Immune-related Adverse Event with Checkpoint Inhibitors Might Be an Emerging Underlying Disease of Steroid-related Osteonecrosis of the Femoral Head: A Case Report.

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced metastatic and immunogenic cancers. However, these therapies could cause immune-related adverse events (irAEs), which require high-dose glucocorticoid administration. Case Report: A 52-year-old man with metastatic renal cell carcinoma received ICI therapy. Two weeks later, he suffered from severe irAEs and received glucocorticoid therapy for 13 months. Twenty-one months after the initiation of glucocorticoid administration, he presented to us with bilateral hip pain and was diagnosed with bilateral osteonecrosis of the femoral head (ONFH). Conclusion: IrAEs associated with ICI therapy might be an emerging underlying disease of ONFH.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Femoral head translation in borderline and definite dysplastic hips during weight-bearing: 2D/3D image registration analysis.

PURPOSE: The aims of this study were to 1) assess femoral head translation during weight-bearing in symptomatic developmental dysplasia of the hip (DDH) and 2) compare it between borderline DDH and definite DDH. METHODS: The study included four individuals with borderline DDH and nine with definite DDH, scheduled for periacetabular osteotomy. Anteroposterior X-ray images of the hip joint were obtained in the standing position, and computed tomography images of the pelvis were obtained in the supine position. Femoral head translation from the supine to a standing position was measured using 2D/3D X-ray image registration. RESULTS: From a supine to a standing position, the femoral head translated 0.3 mm laterally, 0.5 mm anteriorly, and 0.5 mm superiorly on average. The mean femoral head translation in 3D between the supine and standing positions was 1.5 mm. The 3D femoral head translation in the borderline DDH group was significantly greater than that in the definite DDH group. In the definite DDH group, there was a significant correlation between the center edge (CE) angle and 3D femoral head translation (ρ = -0.78, P = 0.012). CONCLUSIONS: Symptomatic DDH showed femoral head translation in the anterior, lateral, and superior directions during weight-bearing. In definite DDH, the amount of femoral head translation was negatively correlated with the CE angle. The amount of 3D translation in patients with borderline DDH was larger than that in definite DDH. Dynamic joint instability during weight-bearing was observed in borderline DDH as well as definite DDH. Treatment to enhance joint stability during weight-bearing is important in both cases.

Early Postoperative Rehabilitation Using the Hybrid Assistive Limb (HAL) Lumbar Type in Patients With Hip Fracture: A Pilot Study.

OBJECTIVE: To extend life expectancy after surgery, patients with hip fractures need to improve their mobility quickly through postoperative rehabilitation. Voluntary hip joint motion supported by the hybrid assistive limb (HAL) lumbar type, an exoskeleton robot suit characterized by its ability to detect the wearer's intentions through the bioelectrical signals and assist hip extension motions at an optimal timing, may be effective to improve mobility in patients with hip joint dysfunction after surgery. We aimed to introduce rehabilitation using the HAL lumbar type in the early period after hip fracture surgery. METHODS: Patients who underwent internal fixation for hip fracture at a single institution were prospectively enrolled. They received early postoperative rehabilitation (forward and backward bending of the lumbar spine, pelvic tilt forward and backward, standing up, and squatting) using the HAL lumbar type (six times a week for 15 min per session). Five-times-sit-to-stand (FTSS) and timed-up-and-go (TUG) tests were conducted at baseline before HAL rehabilitation (pre-HAL) and after the HAL rehabilitation (post-HAL) intervention. RESULTS: We enrolled 14 patients (one man, 13 women) in this study. There were no adverse events, and all patients were able to complete the entire rehabilitation program. Post-HAL FTSS showed significant improvement compared with pre-HAL and had a large effect size of 1.81 (95% CI = 0.93 to 2.66) and sufficient power. CONCLUSIONS: Robotic rehabilitation with HAL lumbar type could be introduced without adverse events, even in the early postoperative period following surgery for hip fracture. Further study is needed to develop an appropriate rehabilitation protocol using the HAL lumbar type.

Effects of porous tantalum on periprosthetic bone remodeling around metaphyseal filling femoral stem: a multicenter, prospective, randomized controlled study.

