Metabolomic profiles of cartilage and bone reflect tissue type, radiography-confirmed osteoarthritis, and spatial location within the joint.

Osteoarthritis is the most common chronic joint disease, characterized by the abnormal remodeling of joint tissues including articular cartilage and subchondral bone. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to identify metabolic differences between articular cartilage and subchondral bone, compare the metabolic shifts in osteoarthritic grade III and IV tissues, and spatially map metabolic shifts across regions of osteoarthritic hip joints. Articular cartilage and subchondral bone from 9 human femoral heads were obtained after total joint arthroplasty, homogenized and metabolites were extracted for liquid chromatography-mass spectrometry analysis. Metabolomic profiling revealed that distinct metabolic endotypes exist between osteoarthritic tissues, late-stage grades, and regions of the diseased joint. The pathways that contributed the most to these differences between tissues were associated with lipid and amino acid metabolism. Differences between grades were associated with nucleotide, lipid, and sugar metabolism. Specific metabolic pathways such as glycosaminoglycan degradation and amino acid metabolism, were spatially constrained to more superior regions of the femoral head. These results suggest that radiography-confirmed grades III and IV osteoarthritis are associated with distinct global metabolic and that metabolic shifts are not uniform across the joint. The results of this study enhance our understanding of osteoarthritis pathogenesis and may lead to potential drug targets to slow, halt, or reverse tissue damage in late stages of osteoarthritis.

Modified osteochondral autograft transplantation for steroid-induced osteonecrosis of femoral head in idiopathic thrombocytopenic purpura: a case report and literature.

Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

Extending the intermedullary nail will not reduce the potential risk of femoral head varus in PFNA patients biomechanically: a clinical review and corresponding numerical simulation.

Femoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.

Risk factors for avascular necrosis of the femoral head after developmental hip dislocation reduction surgery and construction of Nomogram prediction model.

BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.

Development and Validation of an Automated Classification System for Osteonecrosis of the Femoral Head Using Deep Learning Approach: A Multicenter Study.

BACKGROUND: Accurate classification can facilitate the selection of appropriate interventions to delay the progression of osteonecrosis of the femoral head (ONFH). This study aimed to perform the classification of ONFH through a deep learning approach. METHODS: We retrospectively sampled 1,806 midcoronal magnetic resonance images (MRIs) of 1,337 hips from 4 institutions. Of these, 1,472 midcoronal MRIs of 1,155 hips were divided into training, validation, and test datasets with a ratio of 7:1:2 to develop a convolutional neural network model (CNN). An additional 334 midcoronal MRIs of 182 hips were used to perform external validation. The predictive performance of the CNN and the review panel was also compared. RESULTS: A multiclass CNN model was successfully developed. In internal validation, the overall accuracy of the CNN for predicting the severity of ONFH based on the Japanese Investigation Committee classification was 87.8%. The macroaverage values of area under the curve (AUC), precision, recall, and F-value were 0.90, 84.8, 84.8, and 84.6%, respectively. In external validation, the overall accuracy of the CNN was 83.8%. The macroaverage values of area under the curve, precision, recall, and F-value were 0.87, 79.5, 80.5, and 79.9%, respectively. In a human-machine comparison study, the CNN outperformed or was comparable to that of the deputy chief orthopaedic surgeons. CONCLUSION: The CNN is feasible and robust for classifying ONFH and correctly locating the necrotic area. These findings suggest that classifying ONFH using deep learning with high accuracy and generalizability may aid in predicting femoral head collapse and clinical decision-making.

Extension of the Antero-Posterior Necrotic Regions Associated With Collapse Cessation in Osteonecrosis of the Femoral Head.

BACKGROUND: Collapse cessation is of utmost importance following a long period of collapse due to osteonecrosis of the femoral head (ONFH). This study investigated the relationship between collapse cessation and the extent of the necrotic regions of ONFH. METHODS: Overall, 74 patients who had symptomatic ONFH (collapse < 3 mm) at the first visit with a minimum follow-up of 3 years were included in this study. Patients were categorized based on collapse progression or cessation into the progression and stable groups. The extent of the antero-posterior (AP) and medio-lateral necrotic regions between the groups was assessed using sagittal and coronal sections of T1-magnetic resonance imaging. Additionally, the most effective cutoff value was determined from the receiving operating characteristic curve where collapse cessation could be obtained, while the survival rates were determined with collapse progression as the endpoints were evaluated. RESULTS: Overall, 45 and 29 patients were in the progression and stable groups, respectively. The AP and medio-lateral necrotic regions were significantly different (P < .01 and P < .01, respectively) between the progression and stable groups. A cutoff value of 62.1% of the AP necrotic regions was determined from the receiving operating characteristic curve analysis. The 5-year survival rates with collapse progression as the endpoints were 5.4 and 77.8% in the AP necrotic regions of ≥62.1 and <62.1%, respectively (P < .01). CONCLUSIONS: Cases with AP necrotic regions of ≤62.1% can be expected to have collapse cessation, which could be a useful index for ONFH treatment strategies. LEVEL OF EVIDENCE: Level IV.

