and nonunion).
2.1.2. Inclusion and exclusion criteria Patients aged > 50 years who were diagnosed with AFFs treated with intramedullary nailing at our hospital were included in this study. Patients also had to be compatible with the standard followup program and were followed up with for at least 24 months. Patients met the exclusion criteria if they had a follow-up duration less than 24 months or inadequate follow-up data, subtrochanteric AFFs, a previous surgery on the femur, prophylactic intramedullary nailing for an incomplete AFF, fixation with plate and screws, varus malreduction or a > 1.5 cm lateral gap after fixation, use of long-term immunosuppressive therapy, or malignancy.
2.2. Surgical procedure and follow-up At our hospital, there are four orthopedic surgeons who deal with orthopedic trauma cases, and two of them perform routine open surgery and drill bone ends (n = 9 [53%] and n = 8 [47%], consecutively), whereas the other two prefer closed intramedullary nailing (n = 9 [60%] and n = 6 [40%], consecutively) in the treatment of AFF. One g of prophylactic cefazolin was preoperatively administered to all patients. All the closed nailing procedures were performed using a traction table, under fluoroscopy control, and by the anterograde route using ≥ 12 mm diameter standard intramedullary nails (n = 7 [47%]) or cephalomedullary nails (n = 8 [53%]) based on the surgeon’s preference. All the nails were statically locked in both groups. In Group 2 patients, a 4–6 cm long posterolateral approach was used to expose the fracture without interfering with the quadriceps muscle. The thickened sclerotic region of the fracture line was drilled with a 1.5 mm drill until bleeding from the bone ends and fresh bone tissue was observed (Fig. 2). Standard antegrade intramedullary nailing (n = 9 [53%]) or cephalomedullary nailing (n = 8 [47%]) were performed based on the surgeon’s preference, and a drain was placed. Bone grafts were not used in any patient who underwent open reduction. In Group 2 patients, the drains were removed 24 hours after surgery. Patients were mobilized on postoperative day 1, and as much weight-bearing as possible was encouraged. Low-molecularweight heparin was used for the prophylaxis of deep vein thrombosis for 3 weeks. Teriparatide was not used for any patient. Daily calcium and vitamin D support was provided. None of the patients underwent low-intensity ultrasound or extracorporeal shock wave therapy. Patients were followed up with monthly X-ray examinations until radiological consolidation was observed after surgery, and radiographs were also obtained from all patients in the study at the 12-, 18-, and 24-month follow-up examinations. After 24 months, annual examinations were performed.
2.3. Methods of assessment 2.3.1. Assessment of osseous consolidation Postoperative radiographs of the patients were evaluated by two independent orthopedic surgeons without any knowledge of the surgical procedure. Consolidation was defined as cortical bridging of at least three out of four cortices visible in X-rays. Representative radiographs from each group are presented in Figs. 3 and 4.
2.3.2. Assessment of complications Patients without any signs of bone union until postoperative month 12 were considered as having nonunions. Patients who underwent revision due to nonunions or peri-implant fractures were examined. All revisions were performed with closed exchange nailing.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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Fig. 1. Flow diagram of the patient selection process.
Fig. 2. Intraoperative photographs of the proximal fragment of a right atypical femoral fracture of a 75 years old female using alendronate for 7 years. The sclerotic area of lateral cortex (a) was drilled (b) until fresh bone is exposed (c).
2.4. Statistical analysis
3. Results
The statistical analysis was performed using SPSS for Windows 22.0 (IBM Corp., Armonk, NY, USA). Continuous data were reported as means, standard deviations, and ranges. Categorical variables between the two groups were compared using Pearson’s Chi2 test, and continuous data were compared using the Mann–Whitney U-test. A p-value < 0.05 was accepted as statistically significant.
3.1. Patient characteristics All 32 patients in the study were women, and none of them had a history of smoking. The mean age of the entire group was 74 ± 6 (range: 58–84) years. The mean duration of bisphosphonate treatment was 6.9 ± 1.4 (range: 5–11) years. The patient data and laboratory results of the two groups are presented in Table 1.
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Fig. 3. Demonstration of a 70 years old female patient using alendronate for 6 years, with a right atypical femoral fracture (a). She was treated with closed intramedullary nailing and standard statically locked nail is seen in immediate postoperative radiographs (b). Adequate cortical bridging is not present 5 months after surgery (c). Union was achieved after 7 months (d). Radiographs of the same patient 24 months after surgery (e).
