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High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures
Injury, Int. J. Care Injured 46 (2015) 2468–2473
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures Jo¨rg Schilcher * Department of Experimental and Clinical Medicine and Department of Orthopedic Surgery, Faculty of Health Science, Linko¨ping University, Linko¨ping SE-581 85, Sweden
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 29 September 2015
Introduction: Healing of complete, atypical femoral fractures is thought to be impaired, but the evidence is weak and appears to be based on the delayed healing observed in patients with incomplete atypical fractures. Time until fracture healing is difficult to assess, therefore we compared the reoperation rates between women with complete atypical femoral fractures and common femoral shaft fractures. ¨ stergo¨tland County for patients with Methods: We searched the orthopaedic surgical registry in O subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Out of 895 patients with surgically treated femoral shaft fractures, 511 were women 50 years of age or older. Among these we identified 24 women with atypical femoral shaft fractures, and 71 with common shaft fractures. Results: Reoperations were performed in 6 and 5 patients, respectively, odds ratio 4.4 (95% CI 1.2 to 16.1). However, 5 reoperations in the atypical fracture group could not be ascribed to poor healing. In 3 patients the reoperation was due to a new fracture proximal to a standard intramedullary nail. In 2 patients the distal locking screws were removed due to callus formation that was deemed incomplete 5 months post-operatively. The one patient with poor healing showed faint callus formation at 5 months when the fracture was dynamised and callus remained sparse at 11 months. Among patients with common shaft fractures, 2 reoperations were performed to remove loose screws, 2 because of periimplant fractures and 1 reoperation due to infection. Discussion: Reoperation rates in patients with complete atypical femoral fractures are higher than in patients with common shaft fractures. The main reason for failure was peri-implant fragility fractures which might be prevented with the use of cephalomedullary nails at the index surgery. Fracture healing however, seems generally good. A watchful waiting approach is advocated in patients with fractures that appear to heal slowly. ß 2015 Elsevier Ltd. All rights reserved.
Keywords: Atypical femoral fracture Delayed healing Bisphosphonate Fracture healing
Introduction It is a common conception that atypical fractures of the femoral shaft heal poorly [1–4]. By definition, atypical fractures show a periosteal callus reaction–although small–indicating that the fracture has been present as an incomplete fracture for some time before it fractured completely with low-energy trauma [5,6]. Many patients with complete atypical fractures show incomplete fractures on the contralateral side [7], often associated with thigh pain, and atypical fractures are often preceded by prodromal pain [8]. All of this suggests that incomplete atypical
* Tel.: +46 10 1034312; fax: +46 10 1034305. E-mail address: [email protected] http://dx.doi.org/10.1016/j.injury.2015.09.031 0020–1383/ß 2015 Elsevier Ltd. All rights reserved.
fractures develop slowly before becoming complete, and that incomplete fractures have a poor ability to heal, similar to other types of stress fractures in cortical bone. There are cases of incomplete fractures that have lasted for years without healing, despite cessation of bisphosphonate treatment [5]. One possible explanation is that long-term exposure leads to severely suppressed bone turnover, which might decrease the anabolic response of the skeleton [4]. Another hypothetical explanation to the poor healing ability of incomplete fractures is based on the observation that the fracture crack is so thin, that even the slightest strain of the bone as a whole will cause disruptive strain within the crack [9–11]. This hypothesis is based on simple biomechanics [10], and one of its implications is that complete fractures would not be affected. If the hypothesis is correct, complete fractures would heal normally, since bisphosphonate treatment per se does
J. Schilcher / Injury, Int. J. Care Injured 46 (2015) 2468–2473
not affect healing of shaft fractures but only remodelling of healed fractures [12]. The notion that surgically treated complete atypical fractures heal poorly relies mainly on case reports [13,14] and case series [3,4,15,16] without a control group. Therefore, we compared the healing of complete atypical fractures with that of common fractures of the femoral shaft in women of similar age. Healing time is difficult to define and estimate, but the number of reoperations can be objectively recorded. We therefore used the reoperation rate as a surrogate measure for healing. The regional ethics review board approved the study (DNR 2014/407-31). Methods ¨ stergo¨tland We searched the orthopaedic surgical registry in O County for patients with subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Follow up data were registered until March 20th 2015. The registry contains personal identification numbers, date of surgery, diagnosis codes and treatment codes. The validity of the registry is considered high but has never been formally evaluated. We identified 895 patients with surgically treated femoral shaft fractures. Of these, 511 were women 50 years of age or older (Fig. 1) and constituted the cohort for investigation. The number of women on all types of bispho¨ stergo¨tland County was sphonates during the study period in O estimated to 3500, and the number of women, 50 years and older who were registered as residents in the County was 85 500. Inclusion criteria To identify patients with atypical femoral fractures and common fragility fractures of the femoral shaft we reviewed digitised radiographs of all patients. The classification of fracture
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types was blinded from all background information. Information on previous medical history and drug treatment was obtained from digitised medical records. Patients with primary or secondary bone tumors, metabolic disorders of the skeleton apart from osteoporosis, and those with any pre-existing hardware in the femur were excluded (Fig. 1). All fractures were associated with low energy trauma. Patients with atypical femoral fractures were identified by the radiographic pattern consisting of a transverse fracture line on the lateral side of the femoral shaft with focal thickening (callus reaction) around the fracture and no or minimal comminution, according to the American Bone and Mineral Research Taskforce major criteria, 2nd version. [1] Common fractures were defined as spiral, oblique or comminuted shaft fractures below the lesser trochanter and above the supracondylar flare. Study patients We identified 28 patients with 31 atypical femoral fractures. In patients with bilateral fractures during the study period only the first fracture was included and patients with incomplete fractures (4 patients) were not included in the analysis. The final cohort consisted of 24 patients with complete atypical femoral fractures, median age 78 years (range 62–84 years, SD 8.3 years) and 71 patients with common fractures, median age 85 years (range 50–94 years, SD 8.4 years). Patients with atypical femoral fracture used bisphosphonates more often (83%), mean duration of use 6.5 years (range 1–16 years, SD 4 years) compared to those with common shaft fractures (11%), mean duration of use 4.9 years (range 2–7 years, SD 1.9 years). The mean follow-up time for patients with atypical fractures and common shaft fractures was 3.5 years (range 8 months to 7.3 years) and 3.1 years (range, 1 month to 7.3 years).
