Healing of Atypical Subtrochanteric Femur Fractures ... - IngentaConnect

ORIGINAL ARTICLE

Healing of Atypical Subtrochanteric Femur Fractures After Cephalomedullary Nailing: Which Factors Predict Union? Jae-Woo Cho, MD,* Chang-Wug Oh, MD,† Frankie Leung, MD,‡ Ki-Chul Park, MD,§ Merng Koon Wong, MD,k Ernest Kwek, MD,¶ Han-Ju Kim, MD,* and Jong-Keon Oh, MD*

Objectives: The purpose of this study was to determine the healing rate and time to union of atypical subtrochanteric fractures treated with cephalomedullary nailing.

Design: Retrospective review, descriptive, and analytic study.

Conclusions: The healing rate of atypical subtrochanteric femur fractures treated with cephalomedullary nailing is lower than that previously reported for atypical femur fractures. The quality of fracture reduction proved to be the most important factor in bony union and time to union.

Setting: Six level 1 trauma centers.

Key Words: bisphosphonate, subtrochanteric femur fracture, atypical fracture, healing, malalignment

Patients/Participants: The study included 42 patients with 48 displaced, atypical, bisphosphonate-associated subtrochanteric femur fractures who underwent surgical intervention.

Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Intervention: Cephalomedullary femur nailing. Main Outcome Measurement: The main outcome measures were radiologic healing and time to union. Results: The primary healing rate after cephalomedullary nailing of bisphosphonate-associated subtrochanteric femur fractures was 68.7% (33/48 patients). Mean time to union was 10.7 months. Malalignment was determined using the differences in neck–shaft angle (the difference between the normal side and the surgically repaired side) and sagittal angulation. These all proved to be significantly correlated with failure and delayed healing time. The cutoff points for neck–shaft angle, difference in neck–shaft angle, and sagittal angulation were 125.6, 4.4, and 5.5 degrees, respectively (receiver operating characteristic curve analysis).

Accepted for publication October 21, 2016. From the *Department of Orthopaedic Surgery, Guro Hospital, Korea University Medical Center, Seoul, Korea; †Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea; ‡Department of Orthopaedic Surgery, Queen Mary Hospital, Hong Kong, China; §Department of Orthopaedic Surgery, Hanyang University Guri Hospital, Guri-si, Korea; kDepartment of Orthopaedic Surgery, Singapore General Hospital, Singapore; and ¶Department of Orthopaedic Surgery, Tan Tock Seng Hospital, Singapore. Supported by an AOTrauma Research Grant. The authors report no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jorthotrauma. com). Reprints: Jong-Keon Oh, MD, PhD, Department of Orthopaedic Surgery, Guro Hospital, Korea University Medical Center, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea (e-mail: [email protected]). Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/BOT.0000000000000743

138

| www.jorthotrauma.com

(J Orthop Trauma 2017;31:138–145)

INTRODUCTION Bisphosphonates are commonly used for the treatment of osteoporosis, with a long history of proven efficacy.1 Bisphosphonates accumulate in the mineral portion of trabecular bone and inhibit the mevalonate pathway of cholesterol synthesis. They induce osteoclast apoptosis and thus suppress osteoclast-mediated bone resorption. This decreased bone resorption and turnover prevents bone loss and improves bone strength.2,3 Long-term bisphosphonate treatment of osteoporosis is a generally safe and effective therapy. However, long-term therapy can potentially oversuppress bone turnover. Severe and prolonged suppression of bone turnover impairs the ability of bone to remodel, eventually leading to an accumulation of microdamage and insufficiency fractures.4–6 After an initial case report in 2005, the association between long-term bisphosphonate use and atypical femur fractures was recognized and described in subsequent studies.7–9 In 2011, ParkWyllie et al10 reported 716 cases of atypical femur fractures in 205,466 long-term elderly women treated with bisphosphonates (0.3% incidence) in the Canadian population. A recent study from Japan reported a similar incidence rate.11 Furthermore, concerns about surgical treatment of atypical femur fractures have been raised. Compromised mechanical and regenerative properties of bone secondary to bisphosphonate use may result in delayed healing.12–14 In their initial report, the American Society for Bone and Mineral Research (ASBMR) noted a paucity of studies evaluating the individual surgical treatment options and outcomes after surgical intervention for atypical femur fractures.15 Both J Orthop Trauma Volume 31, Number 3, March 2017

Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

J Orthop Trauma Volume 31, Number 3, March 2017

intramedullary nailing and plate fixation have been used to treat atypical femur fractures. The outcomes for these 2 treatment options have only recently been published.16–20 The purpose of this study was to1 determine the healing rate and time to union of atypical subtrochanteric fractures treated with cephalomedullary nailing,2 evaluate the factors that may affect healing of these fractures, and3 report the complications encountered after cephalomedullary nailing. We hypothesized that healing rate after cephalomedullary nailing in atypical subtrochanteric femur fractures would be similar to that in previous reports on the healing rate of atypical femur fractures (including subtrochanteric and femoral shaft), but the healing time (time to union) would be delayed when compared with these previous reports.

PATIENTS AND METHODS Design and Setting Between January 1, 2005 and December 31, 2013, 132 suspicious, atypical femur fractures associated with bisphosphonates in patients presenting to 6 level 1 trauma centers in the Asia-Pacific region were screened for enrollment. All fractures were screened using the 2010 ASBMR task force guidelines at the time of study design and confirmed as atypical femur fractures according to an ASBMR document released in 2013.15,21 Those that included at least 4 criteria among 5 major criteria in the definition of atypical femur fracture were included in the study. Ninetyfour patients with 102 fractures were treated during this 9-year time frame. Institutional review board approval was obtained at each center.

Selection Criteria Inclusion criteria consisted of patients who (1) had a history of bisphosphonate use for more than 2 years, (2) presented with a complete atypical subtrochanteric femur fracture as defined by ASBMR radiologic criteria (transverse or short oblique fracture line, medial spike, focal lateral cortical thickening, and lack of comminution), (3) were treated with a cephalomedullary nail, and (4) had at least 1 year of follow-up postoperatively. Patients who were younger than 50 year and those who sustained high-energy injuries including open fractures were excluded. Patients treated with plate and screw constructs and those with insufficient clinical data and/or follow-up were all excluded. The final cohort included 42 patients with 48 displaced, atypical, bisphosphonate-associated subtrochanteric femur fractures.

Data Collection Data were collected using a unified case report form (CRF) from each center. The CRF consisted of patient demographics, surgical records, postoperative follow-up events, and complications. Patient demographics included age, sex, relevant medical comorbidities, smoking history, bone mineral density (BMD), type of bisphosphonate therapy, and duration of bisphosphonate use. Surgical records included the operative report for the surgical procedure, reduction Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Healing of Atypical Subtrochanteric Femur Fractures

technique, presence of reaming and amount of overreaming of the intramedullary canal, and the type of implant used. The CRF was completed retrospectively by 6 orthopaedic trauma fellowship-trained surgeons from the 6 level 1 trauma centers, using electronic medical records. The data were compiled by the primary author into a single secured file. Radiographic data included standard anteroposterior (AP) and lateral femur views. Radiographs taken preoperatively, in the immediate postoperative hospitalization period, and at 3-month intervals postoperatively were evaluated in the study. All radiographs were converted into digital files and were collected at the primary investigation center and reviewed.

Main Outcome The primary outcome in this study was radiographic healing. Successful treatment with radiographic healing was defined as callus bridging across 3 or 4 cortices within 12 months postoperatively. Failure of treatment was defined as (1) the need for a secondary procedure (dynamization, bone grafting, malunion repair, and nonunion repair) because of a lack of progression of callus formation after 6 months postoperatively, (2) the absence of callus formation after 1 year postoperatively, or (3) a complication that required additional surgery.

