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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.
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@#Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves’ disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs’ formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.
Subject(s)
Diphosphonates , HyperthyroidismABSTRACT
Objective: We report two cases of atypical femoral fracture (AFF) in patients with cancer.Patients: Two patients, a 53-year-old woman with breast cancer and a 77-year-old man with prostate cancer, could not walk after being injured in a fall. They used bone-modifying agents (BMA) for the prevention of bone metastasis for three and four years, respectively.Results: Intramedullary nails were placed to fix the femoral fractures in each patient. Neither of them had pathological metastatic femoral fractures based on fracture site specimens; however, severe suppression of bone turnover at the fracture site was suspected. Both patients could ambulate with a T-cane and were free of hip pain after surgery. Radiographs showed no callus formation at the fracture site.Conclusion: Based on the two cases of AFF in patients with cancer related to BMA use, we should consider that the incidence of AFF may be associated with long-term BMA use.
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PURPOSE: Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ.METHODS: Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed.RESULTS: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy.CONCLUSIONS: The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.
Subject(s)
Female , Humans , Male , Bisphosphonate-Associated Osteonecrosis of the Jaw , Comorbidity , Femoral Fractures , Incidence , Jaw , Osteonecrosis , Osteoporosis , Prevalence , Radionuclide Imaging , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Although bone scan might be useful to detect incomplete atypical femoral fractures (AFFs) earlier than radiographs, there is no study on predicting further progression to a complete fracture among incomplete AFFs. Our purposes are to determine whether bone scan detects impending complete fracture among incomplete AFFs. METHODS: We reviewed 18 patients (20 AFFs) who underwent bone scan at the diagnosis of incomplete AFF and were not treated with prophylactic fixation. A diagnosis of impending complete fracture was made, when the femur completely fractured within 6 months after the scan. We correlated radioisotope uptake with the impending complete fracture to calculate sensitivity, specificity, positive predictive value and negative predictive value of bone scan. RESULTS: Thirteen AFFs (65%, 13/20) showed a positive uptake in bone scan. Among the 13, only one femur was completely fractured within 6 months. None of the 7 femurs without uptake in bone scan fractured. In diagnosing impending complete fracture, the sensitivity of bone scan was 100% and negative predictive value was 100%. However, the specificity (36.8%) and positive predictive value (7.7%) were quite low. CONCLUSION: Bone scan has no significant role in detecting the impending complete fracture, and a positive uptake does not mean the necessity of prophylactic fixation of incomplete AFF.
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Humans , Diagnosis , Femoral Fractures , Femur , Sensitivity and SpecificityABSTRACT
Atypical femoral fractures differ from ordinary femoral diaphyseal or subtrochanteric fractures in several aspects. Although several authors have reported the results of surgical treatment for atypical femoral fractures, the rate of complications (e.g., delayed union, nonunion, fixation failure, and reoperation) is still high. Therefore, we reviewed principles of surgical treatment and describe useful methods for overcoming femoral bowing in these high-risk patients.
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Humans , Femoral Fractures , Hip FracturesABSTRACT
PURPOSE: The purpose of this study is to evaluate the effects of teriparatide administration on fracture healing after intramedullary nailing in atypical femoral fractures. MATERIALS AND METHODS: We retrospectively reviewed 26 patients (26 cases) with atypical femoral fracture who were treated using intramedullary nailing between January 2009 and December 2013. Teriparatide was not administered to 15 patients (non-injection group) and was administered to 11 patients after surgery (injection group). Clinical results were assessed using the Nakajima score and the visual analogue scale (VAS). Radiographic results were compared for the time of callus formation, callus bridge formation, and bone union between the groups. RESULTS: Time to recover walking ability and to decrease pain in the surgery region (VAS≤2) were significantly shorter in the injection group than in the non-injection group. The time of callus formation, callus bridge formation, and bone union was significantly shorter in the injection group than in the non-injection group. There were 5 cases of delayed bone union (33.3%) and 1 case of none union (6.7%) in the non-injection group and all cases obtained bone union in injection group. CONCLUSION: The injection group showed better clinical and radiographic results than the non-injection group after intramedullary nailing in atypical femoral fracture. Therefore, we think that teriparatide administration after intramedullary nailing could be a useful treatment option to promote bone union.
