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Summary: Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. Purpose: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. Methods: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. Results: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. Conclusion: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggested that genetic variants associated with monogenic bone disorders were involved in the pathogenesis of atypical femoral fractures (AFF). Here, we aim to identify rare genetic variants by whole exome sequencing in genes involved in monogenic rare skeletal diseases in 12 women with AFF and 4 controls without any fracture. Results: Out of 33 genetic variants identified in women with AFF, eleven (33.3%) were found in genes belonging to the Wnt pathway (LRP5, LRP6, DAAM2, WNT1, and WNT3A). One of them was rated as pathogenic (p.Pro582His in DAAM2), while all others were rated as variants of uncertain significance according to ClinVar and ACMG criteria. Conclusions: Osteoporosis, rare bone diseases, and AFFs may share the same genes, thus making it even more difficult to identify unique risk factors. [ABSTRACT FROM AUTHOR]

Teriparatide is an anabolic drug sometimes administered to patients who have atypical femoral fracture (AFF). However, whether teriparatide has beneficial effects on bone healing remains uncertain. The present study aimed to analyze the association between teriparatide and bone healing in complete AFF. A total of 59 consecutive cases (58 patients) who underwent intramedullary nailing for complete AFF were categorized based on postoperative use of teriparatide into the non-teriparatide (non-TPTD, n = 34) and teriparatide groups (TPTD, n = 25). Time-to-bone union was evaluated and compared between the two groups. Additionally, multiple regression analysis was performed to evaluate factors affecting time-to-bone union. All participants were women, with a mean age of 77.6 years (range: 62–92). No significant difference in time-to-bone union was found between the non-TPTD and TPTD groups (5.5 months vs. 5.8 months, p = 0.359). Two patients in the non-TPTD group underwent reoperation (p = 0.503) due to failure caused by inadequate fixation, and both achieved bone healing after additional fixation with blocking screws. Multiple regression analysis revealed that the anterior gap of the fracture site postoperatively was a factor affecting time-to-bone union (p = 0.014). The beneficial effect of teriparatide on bone healing in complete AFF could not be confirmed. Additional randomized controlled trials are required. Nonetheless, appropriate techniques, including efforts to reduce the gap on the tensile side during the surgery, are important for reliable bone healing. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions The exact relationship among atypical periprosthetic femoral fractures (APFFs), typical periprosthetic femoral fractures (PFFs), and atypical femur fractures (AFFs) remains unclear. This study aimed to investigate the prevalence of APFFs among PFFs and to identify the clinical characteristics, management, and prognosis that distinguish APFFs from typical PFFs and AFFs to further determine the relationship among these three fracture types.In this retrospective study, we reviewed the clinical data of 117 consecutive patients who had PFFs after hip arthroplasty between January 2012 and December 2022 and further classified them into an APFF group and a typical PFF group according to the revised ASBMR diagnostic criteria for AFF. Moreover, patients who had subtrochanteric or femoral shaft fractures in the same period and met the diagnostic criteria for AFF were recruited and classified into the AFF group. Demographic information, minor features of AFF, comorbidities, history of medication usage, management, and complications were collected and compared among patients with typical PFFs, APFFs, and AFFs.Eleven PFFs were identified as APFFs, and the prevalence of APFFs among PFFs was 9.4%. Significant differences were found in generalized increase in cortical thickness (p = 0.019), prodromal symptoms (p < 0.001), and the incidence of bilateral fractures (p = 0.010) among the groups, where the incidences of these minor features in the APFF group and the AFF group were higher than those in the typical PFF group. Of note, the duration of fracture healing of APFFs was significantly longer than that of typical PFFs and AFFs (p < 0.001 and p = 0.004, respectively). In addition, the APFF group and the AFF group had higher proportions of patients with rheumatoid arthritis (p = 0.004 and p = 0.027, respectively), bisphosphonate (BP) usage (p = 0.026 and p < 0.001, respectively), and longer duration of BP usage (p = 0.003 and p = 0.007, respectively) than the typical PFF group. Furthermore, significant differences were found in management (p < 0.001) and complication rate (p = 0.020) among the groups, and the rate of complications in the APFF group and the AFF group was higher than that in the typical PFF group.APFFs not only fulfilled the mandatory and major diagnostic criteria for AFF but also had many clinical characteristics, management and prognosis distinguishing them from typical PFFs but resembling AFFs; hence, the diagnostic criteria for AFF might be revised to incorporate APFF as a distinct subtype of the condition. [ABSTRACT FROM AUTHOR]

Abstract We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and −3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P

Abstract Background Recent studies suggested that genetic variants associated with monogenic bone disorders were involved in the pathogenesis of atypical femoral fractures (AFF). Here, we aim to identify rare genetic variants by whole exome sequencing in genes involved in monogenic rare skeletal diseases in 12 women with AFF and 4 controls without any fracture. Results Out of 33 genetic variants identified in women with AFF, eleven (33.3%) were found in genes belonging to the Wnt pathway (LRP5, LRP6, DAAM2, WNT1, and WNT3A). One of them was rated as pathogenic (p.Pro582His in DAAM2), while all others were rated as variants of uncertain significance according to ClinVar and ACMG criteria. Conclusions Osteoporosis, rare bone diseases, and AFFs may share the same genes, thus making it even more difficult to identify unique risk factors.

The benefits of denosumab as an antiresorptive therapy and in reducing fragility fractures are well documented. However, its association with atypical femur fractures (AFFs), especially in the absence of prior bisphosphonate use, remains poorly understood and warrants further investigation. This case report presents a rare instance of bilateral AFFs in a 78-year-old bisphosphonate-naïve patient with a history of long-term denosumab therapy for previous metastatic breast cancer. Management involved intramedullary nail fixation after initial presentation with a unilateral AFF and a recommendation to cease denosumab therapy. However, the patient subsequently experienced a contralateral periprosthetic AFF below a total hip implant 5 months thereafter and was treated with open reduction internal fixation. This case report highlights the critical need for orthopedic surgeons to maintain a high level of suspicion and vigilance in screening for impending AFFs, especially in patients with a prolonged history of denosumab therapy without prior bisphosphonate use. Furthermore, the growing report of such cases emphasizes the urgent need for comprehensive research aimed at refining treatment protocols that balance the therapeutic benefits of denosumab and its associated risks of AFFs. [ABSTRACT FROM AUTHOR]

Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BPs). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time-matched patients who either had AFF or did not have AFF. In this study, we performed transiliac bone biopsies in 52 White postmenopausal women with (n  = 20) and without (n  = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4–17 yr. Despite the matched range of treatment duration (4–17 yr), AFF patients received alendronate for significantly longer time (10.7 yr) than non-AFF patients (8.0 yr) (P  = .014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical, and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3–6 mo after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have a similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration. [ABSTRACT FROM AUTHOR]

Introduction: Bisphosphonates (BPs) are one of the most often used drugs to lower fracture risk in osteoporosis patients; nonetheless, BPs have been linked to atypical femoral fracture (AFF). Teriparatide (TPTD) is a parathyroid hormone analogue and anabolic drug that may accelerate fracture repair. TPTD has been considered as a possible treatment for AFF, particularly those caused by BP use. We evaluate the effect of TPTD on AFF in this systematic review and meta-analysis. Materials and methods: A thorough search of: Web of Science, Scopus, PubMed, and Cochrane was conducted on August 2, 2023. Trials evaluating the effect of TPTD on the incidence of: complete bone healing, non-union, early and delayed bone union, progression of incomplete AFF to complete AFF, and time to bone union were included. Using Review Manager (RevMan) version 5.4, the risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence interval (CI) were estimated for dichotomous and continuous outcomes, respectively. The Newcastle–Ottawa Scale was used to assess the quality of studies. Results: Eight studies met the eligibility criteria and were included in our analysis. TPTD significantly increased the incidence of early bone union (RR = 1.45, 95% CI [1.13, 1.87], P = 0.004) and time to bone union (MD = −1.56, 95% CI [−2.86, −0.26], P = 0.02) compared to the control group. No significant differences were observed in terms of complete bone healing (RR = 1.09, 95% CI [0.99, 1.13], P = 0.12), non-union (RR = 0.48, 95% CI [0.22, 1.04], P = 0.06), and progression of incomplete AFF to complete AFF (RR = 0.27, 95% CI [0.04, 1.97], P = 0.19). Conclusions: TPTD is an effective therapy for enhancing and hastening healing following AFF, particularly in postoperative settings. Future large randomized clinical trials are needed to confirm or dispute the results. [ABSTRACT FROM AUTHOR]

The increased incidence of atypical femoral fractures (AFFs) appears to be related to an aging population and a consequent increase in bisphosphonate use. In patients with AFF, the bone healing potential for fracture union is generally suppressed, and the surgical techniques for internal fixation are often challenging. Therefore, complications, such as fixation failure, delayed union, and nonunion, are frequently reported. Prompt discontinuation of bone resorption inhibitors, including bisphosphonates, is fundamental to the successful treatment of AFF. In addition, calcium and vitamin D should be supplemented, and known risk factors for nonunion should be excluded. Intramedullary nailing is considered the treatment of choice in the surgical management of AFF. During surgery, anatomical reduction and the firm internal fixation of fracture fragments are required while preserving the surrounding soft tissue. There are reports on the benefits of postoperative parathyroid hormone administration in fracture healing, but more evidence is needed. [ABSTRACT FROM AUTHOR]

Objectives: Atypical femoral fracture (AFF) is an atypical low-energy subtrochanteric and diaphyseal femoral fracture. Even if bone fusion is achieved in patients with AFF, the risk of AFF in the contralateral femur must be considered. This study aimed to investigate the factors affecting complete AFF in the contralateral femur and conservatively treated incomplete AFF. Subject and Methods: Radiographs of 111 femurs in 104 AFF cases were examined, and the femurs were classified as follows: 85 contralateral femurs with complete AFF; 18 contralateral femurs with incomplete AFF; 8 femurs with incomplete AFF without surgical treatment. Various patients' clinical data were collected, and we investigated the factors affecting the second complete AFF. Results: Complete fractures occurred in 10 (9.7%) of 103 femurs without incomplete AFF at the first visit and in 3 (37.5%) of 8 femurs with incomplete AFF. The Kaplan-Meier curve revealed that lateral cortical bone thickening and thigh pain were associated with significantly poorer prognoses (p = 0.026 and p = 0.013, respectively). Multivariate analyses revealed that eldecalcitol usage after AFF onset (p = 0.0094) and previous use of bisphosphonate or denosumab (p = 0.0126) were protective factors for second complete AFF and that the presence of thigh pain (p = 0.0134) was a risk factor for second complete AFF. Conclusions: Eldecalcitol administration after bone union of first AFF may prevent AFF recurrence. In addition, painful incomplete AFF has a high risk of developing a complete fracture. [ABSTRACT FROM AUTHOR]

Osteoporosis is an important cause of fractures in postmenopausal women. Bisphosphonates are the first line of treatment for osteoporosis. However, long-term use of these medications has been related to atypical femoral fractures (AFF). We present a case of a 71-year-old postmenopausal woman, with a history of osteoporosis being treated with bisphosphonates for 6 years. The patient developed pain in her left hip and thigh over a period of 3-4 months. Radiographic studies showed an AFF and she was managed conservatively. Stopping bisphosphonate therapy should be an initial step in managing or limiting the progression of AFF. A drug holiday should be considered in patients who have been treated for more than 3-5 years to prevent AFFs. The risk of developing AFFs should never be ignored in this subset of patients.

The benefits of denosumab as an antiresorptive therapy and in reducing fragility fractures are well documented. However, its association with atypical femur fractures (AFFs), especially in the absence of prior bisphosphonate use, remains poorly understood and warrants further investigation. This case report presents a rare instance of bilateral AFFs in a 78-year-old bisphosphonate-naïve patient with a history of long-term denosumab therapy for previous metastatic breast cancer. Management involved intramedullary nail fixation after initial presentation with a unilateral AFF and a recommendation to cease denosumab therapy. However, the patient subsequently experienced a contralateral periprosthetic AFF below a total hip implant 5 months thereafter and was treated with open reduction internal fixation. This case report highlights the critical need for orthopedic surgeons to maintain a high level of suspicion and vigilance in screening for impending AFFs, especially in patients with a prolonged history of denosumab therapy without prior bisphosphonate use. Furthermore, the growing report of such cases emphasizes the urgent need for comprehensive research aimed at refining treatment protocols that balance the therapeutic benefits of denosumab and its associated risks of AFFs.