Fig. 4. Demonstration of a 69 years old female patient using alendronate for 8 years, with a right atypical femoral fracture (a). She was treated with open intervention to bone ends followed by standard statically locked intramedullary nail (b). Onset of callus formation is seen in radiographs 3 months after surgery (c). Adequate cortical bridging is visible 5 months after surgery (d). Radiographs of the same patient 24 months after surgery (e).
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Table 1 Characteristics of patients. Variable
Age (years) (range) Gender Male Female Duration of BP Use (years) (range) BMI (range) DXA femoral neck (range) DXA lumbar spine (range) Calcium (mg/dL) (range) 25-OH vitamin D (ng/mL) (range) Parathyroid hormone (pg/mL) (range) Alkaline phosphatase (U/L) (range) Smoking Yes No Diabetes Yes No PPI use Yes No Nail type Cephalomedullary Standard Duration of hospital stay after surgery (days) (range) Follow-up time (months) (range)
Group
p-value
Closed IMN (n = 15)
Open Intervention IMN (n = 17)
72 ± 8 (58 to 83)
75 ± 4 (69 to 84)
0/15 (0%) 15/15 (100%) 6.7 ± 1.4 (5 to 10) 26 ± 2 (22 to 31) −2.3 ± 0.7 (−3.6 to −1.2) −2.9 ± 1 (−4.9 to −1.1) 8.5 ± 0.5 (7.5 to 9.7) 26 ± 6 (17 to 41) 52 ± 17 (30 to 89) 62 ± 13 (50 to 91)
0/17 (0%) 17/17 (100%) 7.2 ± 1.5 (5 to 11) 27 ± 2 (24 to 30) −2.5 ± 0.5 (−3.5 to −1.4) −3.2 ± 0.7 (−4.1 to −1.7) 8.4 ± 0.6 (7.3 to 9.3) 21 ± 10 (5 to 39) 48 ± 18 (23 to 79) 56 ± 12 (36 to 87)
0/15 (0%) 15/15 (100%)
0/17 (0%) 17/17 (100%)
3/15 (20%) 12/15 (80%)
6/17 (35%) 11/17 (65%)
5/15 (33%) 10/15 (67%)
10/17 (59%) 7/17 (41%)
8/15 (53%) 7/15 (47%) 2.7 ± 0.6 (2 to 4)
8/17 (47%) 9/17 (53%) 2.7 ± 0.7 (2 to 4)
41 ± 10 (24 to 54)
34 ± 8 (24 to 49)
0.39 a
0.202 0.941 0.71 0.123 0.655 0.132 0.455 0.35 a
0.337
0.149
0.723
0.941
0.058
BP: Bisphosphonate; IMN: Intramedullary nail; PPI: Proton pump inhibitor. a Because of the exact same distribution of variables, no statistics were computed.
3.2. In the treatment of AFFs, do bone-end interventions have a positive effect on the radiological union rate and radiological union time? Although there was no statistically significant difference between the union rates of patients who were treated with open surgery and closed intramedullary nailing (p = 0.471), patients treated with open surgery had shorter union times (p = 0.004), and their union rate was higher in the first 6 months (p = 0.028). The data on unions are shown in Table 2. 3.3. Do bone-end interventions influence complication rates in the treatment of AFFs? No postoperative infections were encountered in any patients. Twelve months after surgical intervention, primary union did not occur in one patient in Group 1 (7%) and one patient in Group 2 (6%). Both patients had oligotrophic nonunions after being treated with standard intramedullary nails. Both nonunions were revised with closed exchange nailing using cephalomedullary nails 12 months after index surgery. After revision, unions were observed in both Group 1 and Group 2 patients (after 6 months and after 5 months, respectively). Further, 1 patient in Group 1 (7%) showed a delayed union that presented with a femoral neck fracture 10 months after the initial surgery and received a revision with a long femoral stem and peri-prosthetic fixation implants. Fracture union had not
yet occurred 16 months after the second surgery, and another surgical intervention could not be performed due to the refusal of the patient. There were no differences in the infection rates (because none of the patients were infected, no statistics were computed), nonunion rates (p = 0.927), and peri-implant fracture rates (p = 0.279) between the two groups. 4. Discussion Recent studies have shown that similar union rates can be obtained in atypical fractures as in typical fractures with intramedullary nailing, but complications, such as delayed union and reoperation, are more frequent in AFFs [5,8,11,12]. Based on the hypothesis of our study, we predicted that an intervention on the sclerotic surfaces may contribute to union by stimulating the fracture-repair process. Therefore, we aimed to compare the outcomes of patients treated using open surgery and drilling of the bone ends with patients treated using closed intramedullary nailing. To the best of our knowledge, there is no comparative study in the literature about this topic. Both mechanical and histological factors are thought to have an effect in the pathophysiology of delayed unions in AFFs [6–8]. In their study, Lim et al. examined 109 atypical fractures and found that the long-term use of bisphosphonates, supra-isthmic fracture localization, ≥ 10◦ femoral bowing in the coronal plane, ≥ 1.4 lateral/medial cortical thickness ratio, cortical perforation
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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6 Table 2 Data about radiological union. Variable
Primary union Yes No Union within 6 months Yes No Union time (months)(range)
Group
p-value
Closed IMN (n = 15)
Open Intervention IMN (n = 17)
13/15 (87%) 2/15 (13%)
16/17 (94%) 1/17 (6%)
8/15 (53%) 7/15 (47%) 6.8 ± 1.8 (4 to 11)
15/17 (88%) 2/17 (12%) 5.1 ± 1.3 (4 to 9)
0.471
0.028a
0.004a
IMN: Intramedullary nailing. a Indicates significant influences.
