Managing periprosthetic tibia fractures: International perspectives.

Knee arthroplasty, both total knee and unicompartmental, has had a significant impact on millions of patients globally. Although satisfaction is usually high, complications such as periprosthetic fracture are increasingly common. Distal femur periprosthetic fractures are relatively well researched and understood in comparison with periprosthetic proximal tibia fractures (PTFs). The management of PTFs is essentially an evidence-free area. This review explores the literature (or lack thereof) and integrates cases from Australia and Japan. As it stands, there is scant literature relating to all facets of PTFs, including, most concerningly, the management of them. Larger studies are required to help further investigate this important interface between arthroplasty and orthopaedic trauma. As a guide, those with loose prostheses will likely benefit most from revision total knee arthroplasty, while those with well-fixed prostheses can be managad according to the fracture with homage paid to the presence of the prosthesis. The use of periarticular locked plates is likely a better option over conventional large or small fragment plates. Nonoperative management is a viable option for selected individuals and can be associated with favorable outcomes.

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study.

Edoxaban (Edx) has been approved to prevent venous thromboembolism after total knee and/or hip arthroplasty in Japan. However, the risk of anemia with Edx treatment remains elusive. No risk factors for Edx-associated anemia after orthopedic surgery have been reported. This study aimed to clarify the risk of anemia associated with Edx treatment and determine the risk factors for Edx-associated anemia after orthopedic surgery with a high risk for bleeding. First, the association between Edx treatment and the incidence of anemia-related events was retrospectively investigated by pharmacovigilance analyses using data from 5769,866 reports between the first quarters of 2016 and 2020 in the Food and Drug Administration Adverse Event Reporting System and 2752,050 reports between the fourth quarters of 2011 and 2019 in the Japanese Adverse Drug Event Report. Second, 221 patients who underwent Edx treatment after total knee and/or hip arthroplasty between July 2011 and June 2012 at a single center were included in a case-control study to clarify the risk factors for anemia. Edx treatment was associated with an increased risk of anemia-related events in orthopedic patients. Reduced renal function was identified as a critical risk factor for Edx-associated anemia after orthopedic surgery. The present study indicates that renal function should be considered in the risk management of increased Edx-associated anemia after orthopedic surgery.

The Contribution of Deleterious Rare Alleles in ENPP1 and Osteomalacia Causative Genes to Atypical Femoral Fracture.

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). CONCLUSION: 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.

Bimagrumab to improve recovery after hip fracture in older adults: a multicentre, double-blind, randomised, parallel-group, placebo-controlled, phase 2a/b trial.

