Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid-induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15/AKT/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX-induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15/AKT/mTOR signaling. In addition, DEX-induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15-mediated signaling, and D7 ameliorated this DEX-induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX-induced ROS and activation of GDF15/AKT/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.

Biomechanics of the Femoral Head Cartilage and Subchondral Trabecular Bone in Osteoporotic and Osteopenic Fractures.

This study aimed to investigate the relationship between the micro structural properties of the subchondral trabecular bone (STB) and the macro mechanical properties of the articular cartilage (AC) in patients with osteoporotic (OP) and osteopenic (OPE) fractures. Sixteen femoral head samples (OP;OPE, n = 8 each) were obtained from female patients who underwent hip hemiarthroplasty. STB and AC specimens were harvested from those heads. Bone specimens were scanned using µ-CT to determine the micro structural properties. In-situ nondestructive compressive tests were performed for the cartilages to obtain elastic properties. The finite element technique was implemented on STB models created from µ-CT data to compute apparent elastic modulus. In addition, dynamic cyclic destructive tests were performed on STB and AC specimens to assess failure cycles. The results demonstrated that STB specimens in OPE group have more interconnected structure and higher cyclic dynamic strength than those in OP group. Furthermore, bone mineral density, failure cycle, and trabecular number of STB were positively correlated with the cartilage failure cycle, which indicates that STB alteration may affect the macroscopic mechanical properties of AC. The findings suggest that STB loss correlates with a decrease in cartilage strength and that improving of bone quality may prevent cartilage weakness.

Medialization of the Hip's Center with Periacetabular Osteotomy: Validation of Assessment with Plain Radiographs.

BACKGROUND: Periacetabular osteotomy (PAO) increases acetabular coverage of the femoral head and medializes the hip's center, restoring normal joint biomechanics. Past studies have reported data regarding the degree of medialization achieved by PAO, but measurement of medialization has never been validated through a comparison of imaging modalities or measurement techniques. The ilioischial line appears to be altered by PAO and may be better visualized at the level of the inferior one-third of the femoral head, thus, an alternative method of measuring medialization that begins at the inferior one-third of the femoral head may be beneficial. QUESTIONS/PURPOSES: (1) What is the true amount and variability of medialization of the hip's center that is achieved with PAO? (2) Which radiographic factors (such as lateral center-edge angle [LCEA] and acetabular inclination [AI]) correlate with the degree of medialization achieved? (3) Does measurement of medialization on plain radiographs at the center of the femoral head (traditional method) or inferior one-third of the femoral head (alternative method) better correlate with true medialization? (4) Are intraoperative fluoroscopy images different than postoperative radiographs for measuring hip medialization? METHODS: We performed a retrospective study using a previously established cohort of patients who underwent low-dose CT after PAO. Inclusion criteria for this study included PAO as indicated for symptomatic acetabular dysplasia, preoperative CT scan, and follow-up between 9 months and 5 years. A total of 333 patients who underwent PAO from February 2009 to July 2018 met these criteria. Additionally, only patients who were between 16 and 50 years old at the time of surgery were included. Exclusion criteria included prior ipsilateral surgery, femoroacetabular impingement (FAI), pregnancy, neuromuscular disorder, Perthes-like deformity, inadequate preoperative CT, and inability to participate. Thirty-nine hips in 39 patients were included in the final study group; 87% (34 of 39) were in female patients and 13% (5 of 39 hips) were in male patients. The median (range) age at the time of surgery was 27 years (16 to 49). Low-dose CT images were obtained preoperatively and at the time of enrollment postoperatively; we also obtained preoperative and postoperative radiographs and intraoperative fluoroscopic images. The LCEA and AI were assessed on plain radiographs. Hip medialization was assessed on all imaging modalities by an independent, blinded assessor. On plain radiographs, the traditional and alternative methods of measuring hip medialization were used. Subgroups of good and fair radiographs, which were determined by the amount of pelvic rotation that was visible, were used for subgroup analyses. To answer our first question, medialization of all hips was assessed via measurements made on three-dimensional (3-D) CT hip reconstruction models. For our second question, Pearson correlation coefficients, one-way ANOVA, and the Student t-test were calculated to assess the correlation between radiographic parameters (such as LCEA and AI) and the amount of medialization achieved. For our third question, statistical analyses were performed that included a linear regression analysis to determine the correlation between the two radiographic methods of measuring medialization and the true medialization on CT using Pearson correlation coefficients, as well as 95% confidence intervals and standard error of the estimate. For our fourth question, Pearson correlation coefficients were calculated to determine whether using intraoperative fluoroscopy to make medialization measurements differs from measurements made on radiographs. RESULTS: The true amount of medialization of the hip center achieved by PAO in our study as assessed by reference-standard CT measurements was 4 ± 3 mm; 46% (18 of 39 hips) were medialized 0 to 5 mm, 36% (14 hips) were medialized 5 to 10 mm, and 5% (2 hips) were medialized greater than 10 mm. Thirteen percent (5 hips) were lateralized (medialized < 0 mm). There were small differences in medialization between LCEA subgroups (6 ± 3 mm for an LCEA of ≤ 15°, 4 ± 4 mm for an LCEA between 15° and 20°, and 2 ± 3 mm for an LCEA of 20° to 25° [p = 0.04]). Hips with AI ≥ 15° (6 ± 3 mm) achieved greater amounts of medialization than did hips with AI of < 15° (2 ± 3 mm; p < 0.001). Measurement of medialization on plain radiographs at the center of the femoral head (traditional method) had a weaker correlation than using the inferior one-third of the femoral head (alternative method) when compared with CT scan measurements, which were used as the reference standard. The traditional method was not correlated across all radiographs or only good radiographs (r = 0.16 [95% CI -0.17 to 0.45]; p = 0.34 and r = 0.26 [95% CI -0.06 to 0.53]; p = 0.30), whereas the alternative method had strong and very strong correlations when assessed across all radiographs and only good radiographs, respectively (r = 0.71 [95% CI 0.51 to 0.84]; p < 0.001 and r = 0.80 [95% CI 0.64 to 0.89]; p < 0.001). Measurements of hip medialization made on intraoperative fluoroscopic images were not found to be different than measurements made on postoperative radiographs (r = 0.85; p < 0.001 across all hips and r = 0.90; p < 0.001 across only good radiographs). CONCLUSION: Using measurements made on preoperative and postoperative CT, the current study demonstrates a mean true medialization achieved by PAO of 4 mm but with substantial variability. The traditional method of measuring medialization at the center of the femoral head may not be accurate; the alternate method of measuring medialization at the lower one-third of the femoral head is a superior way of assessing the hip center's location. We suggest transitioning to using this alternative method to obtain the best clinical and research data, with the realization that both methods using plain radiography appear to underestimate the true amount of medialization achieved with PAO. Lastly, this study provides evidence that the hip center's location and medialization can be accurately assessed intraoperatively using fluoroscopy. LEVEL OF EVIDENCE: Level III, diagnostic study.

ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

The Acetabular Wall Index Is Associated with Long-term Conversion to THA after PAO.

BACKGROUND: Periacetabular osteotomy (PAO) has been shown to be a valuable option for delaying the onset of osteoarthritis in patients with hip dysplasia. Published studies at 30 years of follow-up found that postoperative anterior overcoverage and posterior undercoverage were associated with early conversion to THA. The anterior and posterior wall indices are practical tools for assessing AP coverage on standard AP radiographs of the pelvis pre-, intra-, and postoperatively. However, no study that we know of has evaluated the relationship between the postoperative anterior and posterior wall indices and survivorship free from arthroplasty. QUESTIONS/PURPOSES: In a study including patients after PAO for developmental dysplasia of the hip (DDH), we evaluated whether the acetabular wall index is associated with conversion to THA in the long-term after PAO. We asked: (1) Is an abnormal postoperative anterior wall index associated with conversion to THA after PAO? (2) Is an abnormal postoperative posterior wall index associated with conversion to THA after PAO? (3) Are there other factors associated with joint replacement after PAO? METHODS: This retrospective study involved pooling data of PAO for DDH from two previously published sources. The first series (1984-1987) comprised the very first 75 PAOs for symptomatic DDH performed at the inventor's institution. The second (1997-2000) comprised a series of PAOs for symptomatic DDH completed at the same institution 10 years later. No patient was lost to follow-up. Fifty hips (44 patients) were excluded for predefined reasons (previous surgery, substantial femoral pathomorphologies, poor-quality radiographs), leaving 115 hips (102 patients, mean age 29 ± 11 years, 28% male) for analysis with a mean follow-up of 22 ± 6 years. One observer not involved in patient treatment digitally measured the anterior and posterior wall indices on postoperative AP pelvic radiographs of all patients. All patients were contacted by mail or telephone to confirm any conversion to THA and the timing of that procedure relative to the index procedure. We performed univariate and multivariate Cox regression analyses using conversion to THA as our endpoint to determine whether the anterior and posterior wall indices are associated with prosthetic replacement in the long-term after PAO. Thirty-one percent (36 of 115) of hips were converted to THA within a mean of 15 ± 7 years until failure. The mean follow-up duration of the remaining patients was 22 ± 6 years. RESULTS: A deficient anterior wall index was associated with conversion THA in the long-term after PAO (adjusted hazard ratio 10 [95% CI 3.6 to 27.9]; p < 0.001). Although observed in the univariate analysis, we could not find a multivariate association between the posterior wall index and a higher conversion rate to THA. Grade 0 Tönnis osteoarthritis was associated with joint preservation (adjusted HR 0.2 [95% CI 0.07 to 0.47]; p = 0.005). Tönnis osteoarthritis Grades 2 and 3 were associated with conversion to THA (adjusted HR 2.3 [95% CI 0.9 to 5.7]; p = 0.08). CONCLUSION: A deficient anterior wall index is associated with a decreased survivorship of the native hip in the long-term after PAO. Intraoperatively, in addition to following established radiographical guidelines, the acetabular wall indices should be measured systematically to ascertain optimal acetabular fragment version to increase the likelihood of reconstructive survival after PAO for DDH. LEVEL OF EVIDENCE: Level III, therapeutic study.