Periprosthetic bone loss due to adaptive bone remodeling is an important unresolved issue in cementless total hip arthroplasty (THA). The use of porous tantalum on the proximal surface of the femoral stem is expected to decrease postoperative bone loss around the prosthesis through early fixation. We conducted a multicenter randomized controlled study to determine if porous tantalum could reduce periprosthetic bone loss after THA. From October 2012 to September 2014, 118 patients (mean age, 61.5 years; 107 females and 11 males) were prospectively enrolled and were randomly allocated at a ratio of 1:1 to either a metaphyseal filling stem with a proximal porous tantalum coating (Trabecular Metal) or a conventional metaphyseal filling stem with fiber mesh coating (VerSys). Patients underwent dual-energy x-ray absorptiometry scans within 1 week after surgery (baseline) and at 6, 12, and 24 months after surgery to assess periprosthetic bone mineral density (BMD) in the 7 Gruen zones. In addition, the Japanese Orthopaedic Association hip score was assessed before surgery and at 6, 12, and 24 months after surgery. In the proximal periprosthetic region (zones 1 and 7), the Trabecular Metal group had significantly smaller reductions in BMD than the VerSys group throughout the study period. In the VerSys group, significant reductions in BMD compared to baseline were seen at each measurement point in all regions, except in zone 6 at 24 months. In the Trabecular Metal group, no significant reductions in BMD relative to baseline were seen in zones 1, 5, or 6 throughout the study period. Both groups demonstrated similar improvement in Japanese Orthopaedic Association hip scores over the study period. This study demonstrated that a proximally coated stem with porous tantalum has superior results over a conventional stem with titanium fiber mesh in terms of periprosthetic bone remodeling.

Outcomes of computer-assisted peri-acetabular osteotomy compared with conventional osteotomy in hip dysplasia.

AIM OF THE STUDY: To compare the outcomes after computer-assisted peri-acetabular osteotomy (PAO) and conventional PAO performed for hip dysplasia (DDH). METHODS: Ninety-one patients (98 hips) were enrolled in this study. In each case, DDH was treated with either conventional PAO, in which the angle and direction of the osteotomy was determined by intra-operative X-ray examination, or with computer-assisted PAO, which used the 3D navigation system. Forty hips underwent conventional PAO and 58 hips underwent computer-assisted PAO. RESULTS: Japanese Orthopaedic Association hip scores improved significantly from 70.0 points pre-operatively to 90.7 points post-operatively in patients with conventional PAO, and from 74.5 points pre-operatively to 94.2 points post-operatively in patients with computer-assisted PAO. In all patients with computer-assisted PAO, the post-operative AHI and VCA angle were within the radiographic target zone. Some patients with conventional PAO had post-operative AHI and VCA angle outside of the target zone. We performed total hip arthroplasty (THA) on five of the 98 PAO hips (5.1%) after an average follow-up period of 5.4 years. None of 58 hips (0%) with computer-assisted PAO was revised. DISCUSSION: Computer-assisted PAO enabled intra-operative confirmation of osteotomy sites, and the position of the osteotomized bone fragment could be confirmed in real time. Adequate anterior and lateral coverage of the femoral head in patients with computer-assisted PAO resulted in no need for early conversion to THA, in contrast to conventional PAO. CONCLUSION: Computer-assisted PAO not only improved accuracy and safety but also achieved sufficient anterior and lateral displacement to prevent the progression of DDH.

Association Between Vertebral Fracture and Diffuse Idiopathic Skeletal Hyperostosis.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To investigate the prevalence and characteristics of diffuse idiopathic skeletal hyperostosis (DISH) in vertebral fracture patients admitted to our hospital. SUMMARY OF BACKGROUND DATA: Although vertebral fracture is generally treated conservatively with rest and use of a corset, surgery with rigid internal fixation is recommended for vertebral fractures in patients with DISH. Thus, treatment strategies for vertebral fracture differ according to the presence or absence of DISH. However, only a few studies have investigated the prevalence of DISH in vertebral fracture patients. METHODS: A total of 159 patients (49 men and 110 women, with a mean age of 82.9 years) who were diagnosed with fresh vertebral fracture and required admission to HITO Hospital. The diagnosis of fresh vertebral fracture was made using x-ray imaging, computed tomography, and magnetic resonance imaging, and the presence or absence of DISH was assessed. In addition, age, sex, bone mineral density ( % young adult mean), blood test results, treatment, and length of hospital stay were compared between patients with and without DISH. RESULTS: The proportion of patients with DISH among the patients with vertebral fracture was 33.9% (54 of 159 patients). The proportions in men and women were 38.8% and 31.8%, respectively, with no significant difference between sexes (P = 0.39). The patients in the DISH group were older than those in the non-DISH group (83.6 vs. 79.4 years, P = 0.009), and the DISH group had higher glycated hemoglobin A1c (P = 0.005), higher bone mineral density (P = 0.042), and longer length of hospital stay (P = 0.0001) compared with those in the non-DISH group. CONCLUSION: The proportion of patients with DISH among the vertebral fracture patients was 33.9%. Given that patients with DISH may require different treatment approaches, careful observation is needed. LEVEL OF EVIDENCE: 3.