Fig. 1. Identification of patients with atypical femoral fractures and common shaft fractures in the study population.
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Surgical procedure and implants All patients were treated according to institutional standards. Early mobilisation and full weight-bearing was advocated in the majority of patients. Intramedullary fixation was used in all patients with atypical fractures and in 63 with common shaft fractures. An intramedullary nail without separate fixation of the femoral head was used in 9 patients with atypical fractures (7 antegrade and 2 retrograde) and 11 patients with common shaft fractures (3 antegrade and 8 retrograde). Plate fixation was used in 8 patients with common shaft fractures (4 plates and 4 sliding hip screws with plates). Statistical analysis The overall data were examined by descriptive statistics for the frequencies in percentages of categorical variables and means and standard deviations for continuous variables. In a non-matched case-control analysis 24 patients with atypical fractures (cases) were compared with 71 patients with common shaft fractures (controls) using odds ratios (OR) based on cross tabulation to estimate the risk difference for reoperation among the two groups. IBM SPSS Statistics, Version 22 was used for all analyses. Results There were 6 reoperations among 24 patients with atypical fractures, all of which were treated with a bisphosphonate, and there were 5 reoperations among 71 patients with ordinary femoral fractures (Table 1; OR 4.4; 95% CI 1.2–16.1). However, 5 of the 6 reoperations in the atypical fracture group were not due to poor healing. Two of the 6 patients with atypical fracture that were reoperated had sustained a fragility fracture proximal to the initial fixation device (Fig. 2). At the time of the second surgery the index (atypical) fracture had healed in both cases. A third patient with atypical fracture sustained a peri-operative spiral fracture during index surgery. The fracture was not detected intraoperatively, and the reoperation was performed 2 weeks after the index surgery. A second reoperation was performed 20 months after the index fracture due to a fatigue fracture of the compression screw. At that time the atypical fracture had healed. The remaining 3 patients with atypical fracture underwent removal of the distal locking screws (dynamisation) to improve fracture healing. In 2 cases, this was done 5 months after index surgery, even though there was circumferential callus present at the time. The procedure was motivated by the notion that atypical fractures are ‘‘known’’ to heal poorly (this indication was verified by contacting the responsible surgeon and review of the medical record). The third patient showed delayed healing and dynamisation was performed 5 months after the index surgery, when only sparse radiographic callus was present (Fig. 3). At 11 months after the index surgery, callus remained sparse with low mineral density. The patient was given teriparatide and the fracture healed after another 4 months. This patient also suffered from rheumatoid arthritis treated with low-dose prednisolone. Healing might have been delayed by the corticosteroid, or due to periosteal stripping during the index surgery when open fracture reduction was performed and a bone biopsy was taken from the fracture surface of the distal fragment. Thus, delayed healing occurred in one out of 6 patients with atypical fracture that underwent reoperation. In the remaining patients no adjuvant therapies to enhance fracture healing were used. Among patients with atypical femoral fracture, 20 showed callus formation at the fracture site within 6 months after surgery.