BACKGROUND: Older adult patients (ie, those aged ≥60 years) undergoing surgery for hip fracture repair frequently experience loss of muscle mass and strength due to poor mobility and delayed functional recovery. No proven treatment is currently available to enhance recovery of physical function in this growing patient population. This study aimed to investigate whether bimagrumab, a human monoclonal antibody targeting activin type 2 receptors, can improve post-surgical recovery. METHODS: This multicentre, double-blind, randomised, parallel-group, placebo-controlled, phase 2a/b trial was done at 50 clinical research centres in 18 countries. Participants aged 60 years or older with a body-mass index of 15-35 kg/m2 who had undergone internal fixation or hemiarthroplasty for a proximal femoral fracture (confirmed by radiography) in the previous 6 weeks were eligible. Patients with a history of a high-energy subtrochanteric fracture or any other lower limb fracture in the past 6 months, or any major surgery of the lower limbs in the past 3 months were excluded. Participants were randomly assigned (2:1:2:2) via interactive response technology to receive intravenous treatment with placebo, bimagrumab 70 mg, bimagrumab 210 mg, or bimagrumab 700 mg every 4 weeks for 24 weeks. Participants, investigators, site personnel, and study sponsor personnel in participating countries were masked to treatment assignment. The primary endpoint was the change from baseline in total lean body mass, measured by dual-energy x-ray absorptiometry, at week 24 in the full analysis set, which included all randomised participants who had received at least one dose of the assigned treatment. Key secondary endpoints included changes in habitual gait speed (measured in m/s) and short physical performance battery score between baseline and 24 weeks. Safety and tolerability were assessed by recording adverse events and vital signs on weeks 4, 8, 12, 24, and 48, and by laboratory assessments and electrocardiography at the screening visit and on days 1, 84, and 168. Safety was assessed in all randomised participants who had received at least one dose of study drug, analysed according to treatment received. This study was registered with ClinicalTrials.gov, NCT02152761. FINDINGS: Between Sept 16, 2014, and Dec 15, 2017, 384 patients were screened, of whom 250 patients were enrolled and randomly assigned to the placebo group (n=72), the bimagrumab 70 mg group (n=34), the bimagrumab 210 mg group (n=69), or the bimagrumab 700 mg group (n=75). A total of 207 (83%) participants completed the 24-week treatment period. There was a significant absolute increase in lean body mass from baseline compared with placebo (0·2 kg [SD 2·0]) in the bimagrumab 210 mg group (1·9 kg [1·7]; p<0·0001) and in the bimagrumab 700 mg group 2·8 kg [2·2]; p<0·0001) but not in the bimagrumab 70 mg group (0·6 kg [SD 2·2]; significance not assessed). Changes in habitual gait speed and short physical performance battery scores between baseline and week 24 were not significantly different across the treatment groups, suggesting no enhancement of physical recovery with bimagrumab over placebo. Bimagrumab was safe and well tolerated. The most frequently reported treatment-emergent adverse events were falls (six [18%] of 34 participants in the bimagrumab 70 mg group; 12 [17%] of 69 participants in the bimagrumab 210 mg group; 14 [19%] of 75 participants in the bimagrumab 700 mg group; and 13 [18%] of 72 participants in the placebo group), muscle spasms (two [6%] in the bimagrumab 70 mg group; 17 [25%] in the bimagrumab 210 mg group; 12 [16%] in the bimagrumab 700 mg group; and six [8%] in the placebo group), and arthralgia (five [15%] in the bimagrumab 70 mg group; six [9%] in the bimagrumab 210 mg group; nine [12%] in the bimagrumab 700 mg group; and five [7%] in the placebo group). Six deaths were reported during the study, none of which were considered by investigators as related to the study drug. INTERPRETATION: Bimagrumab treatment for 24 weeks led to dose-dependent, significant increases in lean body mass in older patients recovering from hip fracture surgery when compared with placebo. However, no functional benefit was observed in recovery of mobility or lower extremity function following bimagrumab treatment compared with placebo. FUNDING: Novartis Pharma.

The clinical impact of edoxaban for the patients with postoperative anemia after total hip arthroplasty.

BACKGROUND: Postoperative anemia is a common complication after total hip arthroplasty (THA). However, the effect of edoxaban on postoperative anemia after THA remains unclear. Here, we retrospectively evaluated the clinical assessment of postoperative anemia and the associated changes of coagulation parameters in patients undergoing thromboprophylaxis with edoxaban compared with fondaparinux as a conventional anticoagulant thromboprophylactic agent after THA. METHODS: One hundred and forty-nine patients who underwent THA from July 2010 to June 2012 were divided into two groups, according to whether they were operated on before or after the approval of edoxaban: the fondaparinux group (Group F: 86 patients) and the edoxaban group (Group E: 63 patients). The frequency of postoperative anemia and blood coagulation values were investigated. RESULTS: Postoperative anemia developed more frequently in Group E than in Group F after surgery. However, the degree of postoperative anemia showed no significant difference between the groups. Meanwhile, prothrombin time (PT), prothrombin time-international normalized ratio (PT-INR), and activated partial thromboplastin time were markedly higher in patients with edoxaban-associated postoperative anemia, which showed an increased potential to predict the occurrence of postoperative anemia. Additionally, both PT and PT-INR in Group E were also correlated with the volume of estimated blood loss. CONCLUSION: The frequency of postoperative anemia was increased in patients treated with edoxaban, compared to fondaparinux, after THA. Edoxaban thromboprophylaxis might, therefore, require more careful monitoring to prevent postoperative anemia. Additionally, particular prolongation of PT and PT-INR induced by edoxaban treatment might predict postoperative anemia.

Calcar Femorale in Patients with Osteoarthritis of the Hip Secondary to Developmental Dysplasia.