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

This meta-analysis demonstrated that a greater prevalence of delayed union and nonunion and a longer time to fracture healing in the group that did not receive TPTD treatment after AFFs than in the group that received TPTD treatment. Purpose: To date, there is no hard evidence for medical management after atypical femoral fracture (AFF), even though weak data indicate faster healing with teriparatide (TPTD). Herein, we aimed to investigate the effect of postfracture TPTD treatment on AFF healing using a pairwise meta-analysis focusing on delayed union, nonunion, and fracture healing time. Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of TPTD after AFF up to October 11, 2022. We compared the incidence of delayed union and nonunion and the time of fracture healing between the TPTD (+) and TPTD (-) groups. Results: The 6 studies analyzed a total of 214 AFF patients, including 93 who received TPTD therapy after AFF and 121 who did not. The pooled analysis showed a significantly higher rate of delayed union in the TPTD (-) group than in the TPTD (+) group (OR, 0.24; 95% CI, 0.11–0.52; P < 0.01; I2 = 0%), and a higher nonunion rate was observed in the TPTD (-) group than in the TPTD (+) group with low heterogeneity (OR, 0.21; 95% CI, 0.06–0.78; P = 0.02; I2 = 0%). The TPTD (-) group required 1.69 months longer to achieve fracture union than the TPTD (+) group, with statistical significance (MD = − 1.69, 95% CI: − 2.44 to − 0.95, P < 0.01; I2 = 13%). Subgroup analysis for patients with complete AFF showed that the TPTD (-) group had a higher rate of delayed union with low heterogeneity (OR, 0.22; 95% CI, 0.10–0.51; P < 0.01; I2 = 0%), but there was no significant difference in the nonunion rate between TPTD (+) and TPTD (-) groups (OR, 0.35; 95% CI, 0.06–2.21; P = 0.25; I2 = 0%). Fracture healing took significantly longer in the TPTD (-) group (MD = − 1.81, 95% CI: − 2.55 to − 1.08; P < 0.01; I2 = 48%). The reoperation rate showed no significant difference between the two groups (OR, 0.29; 95% CI, 0.07–1.20; P = 0.09; I2 = 0%). Conclusions: The current meta-analysis supported the hypothesis that TPTD treatment following AFF might benefit fracture healing, lowering the rate of delayed union and nonunion and shortening the fracture healing time. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of femoral localized periosteal thickening (LPT), which can precede atypical femoral fracture (AFF), is not low (1-10%) in Japanese patients with autoimmune inflammatory rheumatic diseases (AIRDs). We explored the associations between underlying AIRDs and the prevalence of LPT. Methods: We conducted post hoc analyses of two cohorts that included a total of 280 Japanese women, 105 of whom had AIRDs and had been taking bisphosphonate (BP) and prednisolone (PSL) and 175 of whom had rheumatoid arthritis (RA). Results: LPT was detected in a total of 18 patients (6.4%) and 3 (1.1%) developed AFFs. RA was negatively correlated with LPT. A disease other than RA requiring glucocorticoid treatment, BP use ≥5 years, PSL use ≥7 years, and a PSL dose ≥5.5 mg/day were positively correlated with LPT. After adjusting for age, diabetes mellitus, and BP duration or daily PSL dose, RA was no longer associated with LPT. Conclusions: LPT in Japanese patients with AIRDs was associated with BP and glucocorticoid treatment rather than underlying AIRDs. When PSL dose ≥5.5 mg/day is required long-term [typically combined with long-term BP treatment (≥5 years)], clinicians need to pay particular attention in cases LPT and AFF as well as glucocorticoid-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: Bisphosphonates are commonly used medication for the treatment of osteoporosis, and a well-established complication of this medication is bisphosphonate-associated atypical femur fractures (BAAFFs). The aim of this study was to assess the post-operative functional and radiographic outcomes of surgically treated BAAFFs. Methods: An analysis of patients treated at a university-affiliated institution was performed. Patients who had undergone surgical fixation for a subtrochanteric or shaft of femur fracture which had been classified as atypical and treated with bisphosphonate therapy at the time of fracture were included. The outcome measures assessed included post-operative complications, length of stay, discharge destination, post-operative function, independence in activities of daily living (ADLs) and fracture union. Results: Twenty patients were included in this study with a mean age of 75.2 years. The cohort was predominantly female. The average duration of bisphosphonate therapy was 7.35 years. Nine patients had contralateral bisphosphonate-related stress reactions at the time of their initial fracture and underwent prophylactic surgical intervention. The majority of patients received cephalomedullary nail fixation (95%) with more than half (65.0%) of the cohort experiencing one or more post-operative complications. The median length of stay was 6.5 days and 50% of the cohort required inpatient rehabilitation. At final review, independent mobilisation was recorded in only 10.0% of patients, and 70% of patients were dependent with their ADLs at their latest follow-up. Average follow-up was 8 months, and only six cases demonstrated union at the six-month review, with delayed union between 9 and 12 months being common. Conclusion: Patients with BAAFFs experience high rates of complications, record poor post-operative functional outcomes, and demonstrate a delayed time to union. Nearly half of our cohort had radiographic evidence of bilateral pathology. [ABSTRACT FROM AUTHOR]

Purpose of reviewThis review describes the rational for bisphosphonate holidays, summaries key evidence to support the concept, and provides a roadmap to help clinicians initiate, monitor, and discontinue a bisphosphonate drug holiday.Recent findingsRandomized trials and data from large observational studies are available to determine the short and long-term bisphosphonate benefits (prevention of fracture) and harms (principally atypical femoral fractures and osteonecrosis of the jaw). Mounting evidence points towards a causal relationship between bisphosphonate use and AFF and ONJ, particularly with > 5 years of use. Multiple studies now confirm the risk of AFF falls rapidly after BPs are discontinued. Osteoporosis patients without previous hip, vertebral, or multiple non-spine fractures who are successfully treated with oral bisphosphonates for 5 years (3 years if intravenous), should be offered a 3-5 year drug holiday, particularly if hip BMD T-score is > - 2.5. Bisphosphonates should only be continued beyond 10 years (6 years if parenteral) in patients at very high risk of fracture.

Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients with long-term administration of these drugs showed a tendency to have an increased risk of onset. AFF developed earlier in osteoporosis patients with long-term administration of BPs and denosumab than in cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Background Atypical femoral fracture (AFF) is a rare complication in patients with osteoporosis undergoing long-term bisphosphonate therapy. The most common symptom of incomplete AFF is nonspecific thigh pain, which is often difficult to distinguish from other causes. Case presentation We present two cases of AFF misdiagnosed as lumbar radiculopathy. Both patients visited our hospital for thigh pain, and in both cases the findings of lumbar spine magnetic resonance imaging showed substantial nerve compression. These patients had been treated for lumbar radiculopathy, but localized symptoms became conspicuous and femoral radiographs revealed complete AFF. The initial radiographs were reviewed retrospectively and revealed slight lateral cortical thickening in the affected femur, denoting a missed incomplete AFF. Internal fixation with intramedullary nails was performed. Conclusions AFF may mimic lumbar radiculopathy. Therefore, clinicians should consider AFF as a differential diagnosis in older patients with lumbar canal stenosis who are undergoing long-term bisphosphonate therapy and present with thigh pain.

Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone fromovariectomized cynomolgusmonkeys. We analyzed humeral bone from30 animals across five treatment groups. Animals were treated for 12 months with subcutaneous (sc) vehicle (VEH), sc DMAb (25 mg/kg/month), or intravenous (iv) ALN (50 µg/kg/month). Another group received 6 months VEH followed by 6 months DMAb (VEH-DMAb), and the final group received 6 months ALN followed by 6 months DMAb (ALN-DMAb). A total of 240 cortical beam samples were cyclically tested in four-point bending at 80, 100, 120, or 140 MPa peak stress. High-resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (p = 0.014), ALN-DMAb (p = 0.008), and DMAb (p < 0.001) groups illustrated higher fatigue-life measurements than VEH. For example, at 140 MPa the VEH group demonstrated a median ± interquartile range (IQR) fatigue life of 1987 ± 10593 cycles, while animals in the ALN, ALN-DMAb, andDMAb groups survived 9850 ± 13648 (+395% versus VEH), 10493 ± 16796 (+428%), and 14495 ± 49299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (p < 0.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (p = 0.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12 months of treatment may have a protective effect against fatigue fractures. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

High-dose bisphosphonate for multiple myeloma patients might elevate risks of skeletal complications earlier than general expectations. This study aims to find incidences of atypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ), elucidate their risk factors, and suggest cut-off values for the safer dosing of high-dose bisphosphonate treatment. By using the clinical data warehouse of a single institute, retrospective cohort data of multiple myeloma-diagnosed patients with high-dose bisphosphonate (pamidronate or zoledronate) treatment from 2009 to 2019 was extracted. Among 644 patients, the incidence of prominent AFF requiring surgery was 0.93% (6/644) and MRONJ was diagnosed in 11.8% (76/644) of the study population. For both AFF and MRONJ, the total potency-weighted sum of total dose per body weight (OR = 1.010, p = 0.005) were significant on logistic regression. Cutoffs of the potency-weighted total dose (mg) per body weight (kg) for AFF and MRONJ were 77.00 and 57.70 mg/kg, respectively. After roughly one year of treatment with high-dose zoledronate (about four years for pamidronate), an earlier thorough re-evaluation of skeletal complications should be taken. Body weight adjustments for accumulative dose calculation in terms of permissible dosing should be taken into consideration. [ABSTRACT FROM AUTHOR]

Based on the current paradigm, a healthy bone is one with adequate mass without microarchitectural decay. However, these two features may not be sufficient to ensure that a bone is healthy. In addition, components must be correctly assembled and aligned. This ensures "the right amount of bone, at the right place" and thus, an optimal cohesion or interplay between constituents. Disorganization may be an independent contributor to bone abnormalities including fragility fractures. Indeed, many bone diseases may be characterized by the presence of disorganized bone, including osteogenesis imperfecta, hypophosphatasia, and atypical femur fractures (AFFs). Despite its likely importance, currently, there are no tools to quantify disorganization in vivo. We address this unmet need by describing a novel method for quantifying bone disorganization from X‐ray images. Disorganization is quantified as variations in the orientation of bone components in relation to a target reference point. True disorganization created by disarranging (misplacing) pixels within the bone served as "gold standard." To further validate the method in clinical settings, we compared disorganization in three groups of femurs: (i) femurs of women with AFFs (n = 9); (ii) fracture‐free femurs contralateral to AFFs (n = 9); and (iii) fracture‐free femurs from controls (n = 25). There was excellent agreement between measured disorganization and "gold standard," with R2 values ranging from 0.84 to 0.99. Precision error ranged from 1.72% to 4.69%. Disorganization produced by abnormalities associated with AFFs was accurately captured. Disorganization level was lowest in fracture‐free control femurs, higher in fracture‐free contralateral femurs to AFFs, and highest in femurs with AFFs (all p < 0.0001). Quantification of disorganization, a novel biomarker, may provide novel insights into the pathogenesis of metabolic bone diseases beyond that provided by bone mineral density (BMD) or microarchitecture. We provide evidence that measurement of disorganization is likely to help identify patients at risk for fractures, especially in those poorly explained by BMD or microarchitecture such as AFFs. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Bone-modifying agents (BMAs), with bone-resorptive inhibitory effects, such as zoledronic acid and denosumab, are widely used at higher doses for bone-related events caused by bone metastasis of malignant tumors. These drugs have been suggested to be associated with atypical femoral fractures (AFFs), and the relationship between BMAs and AFFs has attracted attention. To investigate the clinical features including bone union time of AFFs in patients administered BMA for bone metastasis, we conducted a retrospective multicenter study. Thirty AFFs from 19 patients were enrolled in this study. Thirteen patients had bilateral AFFs, and nineteen AFFs had prodromal symptoms. Eighteen AFFs underwent surgery after complete fracture, three failed to achieve bone union and required nonunion surgery, and 11 AFFs that achieved bone union had an average period until bone union of 16.2 months, which was much longer than that previously reported for ordinary AFFs. Seven patients discontinued the BMAs, but not due to AFFs. Stopping BMAs in patients with bone metastasis would make it difficult to secure their performance of activities of daily living, and AFF with BMA administration might require a longer time for union. Therefore, it would be important to prevent incomplete AFF from becoming complete AFF via prophylactic internal fixation.