Radiographic Assessment Standard AP and lateral femur and hip radiographs were obtained preoperatively, in the immediate postoperative hospitalization period, and at 3, 6, 9, and 12 months postoperatively. Interval 3-month follow-up radiographs include those taken at least 12 months postoperatively and at additional intervals, until the date of final follow-up. All radiographs were retrieved to a picture archiving and communication system. Two orthopaedic trauma fellowship-trained independent observers performed radiologic assessment. The radiologic evaluation sought to (1) determine the presence of fracture healing and (2) assess the immediate postoperative radiographs for quality of reduction, distraction at the fracture site, mode of proximal and distal interlocking, and presence of iatrogenic fracture. Fracture healing was determined by a consensus of 2 observers using the criteria of callus bridging across 3 or 4 cortices and/or loss of a visible fracture line. Quality of reduction was evaluated in both the coronal and sagittal planes. Coronal alignment was evaluated by measuring the neck–shaft angle (NSA) in an AP radiograph of the hip on the injured side and the contralateral uninjured side. The difference between the 2 sides was then calculated. Sagittal alignment was calculated by the degree of angulation in the anterior cortical line of the proximal fragment, with reference to the anterior cortical line of the distal fragment in a lateral radiograph of the hip (see Figure, Supplemental Digital Content 1, http://links.lww.com/BOT/A820, which demonstrates the Radiologic measurement of quality of reduction). Malalignment was defined by more than 5 degrees of deformity in any plane.22 Distraction was defined as having no contact between the proximal and distal fragments in either the AP or lateral image. This was then measured using the greatest distance in either the AP or lateral radiograph in which www.jorthotrauma.com |

139



Cho et al

there was no contact between the major fragments. All measurements were performed on a picture archiving and communication system. Two orthopaedic trauma fellowship-trained independent observers repeated the same measurement 3 times at intervals of 7 days. The mode of proximal interlocking (spiral blade or recon screws), number of distal interlocking screws, and presence of iatrogenic fracture were also evaluated by reviewing the immediate postoperative radiographs.

Analysis To determine healing rate and time to union of atypical subtrochanteric femur fractures treated with cephalomedullary nailing, we calculated the healing rate after the index procedure and the average time for healing after the initial nailing. To evaluate healing, the data were systematically categorized as variables including patient factors (age, sex, relevant medical comorbidities, BMD, type of bisphosphonate, duration of bisphosphonate use, and smoking history), implant factors (type of cephalomedullary nail, mode of proximal interlocking, and number of distal interlocking screws), and surgical factors (quality of reduction, distraction at the fracture site, intraoperative reaming, amount of overreaming, and iatrogenic complications). Statistical analysis was performed using R software (version 2.12.0, R Foundation for statistical Computing, Vienna, Austria). To verify measurement reliability, intraobserver and interobserver error were analyzed. Univariate and multivariate logistic regression tests were used to determine factors that may influence healing. In addition, receiver operating characteristic curve analysis was performed to identify specific cutoff points for factors that influenced the clinical outcome. The Kruskal–Wallis test, Mann–Whitney test, and Spearman correlation test were performed using the variables to determine correlations between factors and healing time. A P value ,0.05 was considered statistically significant.

RESULTS See Table, Supplemental Digital Content 2, http:// links.lww.com/BOT/A821, which demonstrates patient demographics in 42 atypical subtrochanteric femur fracture patients. Among the 42 patients, 6 sustained subsequent atypical subtrochanteric femur fractures on the contralateral side. The average age was 70.2 years (range 51–88), and 41 were female. Of these, 47.6% (20 of 42) had at least 1 relevant medical comorbidity known to compromise bone healing, such as diabetes, rheumatoid arthritis, renal disease, and thyroid disease. None of the patients were current or previous smokers. The average BMD T-score was 22.1 (range 23.1 to 20.3). The mean duration of bisphosphonate therapy was 69.9 months (range, 24–148), and all patients discontinued bisphosphonates at the time of surgery. Risedronate was used by 10 patients, alendronate by 14, zoledronic acid by 7, ibandronic acid by 6, and a combination by 5.

Surgical Procedure All surgical procedures were performed by the senior surgeon at each center (Table 1).

140


The deformity of subtrochanteric femur fractures is flexion, abduction, and external rotation of the proximal fragment due to the forces of the proximal muscular attachments. When obtaining a reduction, these deforming forces must be initially neutralized. To preserve fracture site biology for healing, closed reduction on a fracture table was initially attempted. Despite this, percutaneous reduction techniques using a small incision to control the proximal fragment were required in all cases (see Figure, Supplemental Digital Content 3, http://links.lww.com/BOT/A822, which demonstrates the percutaneous reduction techniques). PFNA II nail long (DePuy Synthes), A2FN (DePuy Synthes), and Sirus nail (Zimmer) were used in 20, 23, and 5 cases, respectively. In 39 cases, the cephalomedullary nail was inserted after reaming, with an average of 1.3 mm of overreaming (range, 0.5–2.0). For proximal interlocking, a spiral blade was inserted in 20 cases and recon type interlocking screws were inserted in 28 cases. For distal interlocking, 25 cases had 1 interlocking screw placed and 23 cases had 2 or more.