around the fracture, and ≥ 0.2 gap/lateral cortical thickness ratio after reduction were factors associated with problematic healing [8]. Considering the possible impacts on union, patients with subtrochanteric fractures, patients with varus malreduction, and patients with > 1.5 cm gap at the fracture site after reduction were excluded from the study. Thus, we aimed to evaluate the efficacy of bone-end interventions on healing in AFFs by ensuring that the mechanical properties of the groups were as similar as possible. Lee et al. [11] investigated 46 AFFs in patients treated with closed intramedullary nails and found that 96% of patients had primary unions; further, 63% of these patients had unions within 6 months, and the mean union time was 6.5 months. In the study by Lim et al. [8], the primary union rate in AFFs treated with closed intramedullary nailing was 94%, and 70% of the patients showed unions within 6 months. In our study, unions occurred within the first 6 months in 53% of the patients treated with closed intramedullary nailing. The rate of primary union was 87%, and the mean union time was 6.8 months. Although these results are slightly lower than the aforementioned studies, we believe that our results are consistent with the literature. In the group whose bone ends were drilled, unions were achieved in 88% of the patients within 6 months, the rate of primary union was 94%, and the mean union time was 5.1 months. Although there was no significant difference between two groups related to primary union rates, it was found that the union rate obtained in AFFs by intervening with the sclerotic region in the lateral cortex was slightly higher compared to closed nailing. We think that, the low power of this study to reveal a significant difference may have caused these results. However, primary unions occurred significantly faster with bone-end intervention technique than closed intramedullary nailing, and the number of patients with unions within 6 months was significantly higher in bone-end intervention group. These results partially confirm our main hypothesis. Closed intramedullary nailing is the gold-standard treatment for typical femoral fractures, as it provides more biological fixation with minimal damage to the bone [13]. However, the biology of the bone is impaired in AFFs, and the remodeling potential is suppressed [14]. Although we did not have any clear data, during the follow-up, we observed that a fracture line was still visible at the lateral cortex in some patients in the closed nailing group despite the presence of bridging in the other three cortices (Fig. 5). We believe that the lack of bridging at the lateral cortex in these patients was due to the weakness of biological activity in this region. Although the bone-end intervention with open surgery is a more invasive technique and causes much more fracture hematoma loss compared to closed IM nailing, we think that faster union times was achieved as a result of induction of fracture healing process with this method. Cephalomedullary nailing is recommended for the fixation of AFFs [8,15]. It has been reported that femoral neck fractures may occur in the future when standard intramedullary nails are used
Fig. 5. Radiographs of a patient with a left atypical femoral fracture treated with closed intramedullary nailing 24 months after surgery. A fracture line is present at the lateral cortex, despite bridging of other 3 cortices.