Effects of the location of both anterior and lateral boundaries of the necrotic lesion on collapse progression in osteonecrosis of the femoral head.

BACKGROUND: The location of the lateral boundary of the necrotic lesion to the weight-bearing portion of the acetabulum (Type classification) is an important factor for collapse in osteonecrosis of the femoral head (ONFH). Recent studies also reported the significance of the location of the anterior boundary of the necrotic lesion on the occurrence of collapse. We aimed to assess the effects of the location of both anterior and lateral boundaries of the necrotic lesion on collapse progression in ONFH. METHODS: We recruited 55 hips with post-collapse ONFH from 48 consecutive patients, who were conservatively followed for more than one year. Using a plain lateral radiograph (Sugioka's lateral view), the location of the anterior boundary of the necrotic lesion to the weight-bearing portion of the acetabulum was classified as follows: Anterior-area I (two hips) occupying the medial one-third or less; Anterior-area II (17 hips) occupying the medial two-thirds or less; and Anterior-area III (36 hips) occupying greater than the medial two-thirds. The amount of femoral head collapse was measured by biplane radiographs at the onset of hip pain and each follow-up period, and Kaplan-Meier survival curves with collapse progression (≥1 mm) as the endpoint were produced. The probability of collapse progression was also assessed by the combination of Anterior-area and Type classifications. RESULTS: Collapse progression was observed in 38 of the 55 hips (69.0%). The survival rate of hips with Anterior-area III/Type C2 was significantly lower. Among hips with Type B/C1, collapse progression occurred more frequently in hips with Anterior-area III (21 of 24 hips) than in hips with Anterior-area I/II (3 of 17 hips, P < 0.0001). CONCLUSIONS: Adding the location of the anterior boundary of the necrotic lesion to Type classification was useful to predict collapse progression especially in hips with Type B/C1.

Is there still an indication for the Birmingham Hip Resurfacing in femoral head osteonecrosis?

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a progressive hip disease. Hip resurfacing arthroplasty (HRA) is a preferred surgical procedure among hip arthroplasty performed in young patients. The aim of this study is to show the long-term clinical and radiological results of HRA procedures performed for patients suffering from ONFH. METHODS: Forty-five patients who underwent hip resurfacing with the diagnosis of femoral head osteonecrosis were included in the study. The Harris Hip Score (HHS) was used for clinical scoring of the patients. The blood chromium, cobalt, white blood cell (WBC) count, and CRP levels of patients were checked. Ultrasonography (USG) was performed for all patients at mid-term control checked for pseudo-tumours. For the radiological evaluation, acetabular inclination, stem shaft angle, prothesis-to-neck ratio, osteolysis zones, and heterotopic ossification were used. RESULTS: The mean age of the patients was 46.6 ± 9.3 years, and the mean follow-up period was 11.83 ± 2.9 years. The mean HHS was 90.3 ± 12.8 for final follow-up. The mean WBC value was 8.2 109/L, mean CRP value was 6.3 mg/L, mean chromium value was 4.9 µg/L, and mean cobalt value was 1.8 µg/L. Inclination changing 0.2°(p = 0.788), stem shaft angle changing 0.7°(p = 0.424), and neck-to-prosthesis ratio changing 0.01°(p = 0.075). No pseudo-tumours were detected in any patients in USG examination. CONCLUSION: HRA provides long-term implant survival and excellent clinical outcomes for end-stage ONFH patients with low complication rates.

Legg-Calvé-Perthes Disease: Diagnosis, Decision Making, and Outcome.