BACKGROUND: We investigated whether the calcar femorale, a cortical septum in the region of the lesser trochanter of the femur, correlates with results of femoral stem implantation in patients with osteoarthritis of the hip secondary to developmental dysplasia using computed tomography. METHODS: This retrospective study included 277 hips (41 males and 236 females; age, 37 to 92 years) of patients who had presented to Okayama Medical Center with hip pain. Of these, a total of 219 hips (31 males and 188 females) had previously undergone total hip arthroplasty. According to the Crowe classification, 147 hips were classified as Crowe grade I, 72 hips as Crowe grade II-IV, and 58 hips as normal. RESULTS: The calcar femorale was identified in 267 hips (96.4%). The calcar femorale was significantly shorter and more anteverted in Crowe grade II-IV hips than in Crowe grade I or normal hips. Significant differences in the shape of the calcar femorale were found according to the severity of hip deformity. Three stem designs were analyzed: single-wedge (59 hips), double-wedge metaphyseal filling (147 hips), and modular (13 hips). Single-wedge stems were inserted more parallel to the calcar femorale rather than femoral neck anteversion, while other types of stems scraped the calcar femorale. CONCLUSIONS: The angle of the calcar femorale differs according to the severity of hip deformity, and the calcar femorale might thus serve as a more useful reference for stem insertion than femoral neck anteversion in total hip arthroplasty using a single-wedge stem.

Total hip arthroplasty after failed treatment of proximal femur fracture.

INTRODUCTION: Total hip arthroplasty (THA) is a good option as a salvage procedure after failed treatment of proximal femur fracture. The anatomy of the proximal femur, however, makes this surgery complicated and challenging. The purpose of this study was to evaluate the radiographic and clinical outcomes of THA after failed treatment of proximal femur fractures. MATERIALS AND METHODS: We retrospectively analysed 50 consecutive THAs (42 women, 8 men; mean age 77 years) after failed treatment of a proximal femur fracture. Mean postoperative follow-up was 58.1 months. Preoperative diagnoses were femoral neck fracture in 18 hips and trochanteric fracture in 32 hips, including three that were infected. Failure resulted from cutout in 22 cases, osteonecrosis in 12, non-union with failed fixation in nine, postoperative osteoarthritis in four, and infection in three. Factors compared included radiographic assessment, complication rate, visual analogue scale (VAS), and Harris Hip Scores (HHS). Radiographic variables included femoral neck anteversion and cup and stem alignment. RESULTS: Absolute values of the differences in femoral neck anteversion between the affected and healthy sides were 6.0° in the femoral neck fracture group and 19.2° in the trochanteric fracture group (p = 0.01). There were no significant differences in cup anteversion (p = 0.20) or stem anteversion (p = 0.08). The complication rate was significantly higher in the trochanteric fracture group than in the femoral neck fracture group (25 vs 0%, p < 0.0001). Postoperative complications in the trochanteric fracture group included three periprosthetic fractures (9.4%), two dislocations (6.3%), two surgical-site infections (6.3%), and one stem penetration (3.1%). Although no significant differences between groups were seen in the VAS or HHS at final follow-up (p = 0.32, 0.09, respectively), these measures were significantly improved at final follow-up in both groups (p < 0.0001 for both). CONCLUSIONS: Performing THA after failed treatment of trochanteric fractures requires consideration of complication risk and incorrect femoral neck anteversion.

Clinical Assessment of Postoperative Anemia Associated with Edoxaban in Patients Undergoing Total Knee Arthroplasty Compared to Fondaparinux.

Edoxaban, an oral direct factor Xa inhibitor, was developed and approved for anticoagulant thromboprophylaxis after total knee arthroplasty (TKA). We retrospectively investigated the postoperative anemia by oral administration of edoxaban 30 mg compared with fondaparinux 2.5 mg in TKA patients. Two hundred twenty nine patients who underwent TKA in National Hospital Organization Okayama Medical Center from July 2010 to June 2012 were divided into two groups; pre and post approval of edoxaban: fondaparinux-group (F-group) and edoxaban-group (E-group). As the primary endpoint, the frequency of postoperative anemia was evaluated. Blood coagulation values and relations between these parameters and postoperative anemia were also investigated. The frequency of postoperative anemia was significantly higher in E-group than F-group patients (52.7% vs. 37.8%; p<0.05). Hemoglobin (Hgb) levels were decreased with the peak at postoperative day (POD) 3 in both groups, and the change of Hgb values from POD1 (ΔHgb) was significantly increased in the E-group (p=0.04). At each POD, prothrombin time (PT) and international normalized ratio of PT (PT-INR) prolonged from the preoperative day in E-group were significantly higher than F-group. Additionally, PT and PT-INR in the E-group at POD3 were significantly prolonged in patients with postoperative anemia and the sensitivity of cut-off values to predict postoperative anemia was superior to the activated partial thromboplastin time (APTT). Thus, as the frequency of postoperative anemia tended to be higher in E-group, edoxaban 30 mg might require vigilance, and prolonged PT and PT-INR could potentially predict edoxaban-associated postoperative anemia after TKA.

