In the retrospective review of the time to union of atypical femoral fractures after surgical nailing in patients on alendronate therapy for more than 36 months, we found that discontinuation of alendronate and administration of bone-forming agents significantly shortened the time to union as compared to continuation of alendronate. We performed surgical nailing in all fractures through a closed method. Although delayed union was noted in follow-up of all fractures, we chose observation and waiting rather than performing revision surgery because 6 fractures with continuation of alendronate after surgery showed continuing callus formation as compared with previous radiographs during follow up. In addition, there were neither postoperative complications nor revision surgeries. However, Weil et al. described healing of 17 atypical femoral fractures after intramedullary nailing in only 10 (54%) patients, with 7 (46%) patients requiring revision surgery. These secondary procedures included nail dynamization in 4 cases, exchange nailing in 2, and plating in 1. They supposed the higher failure rate seen with bisphosphonate-related fractures might have been due to an impaired bone healing process rather than differences in surgical technique, and qualitative bone defects caused by prolonged bisphosphonate therapy. The authors suggested more aggressive intraoperative biologic augmentation, such as primary bone grafting, the use of human recombinant bone morphogenic protein, or treatment with systemic parathyroid hormone analogs due to apparently impaired bone metabolism associated with bisphosphonate therapy .
Atypical femoral fractures are stress fractures associated with suppression of bone remodeling induced by bisphosphonates . Delayed union in such fractures was reported in previous studies [1–3, 8, 11]. Some studies have suggested potential negative effects of bisphosphonate on the fracture healing process, leading to the suggestion that treatment should be discontinued during the healing phase [1, 8, 12, 13]. Some clinical evidence and a large body of animal data indicate bone-forming agents, such as strontium ranelate or teriparatide, may accelerate fracture healing [14–18]. An increase in biomarkers was also observed in patients with severe osteoporosis who were undergoing treatment with bone-forming agents, despite previous treatment with bisphosphonates . Bone-forming agents have been shown to expert a rapid bone anabolic effect on unhealed atypical fractures associated with chronic alendronate use [2, 3, 7]. In this study, the time to union of fractures with continuation of alendronate was longer than fractures with discontinuation of alendronate and administration of bone-forming agents after surgery. However, our finding is from regular dosage of bone-forming agents for antiosteoporosis. There is possibility that increasing the dosage of bone-forming agents could also reduce the months and increase the union at a faster space and this provides a platform to evaluate further.
We have no control group, that is, lack of fracture, which discontinued alendronate and did not received bone-forming agents after surgery. Even though previous studies have reported that bone-forming agents healed atypical fractures and even with the time course of fracture healing in our patient, we are still not certain that bone-forming agents played a primary role in the positive response to therapy or alendronate discontinuation may have played secondary roles. The bone-forming agent effects might be reduced if alendronate is discontinued, for although bone repair requires increased bone formation, remodeling is also necessary for bone repair. Odvina et al. reported delayed union with mean time 9.2 months (range 8 to 12) of 4 atypical femoral fractures despite discontinuing alendronate therapy . Visekruna et al. also reported no fracture healing after 12, 22 and 6 months after alendronate stopped in 3 atypical femoral fractures. However, Visekruna speculated that delayed union might be attributable to the fact that the patients were taking estrogen or other medications (glucocorticoids, hormone replacement therapy, or raloxifene) that might have resulted in further suppression of bone turnover . Capeci et al. treated 7 patients who sustained bilateral simultaneous or sequential fractures with femoral nailing and discontinuation of alendronate and reported uneventful healing at an average of 4 months (range, 3 to 5 months) . Alendronate therapy was discontinued at the time of the second fracture fixation in the patients with sequential fractures and at the time of injury in the patient with simultaneous fractures. The 7 patients were not taking glucocorticoids, hormone replacement therapy, or raloxifene. The normal time to fracture union in Capeci’s study is in contrast to that noted in most reports, which have shown delayed healing in these patients. However, 4 of these fractures were impending subtrochanteric stress fractures, which received prophylactic fixation and the usage of bone-forming agents or not was not documented. The time to union of fractures which the alendronate has been discontinued and no bone-forming agents have been applied seems longer than fractures with discontinuation of alendronate and administration of bone-forming agents after surgery.
The sequential femoral diaphyseal fractures revealed an interesting finding. We believed bone turnover may remain suppressed several months or years after discontinuation of alendronate. A long skeletal half-life of alendronate which impairs fracture healing has been described , but there was no evidence indicating what duration of treatment with bone-forming agents would counteract the effect of alendronate, or that bone-forming agents could prevent sequential fracture. Further study is needed for this issue.
The major limitations of this study are those inherent within a retrospective case series. This was a small number of patients with limited data available, and statistical comparison was therefore not possible. In addition, not all patients were evaluated for biomarkers as well for bone pathology.