TABLE 1. Details of Surgical Procedures in 48 Cases Choice of implant, n (%) PFNA II nail long (DePuy Synthes) A2FN (DePuy Synthes) Sirus nail (Zimmer) Reaming, n (%) Size of overreaming, mm (range)

20 (41) 23 (48) 5 (11) 39 (81) 1.3 (0.5–2.0)

Mode of interlocking, n (%) Proximal Blade 2 recon screws Distal 1 screw 2 or more than 2 screws Postoperative Measurement Mean NSA 127.6 degrees (119.2–134.9) Mean sagittal anterior angulation 2.37 degrees (28.0 to 15.0) Distraction No. of cases 6 (12%) Mean amount 2.1 mm (1.2–4.5)

20 (42) 28 (58) 25 (52) 23 (48) Intraobserver, ICC (95% CI)

Interobserver, ICC (95% CI)

0.90 (0.83–0.94)

0.86 (0.71–0.93)

0.95 (0.91–0.97) 0.93 (0.91–0.94)

0.87 (0.85–0.88) 0.83 (0.75–0.90)

Quality of reduction Malalignment (.5 degrees in any plane) Mean NSA, degrees Mean sagittal anterior angulation, degrees Good Mean NSA, degrees Mean sagittal anterior angulation, degrees

15 cases 125.8 (119.2–133) 7.40 (2.45–15.0) 33 cases 128.3 (121.0–134.9) 2.31 (0.1–4.7)

CI, confidence interval; ICC, intraclass correlation coefficient.

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.



The average postoperative NSA was 127.6 degrees (range, 119.2–134.9 degrees). The average sagittal angulation was 2.37 degrees of anterior angulation (range, 28.0 to 15.0 degrees). The average distraction was 2.1 mm (range, 1.2–4.5 mm) (Table 1). Quality of reduction was classified for each case as having good reduction or malalignment. Good reduction was determined as having less than 5 degrees of angulation in any plane. Thirty-three cases were classified as having good reduction. These cases had an average NSA of 128.3 degrees (range, 121–134.9 degrees) and an average sagittal angulation of 2.31 degrees (range, 0.1–4.7 degrees). Fifteen cases were classified as having malalignment. These cases had an average NSA of 125.8 degrees (range, 119.2–133 degrees) and an average sagittal angulation of 7.40 degrees (range, 2.45–15.0 degrees).

Outcomes Average patient follow-up duration was 24.2 months (range, 12–72). The primary healing rate in atypical subtrochanteric femur fractures after cephalomedullary nailing was 68.7% (33/48 cases) (Fig. 1). There were 15 cases of failure including 13 cases of delayed union and nonunion, 1 case of peri-implant fracture distally with proximal subtrochanteric fracture nonunion, and 1 case of fixation failure with subsequent subtrochanteric nonunion. Patient factors (age, sex, relevant medical comorbidities, BMD, type of bisphosphonate, and duration of bisphosphonate therapy), implant factors (type of nail, mode of proximal interlocking, and number of distal interlocking screws), and surgical factors (reaming and amount of overreaming) were not correlated with healing rate. Among surgical factors, cases classified as having malalignment (more than 5 degrees off axis in any plane) were significantly correlated with failure in healing (P , 0.010) (Table 2).