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Humans , Bony Callus , Femoral Fractures , Fracture Fixation, Intramedullary , Fracture Healing , Parathyroid Hormone , Retrospective Studies , Teriparatide , WalkingABSTRACT
<p><b>Objective</b>: Monitoring the incidence of atypical femoral fractures (AFFs) using medical claim databases is useful to assess the safety of long-term bisphosphonate exposure. Therefore, we aimed to validate the relationship between clinically-defined suspected AFFs and the candidate patients obtained from claims data at three hospitals in Japan.</p><p><b>Design</b>: A cross-sectional study involving three hospitals that perform bone fracture surgery and from which electronic medical record databases of diagnoses and procedures are available.</p><p><b>Methods</b>: Candidate patients were at the medical databases using two International Classification of Diseases, 10th Edition (ICD-10) codes (subtrochanteric fracture and fracture of shaft of femur) in the claims databases. These potential cases by claim-based definition were validated using clinically-confirmed information such as, the patient operation records, the discharge records, or radiographic imaging findings as suspected AFFs.</p><p><b>Results</b>: Among fracture cases in the hospitals, and 9 cases with subtrochanteric fracture and 23 cases with femoral shaft fracture were identified based on the ICD-10 codes in the claims databases. Clinically confirmed subtrochanteric fracture had a sensitivity of 81.8% (95% CI: 48.2-97.7%), and a specificity of 100.0% (95% CI: 99.9-100.0%). For femoral shaft fracture, the sensitivity was 82.1% (95% CI: 63.1-93.9%), and the specificity was 100.0% (95% CI: 99.9-100.0%). In subgroup analyses, the sensitivities in patients over the age of 50 years with a single fracture site and with osteoporosis were relatively higher than in other subgroups.</p><p><b>Conclusion</b>: The claims-based definitions of suspected AFFs are accurate, indicating the value of pharmacoepidemiological studies using the National Receipt Database.</p>
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PURPOSE: Atypical femoral fracture (AFF), periprosthetic femoral fracture (PPFF) and femoral nonunion (FNU) are recalcitrant challenges for orthopedic surgeons. Teriparatide (TPTD) had been demonstrated to have anabolic effects on bone in various studies. We postulated that adjuvant TPTD after operation would enhance biologic stimulation for bone formation. We investigated (1) whether the adjuvant TPTD could achieve satisfactory union rate of surgically challenging cases such as displaced AFF, PPFF and FNU; (2) whether the adjuvant TPTD could promote development of abundant callus after surgical fixation; (3) whether the adjuvant TPTD had medically serious adverse effects. MATERIALS AND METHODS: Thirteen patients who agreed to off label use of TPTD in combination of operation were included in this retrospective case series. Median patients' age was 68.7 years, and there were three male and ten female patients. Their diagnoses were nonunion in six patients and acute fracture in seven. Medical records and radiographic images were reviewed. RESULTS: Twelve of thirteen fractures were united both clinically and radiologically within a year after adjuvant TPTD. Union completed radiologically median 5.4 months and clinically 5.7 months after the medication, respectively. Callus appeared abundantly showing median 1.4 of fracture healing response postoperatively. There was no serious adverse reaction of medication other than itching, muscle cramp, or nausea. CONCLUSION: Even appropriate surgical treatment is a mainstay of treatment for AFF, PPFF, and FNU, the current report suggested that adjuvant TPTD combined with stable fixation results in satisfactory outcome for the challenging fractures of femur.
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Female , Humans , Male , Anabolic Agents , Bony Callus , Diagnosis , Femoral Fractures , Femur , Fracture Healing , Medical Records , Muscle Cramp , Nausea , Off-Label Use , Orthopedics , Osteogenesis , Periprosthetic Fractures , Pruritus , Retrospective Studies , Surgeons , TeriparatideABSTRACT
Although several publications have reported delayed or non-union, there is a consensus that the standard treatment for atypical femoral fracture (AFF) is an intramedullary nailing. However, no case of tensile insufficiency fracture of femoral neck associated with intramedullary nailing in patients with AFF have been reported. Here, we report an 82-year-old woman with tensile type of insufficiency fracture of the femoral neck after intramedullary nailing for the treatment of AFF.
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Aged, 80 and over , Female , Humans , Consensus , Femoral Fractures , Femur Neck , Fracture Fixation, Intramedullary , Fractures, Stress , OsteoporosisABSTRACT
Atypical femoral fractures are stress or insufficient fractures induced by low energy trauma or no trauma and have specific X-ray findings. Although the American Society for Bone and Mineral Research has excluded periprosthetic fractures from the definition of an atypical femoral fracture in 2013, this is still a matter of controversy because some authors report periprosthetic fractures showing specific features of atypical fractures around a well-fixed femoral stem. We report 3 cases of periprosthetic femur fractures that had specific radiographic features of atypical femoral fractures in patients with a history of prolonged bisphosphonate use; we also review relevant literature.
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Humans , Arthroplasty , Femoral Fractures , Femur , Hip , Periprosthetic FracturesABSTRACT
Bisphosphonate (BP) is a useful anti-resorptive agent which decreases the risk of osteoporotic fracture by about 50%. However, recent evidences have shown its strong correlation with the occurrence of atypical femoral fracture (AFF). The longer the patient takes BP, the higher the risk of AFF. Also, the higher the drug adherence, the higher the risk of AFF. It is necessary to ask the patients who are taking BP for more than 3 years about the prodromal symptoms such as dull thigh pain. Simple radiography, bone scan, and magnetic resonance imaging (MRI) are good tools for the diagnosis of AFF. The pre-fracture lesion depicted on the hip dual energy X-ray absorptiometry (DXA) images should not be missed. BP should be stopped immediately after AFF is diagnosed and calcium and vitamin D (1,000 to 2,000 IU) should be administered. The patient should be advised not to put full weight on the injured limb. Daily subcutaneous injection of recombinant human parathyroid hormone (PTH; 1-34) is recommended if the patient can afford it. Prophylactic femoral nailing is indicated when the dreaded black line is visible in the lateral femoral cortex, especially in the subtrochanteric area.