[4,8]. In our study, standard intramedullary nails were used in 47% of the closed group and 53% of the second group. To increase the number of patients in our study, patients treated with both types of nails were included in the study. A femoral neck fracture occurred in one (7%) patient in the closed group before union, and this was revised with a long-stem prosthesis. Considering the risk of a future femoral neck fracture, we also recommend that cephalomedullary fixation should be preferred for the treatment of AFFs. In our study, no infections occurred in either group. In each group, oligotrophic nonunion occurred in one patient. Although some authors recommend dynamization for treating AFF nonunions, many authors consider exchange nailing, with or without grafting, as a reliable method [12,16–18]. Both of our patients with oligotrophic nonunions were initially treated with standard intramedullary nails. Due to the risk of a femoral neck fracture, revisions for these patients were performed with closed exchange nailing with cephalomedullary nails, and no bone grafts were used. Unions were obtained in both patients. According to these results, it was concluded that treating AFFs through open or closed means does not have any effect on complications.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028
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The limitations of the present study are that it was retrospective, the operations were performed by different surgeons and some important variables such as operative time, postoperative pain levels and wound problems were not investigated. Furthermore, another limitation is that only the radiological unions of the patients were evaluated, and the functional results were not investigated. Although the distribution of intramedullary nail types used for femoral fixation and the number of patients with diabetes mellitus and smoking history between the groups was similar, there was no randomization of the methods applied, the numbers of patients in the groups were small, and the group size required to demonstrate a significant difference was not calculated. 5. Conclusions In the treatment of atypical femoral fractures with intramedullary nails, we found that patients who were treated with open interventions for the bone ends had a similar union rate and complication rate to those treated with a closed method, but the radiological union time was found to be shorter in the open-intervention group. Based on this research, we conclude that interventions for the sclerotic tissue at the bone ends of AFFs is a reasonable alternative method that should be considered in the treatment of selected patients. Ethics approval Before commencement of the study approval was received from the local institutional ethics committee and the study was performed in concordance with the Declaration of Helsinki. Disclosure of interest The authors declare that they have no competing interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Contribution of authors Umut Canbek: conception and design of the study, experimentation, acquisition of data, analysis and interpretation of data, drafting the article, final approval of the version to be submitted. Ulas Akgun: conception and design of the study, analysis and interpretation of data, drafting the article, statistics, final approval of the version to be submitted.
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Nevres Hurriyet Aydogan: conception and design of the study, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be submitted. References [1] Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res 2012;27:2544–50. [2] Stepan JJ, Burr DB, Pavo I, Sipos A, Michalska D, Li J, et al. Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosis. Bone 2007;41:378–85. [3] Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014;29:1–23. [4] Koh A, Guerado E, Giannoudis P. Atypical femoral fractures related to bisphosphonate treatment: issues and controversies related to their surgical management. Bone Joint J 2017;99:295–302. [5] Schilcher J. High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures. Injury 2015;46:2468–73. [6] Schilcher J, Sandberg O, Isaksson H, Aspenberg P. Histology of 8 atypical femoral fractures: remodeling but no healing. Acta Orthop 2014;85:280–6. [7] Bögl H, Aspenberg P, Schilcher J. Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series. Osteoporos Int 2017;28:2439–44. [8] Lim H-S, Kim C-K, Park Y-S, Moon Y-W, Lim S-J, Kim S-M. Factors associated with increased healing time in complete femoral fractures after long-term bisphosphonate therapy. J Bone Joint Surg Am 2016;98:1978–87. [9] Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res 2009;24:1736–40. [10] Kajino Y, Kabata T, Watanabe K, Tsuchiya H. Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy. J Orthop Sci 2012;17:313–8. [11] Lee K-J, Yoo JJ, Oh K-J, Yoo J-H, Rhyu KH, Nam KW, et al. Surgical outcome of intramedullary nailing in patients with complete atypical femoral fracture: a multicenter retrospective study. Injury 2017;48:941–5. [12] Bogdan Y, Tornetta III P, Einhorn TA, Guy P, Leveille L, Robinson J, et al. Healing time and complications in operatively treated atypical femur fractures associated with bisphosphonate use: a multicenter retrospective cohort. J Orthop Trauma 2016;30:177–81. [13] Ricci WM, Gallagher B, Haidukewych GJ. Intramedullary nailing of femoral shaft fractures: current concepts. J Am Acad Orthop Surg 2009;17:296–305. [14] Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000;15:613–20. [15] Larsen MS, Schmal H. The enigma of atypical femoral fractures: a summary of current knowledge. EFORT Open Rev 2018;3:494–500. [16] Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma 2011;71:186–90. [17] Teo BJ, Koh JS, Goh SK, Png MA, Chua DT, Howe TS. Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J 2014;96–b:658–64. [18] Githens M, Garner MR, Firoozabadi R. Surgical management of atypical femur fractures associated with bisphosphonate therapy. J Am Acad Orthop Surg 2018;26:864–71.
Please cite this article in press as: Canbek U, et al. Efficacy of bone-end intervention on fracture healing in bisphosphonate-related atypical femoral fractures. Orthop Traumatol Surg Res (2019), https://doi.org/10.1016/j.otsr.2019.07.028