Abstract. Background. Atypical femur fracture (AFF) is a well known complication of Bisphosphonate therapy. Due to prolonged suppression of bone re-modelling in these fractures, surgical complications are difficult to manage. The aim of this study was to analyze the causes of surgical complications in AFF fixations and provide algorithm for management. Method. In this retrospective 10-year study (2010–2020), we identified patients surgically treated for AFF. We included patients who underwent revision surgery for any cause. Data collection included demographics, surgical complications, details of revision surgery and time to union. Result. Out of 57 patients who were operated for AFF, 17 underwent revision fixation. The average age was 69 with only 2 males. Around two-third (64%) were sub-trochanteric fractures and method of fixation in 64% cases was intra-medullary nail. The most common complication was non-union (12), followed by stress fracture and infection in 3 and 2 cases respectively. In most cases inadequate reduction and sub-optimal fixation was perceived as cause of failure except two cases which got infected. Revision fixation in all cases included improved bone contact (non-union site osteotomy), use of bone morphogenic proteins and improved fixation with augmentation device (either nail or plate). Follow up at 1 year showed fracture union in 12 cases, remaining 5 revision fixations failed, 3 of which were managed with proximal femur replacement. Conclusion. High rate of non-union after fixation in AFF. Optimizing the fixation construct results in union in most cases. However, arthroplasty should be considered in elderly patients with poor bone quality

There is strong evidence to support the use of bisphosphonates in the prevention of osteoporotic fractures. There has, however, been growing concern that prolonged use of bisphosphonates can lead to the development of atypical femoral fractures and can protract healing time. We conducted a retrospective study looking at all femoral fractures between 2011–2013. Of 109 patients, 12 were diagnosed with atypical femoral fractures. The mean age of presentation was 69 (52–92). Five patients held no history of falls and presented with hip pain. The remaining seven sustained minor falls. Seven patients were on bisphosphonates on presentation. Bisphosphonates were discontinued in five cases and continued in two. Bisphosphonates commenced in one patient who subsequently developed second fracture. All fractures were managed with intramedullary nailing. Healing time was prolonged in all cases (mean healing time 7.3 months). Three patients needed further surgeries to achieve union. Overall, we observed that patients with prolonged bisphosphonate intake were more susceptible to atypical fractures with a delayed recovery time. Increasing awareness amongst medical professionals may aid timely diagnoses and subsequent referrals to orthopaedics. Recognition of these fractures may also permit early discontinuation of bisphosphonates, which may prevent future fractures and reduced healing times

Introduction. Atypical femoral fracture focused on relation of bisphosphonate use, frequently. However, the mechanism of atypical femoral fracture was not yet clarified. Atypical femoral fractures have been kept femoral shaft cortical thickness and BMD, practically. We hypothesized that atypical femoral fractures were associated with impaired bone quality and curvature of femoral shaft. Materials & Methods. We experienced four atypical femoral fractures. One was subtrochanteric and three were shaft fracture. Two cases received bisphosphonate therapy for 3–5 years. BMD, bone metabolic markers, and bone quality markers were evaluated. Histomorphometry and collagen cross-link analysis were performed. Curvature of femoral shaft and 3-D finite element analysis in one incomplete fracture case were assessed. Results. BMD values were either maintained or not severely decreased. Deterioration of bone quality were verified by the results of histomorphometry, collagen cross-link analysis, and bone quality maker. Especially, homocystine values, such as one of bone quality markers, were increased in all cases. All atypical femoral shaft fractures showed outward curvature of femoral bone. In one case of incomplete atypical femoral shaft fracture, stress was concentrated at the fracture region according 3-D finite element analysis. Conclusions. The results of this study suggest that atypical femoral fractures were estimated associated with deterioration of bone quality and curvature of femoral shaft