The remaining 4 patients had no X-rays done within 2–6 months after surgery. One year after the end of the study period, 22 patients had radiographically healed fractures (defined as bridging callus across three or four cortices and/or no visible fracture line based on standard AP and lateral femoral radiographs). The remaining 2 patients died during the study period. Discussion To our knowledge this is the first study directly comparing reoperation rates in patients with atypical femoral fractures, treated with intramedullary nails and common fractures of the femoral shaft. A reoperation attributed to poor healing was found in only one out of 24 patients with atypical fracture. However, the overall reoperation rate was increased by 4 times. The single case of revision surgery occurred in a population of about 3500 women treated with bisphosphonates for on average 9 years. The morbidity from this reoperation was minimal. This analysis includes 2 patients that probably underwent dynamisation on a weak indication. In these cases, the decision to reoperate might have been influenced by the presumption that atypical fractures are prone to healing problems. Among the 4 remaining patients that were reoperated, 3 patients were revised due to peri-implant fragility type fractures proximal to the nail. All of these patients had initially been treated with an intramedullary nail without separate fixation of the femoral head leaving the proximal femur unprotected and with possible stress increase [17]. In these patients the atypical fracture healed uneventfully. Reoperations therefore were not directly related to the index atypical fracture but probably to the method of fixation and the underlying fragility of the patient. Probably the use of a cephalomedullary nail in the index operation, reinforcing the proximal metaphyseal bone and femoral neck of the femur, could have prevented the second fracture. Fractures of the femoral shaft treated with intramedullary devices have a generally good healing rate [18–20]. These fractures heal via the formation of an external callus and subsequent endochondral and woven bone formation. This healing process is typically not inhibited by bisphosphonate treatment. Incomplete atypical fractures are known to heal poorly or not at all. Still, increased bone turnover around the crack has been shown by histology [5]. The reason for the slow healing therefore appears to be mainly mechanical. The mechanical problems seem related to the very thin fracture gap and the strains that occur within it upon physiological loading [5]. Perren described interfragmentary strain as a variable dependent on the interfragmentary motion divided by the size of the fracture gap (Strain = Motion/Gap) [10]. The fracture gap of an incomplete fracture is very thin and therefore even minimal displacement will lead to large strains, which inhibits tissue differentiation and therefore bony union. These conditions are not present in a complete fracture. Because the bone around an atypical fracture crack is metabolically active, it is hard to conceive any plausible mechanism for impaired healing in complete fractures. Possibly, the notion that complete atypical fractures heal poorly is based on the unlikely assumption that the healing conditions are similar to those of incomplete fractures. Nevertheless, according to the American Society of Bone and Mineral Research Atypical fracture Taskforce report 2nd version, one of the minor features of atypical femoral fractures is delayed healing [1]. The definition of delayed healing is problematic since it often relies on the individual judgment of the treating surgeon rather than well-delineated criteria. Also the mean time to healing of femoral shaft fracture varies widely, and is influenced by the type and location of the fracture, type and size of the implant, reaming and numerous other factors that are difficult to control for in such a rare event as an atypical fracture. Time to union in ordinary
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Table 1 Patients requiring reoperation. CMN: cephalomedullary nail. IMN: intramedullary nail. LCP: locking compression plate (distal femur). ST: subtrochanteric fracture location. Biopsy: biopsies were taken from the fracture surface for histological analysis of the bone adjacent to the fracture [5]. Fracture-type
Age
Location
Fixation
Reason for reoperation
Comorbidity
Follow-up period
Bisphos-phonate duration
Atypical
84
ST
CMN. Biopsy
Rheumatoid arthritis; Wegener’s granulomatosis
3 years
16 years
Atypical
74
Shaft
CMN. Biopsy
8 years
73
Shaft
CMN
4 years
10 years
Atypical
92
Shaft
CMN
Hypothyroidism; Osteoporosis Hypothyroidism; Osteoporosis Osteoporosis; Hypothyroidism
3 years
Atypical
6 years
3.5 years
Atypical
80
Shaft
Antegrade IMN
Osteoporosis; Angina; Congestive heart failure
7.5 years
3 years
Atypical
78
Shaft
Antegrade IMN
Osteoporosis; Rheumatoid arthritis
6 years
10 years
Common
50
Shaft
LCP
Diabetes.
2.5 years
None
Common
87
Shaft
LCP
No relevant comorbidities
3.5 years
None
Common
89
ST
CMN
Congestive heart failure. Obesity.
4.5 years
None
Common
81
Shaft
Retrograde IMN
Dementia
1 year
None
Common
90
Shaft
Retrograde IMN
Dynamisation 5 months after the index surgery. After 11 months callus formation remained sparse and the patient was given teriparatide 20 micrograms daily for 3 months. After another 4 months callus was seen in 3 of 4 cortices on CT, symptoms had declined and the fractures was judged healed (Fig. 3). Dynamisation 5 months after the index surgery. Dynamisation 5 months after the index surgery Intertrochanteric fracture above the nail after a fall. The nail was extracted and the fracture was treated with a cemented hemiarthroplasty and cerclage wire. Peri-operative intertrochanteric fracture initially undetected. Revision surgery to cephalomedullary nail 2 weeks after the index surgery. The compression screw fractures 20 months after the index surgery and the intertrochanteric fracture remains unhealed. Re-revision is performed with a cemented total hip arthroplasty and cerclage wire. Femoral neck fracture above the nail 2 years after the index fracture (Fig. 2). The fracture is fixed with 2 sliding nails in the femoral neck, behind the intramedullary nail. Another 3 weeks later the fixation fails and all internal fixation material is removed and the femoral head excised for subsequent prosthetic replacement. The wound becomes infected and prosthetic replacement delayed. Finally the patient refrains from any further surgery. Removal of protruding screws 1 year after the index surgery. Peri-implant fracture above the Plate 2 weeks after the index surgery. The fracture is fixed with a locking compression plate and cerclage wires. Soft tissue debridement 2 weeks after the index surgery due to infection in the proximal wound. Due to chronic fistulation the nail is extracted 1.5 years after the index surgery. The fracture had healed at that time point. Removal of loose screws 2 months after the index surgery. Intertrochanteric fracture above the nail 5 years after the index surgery. The fracture was treated with removal of the IMN and fracture fixation with a dynamic hip screw and sliding plate.
No relevant comorbidities.