To specify the values of malalignment that were likely to fail, cutoff points were evaluated by receiver operating characteristic analysis. A restored NSA of more than 125.6 degrees (sensitivity: 66.7%, specificity: 84.8%, P = 0.0021) proved to be a significant cutoff value for healing. A difference in NSA of less than 4.4 degrees in varus angulation when compared with the contralateral hip (sensitivity: 60%, specificity: 90.91%, P = 0.0035) proved to be a significant value in predicting healing. Sagittal angulation more than 5.5 degrees (sensitivity: 60%, specificity: 93.94%, P = 0.0001) was a predictor of failure (Table 3). The average healing time after cephalomedullary nailing in atypical subtrochanteric femur fractures was 10.7 months (range, 6–12). None of the patient factors or implant factors showed a correlation with healing time. For surgical factors, cases with malalignment were correlated with delayed healing time (P = 0.01, Spearman correlation coefficient, 0.543). In addition, although unreamed nailing was statistically weak (Mann–Whitney test, P , 0.068), it proved to be clinically relevant, with these patients all having delayed healing (see Table, Supplemental Digital Content 4, http:// links.lww.com/BOT/A823, which demonstrates the statistical analysis of factors correlated with delayed union). Thirteen of 15 failures were the result of delayed union or nonunion. Early dynamization (at 6 months postoperatively) was performed in 3 cases. Autogenous bone grafting was performed in 2 cases (Fig. 2). Parathyroid hormone (PTH) therapy was initiated in 2 cases at 12 months postoperatively for delayed healing. The combination of both dynamization and PTH therapy was performed in 1 case. Observation alone for nonunion more than 12 months was performed in 5 cases. A total of 13 additional procedures for delayed union and nonunion resulted in 9 cases of healing (69%, 9/13). The remaining 2 failed cases included 1 distal periimplant fracture with subsequent proximal subtrochanteric

FIGURE 1. A, A 61-year-old female with 120 months of bisphosphonate intake history presented with an atypical subtrochanteric femur fracture after a simple fall. B, Radiologically healed at 12 months postoperatively with cephalomedullary nailing. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

www.jorthotrauma.com |

141



Cho et al

TABLE 2. Logistic Regression of Factors Associated With Failure of Cephalomedullary Nailing in Atypical Subtrochanteric Fractures Univariate Analysis Variable Patient factors Age Medical comorbidities None Unrelated conditions Conditions related to bone healing BMD Type of BP Risedronate Alendronate Zoledronic acid Ibandronic acid Combined Duration of BP Implant’s factors Type of nail PFNA II long A2FN Sirus nail Mode of proximal interlocking 2 recon screws Blade No. of distal interlocking screws 2 or more than 2 screws 1 screw Surgical factors Malalignment Distraction Reaming

Multivariate Analysis

OR

95% CI

OR

95% CI

1.0

0.96–1.05

— —

— —

1.0 2.45 2.42

Reference 0.39–15.2 0.40–14.4

1.34

0.54–3.33

— —

— —

1.21 1.32 1.08 1.17 0.98

Reference 0.64–1.56 0.81–1.84 0.93–1.12 0.56–1.47 0.96–1.01

—

—

—

—

4.09 1.47

Reference 0.40–41.6 0.14–15.7

3.00

Reference 0.85–10.6

1.58

0.51–4.83

1.72

Reference 0.21–2.48

1.41

1.07–1.86

19.9 1.754 1.88

4.23–93.9 0.77–3.98 0.19–4.16

13.74 — 1.63

1.883–100.2 — 0.62–4.1

Bolded = significant at P , 0.05. P values ,0.15 by univariate analysis were included in the multivariate logistic regression model. BP, bisphosphonate; CI, confidence interval; OR, odds ratio.

region finally healed at 22 months after the index procedure. The final case with proximal implant failure and nonunion underwent revision and plate conversion at 12 months. This second procedure developed an infected nonunion at 10 months after the plate conversion. Staged salvage operations were performed. Including additional procedures, the overall healing rate in this study increased from 69.7% to 87.5%

fracture nonunion that required revision and 1 case with proximal implant failure and nonunion. The peri-implant fracture occurred at the distal interlocking screw insertion site at 10 months postoperatively. A longer intramedullary nail was inserted for the treatment of the peri-implant fracture, with simultaneous nonunion repair of the proximal subtrochanteric fracture. This atypical fracture at the subtrochanteric TABLE 3. Cutoff Points of Malalignment by ROC Analysis Cutoff Points BMD, T-score Duration of BP, mo Restored NSA, degrees Difference in NSA, degrees Sagittal angulation, degrees

22.3 39 125.6 24.4* 5.5†

Sensitivity (95% CI) 66.7 38.5 66.7 60.0 60

(34.9–90.1) (13.9–68.4) (38.4–88.2) (32.3–83.7) (32.3–83.7)

Specificity (95% CI) 54.2 86.7 84.9 90.9 93.9

(32.8–74.4) (69.3–96.2) (68.1–94.9) (75.7–98.1) (79.8–99.3)

P 0.65 0.21 0.002 0.003 0.0001

*Negative value means varus angulation compared with contralateral side. †Positive value means flexion deformity of proximal fragment. CI, confidence interval.