Introduction and Objective. Some periprosthetic femoral fractures (PFFs) present history and radiographic aspect consistent with an atypical femoral fracture (AFF), fulfilling the criteria for AFF except that PFFs by themselves are excluded from the diagnosis of AFFs. The aim of this study was to evaluate in a single Institution series of PFFs if any of them could be considered a periprosthetic atypical femoral fracture (PAFF), and their prevalence. Materials and Methods. Surgical records were searched for PFFs around a primary hip stem from January 2013 to December 2019. Cases were classified according to Vancouver classification. Demographic and medical history were extracted. Fisher's exact test was used for statistical analysis. Results. One-hundred-fifteen PFFs were identified, 59 of them were type B1 and 16 were type C. Radiographs and medical records were available for all patients. Twenty-four patients (32%) have been treated with bisphosphonates (BPs) for longer than 4 years. Four patients presented a fracture with characteristics of PAFF. When enlarged to all PFFs of the series, no other PAFF was found: prevalence of PAFFs was 5.3% for type B1 and C cases and 3.5% for all surgically treated PFFs. Statistical significative difference between PAFFs and PFFs was found for prolonged BPs assumption and for the level of fracture clear of the stem. Conclusions. Fracture with characteristics of AFFs can also happen over a prosthetic stem, configuring themselves as PAFFs, and they are related to prolonged BPs use. As a correct diagnosis is mandatory for proper treatment, a revision of criteria for AFFs should be considered, accepting that PAFFs exist

Summary Statement. Atypical femoral fractures consist of a thin fracture line extending through the lateral cortex. The adjacent bone is undergoing resorption and mechanical abrasion and is often replaced with woven bone. The mechanical environment seems to inhibit healing. Background. The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself might provide important clues. So far only one case describing the histological appearance of the fracture has been published. Methods. Between 2008 and 2013, bone biopsies comprising the fracture site were collected from 8 patients with 4 displaced and 4 undisplaced atypical femoral fractures. Seven female patients reported continuous bisphosphonate use for an average of 9.5 years. One patient was a man, not using bisphosphonates. The bone biopsies were evaluated histologically, with Fourier transformed infrared imaging (FTIR) and micro-computed tomography. Results. The 4 undisplaced fractures engaged the whole cortical thickness and comprised a 150 to 200 µm wide, meandering fracture gap filled with amorphous necrotic material. Von Kossa staining showed occasional mineralised elements with bony structure within the amorphic material. Active resorption and remodeling was common in the close vicinity of the fracture, but seldom reached into the fracture gap. In some areas, the bone adjacent to the gap appeared to undergo fragmentation and disintegration, possibly due to abrasion. Woven bone was common adjacent to the fracture gap, and appeared to have been formed in defects caused by abrasion or where resorption cavities had reached into the fracture gap. Periosteal and endosteal callus was found in all cases. Far away from the fracture, large areas of osteonal bone with only empty osteocyte lacunae were found in some samples. In one patient, the remodeling process bridged the fracture gap at some points. The fracture was otherwise similar to the other undisplaced fractures. This patient had suffered from thigh pain since her bisphosphonate treatment was discontinued 18 months earlier, when the atypical fracture was diagnosed. Discussion. Atypical femoral fractures show signs of increased remodeling in the vicinity of the fracture gap. The narrow width of the gap and its necrotic contents suggest that micromotion leads to strains between the fracture fragments that precludes survival of ingrowing cells. Moreover, there seemed to be continuous mechanical fragmentation of the bone at the crack, and replacement of fragmented areas with woven bone. Thus, it appears that the fracture line is not static, but moves in the bone over time, like the changes in the course of a meandering river

Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that they may be associated with rare atypical femoral fractures. 1480 patients of proximal femur and shaft fractures over a period of 2 years from Jan 2014 to Jan 2016 were retrospectively reviewed in Gloucestershire Hospitals NHS trust. Hospital trauma database was used.195 patients had fractures in subtrochancteric and femoral shaft area. 11 patients had atypical femur fractures as defined by American society for bone and mineral research (ASBMR) task force 2013, revised criteria. Ten were female, one was male. Patients were aged from 68 to 97. In 6 patients, fractures were in the shaft, 5 in subtrochancteric area and 4 patients out of these had bilateral fractures. 10 out of 11 patients were on bisphosphonates. 4 patients had delayed diagnosis. 5 out of 11 patients did not have contralateral femoral x-rays. Treatment, 9 patients had intramedullary nail, one blade plate, and one treated conservatively. One patient in the IM group, had bilateral nailing. Average follow up was 7.6 months (range 1 to 16 months). At the end of the study, only 4 had united, 6 had not united and one not followed up. 4 out of 7 had low Vitamin D levels, 3 out of 7 had their bisphosphonate treatment stopped and 2 had histology which showed necrotic bone with trabeculae surrounded by fibrosis. Increasing number of patients are on bisphosphonates for osteoporosis. Atypical femur fractures from bisphosphonates are often occult, often bilateral, with delayed healing. Patients on bisphosphonatetreatment should be advised to report any thigh or groin pain. Painful incomplete fractures need treatment with cephalomedullary nailing. Bone biology needs correcting by stopping bisphosphonatesand administering calcium & vitamin D supplements. Implications: We need to raise awareness amongst treating clinicians and have national guidelines

