AFFs are insufficiency fractures in stress fractures and typically characterized by prodromal symptoms [23], i.e., symptoms of pain, discomfort, weakness in the groin area or on the thigh during weight bearing in the weeks or months prior to the fracture[3, 4, 17]. In this study, 9 (9/21) patients had prodromal symptoms, mainly manifesting as pain, weakness during movement or inability to stand on one leg, and fracture(s) were discovered after seeing a doctor. AFF occurred with minor or no trauma; for No.13, the fracture occurred when turning over in bed.
On X-ray, the simple transverse fracture line was revealed. When the fracture line extends to the medial femur, it may become inclined. Complete AFF passes through two layers of cortex, potentially with small tips on the medial side. For incomplete AFF, local periosteal reactions or periosteal thickening of the lateral femoral cortex is often observed [16, 24–26]. In this study, 5 incomplete fractures were found, of which 2 were cured by conservative treatment.
Studies have shown that bilateral femoral fractures occur in 40% of AFF patients but in only 2% of patients with common fractures, and another 21% of AFF patients present with focal cortical thickening of the contralateral femur [7, 27, 28]. Sex patients (6/21) in this study had bilateral AFFs. Therefore, bilateral femoral X-rays, MRI or bone scans are recommended in unilateral AFF patients to avoid missed diagnosis of AFFs.
BPs mainly inhibit the function of osteoclasts. The long-term administration of BPs excessively inhibits bone turnover, increases bone mineral content, decreases the toughness and energy absorption capacity of bone tissue [29, 30], increases bone fragility, and decreases fracture resistance; therefore, fractures may occur even after no or minor trauma, resulting in transverse fractures [31]. In this study, there were six patients with a history of BP use for more than 5 years. The lowest T values for their hip BMD were no significant reduction, and AFF occurred when falling from a standing position. However, some patients had no definite history of trauma and only showed anterolateral pain in the thigh. AFF was found during examinations. Therefore, attention should be paid to these patients to avoid missed diagnosis.
When bone turnover is severely inhibited, the mechanisms involved in fracture union may be dysfunctional, leading to delayed union [32]. Bone turnover markers, iliac crest biopsy and fracture site biopsy have confirmed that bone remodeling is inhibited in typical BPs-related AFFs [3, 7, 33]. After fracture occurs, osteoclasts cannot participate in bone remodeling, and delay fracture union. In this study, the patient of No.17 took alendronate sodium tablets for 5.5 years and continued to take it after surgical treatment of AFF on the left side, and there was no sign of fracture union last 11 months after surgery. When alendronate sodium tablets were stopped, teriparatide was administered and the intramedullary nail was dynamized, after 8 months, the fracture healed. Our recommendation is regularly monitoring bone metabolism markers and conducting femoral MRI or bone scans during BPs treatment, allowing for the early detection and treatment of incomplete AFF [34].
Studies [16, 35] have reported AFFs, that unrelated to BPs. Lim [19] et al. studied 6644 hip fractures and found that the incidence of AFF was 2.95%, of which 24.5% did not involve a history of BPs administration. Kim [20] studied 147 patients with AFF and found that 22% of the patients had no history of BPs using. They both found that severe osteoporosis is an independent risk factor for AFFs.
The T value for hip BMD in this group of patients with severe osteoporosis was range of -4.1 to -5.2SD, involving primary osteoporosis and Secondary osteoporosis that caused by long-term administration of glucocorticoids. A patient (No.10) had X-ray examination before fracture, local periosteal thickening under the left femoral trochanter was found, and conservative treatment found that it progressed to complete AFF. Localized periosteal thickening, i.e., “beaking” or “flaring”, is one of the characteristics of AFFs, often appearing one year before the onset of AFFs [36, 37]. Therefore, the presence of “beaking” or “flaring” is indicative of the early stage of AFFs. For the combined administration of glucocorticoids and BPs, 8–10% of patients with periosteal thickening may develop AFF within two years, thus indicating that “beaking” or “flaring” is an important predictor of AFFs [36–39]. Therefore, for patients with severe osteoporosis who receive glucocorticoids long term for other disease, regular radiology examinations of the femur should be carried out to detect the occurrence of “beaking” or “flaring”, especially for those who use BPs concurrently.