ABSTRACT: Legg-Calvé-Perthes disease (LCPD), or idiopathic avascular necrosis of the proximal capital femoral epiphysis in children, has a variable presentation and can result in significant femoral head deformity that can lead to long-term functional deficits. Plain radiographic imaging is crucial in diagnosing LCPD and guiding treatment. Although the etiology of LCPD remains unknown, the evolution of the disease has been well characterized to include the phases of ischemia, revascularization, and reossification. The mechanical weakening during these phases of healing place the femoral head at high risk of deformity. Treatment of LCPD, therefore, focuses on minimizing deformity through operative and nonoperative strategies to reduce the risk of premature osteoarthritis. Advanced imaging using perfusion MRI may refine surgical decision making in the future, and biological treatments to improve femoral head healing are on the horizon.

Investigating sagittal spinopelvic alignment and equivalent stress on the femoral head in patients with rapidly destructive coxarthrosis.

PURPOSE: Rapidly destructive coxarthrosis (RDC) is a rare syndrome of unknown etiology. This study evaluated sagittal spinopelvic alignment (SSPA) in patients with RDC and compared it with that in patients with hip osteoarthritis (HOA). In addition, finite element analysis (FEA) was performed to investigate the distribution of stress on the femoral head in RDC versus HOA. METHODS: This retrospective study included patients who had undergone primary total hip arthroplasty for RDC (n = 33) and HOA (n = 99; age- and sex-matched to patients with RDC) at three hospitals from June 2014 to September 2020. Preoperative SSPA parameters and inflammatory blood markers were compared between the two groups. FEA on the computed tomography data was performed for four patients from each group with similar pelvic tilt (PT) and lateral center-edge angle (LCEA). The distribution of Drucker-Prager equivalent stress was assessed at the loaded area of the femoral head. RESULTS: Patients with RDC had significantly higher PT, lower sacral slope, decreased lumbar lordosis (LL), higher sagittal vertical axis, and higher pelvic incidence minus LL than patients with HOA, indicating sagittal spinal imbalance. Blood test revealed patients with RDC had higher levels of inflammation markers than patients with HOA. FEA revealed no statistically significant difference in the degree of stress concentration or the maximum equivalent stress between the two groups when PT and LCEA were comparable. CONCLUSION: Patients with RDC tend to have sagittally imbalanced spine. Decreased acetabular coverage of the femoral head may heighten mechanical load of the hip joint in patients with RDC.

Minimally invasive femoral head fracture fixation using three-dimensional navigation: a technical note.

Femoral head fractures are rare traumatic injuries that are usually associated with hip dislocations. Open reduction and internal fixation are performed when indicated, but can be associated with a higher risk of avascular necrosis. We report the case of a 24-year-old patient with a Pipkin type II fracture dislocation of the femoral head fixed via a minimally invasive three-dimensional navigated internal fixation technique. This technique minimizes deep soft tissue dissection to the hip capsule and associated vascularity and allows for accurate implant positioning.Level of evidence: Therapeutic case report Level IV.

Changes of the subchondral bone microchannel network in early osteoarthritis.

OBJECTIVE: We have identified a 3D network of subchondral microchannels that connects the deep zone of cartilage to the bone marrow (i.e., cartilage-bone marrow microchannel connectors; CMMC). However, the pathological significance of CMMC is largely unknown. Here, we quantitatively evaluated how the CMMC microarchitecture is related to cartilage condition, as well as regional differences in early idiopathic osteoarthritis (OA). METHODS: Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified, and a biopsy-based high-resolution micro-CT imaging was employed. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and the CMMC morphology were quantified and compared between the two groups. The effect of joint's region and cartilage condition was examined on each dependent variable. RESULTS: The CMMC number and morphology were affected by region of the joint, but not by cartilage condition. On the other hand, the minimum and maximum CMMC size was changed by both the location on the joint, as well as the cartilage condition. The smallest CMMC were consistently detected at the load-bearing region (LBR) of the joint. Compared to non-pathological subjects, the size of the microchannels was enlarged in early OA, most noticeably at the non-load-bearing region (NLBR) and the peripheral rim (PR) of the femoral head. Furthermore, subchondral bone thinning was observed in early OA as a localized occurrence linked with areas of partial chondral defect. CONCLUSION: Our data point to an enlargement of the SB microchannel network, and a collective structural deterioration of SB in early idiopathic OA.

CT and MRI findings beyond the subchondral bone in osteonecrosis of the femoral head to distinguish between ARCO stages 2 and 3A.