Percutaneous autologous impaction bone graft for advanced femoral head osteonecrosis: a retrospective observational study of unsatisfactory short-term outcomes.

BACKGROUND: Half of osteonecrosis of the femoral head (ONFH) patients suffer femoral head collapse at initial diagnosis, and more than half are bilaterally affected. This study developed a percutaneous autologous impaction bone graft (IBG) technique as a modification of core decompression (CD). We also summarized the short-term results and treatment efficacy of percutaneous autologous IBG in advanced ONFH. METHODS: Twenty patients (12 males, 8 females) with nontraumatic, postcollapse ONFH except one case underwent CD (10-mm core diameter) and reverse IBG. Radiological changes of the ONFH stage and type were analyzed. Survival analysis using Kaplan-Meier estimates was performed with conversion to total hip arthroplasty (THA) as the endpoint. In addition, the Harris hip score (HHS) and University of California, Los Angeles (UCLA) activity rating scale were evaluated. RESULTS: Percutaneous autologous IBG was performed successfully, with an average operation time of < 1 h and small blood loss, and 7 patients (35%) needed conversion to THA at an average of 17 months postoperatively. We observed radiological progressive change in 60% of the patients during a mean observation period of 3 years. The mean clinical scores, except data recorded, after THA significantly improved (before vs. after 3 years: UCLA activity score, 3.7 vs. 5.2 [P = 0.014]; HHS, 57.6 vs. 76.5 points [P = 0.005]). In addition, 6 patients showed radiological progression but no clinical deterioration. CONCLUSIONS: Percutaneous autologous IBG was technically simple and minimally invasive, but short-term results were unsatisfactory for advanced ONFH. Indications for this procedure should be carefully examined to improve it in order to enable bone formation.

What Are the Early Outcomes of True Reverse Periacetabular Osteotomy for Symptomatic Hip Overcoverage?