In this study, four patients with hip joint dysfunction were found (6 femurs, 2 of which developed contralateral fracture after 1 year). These patients had long-term hip pain and X-ray examination of the hip showed that the hip joint degenerated seriously and the cervical shaft angle decreased significantly. At the same time, we found that the most common location of the fracture at the subtrochanteric region of the femur (5/6). It is Consider that the abnormal hip structure affects the stress distribution in the proximal femur. Taormina, D. P. [21] reported that there is an obvious relationship between the cervical shaft angle and the development of AFFs. Oh Y[22] et al. Using a computed tomography (CT)-based nonlinear finite element analysis model, showed that with a decrease in the cervical shaft angle, the tensile stress in the lateral cortex of the subtrochanteric region increased, eventually resulting in AFF. At present, there is no literature report on AFF caused by hip joint dysfunction, and more clinical cases are needed for analysis.
By this study, we found that AFF can occur when combined with abnormal femoral structure (coxa vara or abnormal the lateral FBA). Many studies[7, 40, 41] report that AFF is a stress fracture related to tension failure of the lateral femoral cortex caused by biomechanical effects over time. Yoo H[42] et al. measured the femurs of 56 individuals and suggested that the lateral FBA threshold should be 5.25°. The average value of the lateral FBA in this group was 35.4 ± 2.41 °, which was much greater than that reported in the literature. These patients often have no history of trauma. During physical examination, X-ray examination showed local cortical thickening at the apex of curvature. As time goes on osteoporosis gets worse, the tensile stress on the lateral femoral cortex and the compressive stress on the medial femoral cortex increase at the same time, daily load can lead to the fracture and opening of the lateral cortex, and then lead to complete fracture. Such patients are often accompanied by knee degeneration, and their treatment should be implemented according to the specific conditions of the patients. In this group of cases, 2 patients (3 femurs) had previously undergone total knee arthroplasty. In order not to affect the function of knee prosthesis, they were treated with plate internal fixation, combined with bone forming drugs to promote fracture healing and treat osteoporosis. Another young patient (32 years old) underwent osteotomy at the fracture end to correct the bending angle of the lateral FBA and was fixed with intramedullary nails. The fracture healed well after operation.
In short, through the comprehensive analysis of risk factors, treatment and prognosis of 21 patients (27 femurs) with AFF, in order to improve the further understanding of the disease. when the patient has prodrome or low-energy injury leading to "simple transverse" fracture, it is necessary to be alert to the possibility of AFFs. That are necessary for carefully asking about the application history of BPs and the treatment history of osteoporosis, checking the hip joint function, and evaluating the femoral structure, especially whether the opposite side has AFF at the same time. For the long-term administration of anti-osteoporosis drugs (BPs or denosumab and so on) that inhibit bone resorption, attention should be paid to the possibility of AFF. For the intravenous administration of BPs, the recommended administration time should not exceed three years, and oral administration should not exceed five years. Bone metabolism markers in patients should be evaluated regularly. If prodromal symptoms occur, the possibility of AFF should be considered, and femoral imaging examinations (including X-ray, MRI, and bone scans) should be performed. If bone scans show local nuclide abnormal concentration in the femur, care should be taken to distinguish between metastasis of local tumor foci and AFF. The treatment of AFF should be analyzed according to the patient's condition. Anti-osteoporosis is the basis for the treatment of AFFs. For patients who are suitable for conservative treatment, they must be reexamined regularly; The main surgical treatment is intramedullary fixation, and the influence of internal fixation on adjacent joints should be considered.
There are several limitations in the present study that must be appreciated when interpreting these findings. Firstly, data collection was done in a retrospective manner, with low level of evidence and a small number of cases, which requires a larger prospective clinical study. But despite this, matched groups for both treatment modalities were created to identify the main risk factors for AFF. Another, this is a some surgeons series and there might be an element of bias due to the choice of operation mode and further treatment post-operative regimen and advice about anti-osteoporosis treatment, after all, there is no unified guide for reference.