5 years
None
femoral shaft fractures has been reported between 16 and 36 weeks [20] and in one study 20–50% of fractures had a healing time exceeding 9 months [21]. Also the effect of dynamisation in the treatment of delayed or non-unions is weak [22–26], still it is frequently used in the treatment of suspected delayed healing. The perception of delayed healing in the case of atypical fractures might be an over-interpretation due to an increased awareness in these patients. However, this assumption is speculative and needs further investigation. The need for revision surgery can be
described with a function defined by the risk for implant failure over time and speed of healing, but also by the patience of the treating surgeon and patient. This patience might be negatively influenced when these fractures are expected to heal poorly, so that this expectation becomes a self-fulfilling prophecy. Numerous authors have reported healing complications and delayed healing in patients with atypical fractures. One study reported a reoperation rate as high as 46% with the majority of reoperations being dynamisations with removal of the distal
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Fig. 2. AP radiographs of a patient with atypical femoral fracture (a) treated with an intramedullary nail (b) and peri-implant fracture of the femoral neck (c) 2 years after the index surgery. Note the healed atypical fracture at 2 years (c). For more information on the treatment of this patient please see the table. Section C contains X-ray images of the proximal and distal femur that were superimposed digitally to form one picture (Photoshop CS6).
Fig. 3. AP radiographs of a patient with atypical fracture (a) treated with a cephalomedullary nail and excision of a bone biopsy from the distal fracture fragment (b). At 5 months post-op only minimal callus could be seen prompting to dynamise the nail (c). 9 months post-op there is bridging callus in the medial cortex but no signs of callus formation laterally (d). For more information on the treatment of this patient please see the table.
J. Schilcher / Injury, Int. J. Care Injured 46 (2015) 2468–2473
locking screws [15]. In a case series from Singapore, a reoperation rate of 30% was reported [16]. All patients had fractures in the subtrochanteric region and 7 out of 10 patients were revised due to implant failure. The use of plates instead of intramedullary fixation devices might have contributed to the high reoperation rate. Similar reasons might explain the high complication rate (44%) in the so far only comparative analysis of complication rates in surgically treated complete atypical fractures and common shaft fractures [27]. A more recent case series reported 40 of 41 atypical fractures healed within less than 18 months after the index surgery [28]. In our analysis, intramedullary nails were used in all cases, which is the recommended treatment for fractures of the femoral shaft in the subtrochanteric region and further distal in the shaft [29]. This study was performed retrospectively and the quality and duration of follow up after surgery was not standardised. Healing could not be confirmed on radiographs in all cases. However, these patients reported no symptoms indicative of healing complications, and callus was seen in all patients that had radiographs taken within 6 months from the index surgery. We did not control for other factors influencing healing such as fracture morphology or quality of reduction since the small sample size would not have allowed for corrections in the analysis. The review of each patient’s medical record and radiographs makes it unlikely that we have underestimated the amount of reoperations and healing complications. The high rates of reoperation due to peri-implant fractures and nail dynamisations on weak indications are accidental findings. These findings prompted a secondary analysis with a change of the study hypothesis from a difference in reoperation rate to a difference in reoperation rate due to poor healing. The conclusions therefore need to be interpreted with caution. Conclusion Even though we were not able to evaluate the speed of healing, the results from our study should be reassuring, and motivate a watchful waiting approach in patients with surgically treated atypical fractures that seem to heal slowly. The use of cephalomedullary nails rather than standard intramedullary nails in the fixation of atypical femoral fractures might prevent future fragility fractures in the proximal femur. Conflict of interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Acknowledgements I thank professor Per Aspenberg for discussions leading to the research idea behind this work, and for commenting on the ¨ stergo¨tland County manuscript. The study was funded by O Council, Sweden. References [1] 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.
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[2] Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, et al. Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am 2013;95:297–307. [3] Ing-Lorenzini K, Desmeules J, Plachta O, Suva D, Dayer P, Peter R. Low-energy femoral fractures associated with the long-term use of bisphosphonates. Drug Saf 2009;32:775–85. [4] Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:1294–301. [5] Schilcher J, Sandberg O, Isaksson H, Aspenberg P. Histology of 8 atypical femoral fractures: remodeling but no healing. Acta Orthop 2014;85:280–6. [6] Ettinger B, Burr DB, Ritchie RO. Proposed pathogenesis for atypical femoral fractures: lessons from materials research. Bone 2013;55:495–500. [7] Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, 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;25:2267–94. [8] Kharazmi M, Michaelsson K, Hallberg P. Prodromal symptoms in patients with bisphosphonate-associated atypical fractures of the femur. J Bone Miner Metab 2014. [9] Schilcher J. Epidemiology, radiology and histology of atypical femoral fractures. Acta Orthop Suppl 2013;84:1–26. [10] Perren SM. Physical and biological aspects of fracture healing with special reference to internal fixation. Clin Orthop Relat Res 1979;175–96. [11] Meier