ABSTRACT Based on the current paradigm, a healthy bone is one with adequate mass without microarchitectural decay. However, these two features may not be sufficient to ensure that a bone is healthy. In addition, components must be correctly assembled and aligned. This ensures “the right amount of bone, at the right place” and thus, an optimal cohesion or interplay between constituents. Disorganization may be an independent contributor to bone abnormalities including fragility fractures. Indeed, many bone diseases may be characterized by the presence of disorganized bone, including osteogenesis imperfecta, hypophosphatasia, and atypical femur fractures (AFFs). Despite its likely importance, currently, there are no tools to quantify disorganization in vivo. We address this unmet need by describing a novel method for quantifying bone disorganization from X‐ray images. Disorganization is quantified as variations in the orientation of bone components in relation to a target reference point. True disorganization created by disarranging (misplacing) pixels within the bone served as “gold standard.” To further validate the method in clinical settings, we compared disorganization in three groups of femurs: (i) femurs of women with AFFs (n = 9); (ii) fracture‐free femurs contralateral to AFFs (n = 9); and (iii) fracture‐free femurs from controls (n = 25). There was excellent agreement between measured disorganization and “gold standard,” with R2 values ranging from 0.84 to 0.99. Precision error ranged from 1.72% to 4.69%. Disorganization produced by abnormalities associated with AFFs was accurately captured. Disorganization level was lowest in fracture‐free control femurs, higher in fracture‐free contralateral femurs to AFFs, and highest in femurs with AFFs (all p

Background: Atypical femoral fracture (AFF) is a rare complication in patients with osteoporosis undergoing long-term bisphosphonate therapy. The most common symptom of incomplete AFF is nonspecific thigh pain, which is often difficult to distinguish from other causes. Case presentation: We present two cases of AFF misdiagnosed as lumbar radiculopathy. Both patients visited our hospital for thigh pain, and in both cases the findings of lumbar spine magnetic resonance imaging showed substantial nerve compression. These patients had been treated for lumbar radiculopathy, but localized symptoms became conspicuous and femoral radiographs revealed complete AFF. The initial radiographs were reviewed retrospectively and revealed slight lateral cortical thickening in the affected femur, denoting a missed incomplete AFF. Internal fixation with intramedullary nails was performed. Conclusions: AFF may mimic lumbar radiculopathy. Therefore, clinicians should consider AFF as a differential diagnosis in older patients with lumbar canal stenosis who are undergoing long-term bisphosphonate therapy and present with thigh pain. [ABSTRACT FROM AUTHOR]

Introduction: A residual fracture gap after intramedullary nailing is a known risk factor for delayed union and non-union. This study aimed to report the outcomes of a forward-striking technique to reduce fracture gaps during long cephalomedullary nailing in subtrochanteric femoral fractures (SFFs).Methods: A retrospective cohort study was conducted on patients with SFFs treated in a single institution between February 2013 and October 2018. A total of 58 patients treated via long cephalomedullary nailing with a forward-striking technique were included. The width of the fracture gap, location of the cephalic screw, tip-apex distance (TAD), and time to bone union were evaluated using intraoperative and postoperative radiographs. Complication rates, including fixation failure, non-union, implant breakage, and infection, were assessed. The mean follow-up duration was 4 (range, 2‒8) years.Results: Of the 58 patients (mean age, 67.9 years), 38 (65.5%) were female. Thirty-two cases (55.2%) were classified as atypical femoral fractures. The mean fracture gap reduced from 5.1 mm to 1.6 mm by forward striking (P<0.001). The reduced fracture gap was significantly greater in atypical SFFs (mean, 4.9 mm vs. 1.7 mm; P<0.001). The lag screw was located in the center-center or center-inferior zones of the femoral head in 54 patients (93.1%). The mean TAD was 14.2 mm and was under 25 mm in 55 patients (94.8%). Bone union was achieved in all cases without reoperation at a mean of 5.4 months. One incident of lag screw breakage was noted at 5 months, but bone union was achieved at 7 months.Conclusions: The forward-striking technique with a long cephalomedullary nail demonstrated a 100% bone union rate in a consecutive series of 58 SFFs. This technique is effective in reducing the fracture gap as well as placing the cephalic screw into the optimal position. The forward-striking technique was particularly effective in reducing atypical SFFs with a transverse or short oblique configuration. [ABSTRACT FROM AUTHOR]

Summary: A post-menopausal Caucasian woman sustained an atypical femoral fracture (AFF) after 5-years continuous denosumab for osteoporosis without prior bisphosphonate exposure. This is only the fifth case reported of AFF in a bisphosphonate-naïve patient receiving denosumab for osteoporosis. Although rare, physicians should consider AFF in patients taking denosumab even without prior bisphosphonate exposure. Introduction: Denosumab has demonstrated overwhelmingly favourable skeletal benefit/risk profile in managing post-menopausal osteoporosis with up to 10-year exposure in the extension of the pivotal FREEDOM randomised placebo-controlled trial. Four previous cases of atypical femoral fracture have been reported in bisphosphonate-naïve patients receiving denosumab for osteoporosis. Methods: We present an 85-year-old Caucasian post-menopausal woman without prior fragility fracture who sustained unilateral atypical femoral fracture after 5-years continuous subcutaneous denosumab for osteoporosis. She had no prior bisphosphonate or glucocorticoid exposure and had known chronic kidney disease. Results: X-ray scan demonstrated complete, non-comminuted left proximal femoral shaft fracture meeting radiographic criteria for an atypical femoral fracture. Computed tomography (CT) scan lower limbs revealed unusual side-by-side appearance of proximal and distal fragments of left proximal femur. DXA BMD was artefactually elevated at lumbar spine (1.504 g/cm2, T-score + 2.5) and low-normal at right femoral neck (0.856 g/cm2, T-score -1.0). Serum biochemistry showed renal impairment at baseline (eGFR 30 mL/min/1.73m2). Low-normal serum C telopeptide of type 1 collagen (CTX) (230 ng/L) indicated therapeutic suppression of bone resorption. Conclusion: The patient underwent intramedullary nailing of the femur and denosumab was ceased. This is only the fifth case reported of atypical femoral fracture in a bisphosphonate-naïve patient receiving denosumab for osteoporosis. Although rare, physicians should maintain a high index of suspicion for atypical femoral fracture in a patient taking denosumab even without prior bisphosphonate exposure. [ABSTRACT FROM AUTHOR]