142






FIGURE 2. A, A 68-year-old female with 60 months of bisphosphonate intake history presented with a right atypical subtrochanteric femur fracture. B, After cephalomedullary nailing, quality of reduction could be classified as malalignment. Autogenous bone graft was performed at postoperative 9 months because of delayed healing. C, Complete union was achieved at 18 months after the initial procedure.

(43/48 cases) (see Table, Supplemental Digital Content 5, http://links.lww.com/BOT/A824, which demonstrates the analysis of primary failure cases and healing rate after secondary intervention).

DISCUSSION Traditionally, intramedullary nailing of subtrochanteric femur fractures is the standard of care with 96% healing rate.23,24 In atypical femur fractures, a recent retrospective study demonstrated excellent clinical results with intramedullary nailing, with reported 98% healing in 41 cases.17 There have been few reports in the literature of a single treatment modality focused on a specific area of atypical femur fracture. In our multicenter retrospective study, we analyzed 48 atypical subtrochanteric femur fractures associated with bisphosphonates and treated with cephalomedullary nailing. The healing rate in these fractures was only 69%, with the remaining 31% of patients requiring additional procedures. In addition, our study helped determine the healing time of atypical subtrochanteric femur fractures after cephalomedullary nailing. Radiologic healing was observed at a mean of 10.7 months. This is significantly longer than that reported for standard subtrochanteric femur fractures, which heal at an average of 6 months.24,25 Subtrochanteric fractures have a high incidence of fracture malalignment, with difficulty obtaining and maintaining reduction. The typical subtrochanteric femur fracture deformity is flexion, abduction, and external rotation of the proximal fragment due to the forces of the proximal muscular attachments. When obtaining a reduction, these deforming forces must be initially neutralized, and the subsequent reduction needs to be maintained. Malreduction was reported in up to 21% of stable fracture patterns and up to 37% of cases of unstable fractures.22 In our study, fracture malalignment in atypical subtrochanteric fractures was present in 31% of cases (15/48). The classic atypical femur fracture has a transverse or short oblique pattern. These fracture patterns are characteristically unstable because of the decreased contact area between the main fragments, as compared to fractures with a spiral or long oblique type pattern. Achieving and maintaining fracture reduction is technically demanding. In subtrochanteric femur fractures with a normal healing potential, malreduction does not always correlate with Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

nonunion and implant failure,22,24 although anatomic reduction can improve union rates through greater bony contact and less stress on the implant. Using our definition of malalignment, the total cohort was divided into cases with good reduction (N: 33) and cases with malalignment (N: 15). Although there were no significant differences in patient factors, implant factors, and remaining surgical factors between the 2 groups, a statistically significant difference was evident in the rate of healing (88% vs. 27%, P , 0.05). Although anatomic reduction should be attempted in all cases, our findings suggest that malreduction in the treatment of atypical subtrochanteric fractures is less forgiving than in those fractures with otherwise normal bone. To create specific guidelines for reduction, our study determined significant cutoff values for measuring reduction. The cutoff value for restored NSA was 125.6 degrees (sensitivity: 66.7%, specificity: 84.8%, P = 0.0021). This meant that when the NSA was greater than 125.6 degrees, we expected successful healing in 84.8% of cases. Similarly, the cutoff value for the difference in NSA was less than 4.4 degrees of varus angulation (sensitivity: 60%, specificity: 90.91%, P = 0.0035), and we expected successful healing in 90.9% of fractures. Finally, the cutoff value for sagittal angulation was 5.5 degrees (sensitivity: 60%, specificity: 93.94%, P = 0.0001). Thus, if we restored the sagittal angulation to less than 5.5 degrees, we could have expected a 93.94% rate of healing. These findings indicate that a more accurate reduction (less than approximately 5 degrees off alignment) is needed in atypical femur subtrochanteric fractures than has been accepted for normal healing potential.26,27 Many surgical instrument tips and minimally invasive instruments have been developed to improve the reduction of subtrochanteric fractures.28–32 The authors found that the joystick method was one of the most useful techniques to control the proximal fragment. We also often used additional percutaneous reduction instruments (Hoffman retractor, Kelly clamp, ball spike pusher, pointed reduction clamp, and bone hook) to neutralize the deforming forces (Fig. 2). It is also critical to properly control the trajectory of the entry portal to avoid secondary reduction loss and malreduction.33 The limitations of our study are inherent in a retrospective case series. First, clinical indices such as serum vitamin D levels and a full list of medications were not available for all patients from the multiple centers. This makes it harder to interpret whether other factors may have influenced www.jorthotrauma.com |