RPH, Lorenzini KI, Uebelhart B, Stern R, Peter RE, Rizzoli R. Atypical femoral fracture following bisphosphonate treatment in a woman with osteogenesis imperfecta—a case report. Acta Orthop 2012;83:548–50. [12] McDonald MM, Schindeler A, Little DG. Bisphosphonate treatment and fracture repair. IBMS BoneKEy 2007;4:236–51. [13] O’Neill BJ, O’H.Eireamhoin S, Morrissey DI, Keogh P. Implant failure caused by non-union of bisphosphonate-associated subtrochanteric femur fracture. BMJ Case Rep 2014;2014. [14] Schneider JP. Should bisphosphonates be continued indefinitely? An unusual fracture in a healthy woman on long-term alendronate. Geriatrics 2006;61:31–3. [15] 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. [16] 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. [17] Lee JY, Soh T, Howe TS, Koh JS, Kwek EB, Chua DT. Bisphosphonate-associated peri-implant fractures: a new clinical entity. Acta Orthop 2015;1–5. [18] van Doorn R, Stapert JW. The long gamma nail in the treatment of 329 subtrochanteric fractures with major extension into the femoral shaft. Eur J Surg 2000;166:240–6. [19] Canadian Orthopaedic Trauma Society. Nonunion following intramedullary nailing of the femur with and without reaming. Results of a multicenter randomized clinical trial. J Bone Joint Surg Am 2003;85-A:2093–6. [20] Salminen S. Femoral shaft fractures in adults: academic dissertation from the faculty of medicine. University of Helsinki 2005. [21] Clatworthy MG, Clark DI, Gray DH, Hardy AE. Reamed versus unreamed femoral nails. A randomised, prospective trial. J Bone Joint Surg Br 1998;80:485-9. [22] Wu CC, Chen WJ. Healing of 56 segmental femoral shaft fractures after locked nailing. Poor results of dynamization. Acta Orthop Scand 1997;68:537–40. [23] Brumback RJ, Uwagie-Ero S, Lakatos RP, Poka A, Bathon GH, Burgess AR. Intramedullary nailing of femoral shaft fractures. Part II: Fracture-healing with static interlocking fixation. J Bone Joint Surg Am 1988;70:1453–62. [24] Wiss DA, Fleming CH, Matta JM, Clark D. Comminuted and rotationally unstable fractures of the femur treated with an interlocking nail. Clin Orthop Relat Res 1986;3:5–47. [25] Sojbjerg JO, Eiskjaer S, Moller-Larsen F. Locked nailing of comminuted and unstable fractures of the femur. J Bone Joint Surg Br 1990;72:23–5. [26] Papakostidis C, Psyllakis I, Vardakas D, Grestas A, Giannoudis PV. Femoralshaft fractures and nonunions treated with intramedullary nails: the role of dynamisation. Injury 2011;42:1353–61. [27] Prasarn ML, Ahn J, Helfet DL, Lane JM, Lorich DG. Bisphosphonate-associated femur fractures have high complication rates with operative fixation. Clin Orthop Relat Res 2012;470:2295–301. [28] Egol KA, Park JH, Rosenberg ZS, Peck V, Tejwani NC. Healing delayed but generally reliable after bisphosphonate-associated complete femur fractures treated with IM nails. Clin Orthop Relat Res 2014;472:2728–34. [29] Roberts KC, Brox WT, Jevsevar DS, Sevarino K. Management of hip fractures in the elderly. J Am Acad Orthop Surg 2015;23:131–7.
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures Jo¨rg Schilcher * Department of Experimental and Clinical Medicine and Department of Orthopedic Surgery, Faculty of Health Science, Linko¨ping University, Linko¨ping SE-581 85, Sweden
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 29 September 2015
Introduction: Healing of complete, atypical femoral fractures is thought to be impaired, but the evidence is weak and appears to be based on the delayed healing observed in patients with incomplete atypical fractures. Time until fracture healing is difficult to assess, therefore we compared the reoperation rates between women with complete atypical femoral fractures and common femoral shaft fractures. ¨ stergo¨tland County for patients with Methods: We searched the orthopaedic surgical registry in O subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Out of 895 patients with surgically treated femoral shaft fractures, 511 were women 50 years of age or older. Among these we identified 24 women with atypical femoral shaft fractures, and 71 with common shaft fractures. Results: Reoperations were performed in 6 and 5 patients, respectively, odds ratio 4.4 (95% CI 1.2 to 16.1). However, 5 reoperations in the atypical fracture group could not be ascribed to poor healing. In 3 patients the reoperation was due to a new fracture proximal to a standard intramedullary nail. In 2 patients the distal locking screws were removed due to callus formation that was deemed incomplete 5 months post-operatively. The one patient with poor healing showed faint callus formation at 5 months when the fracture was dynamised and callus remained sparse at 11 months. Among patients with common shaft fractures, 2 reoperations were performed to remove loose screws, 2 because of periimplant fractures and 1 reoperation due to infection. Discussion: Reoperation rates in patients with complete atypical femoral fractures are higher than in patients with common shaft fractures. The main reason for failure was peri-implant fragility fractures which might be prevented with the use of cephalomedullary nails at the index surgery. Fracture healing however, seems generally good. A watchful waiting approach is advocated in patients with fractures that appear to heal slowly. ß 2015 Elsevier Ltd. All rights reserved.
Keywords: Atypical femoral fracture Delayed healing Bisphosphonate Fracture healing
Introduction It is a common conception that atypical fractures of the femoral shaft heal poorly [1–4]. By definition, atypical fractures show a periosteal callus reaction–although small–indicating that the fracture has been present as an incomplete fracture for some time before it fractured completely with low-energy trauma [5,6]. Many patients with complete atypical fractures show incomplete fractures on the contralateral side [7], often associated with thigh pain, and atypical fractures are often preceded by prodromal pain [8]. All of this suggests that incomplete atypical
* Tel.: +46 10 1034312; fax: +46 10 1034305. E-mail address: [email protected] http://dx.doi.org/10.1016/j.injury.2015.09.031 0020–1383/ß 2015 Elsevier Ltd. All rights reserved.