Preoperative planning and postoperative evaluation of total hip arthroplasty that takes combined anteversion.

The purpose of this study was to investigate whether postoperative combined anteversion (CA) can be kept within the safe zone while using cementless total hip arthroplasty (THA) using the operative technique which prepares the socket first for developmental dysplasia of the hip (DDH), by estimating the anteversion of the metaphyseal fit stem using preoperative three-dimensional (3D) computerized planning and by adjusting the anteversion of the socket using a navigation system that considers CA. Our subjects were 65 patients (65 hips) that had undergone cementless THA for DDH that could be observed for 1 year or more. Clinical assessments were made using the Japanese Orthopaedic Association's (JOA) hip score. For a radiological evaluation, we investigated 3D-planned stem versions, postoperative stem versions, preoperative and postoperative CA, and the relationship between CA and dislocation tendencies with temporary intraoperative reductions. JOA hip scores improved from 52.3 ± 11.4 points to 88.9 ± 8.6 points. CT evaluations revealed that 3D-planned stem versions were strongly correlated with postoperative stem versions (r = 0.80; p < 0.01). Preoperative CA was 50.5° ± 7.2°, and postoperative CA was 41.3° ± 8.6°. Postoperative CA was kept within the safe zone in 61 hips. No intraoperative dislocation tendencies were observed in any hips. By estimating the anteversion of the cementless metaphyseal fit stem using 3D planning preoperatively and adjusting the angle of anteversion of the socket using a navigation system that considers CA intraoperatively, postoperative CA can very frequently be kept within the safe zone, even with cementless THA using the operative technique which prepares the socket first for DDH.

Long term results with the interlocking uncemented long stem in revision hip arthroplasty: a mean 15-year follow-up.

Stem fixation is difficult to achieve in severe proximal bone loss in revision hip surgery. In this study, we sought to present the results of distally-locked stem with screws (HUCKESTEP HIP stem) in 21 revision hips with mean follow-up period of 15 years. The preoperative mean Japanese Orthopaedic Association hip score had improved from 54 to 75 points. Further revisions were required for 2 stems, in one because of infection and the other because of screws fracture and subsidence. With removal of the stem for any reason as an end-point, the cumulative survival at 15 years was 90.4%. While this study had small number, the use of this interlocking stem for revision hips with extensive proximal bone defects provided satisfactory 15-year clinical and radiographic results.

Mid-term clinical and radiographic outcomes of porous tantalum modular acetabular components for hip dysplasia.

It is still challenging to perform successful cementless cup fixation during total hip arthroplasty for hip dysplasia. In this multicenter study we evaluated the clinical results of porous tantalum modular acetabular cups (TM cups) in 45 dysplastic hips with a mean follow-up period of 9.8 years. The mean Japanese Orthopaedic Association hip score improved from 48.2 preoperatively to 92.1 at the most recent follow-up. All of the cups were radiographically stable with no evidence of progressive radiolucencies or osteolysis regardless of bone grafting. Sixteen hips with bone grafts showed the integration of grafted bone without any radiolucencies. There were no revisions of TM cups. The use of TM cups for dysplastic hips provided satisfactory 10-year clinical and radiographic results.

Anterior coverage after eccentric rotational acetabular osteotomy for the treatment of developmental dysplasia of the hip.