Mechanical prophylaxis is a heparin-independent risk for anti-platelet factor 4/heparin antibody formation after orthopedic surgery.

Platelet-activating antibodies, which recognize platelet factor 4 (PF4)/heparin complexes, induce spontaneous heparin-induced thrombocytopenia (HIT) syndrome or fondaparinux-associated HIT without exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). This condition mostly occurs after major orthopedic surgery, implying that surgery itself could trigger this immune response, although the mechanism is unclear. To investigate how surgery may do so, we performed a multicenter, prospective study of 2069 patients who underwent total knee arthroplasty (TKA) or hip arthroplasty. Approximately half of the patients received postoperative thromboprophylaxis with UFH, LMWH, or fondaparinux. The other half received only mechanical thromboprophylaxis, including dynamic (intermittent plantar or pneumatic compression device), static (graduated compression stockings [GCSs]), or both. We measured anti-PF4/heparin immunoglobulins G, A, and M before and 10 days after surgery using an immunoassay. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (DMT) was an independent risk factor for seroconversion (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.34-3.02; P = .001), which was confirmed with propensity-score matching (OR, 1.99; 95% CI, 1.17-3.37; P = .018). For TKA, the seroconversion rates in patients treated with DMT but no anticoagulation and in patients treated with UFH or LMWH without DMT were similar, but significantly higher than in patients treated with only GCSs. The proportion of patients with ≥1.4 optical density units appeared to be higher among those treated with any anticoagulant plus DMT than among those not treated with DMT. Our study suggests that DMT increases risk of an anti-PF4/heparin immune response, even without heparin exposure. This trial was registered to www.umin.ac.jp/ctr as #UMIN000001366.

Four-year results of Summit stems for total hip arthroplasty in Japanese patients.

PURPOSE: A retrospective study to evaluate the clinical and radiographic outcome of the Summit primary total hip arthroplasty (THA) at a minimum follow-up of 4 years. METHODS: 87 hips in 84 Japanese patients underwent THA using Summit stems. 3 patients were lost to follow-up, and 4 patients were excluded because a Summit stem was judged to be inappropriate for their narrow femoral canals. The remaining 80 hips in 77 patients were evaluated. Mean age was 66 years (range, 33-86 y). Mean postoperative follow-up period was 52 months (range, 48-66 m). RESULTS: There was no early stem subsidence after surgery. Of the 80 hips, 60 (75%) showed radiographic signs of stem osseointegration including zones 3 and 5 at final follow-up. Stress shielding occurred in 50 hips (62.5%), and third-degree stress shielding was observed in 12 hips (15%). 3 patients experienced postoperative thigh pain due to distal fixation. CONCLUSIONS: These short-term results indicate that the Summit stem achieved good initial fixation, although there were some cases of distal fixation. Careful long-term follow-up and observation will be necessary for hips in which stress shielding occurs.

Comparison of Continuous Epidural Analgesia, Patient-Controlled Analgesia with Morphine, and Continuous Three-in-One Femoral Nerve Block on Postoperative Outcomes after Total Hip Arthroplasty.

BACKGROUND: Postoperative pain relief can be achieved with various modalities. However, there are only few reports that have analyzed postoperative analgesic techniques in total hip arthroplasty patients. The aim of this retrospective study was to compare the postoperative outcomes of three different analgesic techniques after total hip arthroplasty. METHODS: We retrospectively reviewed the influence of three analgesic techniques on postoperative rehabilitation after total hip arthroplasty in 90 patients divided into three groups (n = 30 patients per group). Postoperative analgesia consisted of continuous epidural analgesia (Epi group), patient-controlled analgesia with morphine (PCA group), or a continuous femoral nerve block (CFNB group). We measured the following parameters relating to postoperative outcome: visual analog scale scores, the use of supplemental analgesia, side effects, length of the hospital stay, plasma D-dimer levels, and the Harris hip score. RESULTS: Each group had low pain scores with no significant differences between the groups. The PCA group had a lower frequency of supplemental analgesia use compared to the Epi and CFNB groups. Side effects (nausea/vomiting, inappetence) and day 7 D-dimer levels were significantly lower in the CFNB group (p < 0.05). There were no significant differences between the groups in terms of the length of the hospital stay or the Harris hip score. CONCLUSIONS: Although there were no clinically significant differences in outcomes between the three groups, the CFNB provided good pain relief which was equal to that of the other analgesics with fewer side effects and lower D-dimer levels in hospitalized patients following total hip arthroplasty.