fractures develop slowly before becoming complete, and that incomplete fractures have a poor ability to heal, similar to other types of stress fractures in cortical bone. There are cases of incomplete fractures that have lasted for years without healing, despite cessation of bisphosphonate treatment [5]. One possible explanation is that long-term exposure leads to severely suppressed bone turnover, which might decrease the anabolic response of the skeleton [4]. Another hypothetical explanation to the poor healing ability of incomplete fractures is based on the observation that the fracture crack is so thin, that even the slightest strain of the bone as a whole will cause disruptive strain within the crack [9–11]. This hypothesis is based on simple biomechanics [10], and one of its implications is that complete fractures would not be affected. If the hypothesis is correct, complete fractures would heal normally, since bisphosphonate treatment per se does
J. Schilcher / Injury, Int. J. Care Injured 46 (2015) 2468–2473
not affect healing of shaft fractures but only remodelling of healed fractures [12]. The notion that surgically treated complete atypical fractures heal poorly relies mainly on case reports [13,14] and case series [3,4,15,16] without a control group. Therefore, we compared the healing of complete atypical fractures with that of common fractures of the femoral shaft in women of similar age. Healing time is difficult to define and estimate, but the number of reoperations can be objectively recorded. We therefore used the reoperation rate as a surrogate measure for healing. The regional ethics review board approved the study (DNR 2014/407-31). Methods ¨ stergo¨tland We searched the orthopaedic surgical registry in O County for patients with subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Follow up data were registered until March 20th 2015. The registry contains personal identification numbers, date of surgery, diagnosis codes and treatment codes. The validity of the registry is considered high but has never been formally evaluated. We identified 895 patients with surgically treated femoral shaft fractures. Of these, 511 were women 50 years of age or older (Fig. 1) and constituted the cohort for investigation. The number of women on all types of bispho¨ stergo¨tland County was sphonates during the study period in O estimated to 3500, and the number of women, 50 years and older who were registered as residents in the County was 85 500. Inclusion criteria To identify patients with atypical femoral fractures and common fragility fractures of the femoral shaft we reviewed digitised radiographs of all patients. The classification of fracture
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types was blinded from all background information. Information on previous medical history and drug treatment was obtained from digitised medical records. Patients with primary or secondary bone tumors, metabolic disorders of the skeleton apart from osteoporosis, and those with any pre-existing hardware in the femur were excluded (Fig. 1). All fractures were associated with low energy trauma. Patients with atypical femoral fractures were identified by the radiographic pattern consisting of a transverse fracture line on the lateral side of the femoral shaft with focal thickening (callus reaction) around the fracture and no or minimal comminution, according to the American Bone and Mineral Research Taskforce major criteria, 2nd version. [1] Common fractures were defined as spiral, oblique or comminuted shaft fractures below the lesser trochanter and above the supracondylar flare. Study patients We identified 28 patients with 31 atypical femoral fractures. In patients with bilateral fractures during the study period only the first fracture was included and patients with incomplete fractures (4 patients) were not included in the analysis. The final cohort consisted of 24 patients with complete atypical femoral fractures, median age 78 years (range 62–84 years, SD 8.3 years) and 71 patients with common fractures, median age 85 years (range 50–94 years, SD 8.4 years). Patients with atypical femoral fracture used bisphosphonates more often (83%), mean duration of use 6.5 years (range 1–16 years, SD 4 years) compared to those with common shaft fractures (11%), mean duration of use 4.9 years (range 2–7 years, SD 1.9 years). The mean follow-up time for patients with atypical fractures and common shaft fractures was 3.5 years (range 8 months to 7.3 years) and 3.1 years (range, 1 month to 7.3 years).
Fig. 1. Identification of patients with atypical femoral fractures and common shaft fractures in the study population.
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Surgical procedure and implants All patients were treated according to institutional standards. Early mobilisation and full weight-bearing was advocated in the majority of patients. Intramedullary fixation was used in all patients with atypical fractures and in 63 with common shaft fractures. An intramedullary nail without separate fixation of the femoral head was used in 9 patients with atypical fractures (7 antegrade and 2 retrograde) and 11 patients with common shaft fractures (3 antegrade and 8 retrograde). Plate fixation was used in 8 patients with common shaft fractures (4 plates and 4 sliding hip screws with plates). Statistical analysis The overall data were examined by descriptive statistics for the frequencies in percentages of categorical variables and means and standard deviations for continuous variables. In a non-matched case-control analysis 24 patients with atypical fractures (cases) were compared with 71 patients with common shaft fractures (controls) using odds ratios (OR) based on cross tabulation to estimate the risk difference for reoperation among the two groups. IBM SPSS Statistics, Version 22 was used for all analyses. Results There were 6 reoperations among 24 patients with atypical fractures, all of which were treated with a bisphosphonate, and there were 5 reoperations among 71 patients with ordinary femoral fractures (Table 1; OR 4.4; 95% CI 1.2–16.1). However, 5 of the 6 reoperations in the atypical fracture group were not due to poor healing. Two of the 6 patients with atypical fracture that were reoperated had sustained a fragility fracture proximal to the initial fixation device (Fig. 2). At the time of the second surgery the index (atypical) fracture had healed in both cases. A third patient with atypical fracture sustained a peri-operative spiral fracture during index surgery. The fracture was not detected intraoperatively, and the reoperation was performed 2 weeks after the index surgery. A second reoperation was performed 20 months after the index fracture due to a fatigue fracture of the compression screw. At that time the atypical fracture had healed. The remaining 3 patients with atypical fracture underwent removal of the distal locking screws (dynamisation) to improve fracture healing. In 2 cases, this was done 5 months after index surgery, even though there was circumferential callus present at the time. The procedure was motivated by the notion that atypical fractures are ‘‘known’’ to heal poorly (this indication was verified by contacting the responsible surgeon and review of the medical record). The third patient showed delayed healing and dynamisation was performed 5 months after the index surgery, when only sparse radiographic callus was present (Fig. 3). At 11 months after the index surgery, callus remained sparse with low mineral density. The patient was given teriparatide and the fracture healed after another 4 months. This patient also suffered from rheumatoid arthritis treated with low-dose prednisolone. Healing might have been delayed by the corticosteroid, or due to periosteal stripping during the index surgery when open fracture reduction was performed and a bone biopsy was taken from the fracture surface of the distal fragment. Thus, delayed healing occurred in one out of 6 patients with atypical fracture that underwent reoperation. In the remaining patients no adjuvant therapies to enhance fracture healing were used. Among patients with atypical femoral fracture, 20 showed callus formation at the fracture site within 6 months after surgery.