OBJECTIVES: To determine the diagnostic values of deep changes beyond the subchondral bone in osteonecrosis of the femoral head (ONFH) to distinguish between Association Research Circulation Osseous (ARCO) stages 2 and 3A. METHODS: This retrospective study included 124 hips with ONFH of stages 2 (n = 49; 23 females; mean age, 50.7 years) and 3A (n = 75; 20 females; mean age, 53.2 years) from May 2017 to August 2022, who underwent CT (n = 124) and MRI (n = 85). Deep changes beyond subchondral bone were analyzed on CT (bone resorption area and cystic change) and on MRI (bone marrow edema [BME] and joint effusion). Diagnostic performance and multivariate analysis were evaluated for detecting stage 3A. RESULTS: Stage 3A showed more frequent bone resorption area (72.0% vs. 4.1%), cystic change (52.0% vs. 0.0%), BME (93.5% vs. 43.6%), and joint effusion (76.0% vs. 24.5%) than stage 2 (p < 0.001, all). Bone resorption area and cystic change showed low sensitivities (52.0~72.0%) but high specificities (96.0~100.0%), while BME and joint effusion showed high sensitivities (76.0~93.0%) but low specificities (56.0~76.0%) for stage 3A. Predictors were in the order of bone resorption area, cystic change, and joint effusion (odds ratio: 32.952, 26.281, 9.603, respectively), and combined bone resorption area and cystic change had the best predictive value (AUC, 0.900) for stage 3A. CONCLUSIONS: Among deep changes, bone resorption area and cystic changes were highly specific and BME and joint effusion were highly sensitive for stage 3A. Combined bone resorption area and cystic change had the best predictive value for predicting ARCO stage 3A. KEY POINTS: • The exact classification between ARCO stage 2 and 3A is essential but it is sometimes difficult to distinguish between ARCO stage 2 and 3A only by subchondral fracture, especially early post-collapse stage with preservation of femoral head contour. • The predictors of stage 3A were in the order of bone resorption area, cystic change, and joint effusion and combined bone resorption area and cystic change had the best predictive value for predicting stage 3A. • Analysis of deep changes beyond the subchondral bone may make it easier to distinguish between ARCO stage 2 and 3A.

Evaluating blood supply changes in the osteonecrosis of the femoral head using gadobutrol-based steady-state MR angiography.

OBJECTIVES: Assess the feasibility of using gadobutrol-based steady-state (SS) MR angiography (MRA) to evaluate the blood supply changes of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Participants were recruited in this prospective study from December 2021 to May 2022 in a single center. The number of superior retinacular arteries (SRAs), inferior retinacular arteries (IRAs), anterior retinacular arteries (ARAs), and overall retinacular arteries (ORAs), as well as the affected rates of SRA and IRA, were determined and compared between healthy and ONFH hips and between hips across the Association Research Circulation Osseous (ARCO) staging I-IV. RESULTS: Twenty healthy and 64 ONFH hips were evaluated in 54 participants. There were significant differences between ARCO I-IV for the number of ORAs (mean of 3.5, 2.3, 1.7, and 0.8 for ARCO I-IV, respectively; p < .001), SRAs (median of 2.5, 1, 0.5, and 0 for ARCO I-IV, respectively; p < .001), and the affected rate of SRAs (20.00%, 65.22%, 77.78%, 92.31% for ARCO I-IV, respectively, p = 0.002). There were significant differences between ONFH and healthy hips for the number of ORAs (median of 5 vs. 2; p < .001), SRAs (median of 3 vs. 1; p < .001), IRAs (median of 1 vs. 1; p < .001), ARAs (median of 0 vs. 0; p = 0.04), and also the affected rate of SRAs (5.00% vs. 67.20%, p < .001) and IRAs (30% vs. 84.4%, p < .001). CONCLUSION: Gadobutrol-enhanced SS MRA is a feasible method for evaluation of hemodynamics in ONFH. CLINICAL RELEVANCE STATEMENT: Gadobutrol-enhanced magnetic resonance angiography can evaluate blood supply changes of ONFH and therefore helps to aid in the diagnosis and guide treatment of ONFH. KEY POINTS: • Gadobutrol-enhanced magnetic resonance angiography showed changes in the retinacular artery related to the severity of femoral osteonecrosis. • Gadobutrol-enhanced magnetic resonance angiography revealed a reduced blood supply to the ischemic necrotic femoral head compared to the healthy counterparts.