143


Cho et al


outcomes. In addition, full clinical information was not adequate to evaluate clinical healing and functional outcomes. Our study design focused on radiologic healing, which could be assessed by simple radiographs. This limits the full understanding of the clinical prognosis of atypical femur subtrochanteric fractures after nailing. Second, the lack of a standardized definition of nonunion in atypical femur fractures may have influenced outcomes. Although, in our methodology, “failure” was defined as a nonunion at 1 year postoperatively, 3 of the 5 nonunion cases ended up united at the final follow-up with an average healing at 62 months (range, 18–108 months) without any surgical interventions. Furthermore, those patients who were diagnosed as a delayed union and required a secondary intervention were classified into the failure group. These second interventions included nail dynamization and more extensive procedures including bone grafting and exchange nailing. There were 2 cases in which one of the investigators tried PTH as a treatment of delayed healing. In those 2 cases, the patient and family were very reluctant to undergo a second surgical procedure, and these cases ended up with nonunion. Although these interventions could have lowered the overall healing rate that was observed for cases without intervention, they were performed at the discretion of each senior surgeon. In addition, all procedures were performed after 6 months, when there was no evidence of healing or callus formation. The mean time before a second procedure was 9.6 months (range, 6–14). Although we observed a lower healing rate (69%) than previously reported for all atypical femur fractures, the rate of healing after a second intervention was 89.6% (43/48 cases) (see Table, Supplemental Digital Content 5, http://links.lww.com/BOT/A824, which demonstrates the analysis of primary failure cases and healing rate after secondary intervention). Intermittent teriparatide administration has been reported to accelerate pelvic and distal radius fracture healing by enhancing callus formation.34,35 A recent report on 14 patients also concluded that teriparatide seems to assist in healing of atypical femur fractures and restoration of bone quality.36 These results suggest that biologic reversal by teriparatide could enhance the fracture healing in patients with compromised bone healing potential caused by long-term bisphosphonate intake. Although this would still need a prospective and large cohort size study to prove its efficacy and cost-effectiveness, adjuvant teriparatide administration after fixation of these atypical fractures could result in a better clinical outcome. In summary, bisphosphonate-associated atypical subtrochanteric femur fractures are difficult to treat. This is due to a combination of factors. The decreased healing potential from long-term bisphosphonate use, the deforming forces of the proximal segment making reduction difficult, and high stress seen in the subtrochanteric region are all contributing factors. Although cephalomedullary nailing has proven to be a good treatment option for atypical femur fractures, there is a higher rate of failure than that in subtrochanteric femur fractures with normal healing potential. There is also a higher failure rate than that in atypical fractures in other regions of the femoral shaft. Our findings suggest that accurate reduction