The remaining 4 patients had no X-rays done within 2–6 months after surgery. One year after the end of the study period, 22 patients had radiographically healed fractures (defined as bridging callus across three or four cortices and/or no visible fracture line based on standard AP and lateral femoral radiographs). The remaining 2 patients died during the study period. Discussion To our knowledge this is the first study directly comparing reoperation rates in patients with atypical femoral fractures, treated with intramedullary nails and common fractures of the femoral shaft. A reoperation attributed to poor healing was found in only one out of 24 patients with atypical fracture. However, the overall reoperation rate was increased by 4 times. The single case of revision surgery occurred in a population of about 3500 women treated with bisphosphonates for on average 9 years. The morbidity from this reoperation was minimal. This analysis includes 2 patients that probably underwent dynamisation on a weak indication. In these cases, the decision to reoperate might have been influenced by the presumption that atypical fractures are prone to healing problems. Among the 4 remaining patients that were reoperated, 3 patients were revised due to peri-implant fragility type fractures proximal to the nail. All of these patients had initially been treated with an intramedullary nail without separate fixation of the femoral head leaving the proximal femur unprotected and with possible stress increase [17]. In these patients the atypical fracture healed uneventfully. Reoperations therefore were not directly related to the index atypical fracture but probably to the method of fixation and the underlying fragility of the patient. Probably the use of a cephalomedullary nail in the index operation, reinforcing the proximal metaphyseal bone and femoral neck of the femur, could have prevented the second fracture. Fractures of the femoral shaft treated with intramedullary devices have a generally good healing rate [18–20]. These fractures heal via the formation of an external callus and subsequent endochondral and woven bone formation. This healing process is typically not inhibited by bisphosphonate treatment. Incomplete atypical fractures are known to heal poorly or not at all. Still, increased bone turnover around the crack has been shown by histology [5]. The reason for the slow healing therefore appears to be mainly mechanical. The mechanical problems seem related to the very thin fracture gap and the strains that occur within it upon physiological loading [5]. Perren described interfragmentary strain as a variable dependent on the interfragmentary motion divided by the size of the fracture gap (Strain = Motion/Gap) [10]. The fracture gap of an incomplete fracture is very thin and therefore even minimal displacement will lead to large strains, which inhibits tissue differentiation and therefore bony union. These conditions are not present in a complete fracture. Because the bone around an atypical fracture crack is metabolically active, it is hard to conceive any plausible mechanism for impaired healing in complete fractures. Possibly, the notion that complete atypical fractures heal poorly is based on the unlikely assumption that the healing conditions are similar to those of incomplete fractures. Nevertheless, according to the American Society of Bone and Mineral Research Atypical fracture Taskforce report 2nd version, one of the minor features of atypical femoral fractures is delayed healing [1]. The definition of delayed healing is problematic since it often relies on the individual judgment of the treating surgeon rather than well-delineated criteria. Also the mean time to healing of femoral shaft fracture varies widely, and is influenced by the type and location of the fracture, type and size of the implant, reaming and numerous other factors that are difficult to control for in such a rare event as an atypical fracture. Time to union in ordinary
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Table 1 Patients requiring reoperation. CMN: cephalomedullary nail. IMN: intramedullary nail. LCP: locking compression plate (distal femur). ST: subtrochanteric fracture location. Biopsy: biopsies were taken from the fracture surface for histological analysis of the bone adjacent to the fracture [5]. Fracture-type
Age
Location
Fixation
Reason for reoperation
Comorbidity
Follow-up period
Bisphos-phonate duration
Atypical
84
ST
CMN. Biopsy
Rheumatoid arthritis; Wegener’s granulomatosis
3 years
16 years
Atypical
74
Shaft
CMN. Biopsy
8 years
73
Shaft
CMN
4 years
10 years
Atypical
92
Shaft
CMN
Hypothyroidism; Osteoporosis Hypothyroidism; Osteoporosis Osteoporosis; Hypothyroidism
3 years
Atypical
6 years
3.5 years
Atypical
80
Shaft
Antegrade IMN
Osteoporosis; Angina; Congestive heart failure
7.5 years
3 years
Atypical
78
Shaft
Antegrade IMN
Osteoporosis; Rheumatoid arthritis
6 years
10 years
Common
50
Shaft
LCP
Diabetes.
2.5 years
None
Common
87
Shaft
LCP
No relevant comorbidities
3.5 years
None
Common
89
ST
CMN
Congestive heart failure. Obesity.