BACKGROUND: Acetabular overcoverage is associated with pincer-type femoroacetabular impingement (FAI). A subtype of acetabular overcoverage is caused by a deep acetabulum with a negatively tilted acetabular roof, in which acetabular reorientation may be a preferable alternative to rim trimming to uncover the femoral head. We introduced the true reverse periacetabular osteotomy (PAO) in 2003, which in contrast to an anteverting PAO, also flexes and abducts the acetabulum relative to the intact ilium to decrease anterior and lateral femoral head coverage and correct negative tilt of the acetabular roof. To our knowledge, the clinical results of the true reverse PAO have not been evaluated. QUESTIONS/PURPOSES: For a group of patients who underwent reverse PAO, (1) Do patients undergoing reverse PAO demonstrate short-term improvement in pain, function, and hip ROM, and decreased acetabular coverage, as defined by lateral and anterior center-edge angle and Tönnis angle? (2) Are there identifiable factors associated with success or adverse outcomes of reverse PAO as defined by reoperation, conversion to THA, or poor patient-reported outcome scores? (3) Are there identifiable factors associated with early complications? METHODS: Between 2003 and 2017, two surgeons carried out 49 reverse PAOs in 37 patients. Twenty-five patients had unilateral reverse PAO and 12 patients had staged, bilateral reverse PAOs. To ensure that each hip was an independent data point for statistical analysis, we chose to include in our series only the first hip in the patients who had bilateral reverse PAOs. During the study period, our general indications for this operation were symptomatic lateral and anterior acetabular overcoverage causing FAI that had failed to respond to previous conservative or surgical treatment. Thirty-seven hips in 37 patients with a median (range) age of 18 years (12 to 41; interquartile range 16 to 21) were included in this retrospective study at a minimum follow-up of 2 years (median 6 years; range 2 to 17). Thirty-four patients completed questionnaires, 24 patients had radiographic evaluation, and 23 patients received hip ROM clinical examination. However, seven patients had not been seen in more than 5 years. The clinical and radiographic parameters of all 37 hips that underwent reverse PAO in 37 patients from a longitudinally maintained institutional database were retrospectively studied preoperatively and postoperatively. Adverse outcomes were considered conversion to THA or a WOMAC pain score greater than 10 at least 2 years postoperatively. Patient-reported outcomes, radiographic measurements, and hip ROM were evaluated preoperatively and at most recent follow-up using a paired t-test or McNemar test, as appropriate. Linear regression analysis was used to assess for identifiable factors associated with clinical outcomes. Logistic regression analysis was used to assess for identifiable factors associated with adverse outcomes and surgical complications. All tests were two-sided, and p values less than 0.05 were considered significant. RESULTS: At a minimum of 2 years after reverse PAO, patients experienced improvement in WOMAC pain (-7 [95% CI -9 to -5]; p < 0.001), stiffness (-2 [95% CI -3 to -1]; p < 0.001), and function scores (-18 [95% CI -24 to -12]; p < 0.001) and modified Harris Hip Score (mHHS) (20 [95% CI 13 to 27]; p < 0.001). The mean postoperative hip ROM improved in internal rotation (8° [95% CI 2° to 14°]; p = 0.007). Acetabular coverage, as defined by lateral center-edge angle (LCEA), anterior center-edge angle (ACEA), and Tönnis angle, improved by -8° (95% CI -12° to -5°; p < 0.001) for LCEA, -12° (95% CI -15° to -9°; p < 0.001) for ACEA, and 9° (95% CI 6° to 13°; p < 0.001) for Tönnis angle. The postoperative severity of radiographic arthritis was associated with worse WOMAC function scores such that for each postoperative Tönnis grade, WOMAC function score increased by 12 points (95% CI 2 to 22; p = 0.03). A greater postoperative Tönnis grade was also correlated with worse mHHS, with an average decrease of 12 points (95% CI -20 to -4; p = 0.008) in mHHS for each additional Tönnis grade. Presence of a positive postoperative anterior impingement test was associated with a decrease in mHHS score at follow-up, with an average 23-point decrease in mHHS (95% CI -34 to -12; p = 0.001). Nineteen percent (7 of 37) of hips had surgery-related complications. Four hips experienced adverse outcomes at final follow-up, with two patients undergoing subsequent THA and two with a WOMAC pain score greater than 10. We found no factors associated with complications or adverse outcomes. CONCLUSION: The early clinical and radiographic results of true reverse PAO compare favorably to other surgical treatments for pincer FAI, suggesting that reverse PAO is a promising treatment for cases of pincer FAI caused by global acetabular overcoverage. However, it is a technically complex procedure that requires substantial training and preparation by a surgeon who is already familiar with standard PAO, and it must be carefully presented to patients with discussion of the potential risks and benefits. Future studies are needed to further refine the indications and to determine the long-term outcomes of reverse PAO. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Does the Rule of Thirds Adequately Detect Deficient and Excessive Acetabular Coverage?