Quantitative dynamic contrast-enhanced MRI of bone marrow perfusion at the proximal femur: influence of femoral head osteonecrosis risk factor and overt osteonecrosis.

OBJECTIVE: To evaluate the MRI perfusion changes in patients with risk factors for osteonecrosis and normally appearing femoral heads prior to overt femoral head osteonecrosis. METHODS: Fifty-eight patients (105 hips) were prospectively included in this ethics committee-approved study. There were 46 hips with no image anomalies and no risk factors for osteonecrosis of the femoral head (ONFH) risk factors, 38 with ONFH risk factors and no image abnormalities, and 21 with overt ONFH. All patients underwent DCE-MRI. Semi-quantitative (peak enhancement [PE], area under the curve [AUC], time to maximum enhancement [TME]) and quantitative perfusion parameters (volume plasma, KTRANS, and KEP) were calculated. Excessive alcohol consumption, corticosteroid use, and trauma were considered major risk factors for osteonecrosis of the femoral head. RESULTS: Measured at the femoral neck and compared to the healthy hips without OFNH risk factors, PE was significantly lower in the hips of patients with OFNH risk factors. Moreover, the difference was greater in females with risk factors, who presented significantly lower PE values (p = 0.0096). A PE threshold of 1.4% yielded a 92% sensitivity and 54% specificity for the presence of associated ONFH risk factors. The hips with overt OFNH compared to those with normally appearing showed an increase of PE of 45% in the neck (p < 0.014). Various epiphyseal femoral head perfusion parameters (PE, TME, AUC, and Ktrans) presented statistically significant differences in hips with ONFH and those without (p < 0.0001). CONCLUSION: DCE-MRI can identify perfusion marrow changes related to the presence of ONFH risk factors and adjacent to osteonecrosis areas. KEY POINTS: • Bone marrow perfusion changes may occur prior to overt ONFH and extend beyond the osteonecrosis area to the entire femoral head and neck. • Peak enhancement values were significantly reduced in patients with ONFH risk factors, compared to those without. • The presence of ONFH led to a significant increase in marrow perfusion adjacent to the osteonecrosis area.

Avascular necrosis of the femoral head in a cynomolgus macaque (Macaca fascicularis).

A cynomolgus macaque presented with right hindlimb lameness as well as crepitus and decreased passive range of motion of the right coxal joint. Radiography and histopathology were consistent with avascular necrosis of the femoral head. This case is the first published report of this condition in a cynomolgus macaque.

Study on the association of the microstructure and bone metabolism in the osteoporotic femoral head.

BACKGROUND: We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment. METHODS AND RESULTS: From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< - 2.5) and non-OP (T > - 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson's trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity. CONCLUSIONS: Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.

What Is New in Stage 3 of the 2019 Revised Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head: A Relationship to Bone Resorption.

PURPOSE: The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. MATERIALS AND METHODS: We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. RESULTS: All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance ( P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A ( P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. CONCLUSIONS: The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.

Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a childhood hip disease characterized by osteonecrosis of the femoral head. Because severe deformity of the femoral head can cause secondary osteoarthritis in adulthood, progressive collapse should be prevented in children with a necrotic epiphysis. The prognosis of patients with LCPD generally worsens as the age at disease onset increases, and the appropriate treatment for late-onset LCPD remains unclear. Based on the limited effect of nonoperative treatment using a nonweightbearing brace, flexion varus osteotomy (FVO) was introduced in 2010 as an initial treatment for late-onset LCPD in place of brace treatment, which we used in our institution before that time. QUESTIONS/PURPOSES: We asked, (1) Which treatment, FVO or a nonweightbearing brace, is associated with a lower likelihood of progressive femoral head collapse in children whose diagnosis of LCPD was made at the age of ≥ 8 years and who were followed for a minimum of 3 years after their intervention? (2) What proportion of patients in the brace group had surgery despite the treatment, and what percentage of children in the FVO group had a second operation to remove hardware and/or additional operations? METHODS: The initial treatment was applied in 181 patients with LCPD between 1995 and 2018 in our institution. Patients whose disease onset was at ≥ 8 years old (late-onset LCPD) with complete clinical and radiologic data were considered potentially eligible. In 2010, treatment for these patients changed from brace treatment to FVO for all patients. A total of 35% (42 of 121) of patients who were treated with a nonweightbearing brace between 1995 and 2009 and 40% (24 of 60) of patients who were treated with FVO between 2010 and 2018 were eligible. Among patients treated with a brace, 21% (nine of 42 patients) were excluded because of hospital transfer (three patients), short-term follow-up (three), the period from onset to the first visit was ≥ 7 months (two), and inability to use the brace because of mental incapacity (one patient). In patients treated with FVO, 12% (three of 24 patients) were excluded (two patients with a period from onset to the first visit ≥ 7 months and one with a comorbidity and multiple-epiphyseal dysplasia). Among the remaining patients, 79% (33 of 42 patients) were classified into the brace group and 88% (21 of 24 patients) were classified into the FVO group for analyses. There were no overlapping patients at the timepoint when the treatment strategy for late-onset LCPD changed. In the FVO group, subtrochanteric osteotomy with 35° to 40° of flexion and 15° to 20° of varus was performed using a locking compression plate for pediatric use. Patient demographics, radiographic parameters, and the assessment of femoral head deformity using the Stulberg classification were compared between the two groups. There was a greater proportion of boys than girls in both groups (brace: 88% and FVO: 86%), and there were no differences in the distribution of genders between the groups (p = 0.82). The right side was more frequently treated in the brace group, but there was no difference in laterality between the groups (brace: 58% right and FVO: 62% left; p = 0.16). There was no difference between groups in the median age at disease onset (9.0 years [range 8.0 to 12.5 years] in the brace group and 9.6 years [range 8.0 to 12.4 years] in the FVO group; p = 0.26). There was no difference between the groups in the period of treatment from onset (1.7 ± 1.9 months in the brace group and 1.5 ± 1.5 months in the FVO group; p = 0.73) or the follow-up period (6.7 ± 2.1 years in the brace group and 6.2 ± 2.1 years in the FVO group; p = 0.41). The LCPD stage at the first visit was assessed using the modified Waldenström classification. The intraobserver and interobserver values of the modified Waldenström classification, evaluated using kappa statistics, were excellent (kappa value 0.89 [95% CI 0.75 to 0.97]; p < 0.01) and good (kappa value 0.65 [95% CI 0.43 to 0.87]; p < 0.01). The radiographic degree of collapse at the maximum fragmentation stage was assessed using the lateral pillar classification. The intraobserver and interobserver reliabilities of the lateral pillar classification were excellent (kappa value 0.84 [95% CI 0.73 to 0.94]; p < 0.01) and excellent (kappa value 0.83 [95% CI 0.71 to 0.94]; p < 0.01). The degree of femoral head deformity at the most recent follow-up examination was compared between the groups in terms of the Stulberg classification, in which Classes I and II were classified as good and Classes III through V were classified as poor. The intraobserver and interobserver reliabilities of the Stulberg classification were good (kappa value 0.74 [95% CI 0.55 to 0.92]; p < 0.01) and good (kappa value 0.69 [95% CI 0.50 to 0.89]; p < 0.01). The evaluators were involved in the patients' clinical care as part of the treating team. RESULTS: Good radiographic results (Stulberg Class I or II) were obtained more frequently in the FVO group (76% [16 of 21 patients]) than in the brace group (36% [12 of 33 patients]), with an odds ratio of 5.6 (95% CI 1.7 to 18.5; p < 0.01). In the brace group, a subsequent femoral varus osteotomy was performed in 18% (six of 33) of patients with progressive collapse and hinge abduction, and implant removal surgery was performed approximately 1 year after the first procedure. This traditional varus osteotomy was occasionally performed in patients who were considered for conversion from nonoperative treatment before 2009 because FVO had not yet been introduced. In the FVO group, all patients (n = 21) had a second procedure to remove the implant at a mean of 10.5 ± 1.2 months postoperatively. Additional procedures were performed in 24% (five of 21) of patients, including a second FVO for progressive collapse (one patient), guided growth for a limb length discrepancy (one patient), and flexion valgus osteotomy for coxa vara in patients with a limb length discrepancy (three patients). CONCLUSION: Our historical control study found that FVO may increase the possibility of obtaining good radiographic results (Stulberg Class I or II) compared with brace treatment for patients with late-onset LCPD, although surgical interventions after the first and second implant removal procedures may be indicated. Surgeons can consider FVO if they encounter patients with late-onset LCPD, which is a challenging condition. A larger study with long-term follow-up is needed to confirm the efficacy of FVO. LEVEL OF EVIDENCE: Level III, therapeutic study.