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Humans , Absorptiometry, Photon , Calcium , Diagnosis , Extremities , Femoral Fractures , Hip , Injections, Subcutaneous , Magnetic Resonance Imaging , Osteoporotic Fractures , Parathyroid Hormone , Prodromal Symptoms , Radiography , Thigh , Vitamin DABSTRACT
Bisphosphonate, a potent anti-resorptive agent, is generally accepted as a safe, effective, well tolerated treatment for postmenopausal osteoporosis. Atypical femoral fracture (AFF) and bisphosphonate related osteonecrosis of jaw (BRONJ) are the increasing morbidities in patients treated with long term bisphosphonate. Pathogenic mechanisms of AFF and BRONJ are not fully identified and not identical. We report a case of BRONJ followed by AFF and its nonunion in a 67-year-old woman patient receiving an oral bisphosphonate during 7 years for the treatment of osteoporosis.
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Aged , Female , Humans , Femoral Fractures , Jaw , Osteonecrosis , Osteoporosis , Osteoporosis, PostmenopausalABSTRACT
Atypical femoral fractures occur at the subtrochanteric or diaphyseal area, unlike typical hip fractures. Characteristics of atypical femoral fractures include their location in the subtrochanteric region and the femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution. The incidence of atypical femoral fracture is very low, and several studies have reported statistically significant association of long-term bisphosphonate therapy with atypical femoral shaft fractures; however, this has not been proven. We review the epidemiology and clinical features of atypical femoral fracture in the literature, and also discuss the association between atypical femoral fracture and long-term use of bisphosphonate.
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Femoral Fractures , Hip Fractures , Incidence , OrientationABSTRACT
PURPOSE: We attempted to determine the differences in frequency, as well as clinical, radiologic characteristics of atypical femoral fracture between groups of patients who have taken bisphosphonate and those who have not by conduct of a retrospective analysis of patients with low energy subtrochanteric and shaft fractures of the femur. MATERIALS AND METHODS: We conducted a retrospective study of 44 cases of 41 female patients over 60 years old who underwent surgery due to femoral shaft/subtrochanteric fractures from August 2001 to October 2011. The patients were divided into two groups: Group A, 22 cases in 19 patients with a history of bisphosphonate treatment; Group B, 22 cases in 22 patients without a history of bisphosphonate treatment as a control group. We assessed the duration of bisphosphonate treatment, presence of prodromal symptoms, and radiological results, and compared age, BMD results, union period, and nonunion rate between the two groups. RESULTS: Mean medication period was 56.8 months(12-132 months) and prodromal symptoms were observed in one case. Lateral cortical thickening and transverse fracture with a medial cortical bone beak were observed in all patients of Group A, and contralateral cortical hypertrophy of the femur was noted in 15 patients(17 cases) (77.3%). Mean age was 73.2 years in Group A and 78.2 years in Group B, which showed significant difference (P=0.021), while no difference was observed in BMD, union period, and nonunion rate. CONCLUSION: An atypical femoral fracture can occur in the subtrochanteric or shaft of the femur. The typical radiological characteristics of this fracture are lateral cortical thickening and transverse fracture with a medial cortical bone beak and contralateral abnormality of cortical bone. Findings of this study suggest that medical practitioners should be careful of atypical fractures with osteoporosis patients who use prolonged bisphosphonate.
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Animals , Female , Humans , Beak , Femoral Fractures , Femur , Hypertrophy , Osteoporosis , Prodromal Symptoms , Retrospective StudiesABSTRACT
Little literature exists about the risk of atypical femoral fracture in patients received zoledronic acid for prevention of skeletal metastasis. We report an atypical subtrochanteric femoral fracture in a patient with multiple myeloma received zoledronic acid. The patient was treated by closed reduction and internal fixation with cephalomedullary nailing.
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Humans , Diphosphonates , Femoral Fractures , Imidazoles , Multiple Myeloma , Nails , Neoplasm MetastasisABSTRACT
Increasing numbers of atypical subtrochanteric fractures have been reported among long-term bisphosphonate users. However, the nature and extent of the problem are unknown despite recent investigations. The task force of American Society for Bone and Mineral Research (ASBMR) defined major and minor features of complete and incomplete atypical femoral fractures; transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including bisphosphonate, glucocorticoids, and proton pump inhibitors. Based on published data, the incidence of atypical femoral fractures associated with bisphosphonate therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by bisphosphonate. Physicians and patients should be aware of the possibility of atypical femoral fractures and of the potential for bilaterality.