Abstract Background Atypical femoral fractures (AFF) are diaphyseal fractures of the elderly that occur at the end of a minor trauma. The objective of this biomechanical study, using finite element modelling, was to evaluate the variations of the femoral diaphysis fracture indicator according to the variations of the mechanical axis of the lower limb, which can explain all the different atypical fracture types identified in the literature. Methods In order to measure variations in stress and risk factors for fracture of the femoral diaphysis, the distal end of the femur was constrained in all degrees of freedom. An axial compression load was applied to the femoral head to digitally simulate the bipodal support configuration in neutral position as well as in different axial positions in varus/valgus (− 10°/10°). Results The maximum stress value of Von Mises was twice as high (17.96 ± 4.87 MPa) at a varus angle of − 10° as in the neutral position. The fracture risk indicator of the femoral diaphysis varies proportionally with the absolute value of the steering angle. However, the largest simulated varus deformation (− 10°) found a higher risk of diaphysis fracture indicator than in valgus (10°). Conclusions Variations in the mechanical axis of the lower limb influence the stress distribution at the femur diaphysis and consequently increase the risk of AFF. The axial deformation in varus is particularly at risk of AFF. The combination of axial deformation stresses and bone fragility consequently contribute to the creation of an environment favorable to the development of AFF. Trial registration: ‘retrospectively registered’.

Although the American Society for Bone and Mineral Research definition of atypical femoral fracture excludes periprosthetic fractures, fractures around the prosthesis with clinical features of atypical femoral fractures have been reported in the literature. All fractures reported thus far have been distal to the prosthetic segment; however, we encountered a case of a stress fracture in the middle of the femoral component segment. An 86-year-old woman with a history of bisphosphonate osteoporosis treatment and revisional total hip arthroplasty visited our outpatient clinic complaining of pain in the left thigh and groin. We diagnosed an incomplete atypical femoral fracture around the hip prosthesis; medical treatment was implemented. Two months later, the patient visited the emergency department with a complete subtrochanteric fracture with stem breakage. Without revision of the broken stem, two plates were applied after reduction. In this case, we recognized the possibility of a stress fracture but overlooked the possibility of stem breakage in an atypical femoral fracture. Even if it is not evident on the radiograph before complete fracture, clinicians should be alert to the signs of stress fracture in the middle of the femoral component segment, as they may be clues to atypical periprosthetic femoral fracture with stem failure. Isolated medical treatment plans are not recommended for incomplete subtrochanteric atypical periprosthetic femoral fracture. Instead, concomitant prophylactic plate fixation is recommended. [ABSTRACT FROM AUTHOR]

Femoral neck fractures are considered exclusion criteria for atypical femoral fractures; however, femoral neck fractures with atypical femoral fractures have also been reported. Here, we report a case of a femoral neck fracture with features of atypical femoral fractures and a review of the related literature. A 76-year-old woman had been treated with denosumab for five years. The patient had no history of trauma, but complained of pain in the right hip. Radiological examination revealed an incomplete fracture of the right femoral neck. Internal fixation was performed, but fusion was delayed. Bipolar hemiarthroplasty was performed four months after surgery. In a patient with long-term bisphosphonate use, complaints of hip pain could indicate the possibility of an atypical fracture. According to the existing literature, as with atypical femoral fractures, this fracture has a high risk of delayed union; therefore, temporary prosthetic replacement should be considered as a treatment option., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Ltd.)

Atypical femoral fracture (AFF) is generally a rare complication of long-term use of bisphosphonate (BP); glucocorticoid (GC) use and Asian race are also risk factors. Femoral localized periosteal thickening (LPT, also termed "beaking") of the lateral cortex often precedes AFF. This cohort study investigated the incidence of LPT and AFF and their clinical courses over 10 yr in patients with autoimmune inflammatory rheumatic diseases (AIRDs) treated with BP and GC. The study population consisted of 121 patients with AIRDs taking BP and GC. LPT was screened by X-ray, and the LPT shape was evaluated. Prednisolone (PSL) dose was 10 (8-12) mg/d at enrollment and 9 (6-10) mg/d at the last observation. LPT was evident in 10 patients at enrollment and increased linearly to 31 patients (26%) at the last observation. AFF occurred in 9 femurs of 5 patients with LPT. All patients with AFF had bilateral LPT, and the prevalence of pointed type and LPT height were higher in the AFF-positive group than in the AFF-negative group. AFF occurred before BP discontinuation in 2 patients, 1 yr after BP discontinuation in 1, after BP discontinuation followed by 7 yr of alfacalcidol use in 1, and after switching from alfacalcidol to denosumab in 1. The prevalence rates of AFF and LPT associated with long-term BP use with concomitant use of GC (mostly PSL ≥ 6 mg/d) in Japanese patients with AIRD increased over time. The selection of long-term osteoporosis treatment for LPT-positive patients is difficult in some cases., Competing Interests: H.S. received lecture fee from Asahi Kasei Pharma, Daiichi Sankyo Company and Astellas pharma Inc. N.K., Y.K., E.H., A.W., Y.N., D.K., T.N., Y.W., J.J.K., T.K., M.N., N.E., and I.N. declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients with long-term administration of these drugs showed a tendency to have an increased risk of onset. AFF developed earlier in osteoporosis patients with long-term administration of BPs and denosumab than in cancer patients.

