Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the ...incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors.
We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented.
Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval CI, 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians.
The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.).
From February 20 to April 2020, the coronavirus SARS (severe acute respiratory syndrome)-CoV-2 spread in northern Italy, drastically challenging the care capacities of the national health care ...system. Unprepared for this emergency, hospitals have quickly reformulated paths of assistance in an effort to guarantee treatment for infected patients. Orthopaedic departments have been focused on elderly traumatology, especially the treatment of femoral neck fractures in patients with coronavirus disease-2019 (COVID-19). The purpose of the present study was to evaluate the orthopaedic management strategy for femoral fragility fractures in COVID-19-positive patients with the hypothesis that operative treatment may contribute to the overall stability of the patient.
Sixteen patients affected by proximal femoral fracture and a recent history of fever, shortness of breath, and desaturation were admitted to the emergency room. Thoracic computed tomography (CT) and oropharyngeal swabs confirmed that they were positive for COVID-19, requiring hospitalization and prophylaxis with low-molecular-weight heparin.
Three patients died before surgery because of severe respiratory insufficiency and multiple-organ-failure syndrome. Ten patients underwent surgery on the day after admission, whereas 3 patients had suspended their use of direct thrombin inhibitors and needed surgery to be delayed until the third day after admission. In all patients except 1, we noted an improvement in terms of O2 saturation and assisted respiration. In 9 patients, hemodynamic and respiratory stability was observed at an average of 7 days postoperatively. Four patients who underwent surgical treatment died of respiratory failure on the first day after surgery (1 patient), the third day after surgery (2 patients), or the seventh day after surgery (1 patient).
We noted a stabilization of respiratory parameters in 12 COVID-19-positive patients who underwent surgery treatment of proximal femoral fractures. We believe that in elderly patients with COVID-19 who have proximal femoral fractures, surgery may contribute to the overall stability of the patient, seated mobilization, improvement in physiological ventilation, and general patient comfort in bed.
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Summary
The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or ...osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment.
Introduction
To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing.
Methods
We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing.
Results
The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1–17 years). The use of BPs was significantly associated with AFFs (
p
< 0.001, odds ratio = 25.65; 95% confidence interval = 10.74–61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment.
Conclusions
The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.
Abstract
Context
Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
Evidence acquisition
We performed a systematic review to ...evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF.
Evidence synthesis
We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient.
Conclusions
There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
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.
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High-strength fully porous biomaterials built with additive manufacturing provide an exciting opportunity for load-bearing orthopedic applications. While factors controlling their ...mechanical and biological response have recently been the subject of intense research, the interplay between mechanical properties, bone ingrowth requirements, and manufacturing constraints, is still unclear. In this paper, we present two high-strength stretch-dominated topologies, the Tetrahedron and the Octet truss, as well as an intuitive visualization method to understand the relationship of cell topology, pore size, porosity with constraints imposed by bone ingrowth requirements and additive manufacturing. 40 samples of selected porosities are fabricated using Selective Laser Melting (SLM), and their morphological deviations resulting from SLM are assessed via micro-CT. Mechanical compression testing is used to obtain stiffness and strength properties, whereas bone ingrowth is assessed in a canine in vivo model at four and eight weeks. The results show that the maximum strength and stiffness ranged from 227.86±10.15 to 31.37±2.19MPa and 4.58±0.18 to 1.23±0.40GPa respectively, and the maximum 0.2% offset strength is almost 5 times stronger than that of tantalum foam. For Tetrahedron samples, bone ingrowth after four and eight weeks is 28.6%±11.6%, and 41.3%±4.3%, while for the Octet truss 35.5%±1.9% and 56.9%±4.0% respectively. This research is the first to demonstrate the occurrence of bone ingrowth into high-strength porous biomaterials which have higher structural efficiency than current porous biomaterials in the market.
We present two stretch-dominated cell topologies for porous biomaterials that can be used for load-bearing orthopaedic applications, and prove that they encourage bone ingrowth in a canine model. We also introduce an intuitive method to visualize and understand the relationship of cell topology, pore size, porosity with constraints imposed by bone ingrowth requirements and additive manufacturing. We show this strategy helps to gain insight into the interaction of exogenous implant factors and endogenous system factors that can affect the success of load-bearing orthopaedic devices.
•The incidence of secondary hip fractures (SHFs) after nailing fixations for femoral fractures was 0.7%.•The absence of femoral head fixation was significantly associated with SHF following ...intramedullary nailing for femoral shaft fractures.•There were two reoperations (16.7%) following management of secondary femoral neck fractures.•Secondary trochanteric fracture patients were less likely to regain walking ability than secondary femoral neck fracture patients.
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.
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.
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%).
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.
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