BACKGROUND: Assessment of AP acetabular coverage is crucial for choosing the right surgery indication and for obtaining a good outcome after hip-preserving surgery. The quantification of anterior and posterior coverage is challenging and requires either other conventional projections, CT, MRI, or special measurement software, which is cumbersome, not widely available and implies additional radiation. We introduce the "rule of thirds" as a promising alternative to provide a more applicable and easy method to detect an excessive or deficient AP coverage. This method attributes the intersection point of the anterior (posterior) wall to thirds of the femoral head radius (diameter), the medial third suggesting deficient and the lateral third excessive coverage. QUESTION/PURPOSE: What is the validity (area under the curve [AUC], sensitivity, specificity, positive/negative likelihood ratios [LR(+)/LR(-)], positive/negative predictive values [PPV, NPV]) for the rule of thirds to detect (1) excessive and (2) deficient anterior and posterior coverages compared with previously established radiographic values of under-/overcoverage using Hip2Norm as the gold standard? METHODS: We retrospectively evaluated all consecutive patients between 2003 and 2015 from our institutional database who were referred to our hospital for hip pain and were potentially eligible for joint-preserving hip surgery. We divided the study group into six specific subgroups based on the respective acetabular pathomorphology to cover the entire range of anterior and posterior femoral coverage (dysplasia, overcoverage, severe overcoverage, excessive acetabular anteversion, acetabular retroversion, total acetabular retroversion). From this patient cohort, 161 hips were randomly selected for analysis. Anterior and posterior coverage was determined with Hip2Norm, a validated computer software program for evaluating acetabular morphology. The anterior and posterior wall indices were measured on standardized AP pelvis radiographs, and the rule of thirds was applied by one observer. RESULTS: The detection of excessive anterior and posterior acetabular wall using the rule of thirds revealed an AUC of 0.945 and 0.933, respectively. Also the detection of a deficient anterior and posterior acetabular wall by applying the rule of thirds revealed an AUC of 0.962 and 0.876, respectively. For both excessive and deficient anterior and posterior acetabular coverage, we found high specificities and PPVs but low sensitivities and NPVs. CONCLUSION: We found a high probability for an excessive (deficient) acetabular wall when this intersection point lies in the lateral (medial) third, which would qualify for surgical correction. On the other hand, if this point is not in the lateral (medial) third, an excessive (deficient) acetabular wall cannot be categorically excluded. Thus, the rule of thirds is very specific but not as sensitive as we had expected. LEVEL OF EVIDENCE: Level II, diagnostic study.

What Mid-term Patient-reported Outcome Measure Scores, Reoperations, and Complications Are Associated with Concurrent Hip Arthroscopy and Periacetabular Osteotomy to Treat Dysplasia with Associated Intraarticular Abnormalities?

BACKGROUND: Periacetabular osteotomy (PAO) is a well-accepted treatment for acetabular dysplasia, but treatment success is not uniform. Concurrent hip arthroscopy has been proposed for select patients to address intraarticular abnormalities. The patient-reported outcomes, complications, and reoperations for concurrent arthroscopy and PAO to treat acetabular dysplasia remain unclear. QUESTIONS/PURPOSES: (1) What are the functional outcome scores among select patients treated with PAO plus concurrent hip arthroscopy at mid-term follow-up? (2) What factors are associated with conversion to THA or persistent symptoms (modified Harris hip score ≤ 70 or WOMAC pain subscore ≥ 10)? (3) What proportion of patients underwent further hip preservation surgery at mid-term follow-up? (4) What are the complications associated with the procedure? METHODS: Between November 2005 and December 2012, 78 patients (81 hips) who presented with symptomatic acetabular dysplasia-defined as a lateral center-edge angle less than 20° with hip pain for more than 3 months that interfered with daily function-had undergone unsuccessful nonsurgical treatment, had associated intraarticular abnormalities on MRI, and underwent combined hip arthroscopy and PAO. Eleven patients did not have minimum 4-year follow-up and were excluded, leaving 67 patients (70 hips) who met our inclusion criteria and had a mean follow-up duration of 6.5 ± 1.6 years. We retrospectively evaluated patient-reported outcomes at final follow-up using the University of California Los Angeles (UCLA) activity score, the modified Harris Hip Score (mHHS), and the WOMAC pain subscore. Conversion to THA or persistent symptoms were considered clinical endpoints. Repeat surgical procedures were drawn from a prospectively maintained database, and major complications were graded according to the validated Clavien-Dindo classification (Grade III or IV). Student t-tests, chi-square tests, and Fisher exact tests identified the association of patient factors, radiographic measures, and surgical details with clinical endpoints. For patients who underwent bilateral procedures, only the first hip was included in our analyses. RESULTS: At final follow-up, the mean mHHS for all patients improved from a mean ± SD of 55 ± 19 points to 85 ± 17 points (p < 0.001), the UCLA activity score improved from 6.5 ± 2.7 points to 7.5 ± 2.2 points (p = 0.01), and the WOMAC pain score improved from 9.1 ± 4.3 points to 3.2 ± 3.9 points (p < 0.001). Three percent (2 of 67) of patients underwent subsequent THA, while 21% (15 of 70) of hips were persistently symptomatic, defined as mHHS less than or equal to 70 or WOMAC pain subscore greater than or equal to 10. Univariate analyses indicated that no patient demographics, preoperative or postoperative radiographic metrics, or intraoperative findings or procedures were associated with subsequent THA or symptomatic hips. Worse baseline mHHS and WOMAC pain scores were associated with subsequent THA or symptomatic hips. Seven percent (5 of 67) of patients underwent repeat hip preservation surgery for recurrent symptoms, and 4% (3 of 67) of patients had major complications (Clavien-Dindo Grade III or IV). CONCLUSION: This study demonstrated that concurrent hip arthroscopy and PAO to treat symptomatic acetabular dysplasia (with intraarticular abnormalities) has good clinical outcomes at mid-term follow-up in many patients; however, persistent symptoms or conversion to THA affected almost a quarter of the sample. We noted an acceptable complication profile. Further study is needed to directly compare this approach to more traditional techniques that do not involve arthroscopy. We do not use isolated hip arthroscopy to treat symptomatic acetabular dysplasia. LEVEL OF EVIDENCE: Level IV, therapeutic study.