4.5 years
None
Common
81
Shaft
Retrograde IMN
Dementia
1 year
None
Common
90
Shaft
Retrograde IMN
Dynamisation 5 months after the index surgery. After 11 months callus formation remained sparse and the patient was given teriparatide 20 micrograms daily for 3 months. After another 4 months callus was seen in 3 of 4 cortices on CT, symptoms had declined and the fractures was judged healed (Fig. 3). Dynamisation 5 months after the index surgery. Dynamisation 5 months after the index surgery Intertrochanteric fracture above the nail after a fall. The nail was extracted and the fracture was treated with a cemented hemiarthroplasty and cerclage wire. Peri-operative intertrochanteric fracture initially undetected. Revision surgery to cephalomedullary nail 2 weeks after the index surgery. The compression screw fractures 20 months after the index surgery and the intertrochanteric fracture remains unhealed. Re-revision is performed with a cemented total hip arthroplasty and cerclage wire. Femoral neck fracture above the nail 2 years after the index fracture (Fig. 2). The fracture is fixed with 2 sliding nails in the femoral neck, behind the intramedullary nail. Another 3 weeks later the fixation fails and all internal fixation material is removed and the femoral head excised for subsequent prosthetic replacement. The wound becomes infected and prosthetic replacement delayed. Finally the patient refrains from any further surgery. Removal of protruding screws 1 year after the index surgery. Peri-implant fracture above the Plate 2 weeks after the index surgery. The fracture is fixed with a locking compression plate and cerclage wires. Soft tissue debridement 2 weeks after the index surgery due to infection in the proximal wound. Due to chronic fistulation the nail is extracted 1.5 years after the index surgery. The fracture had healed at that time point. Removal of loose screws 2 months after the index surgery. Intertrochanteric fracture above the nail 5 years after the index surgery. The fracture was treated with removal of the IMN and fracture fixation with a dynamic hip screw and sliding plate.
No relevant comorbidities.
5 years
None
femoral shaft fractures has been reported between 16 and 36 weeks [20] and in one study 20–50% of fractures had a healing time exceeding 9 months [21]. Also the effect of dynamisation in the treatment of delayed or non-unions is weak [22–26], still it is frequently used in the treatment of suspected delayed healing. The perception of delayed healing in the case of atypical fractures might be an over-interpretation due to an increased awareness in these patients. However, this assumption is speculative and needs further investigation. The need for revision surgery can be
described with a function defined by the risk for implant failure over time and speed of healing, but also by the patience of the treating surgeon and patient. This patience might be negatively influenced when these fractures are expected to heal poorly, so that this expectation becomes a self-fulfilling prophecy. Numerous authors have reported healing complications and delayed healing in patients with atypical fractures. One study reported a reoperation rate as high as 46% with the majority of reoperations being dynamisations with removal of the distal
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Fig. 2. AP radiographs of a patient with atypical femoral fracture (a) treated with an intramedullary nail (b) and peri-implant fracture of the femoral neck (c) 2 years after the index surgery. Note the healed atypical fracture at 2 years (c). For more information on the treatment of this patient please see the table. Section C contains X-ray images of the proximal and distal femur that were superimposed digitally to form one picture (Photoshop CS6).
Fig. 3. AP radiographs of a patient with atypical fracture (a) treated with a cephalomedullary nail and excision of a bone biopsy from the distal fracture fragment (b). At 5 months post-op only minimal callus could be seen prompting to dynamise the nail (c). 9 months post-op there is bridging callus in the medial cortex but no signs of callus formation laterally (d). For more information on the treatment of this patient please see the table.
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locking screws [15]. In a case series from Singapore, a reoperation rate of 30% was reported [16]. All patients had fractures in the subtrochanteric region and 7 out of 10 patients were revised due to implant failure. The use of plates instead of intramedullary fixation devices might have contributed to the high reoperation rate. Similar reasons might explain the high complication rate (44%) in the so far only comparative analysis of complication rates in surgically treated complete atypical fractures and common shaft fractures [27]. A more recent case series reported 40 of 41 atypical fractures healed within less than 18 months after the index surgery [28]. In our analysis, intramedullary nails were used in all cases, which is the recommended treatment for fractures of the femoral shaft in the subtrochanteric region and further distal in the shaft [29]. This study was performed retrospectively and the quality and duration of follow up after surgery was not standardised. Healing could not be confirmed on radiographs in all cases. However, these patients reported no symptoms indicative of healing complications, and callus was seen in all patients that had radiographs taken within 6 months from the index surgery. We did not control for other factors influencing healing such as fracture morphology or quality of reduction since the small sample size would not have allowed for corrections in the analysis. The review of each patient’s medical record and radiographs makes it unlikely that we have underestimated the amount of reoperations and healing complications. The high rates of reoperation due to peri-implant fractures and nail dynamisations on weak indications are accidental findings. These findings prompted a secondary analysis with a change of the study hypothesis from a difference in reoperation rate to a difference in reoperation rate due to poor healing. The conclusions therefore need to be interpreted with caution. Conclusion Even though we were not able to evaluate the speed of healing, the results from our study should be reassuring, and motivate a watchful waiting approach in patients with surgically treated atypical fractures that seem to heal slowly. The use of cephalomedullary nails rather than standard intramedullary nails in the fixation of atypical femoral fractures might prevent future fragility fractures in the proximal femur. Conflict of interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Acknowledgements I thank professor Per Aspenberg for discussions leading to the research idea behind this work, and for commenting on the ¨ stergo¨tland County manuscript. The study was funded by O Council, Sweden. References [1] 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.
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