1. Inderjeeth CA, Foo AC, Lai MM, et al. Efficacy and safety of pharmacological agents in managing osteoporosis in the old old: review of the evidence. Bone. 2009;44:744–751. 2. Russell RG, Muhlbauer RC, Bisaz S, et al. The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomised rats. Calcif Tissue Res. 1970;6:183–196. 3. Plotkin LI, Bivi N, Bellido T. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. Bone. 2011;49: 122–127. 4. Dell RM, Adams AL, Greene DF, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012;27: 2544–2550. 5. Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J Bone Miner Res. 2013;28:1729–1737. 6. Mashiba T, Mori S, Burr DB, et al. The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab. 2005;23(suppl):36–42. 7. Schilcher J, Koeppen V, Aspenberg P, et al. Risk of atypical femoral fracture during and after bisphosphonate use: full report of a nationwide study. Acta Orthop. 2015;86:100–107. 8. Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008;358:1304–1306. 9. Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–1301. 10. Park-Wyllie LY, Mamdani MM, Juurlink DN, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011;305:783–789. 11. Saita Y, Ishijima M, Mogami A, et al. The incidence of and risk factors for developing atypical femoral fractures in Japan. J Bone Miner Metab. 2015;33:311–318. 12. Yue B, Ng A, Tang H, et al. Delayed healing of lower limb fractures with bisphosphonate therapy. Ann R Coll Surg Engl. 2015;97:333–338. 13. Cao Y, Mori S, Mashiba T, et al. Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res. 2002;17:2237–2246. 14. Fisher JE, Rogers MJ, Halasy JM, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A. 1999;96:133–138. 15. Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010;25:2267–2294. 16. Das De S, Setiobudi T, Shen L, et al. A rational approach to management of alendronate-related subtrochanteric fractures. J Bone Joint Surg Br. 2010;92:679–686. 17. Egol KA, Park JH, Rosenberg ZS, et al. Healing delayed but generally reliable after bisphosphonate-associated complete femur fractures treated with IM nails. Clin Orthop Relat Res. 2014;472:2728–2734. 18. Teo BJ, Koh JS, Goh SK, et al. Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J. 2014;96-B:658–664. 19. Weil YA, Rivkin G, Safran O, et al. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma. 2011;71:186–190. 20. Prasarn ML, Ahn J, Helfet DL, et al. Bisphosphonate-associated femur fractures have high complication rates with operative fixation. Clin Orthop Relat Res. 2012;470:2295–2301. 21. Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the

144



is essential when treating atypical subtrochanteric femur fractures with cephalomedullary nailing. REFERENCES



22. 23. 24.

25. 26.

27. 28.

American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29:1–23. Ricci WM, Bellabarba C, Lewis R, et al. Angular malalignment after intramedullary nailing of femoral shaft fractures. J Orthop Trauma. 2001;15:90–95. Wiss DA, Brien WW. Subtrochanteric fractures of the femur results of treatment by interlocking nailing. Clin Orthop Relat Res. 1992; 283:231–236. Matre K, Havelin LI, Gjertsen JE, et al. Sliding hip screw versus IM nail in reverse oblique trochanteric and subtrochanteric fractures. A study of 2716 patients in the Norwegian Hip Fracture Register. Injury. 2013;44: 735–742. Sanders R, Regazzoni P. Treatment of subtrochanteric femur fractures using the dynamic condylar screw. J Orthop Trauma. 1989;3: 206–213. Miedel R, Ponzer S, Törnkvist H, et al. The standard Gamma nail or the Medoff sliding plate for unstable trochanteric and subtrochanteric fractures A randomised, controlled trial. J Bone Joint Surg Br. 2005; 87:68–75. Thoresen B, Alho A, Ekeland A, et al. Interlocking intramedullary nailing in femoral shaft fractures. A report of forty-eight cases. J Bone Joint Surg Am. 1985;67:1313–1320. Stedtfeld HW, Mittlmeier T, Landgraf P, et al. The logic and clinical applications of blocking screws. J Bone Joint Surg Am. 2004;86:17–25.



29. Pape HC, Tarkin IS. Intraoperative reduction techniques for difficult femoral fractures. J Orthop Trauma. 2009;23:S6–S11. 30. Park J, Yang KH. Correction of malalignment in proximal femoral nailing–Reduction technique of displaced proximal fragment. Injury. 2010;41:634–638. 31. Yoon YC, Jha A, Oh CW, et al. The pointed clamp reduction technique for spiral subtrochanteric fractures: a technical note. Injury. 2014;45: 1000–1005. 32. Afsari A, Liporace F, Lindvall E, et al. Clamp-assisted reduction of high subtrochanteric fractures of the femur. J Bone Joint Surg Am. 2009;91: 1913–1918. 33. Russell TA, Mir HR, Stoneback J, et al. Avoidance of malreduction of proximal femoral shaft fractures with the use of a minimally invasive nail insertion technique (MINIT). J Orthop Trauma. 2008;22:391–398. 34. Peichl P, Holzer LA, Maier R, et al. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011;93:1583–1587. 35. Aspenberg P, Genant HK, Johansson T, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, doubleblind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res. 2010;25:404–414. 36. Chiang CY, Zebaze RMD, Ghasem-Zadeh A, et al. Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone. 2013;52:360–365.

www.jorthotrauma.com |

145