Context: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. Objective: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. Methods: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). Results: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10–5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10–5, OR 5.21, 95% CI 2.76-9.86). AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1 [ABSTRACT FROM AUTHOR]

Introduction: When performing intramedullary nailing for atypical femoral fractures (AFF), especially in lateral bowing femurs, a medial opening wedge-shaped gap in the fracture site may occur after nailing. We intended to analyse and compare clinical outcomes according to the medial gap in AFF cases after intramedullary nailing. Materials and Methods: Of the 38 consecutive patients with complete AFF treated by intramedullary nailing, 22 patients (all female, mean age of 76.5 years [range, 62–87]) available for follow-up for more than 12 months were included. According to the size of the medial gap, the patients were divided into 2 groups: large and small medial gaps. Comparative analysis was performed between groups in terms of patient, fracture characteristics and post-operative clinical outcomes. Results: There was no significant difference in bone union time between the 2 groups (5.4 months vs 5.6 months, P =.628). When comparing the amount of change in the hip–knee–ankle angle after the surgery with reference to the contralateral side, there was a significant difference between the 2 groups (−4.4° [femoral straightening and relatively changed to a more valgus pattern, that is, in cases of varus alignment, towards neutral alignment] vs.5°, P =.002). There was no significant difference in leg length discrepancy between the 2 groups (4.1 mm vs 3.2 mm, P =.674). In terms of functional outcomes, there was no significant difference in the recovery of ambulatory ability (ΔKoval grade: post-operative Koval grade–pre-operative Koval grade, 0 vs.1, P =.771). Conclusion: Even if the medial gap occurs following intramedullary nailing in AFF, post-operative clinical outcomes seem to be acceptable. However, if previous total knee arthroplasty is performed and neutral alignment is maintained, care should be taken as the occurrence of the gap may result in lower limb malalignments. [ABSTRACT FROM AUTHOR]

• Reports on periprosthetic femoral fracture with characteristics of atypical femoral fracture (AFF) are becoming increasingly common. • Periprosthetic AFFs (PAFFs) after total knee arthroplasty (TKA) accounted for 6.6% of all AFFs in this multicenter prospective study. • PAFFs had characteristics including mechanical stress due to bowing deformity and potentially suppressed bone turnover due to specific drugs. • Biomechanical analysis demonstrated that stress fracture can develop in proximal diaphysis due to the change in lower limb alignment by TKA. • X-rays of full-length femurs should be checked after TKA especially in patients with bowed femurs or with long-term exposure to specific drugs. Although the diagnostic criteria for atypical femoral fracture (AFF) exclude periprosthetic fractures, reports of periprosthetic femoral fractures with characteristics of AFF are rapidly increasing. In this study, we investigated the frequency and pathogenesis of periprosthetic AFF associated with total knee arthroplasty (TKA) based on a theory of AFF subtypes that divides AFFs into two main types: fragility stress fractures of the bowed femoral shaft in the mid-shaft and "typical" subtrochanteric AFFs due to suppression of bone turnover (e.g., by bisphosphonates). This multicenter prospective study of AFFs was conducted from 2015 through 2022. Clinical, pathological, and morphological characteristics were investigated in patients with periprosthetic AFFs associated only with non-stem TKA. Then, biomechanical investigation of the periprosthetic AFF was performed by computer tomography-based finite element analysis (CT/FEA) using two models with different load axes to examine how the correction of lower limb alignment by TKA influences the tensile stress distribution of the femur and the location of the AFF. Four of 61 AFFs (6.6%) were identified to be periprosthetic AFF (1 mid-shaft; 3 subtrochanteric). Periprosthetic AFFs had characteristics including mechanical stress due to bowing deformity and potentially suppressed bone turnover due to long-term exposure to specific drugs (e.g., bisphosphonates and glucocorticoids). Although 2 periprosthetic AFFs appeared to involve a bowed femur, one with both of the aforementioned characteristics occurred in the subtrochanteric region, which would be an unusual site for a bowed AFF, and it was demonstrated histologically to have biological activity at the fracture site, suggesting a stress fracture. Furthermore, CT/FEA revealed that tensile stress distribution changed proximally as load axis was shifted laterally according to correction of lower limb alignment by TKA. Orthopedic surgeons should recognize the presence of TKA-associated periprosthetic AFF caused by various factors including specific drugs, bowing deformity, and lower limb alignment. X-rays of the full-length femurs should be checked regularly after TKA, especially in patients with bowed femurs or long-term exposure to specific drugs. [ABSTRACT FROM AUTHOR]

High-dose bisphosphonate for multiple myeloma patients might elevate risks of skeletal complications earlier than general expectations. This study aims to find incidences of atypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ), elucidate their risk factors, and suggest cut-off values for the safer dosing of high-dose bisphosphonate treatment. By using the clinical data warehouse of a single institute, retrospective cohort data of multiple myeloma-diagnosed patients with high-dose bisphosphonate (pamidronate or zoledronate) treatment from 2009 to 2019 was extracted. Among 644 patients, the incidence of prominent AFF requiring surgery was 0.93% (6/644) and MRONJ was diagnosed in 11.8% (76/644) of the study population. For both AFF and MRONJ, the total potency-weighted sum of total dose per body weight (OR = 1.010, p = 0.005) were significant on logistic regression. Cutoffs of the potency-weighted total dose (mg) per body weight (kg) for AFF and MRONJ were 77.00 and 57.70 mg/kg, respectively. After roughly one year of treatment with high-dose zoledronate (about four years for pamidronate), an earlier thorough re-evaluation of skeletal complications should be taken. Body weight adjustments for accumulative dose calculation in terms of permissible dosing should be taken into consideration.

Background: Atypical femoral fractures (AFF) are diaphyseal fractures of the elderly that occur at the end of a minor trauma. The objective of this biomechanical study, using finite element modelling, was to evaluate the variations of the femoral diaphysis fracture indicator according to the variations of the mechanical axis of the lower limb, which can explain all the different atypical fracture types identified in the literature. Methods: In order to measure variations in stress and risk factors for fracture of the femoral diaphysis, the distal end of the femur was constrained in all degrees of freedom. An axial compression load was applied to the femoral head to digitally simulate the bipodal support configuration in neutral position as well as in different axial positions in varus/valgus (− 10°/10°). Results: The maximum stress value of Von Mises was twice as high (17.96 ± 4.87 MPa) at a varus angle of − 10° as in the neutral position. The fracture risk indicator of the femoral diaphysis varies proportionally with the absolute value of the steering angle. However, the largest simulated varus deformation (− 10°) found a higher risk of diaphysis fracture indicator than in valgus (10°). Conclusions: Variations in the mechanical axis of the lower limb influence the stress distribution at the femur diaphysis and consequently increase the risk of AFF. The axial deformation in varus is particularly at risk of AFF. The combination of axial deformation stresses and bone fragility consequently contribute to the creation of an environment favorable to the development of AFF. Trial registration: 'retrospectively registered'. [ABSTRACT FROM AUTHOR]

