Although atypical femoral fractures have been reported to be at risk of failure of healing12,15-17,19, few studies have analyzed factors affecting healing time in long-term bisphosphonate users. The present study sought to determine factors predictive of delayed union or nonunion in a consecutive series of 109 complete femoral fractures associated with long-term use of bisphosphonates. Specifically, we focused on operatively controllable factors related to fracture-healing time.
In our series of 109 fractures, 76 (69.7%) showed osseous union within 6 months after the index surgery, whereas the remaining 33 (30.3%) showed delayed union or nonunion. The overall union rate was 94.5% (103 of 109). In a previous study12 that evaluated 41 atypical low-energy femoral fractures associated with ≥5 years of bisphosphonate use, 98% (40 of 41) showed radiographic union at a mean of 8.3 months (range, 2 to 18 months). The average healing time of almost 8 months for those fractures appeared to be longer than that for typical femoral fractures, which heal at an average of 3 to 6 months.
We identified a difference in the duration of bisphosphonate use between the successful healing and problematic healing groups. A longer duration of bisphosphonate use was significantly associated with a higher rate of problematic healing, which is consistent with the results of other studies17,23. Prodromal symptoms can serve as an indicator of impending fracture associated with long-term use of bisphosphonates24. However, there are limited data regarding the relationship between prodromal symptoms and the healing time of these fractures. Moreover, it is uncertain whether longer prodromal symptoms are associated with the changes in radiographic features, including increase in the cortical thickness.
Bisphosphonate-associated complete femoral fractures have been reported to have high complication rates with operative fixation13,16,17. Prasarn et al.15 concluded that the higher complication rate in bisphosphonate-associated fractures was primarily attributable to cortical breakage during nail insertion (5 of 17, 29%) and postoperative plate failure (3 of 10, 30%). In our series, iatrogenic cortical breakage around the fracture site occurred in 5 fractures, of which 4 showed delayed union. Asians have differences in femoral geometry, with higher rates of bowing, compared with Western populations17. Some authors have suggested that increased femoral bowing might be an important causative factor for low-energy diaphyseal femoral fractures19,26. In the present study, coronal bowing of the femur was more severe in the problematic healing group compared with the successful healing group, suggesting that the severity of femoral bowing may contribute to the high rate of delayed union.
With intramedullary nailing of atypical fractures, there are concerns regarding the later occurrence of a femoral neck fracture or cortical perforation distal to the fracture site. We believe that cephalomedullary screw insertion through the proximal portion of the nail could be advantageous, not only to prevent femoral neck fracture but also to obtain more rigid fixation. However, this type of nail was not used in our series. We attempted to insert nails that were as long as possible and statically locked to secure sufficient working length and thus acquire firm fixation. However, in an excessively bowed femur, there may be a risk of cortical perforation distal to the fracture site.
There has been no definitive conclusion regarding the optimal entry point of the nail (piriformis versus trochanteric starting point) in surgical treatment of atypical femoral fractures. The mismatch of curvature between the implant and femur makes it difficult to pass the nail into the medullary canal. In a case report27, a good result was achieved after fixation with a trochanteric starting nail of the opposite curvature. In our series, piriformis nails starting in the tip of the greater trochanter were used to reduce the risk of cortical perforation.
It has become widely accepted that tensile strain increase in focally thickened anterolateral cortex locations precedes an atypical femoral fracture26,28. In the present study, delayed union or nonunion occurred primarily at anteriorly or laterally thickened cortex at the fracture site. Thus, we believe that reducing the anterior and lateral fracture gaps as much as possible during surgery is critical to achieving osseous union. Intraoperative anatomical or valgus reduction of the femur is required to reduce the lateral fracture gap. In a retrospective series of surgically treated atypical fractures, varus malreduction at the fracture site negatively affected fracture-healing12. In our study, the remaining fracture gap was measured on radiographs in more detail in 4 locations (anterior, posterior, medial, and lateral). We focused not only on the absolute gap size but also on the relative ratio of gap size to cortical thickness because the cortical thickness at the fracture site was found to be associated with healing time. Anterior and lateral fracture gap sizes divided by cortical thickness were independent predictive factors for delayed union or nonunion.
This study has some limitations. First, the number of patients was limited. It is not easy to recruit a large sample of patients with a relatively rare injury. However, investigation of the available studies on the surgical outcome of such an injury revealed that the current study is one of the largest single-center series. Second, the retrospective nature of this study results in an inherent risk of observer bias, including the potential for missing data and inability to control confounding variables. We performed 46 statistical comparisons. Although an alpha level of 5% is known to represent an appropriate value for a single comparison, it may not be appropriate when numerous comparisons are performed. Third, we did not evaluate functional outcomes. Egol et al.12 reported that 66% of patients with surgically treated complete atypical fractures became pain-free, and pain combined with apprehension was a major cause of functional limitations in the remaining patients. Lastly, PTH (parathyroid hormone) 1-34 was not used in this study. The termination of the bisphosphonates and the addition of that agent could have changed some of the healing results. In addition, we did not investigate calcium and vitamin-D treatment and the possible role of low vitamin D in those with poor healing.
In conclusion, 30.3% of all patients with operatively treated complete femoral fractures associated with long-term use of bisphosphonates had delayed union or nonunion. Supra-isthmic fracture location, femoral bowing of ≥10° in the coronal plane, and a lateral/medial cortical thickness ratio of ≥1.4 were predictive of problematic healing but were uncontrollable. Cortical breakage around the fracture site and a ratio of remaining gap to cortical thickness of ≥0.2 on the anterior and lateral sides of the fracture sites were operatively controllable predictive factors associated with problematic healing. Our data suggest that intramedullary nailing without cortical breakage around the fracture site and decreasing the anterior and lateral fracture gaps as much as possible (minimal fracture distraction) could be helpful in reducing healing time in complete femoral fractures associated with long-term bisphosphonate use.
Investigation performed at the Department of Orthopaedic Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
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