Posterior buttress plate with locking compression plate for Hoffa fracture.

BACKGROUND: Many difficulties are associated with treating fractures of the posterior condyle of the femur (Hoffa fractures). Anatomical reduction and internal fixation are optimum for such intra-articular fractures. Some surgeons use anteroposterior screws to achieve direct stability. However, screw fixation is not adequate in some cases. To increase stability, we treat Hoffa fractures with a posterior buttress plate; we use a twisted, 1/3 tubular plate at the posterior surface and a supplementary, locking compression plate (LCP) for additional stability. METHODS: Patients who had sustained Hoffa fractures between January 2006 and March 2009 were included in this study. Patients comprised three males and two females with a mean age of 73.6 years at the time of surgery. A 3.5-mm 1/3 tubular plate was twisted and applied to the posterolateral aspect of the distal femur. This was combined with an LCP on the distal femur to achieve a rafting effect. RESULTS: All fractures were healed within 15 weeks. There were no instances of nonunion, infection, or implant removal. The mean range of motion was -3° to 121°. Four patients had no pain in the treated limb and one had mild pain on weight bearing. The average Oxford Knee Score was 44.6 points. All patients achieved satisfactory joint function and regained their walking ability with good clinical results. CONCLUSIONS: Improved stability associated with this technique enables patients to begin range-of-motion training and return to their normal activities sooner; this resulted in good outcome.

The relationship between ambulation ability before surgery and the D-dimer value after total hip arthroplasty: the evaluation of ambulation ability by the timed "Up & Go" test.

We examined whether ambulatory ability before surgery might influence the post-operative D-dimer level after total hip arthroplasty (THA). One hundred two patients with hip osteoarthritis receiving THA were included in the current study. The patients were all female, and their ages ranged from 45 to 81 (average 65.0 +- 9.3 years). Age, operated side, body mass index (BMI), disease duration before surgery, pre-operative pain evaluated by visual analogue scale (VAS), total cholesterol value, maximal circumference of the lower leg of the operated side, and timed "Up & Go"test (TUG) before surgery, were retrospectively investigated to examine their relationship with D-dimer levels on post-operative day 7. Patients were divided into 2 groups according to the D-dimer value: over 10 microg/ml (Group D), and under (Group N). Patients in group D (N= 52)were older, had a higher BMI, and had less ambulatory ability than patients in group N (N= 50). As age showed a relationship with the D-dimer value on the 7th day and TUG results, patients in the 2 groups were further subdivided into 50's, 60's, and 70's age brackets. In the 50's bracket, patients in group D had higher BMI than patients in group N, but time for TUG was not significantly different. In the 60's and 70's bracket, patients in group D had less ambulatory ability than patients in group N, but the time for TUG was not directly correlated with the D-dimer value. The results suggest that pre-operative low ambulatory ability in patients with osteoarthritis over 60 years might influence the postoperative D-dimer after THA, indicating the potential risk for post-operative deep venous thrombosis.

Changes in LPIA D-dimer levels after total hip or knee arthroplasty relevant to deep-vein thrombosis diagnosed by bilateral ascending venography.

The purpose of the current retrospective study was to determine the most sensitive and specific cutoff value of plasma D-dimer level associated with deep-vein thrombosis (DVT) after total hip (THA) or knee (TKA) joint arthroplasty. Diagnosis of DVT was determined by bilateral ascending venography pre- and postoperatively. Plasma D-dimer levels were measured by a latex photometric immunoassay system (LPIA) preoperatively and postoperatively on days 1, 3, 7, 10, 14, and 21. Postoperative DVT diagnosed by venography was found in 22 patients (40.1%) after THA and in 18 patients (64.3%) after TKA. Plasma D-dimer levels were significantly higher ( P < 0.01) in patients with DVT than in those without DVT on days 1, 7, and 10 after THA, but only on day 7 after TKA. Statistical analysis confirmed that a cutoff value of 10.0 microg/ml for D-dimer on day 7 was most sensitive (THA, 95.5%; TKA, 94.4%) and most specific (THA, 96.9%; TKA, 90.0%) in the diagnosis of DVT after THA as well as TKA. It was concluded that over 10 microg/ml of LPIA D-dimer on postoperative day 7 appears to be an indication of the occurrence of DVT after THA and TKA.