BACKGROUND: In periacetabular osteotomy for the treatment of developmental dysplasia of the hip, impairments in ADL due to limitations in hip flexion can occur when anterior displacement is added to lateral displacement in order to obtain sufficient femoral head coverage. This study was conducted to determine, by the range of motion (ROM) simulation based on CT images, the minimum angle of hip flexion and internal rotation at 90° of flexion that is necessary to avoid ADL impairments after eccentric rotational acetabular osteotomy (ERAO) and to estimate the angles of anterior femoral head coverage on plain radiography that enable the above flexion. METHODS: Of 47 hips treated with ERAO at our hospital from December 2007 to May 2012, 27 hips without progressive osteoarthritis which could be CT scanned were examined and included. The mean age at the time of surgery was 40.7 years (SD 1.8). The postoperative follow-up period was 30.2 months (SD 3.6). Two hips were in male patients and 25 hips were in female patients. The disease stage prior to surgery was pre-osteoarthritis in 5 hips, early in 11 hips, and progressive in 11 hips. We checked whether the patients were capable of activities that require deep hip flexion for the evaluation of postoperative ADL. Radiographic examination was performed before and one year after surgery to calculate LCE angle, Sharp angle, AHI, and VCA angle. The angle at which impingement of the displaced fragment of the bone and the femur appeared was measured using 3D CAD software, and the relationship between this angle and the physical findings, ADL impairment, or radiographic findings, were also examined. RESULTS: 22 out of 27 hips that were capable of 116° or more of flexion or 42° or more of internal rotation at 90° of flexion in ROM simulation showed the absence of ADL impairment and a postoperative VCA angle ≤42°, whereas 5 hips with 110° or less of flexion or 40° or less of internal rotation at 90° of flexion in ROM simulation had ADL impairments associated with limitations in hip flexion and a postoperative VCA angle ≥46°. CONCLUSIONS: Anterior and lateral coverage requires a postoperative VCA angle of ≥20° to achieve anterior structural stability and an LCE angle of >25° to obtain adequate superior lateral coverage of the femoral head. A VCA angle ≤42° is required to avoid impingement during deep flexion. A VCA angle ≥46° is a probable risk factor for pincer FAI syndrome after ERAO.

Correction of hallux valgus deformity using the center of rotation of angulation method.

BACKGROUND: To correct a hallux valgus (HV) deformity quantitatively and prevent unexpected postoperative deformity, the center of rotation of angulation (CORA) method was applied during HV surgery. To correct a hallux valgus (HV) deformity quantitatively and prevent unexpected postoperative deformity, the center of rotation of angulation (CORA) method was applied during HV surgery. METHODS: To create a normal foot model, radiographs of 64 normal female feet were measured. Points A and B were defined as the intersection of the intermetatarsal angle and the HV angle. CORA1 and CORA2 were defined as the intersection of the axes of the first metatarsal and the first proximal phalanx in the normal and HV models, respectively. Procedures to correct HV deformity using the CORA method were devised and were applied to HV feet, which underwent a focal dome osteotomy or medial wedge osteotomy. RESULTS: Point A was 2.3 times the length of the second metatarsal proximally from the top of the second metatarsal head, and point B was 0.17 times the length of the first metatarsal proximally from the top of the first metatarsal head. Two methods were used to correct the deformity. With one method, a focal dome osteotomy was performed at the first metatarsal on the circle at the CORA1 and the distal fragment was moved to the standard first metatarsal axis. The first proximal phalanx was then moved around the metatarsal head to the standard axis of the first proximal phalanx at the CORA2. With the other method, a medial wedge osteotomy was performed on or proximal to the CORA2, and the distal fragment was moved to the first standard metatarsal axis. CONCLUSIONS: We propose a preoperative plan to use the CORA method to correct deformities that prevent translation of the axis or an angulation deformity. HV deformity can be corrected effectively using the CORA method.

Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line.

PURPOSE: The aim of this study is to investigate whether cortisol inhibited cell proliferation and the expressions of lipoprotein lipase (LPL), a key enzyme involved in the energy metabolism in tumor cells, and vascular endothelial growth factor (VEGF), a potent angiogenic factor in the tumor, in cultures of OST cells, a human osteosarcoma cell line. METHODS: OST cells were treated for 48 h with or without cortisol. To examine the effect of cortisol on cell proliferation, the expression of proliferating cell nuclear antigen (PCNA) was examined by Western blotting, and the amount of (3)H-thymidine incorporated into DNA during the last 30 min of the 48-h treatment period was measured. To examine the effect of cortisol on the expression of LPL, the activity and mass of LPL were measured in the extract of acetone/ether powder of cells, and the amount of (35)S-methionine incorporated into LPL during the last 2 h of the 48-h treatment period was measured by immunoprecipitation. The expression of VEGF was examined by immunohistochemistry and Western blotting. RESULTS: The amount of (3)H-thymidine incorporated into DNA and the level of PCNA were lower in the cortisol-treated cultures than in the untreated cultures, thus indicating that cortisol inhibited the proliferation of OST cells. The synthetic rate and activity of LPL were lower in the cortisol-treated cultures than in the untreated cultures but no difference in the specific activity of LPL between the two cultures was observed, thus indicating that cortisol inhibited LPL synthesis, thereby resulting in a decreased LPL activity. The expression of VEGF was lower in the cortisol-treated cultures than in the untreated cultures. CONCLUSION: Cortisol not only has the ability to inhibit cell proliferation but also the ability to inhibit the expressions of LPL and VEGF in cultures of OST cells.