Introduction: Proximal peri-implant femoral fractures occur following intramedullary nailing (IMN) fixation for trochanteric, femoral shaft, and distal femoral fractures. However, analyses of secondary hip fractures (SHFs) using large clinical samples are lacking. Therefore, we aimed to report the incidence and clinical outcomes of SHF after nailing fixation (IMN or cephalomedullary nailing [CMN]) for overall femoral fractures. In addition, we focused on IMN for femoral shaft fractures and investigated the risk factors for SHF.Methods: This multicenter, retrospective, cohort study included 2,293 patients aged > 60 years who underwent nailing fixation for femoral fractures. The primary outcome was the incidence of SHF. In the assessment of clinical outcomes, we evaluated reoperation and the regaining of walking ability following SHF management. In addition, we conducted multivariable logistic regression analyses to examine the association between risk factors and SHF.Results: Seventeen (0.7%) patients had SHFs, including 12 femoral neck fractures and 5 trochanteric fractures. Antegrade IMN was the most common type of nailing fixation. Multivariable analysis demonstrated that the absence of femoral head fixation was significantly associated with the incidence of SHF following IMN for femoral shaft fractures (odds ratio, 17.0; 95% confidence interval, 1.9-2265.7; p=0.006). In the assessment of clinical outcomes, there were two reoperations (16.7%) in the secondary femoral neck fracture group. Patients with secondary trochanteric fractures tended to have a lower probability of regaining walking ability than those with secondary femoral neck fractures (20% vs. 50%).Conclusions: In this multicenter study, the incidence of SHF after nail fixation for femoral fractures was 0.7%. The absence of femoral head fixation was significantly associated with SHF, and the clinical outcomes were poor. Therefore, femoral head fixation at the initial IMN fixation for femoral fractures may be a fixation option for surgeons to consider as an SHF prevention measure. [ABSTRACT FROM AUTHOR]

Introduction: This real-world study evaluated whether long-term use of eldecalcitol (ELD) increases the risk of adverse events (AEs), namely, hypercalcemia, acute kidney injury (AKI), and urolithiasis, and analyzed the ELD-induced risk of rare AEs such as osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF). Materials and methods: Patient records were retrieved from Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. The ELD-treated osteoporosis patient cohort (ELD cohort) was analyzed to determine the incidence rate of the aforementioned AEs. The patient cohort that was prescribed active vitamin D3 other than ELD (AVD cohort) was analyzed as the reference. Results: Incidence rates of hypercalcemia, AKI, and urolithiasis in the ELD cohort were 0.942, 0.517, 2.465 events per 100 person-years, respectively, in the MDV dataset, and 0.687, 0.155, 3.785, respectively, in the JMDC dataset. The incidence rates of these AEs in the ELD cohort remained relatively constant throughout ELD treatment. A small number of patients experienced ONJ or AFF during ELD or AVD treatment. The number of ONJ and AFF cases in the both cohorts decreased over time. The two cohorts showed no difference in the concomitant use of anti-bone resorptive agents such as bisphosphonates and denosumab. Conclusion: The risk of hypercalcemia and AKI associated with ELD use observed in this retrospective analysis is similar to that reported previously in the Japanese post-marketing surveillance of ELD. Furthermore, ELD, similar to AVD, may not increase the risk of ONJ and AFF. [ABSTRACT FROM AUTHOR]

Introduction: When performing intramedullary nailing for atypical femoral fractures (AFF), especially in lateral bowing femurs, a medial opening wedge-shaped gap in the fracture site may occur after nailing. We intended to analyse and compare clinical outcomes according to the medial gap in AFF cases after intramedullary nailing. Materials and Methods: Of the 38 consecutive patients with complete AFF treated by intramedullary nailing, 22 patients (all female, mean age of 76.5 years [range, 62-87]) available for follow-up for more than 12 months were included. According to the size of the medial gap, the patients were divided into 2 groups: large and small medial gaps. Comparative analysis was performed between groups in terms of patient, fracture characteristics and post-operative clinical outcomes. Results: There was no significant difference in bone union time between the 2 groups (5.4 months vs 5.6 months, P = .628). When comparing the amount of change in the hip-knee-ankle angle after the surgery with reference to the contralateral side, there was a significant difference between the 2 groups (-4.4° [femoral straightening and relatively changed to a more valgus pattern, that is, in cases of varus alignment, towards neutral alignment] vs .5°, P = .002). There was no significant difference in leg length discrepancy between the 2 groups (4.1mmvs 3.2mm, P = .674). In terms of functional outcomes, there was no significant difference in the recovery of ambulatory ability (ΔKoval grade: post-operative Koval grade-pre-operative Koval grade, 0 vs .1, P = .771). Conclusion: Even if the medial gap occurs following intramedullary nailing in AFF, post-operative clinical outcomes seem to be acceptable. However, if previous total knee arthroplasty is performed and neutral alignment is maintained, care should be taken as the occurrence of the gap may result in lower limb malalignments. [ABSTRACT FROM AUTHOR]

Atypical femoral fractures (AFF) are more difficult to treat than typical femoral fractures; they require strong fixation and good reduction. Intramedullary (IM) nailing is the first option for the treatment of complete AFF; however, there are few reports comparing IM nailing and extramedullary fixation. Moreover, there are no reports on the outcomes of bilateral atypical subtrochanteric femoral fractures treated with an IM nail on one side and a compression hip screw (CHS) on the other. We report the case of a 69-year-old woman who had been on risedronate sodium once a month since she was 58 years old. She reportedly felt pain in both her thighs due to an undiagnosed cause. Six months later, she fell and was diagnosed with bilateral complete atypical femoral subtrochanteric fractures (right side: Seinsheimer type IIC; left side: Seinsheimer type IIA). Four days later, she underwent CHS on the right side and IM nailing after open reduction surgery on the left. The reduction was successful. The left side healed 6 months after surgery, but the right side healed only after 14 months, despite assistance with low-intensity pulsed ultrasound. In atypical femoral subtrochanteric fractures, good reduction is important for healing, but, in this case, the CHS side healed slowly despite achievement of good reduction because of the difference in the fixation force between IM nailing and CHS, in addition to a probable occurrence of severely suppressed bone turnover (SSBT). Furthermore, reaming was not done on the CHS side, which may have contributed to the delay in bony union. IM nailing is the first option for atypical femoral subtrochanteric fractures because of faster union and lower reoperation rate than extramedullary fixation. Based on our findings, we recommend IM nailing as the first option for atypical femoral subtrochanteric fractures when good reduction can be achieved.