Atypical femoral fracture non-union (AFFNU) is both, rare (3–5 per 1000 proximal femur fractures) and difficult to treat. Lack of standardised guidelines leads to a variability in fixation constructs, use of bone grafting and restricted weight bearing protocols, which are not evidence based. We hypothesised that there is no change in union rates without the use of bone grafting and immediate weight bearing post-operatively does not lead to increased complications. Materials & Methods. A retrospective review of all consecutively treated AFFNU cases between March 2015 to December 2019 was carried out. 9 patients with a mean age of 63.87 years and M:F ratio of 7:2 met the inclusion criteria. Primary outcome variable was radiographic union at 12 months after revision surgery. All surgeries were carried out by a single surgeon. Fixation construct, neck-shaft angle, use of bone graft and immediate postoperative weight bearing protocols were recorded. Results. Radiographic union was achieved in 7 of 9 patients (78%) after first revision surgery. 1 patient achieved union after 2nd revision surgery and 1 patient died in the early post-operative period due to pulmonary embolism. No bone grafting was used in any of the patients and weight-bearing as tolerated was allowed from the first post-operative day. The mean neck-shaft angle after non-union surgery was 136 degrees. Conclusions. In this case series, the union rate was comparable to those reported in literature previously and achieved without any form of bone grafting. To our knowledge, this is the only case series where no bone grafting was used in the management of AFFNU. Limited by a small sample size and retrospective study design, still, this study brings into question the efficacy of practice of bone grafting and restricted weight-bearing in the management of AFFNU. Bone grafting is associated with the risk of infection at donor site, postoperative pain, and morbidity, while early weight bearing is critical in elderly patients. There is no evidence supporting restricted weight-bearing and it should not be adopted as the default practice as it may even be detrimental to patients

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression. We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months). 109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation. Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs

Introduction. Since the concept of severely suppressed bone turnover (SSBT) after long-term bisphosphonate (BPs) use, SSBT have been believed as the major cause of low-energy femoral fractures, which are called atypical femoral fractures. Here we present several cases of stress fractures with bowing femoral shaft deformity, which can be another cause of low-energy femoral fractures in the elderly. Materials and Methods. From 1998 to 2012, we treated thirteen cases of low-energy fractures of femoral shaft. All cases were females with an average age of 77.0 (67–88) years. Retrospectively, we assessed fracture type, X-ray of contralateral side, bowing deformity of femur, and duration of BPs use. Result. All cases were classified as simple fracture; AO/OTA type 32-A. In eleven cases, incomplete fracture of contralateral side was found by X-ray and confirmed by a bone scintigram. In twelve cases, obvious bowing deformity of the femoral shaft was noted. BPs were used only in seven cases, and the medication period was not so long. Just one case had taken Alendronate for ten years, and this case showed no bowing deformity. Discussion. Shane defined atypical femoral fracture, and indicated that the same fractures may develop even without BPs use. According to this definition, our advocating stress fractures by bowing deformity will also be included in atypical fractures. We think stress fractures by bowing deformity should be discriminated from atypical fractures by SSBT

Atypical femoral fractures (AFFs) are reported in patients taking bisphosphonates (BPs). This study aims to describe demographics, potential risk factors and outcome of fixation in AFFs. Forty-three patients with AFF were identified retrospectivity from all identified patients with subtrochanteric or diaphyseal fractures within NHS Grampian between 2008–2018. Patients were identified via hospital coding and electronic search of patients undergoing femoral fixation. AFFs were diagnosed by the 2014 American Society of Mineral and Bone Research diagnostic criteria by electronic patient record review by two investigators. Within this cohort, the incidence of AFF was 8.25% with male to female ratio of 10:1 and a mean of presentation age 73.3 years. 27.9% of AFFs occurred in the diaphysis. 22% of AFFs were bilateral. Mean follow-up was 11.5 months. 87.5% of patients had documented prodromal symptoms. 35% had proven radiological changes before fracture. All patients identified were on BPs. Duration of BPs before fracture was 5 months- 13.2 years (mean 6.3 years). Concurrent use of BPs with steroid and proton pump inhibitors was seen in 58.5%. All patients had intramedullary fixation with 8 (18.6%) requiring revision for non-union. For those that united radiologically it took on average 304 days (220–513). BPs were only stopped in 45% of patients after fixation. AFFs in this cohort appear to be associated with BP use, female sex, clinical and radiological prodrome. AFF remain a difficult clinical problem with a high revision rate. Further work is required to identify the temporal relationships and to raise awareness to improve surveillance/management

Over the last 10 years atypical femoral fractures (AFFs) have become recognised as a complication of standard-dose bisphosphonate use. In 2014 the American Society for Bone and Mineral Research published updated diagnostic criteria for AFF. We undertook a 5-year retrospective analysis of the trauma admission database at a major trauma centre to establish the incidence of this problem in our patient population. Initial screening was performed using keyword-matching methodology to produce a shortlist of patients with low-energy femoral fractures. These patients’ case notes, radiographs, and electronic discharge summaries were reviewed to discriminate AFF from typical femoral fractures. Initial filtering identified a total of 112 low energy femoral fractures. Of these, 12 were confirmed as AFFs. 58% (7/12) of the AFF group were on bisphosphonates compared to 15% (15/100) of the typical femoral fracture group. This finding was statistically significant (p = 0.0004). These data show that there is a link between bisphosphonate use and AFF. However, a causal relationship cannot be inferred. The incidence of AFF in our study is broadly in line with the published data

There has been evidence of association between femoral shaft fractures and prolonged bisphosphonate therapy. We present a case series of bisphosphonate-associated fractures and invaluable lessons we have learnt. Over the last three years at our unit we have collected a case series of eight patients who have had atypical femoral fractures whilst on bisphosphonate therapy. We present illustrative cases, a summary of key findings, and invaluable lessons we have learnt. There was a long period of prodromal pain for two years before incomplete fractures developed. We speculate this is a warning sign of impending fracture. This may have been prevented with screening. Between incomplete fracture and complete fracture there was a short window of one month. Five patients presented with complete fracture, and three with thigh pain +/- evidence of incomplete fracture. Of the latter group all but one went on to develop complete fractures. The one patient who did not progress died six years after diagnosis. Of those five patients who presented with initial complete fracture, three patients recall thigh pain before fracture on further questioning. Despite being diaphyseal femoral fractures, there is a higher risk of neck of femur fractures in this patient cohort (both patients with initial interlocked nails subsequently developed neck of femur fractures soon after and were revised to cephalomedullary nails). Excluding one death from unrelated cause, only one patient has signs of complete fracture healing. All other patients are still receiving follow-up (mean 490 days). Three patients reported bilateral symptoms (pain). Two had had bilateral symptoms for one year. Both had visible incomplete fractures on further radiographic scrutiny; one underwent prophylactic cephalomedullary nailing, one was managed with active surveillance. We suggest that improved pain and radiographic changes of cortical healing may be misleading and should not be relied upon. Cephalomedullary nailing is the treatment of choice in these fractures due to higher risk of neck of femur fractures in this cohort. We suggest prompt prophylactic cephalomedullary nailing when radiographic incomplete fractures are identified due to a short window before progression to complete fracture, and the need to consider contralateral prophylactic nailing in patients describing bilateral symptoms. We speculate that thigh pain is a warning sign of impending fracture and fracture-progression can be prevented with appropriate screening

Aims

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model.

Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.