High Risk of Conversion to THA After Femoroacetabular Osteoplasty for Femoroacetabular Impingement in Patients Older than 40 Years.

BACKGROUND: Femoroacetabular impingement (FAI) is a recognized cause of hip pain and decreased quality of life and has been linked to primary idiopathic hip osteoarthritis (OA). Although the operative indications for FAI have expanded to include older patients, we do not know whether there is an increased risk of conversion to THA after femoroacetabular osteoplasty (FAO) via the mini-open approach for FAI in patients older than 40 years compared with younger patients, after controlling for other confounding variables. QUESTIONS/PURPOSES: (1) After matching for gender, BMI, preoperative symptomatic period, surgeon experience, Tönnis grade, and degree of chondral lesion, are patients older than 40 years who undergo FAO for FAI more likely to be revised to THA at a minimum of 2 years' follow-up than are patients younger than 40? (2) Is there a difference in delta (postoperative minus preoperative) improvement in functional outcome scores in those patients who did not go on to THA between patients older than and younger than 40 years? METHODS: Between 2003 and 2017, one surgeon performed 281 FAOs via the mini-open approach in patients older than 40 years and 544 of the same procedure in patients younger than 40 years. During that period, the general indications for FAO were the same in both age groups: (1) history and physical exam consistent with FAI, (2) radiographic evidence of focal impingement (cam, pincer, or both), (3) evidence of labral or chondrolabral tears, and (4) minimal to no arthritic changes (all four criteria required). In general, age was not used as a contraindication for surgery. A total of 86% (241 of 281) of patients older than 40 and 91% (494 of 544) of those younger than 40 were available for minimum of 2 years' follow-up, had complete datasets (radiographs as well as preoperative and most recent patient-reported outcomes scores) at a minimum of 2 years after surgery, and were considered eligible for the match. Propensity score matching was used to match for BMI, gender, preoperative symptomatic period, surgeon experience, Tönnis grade, and degree of intraoperative chondral lesion. We matched at a 1:2 ratio 130 patients older than age 40 with 260 patients younger than age 40. The mean ± SD follow-up duration for both groups was 5 ± 2 years. The mean age of the cohort of interest was 47 ± 5 years compared with 28 ± 7 years in the control. Fifty-four percent (70 of 130) of patients older than 40 years were women and 46% (60 of 130) were men; for those younger than 40, 51% (133 of 260) of participants were women and 49% (127 of 260) were men. Tönnis grade distribution for patients older than 40 was as follows: 46% (60 of 130) had Grade 0, 42% (55 of 130) had Grade 1, and 12% (15 of 130) had Grade 2. In comparison, Tönnis grade for patients younger than 40 was as follows: 52% (136 of 260) had Grade 0, 38% (100 of 260) had Grade 1, and 9% (24 of 260) had Grade 2 (p = 0.49). Chondral lesion degree was determined intraoperatively as none, a partial-thickness tear, or a full-thickness tear. Tönnis grade was determined based on preoperative plain AP hip radiographs. We then compared the percentage of patients who converted to THA during the surveillance period (our primary study outcome). We also compared the difference in delta (preoperative minus postoperative) improvement in functional outcome scores using the modified Harris Hip Score (mHHS) between the groups, excluding those who had already been converted to THA. RESULTS: In patients older than 40 years, 16% (21 of 130) converted to THA at a mean time to conversion of 2 ± 1 years compared with 7% (17 of 260) at a mean time of 2 ± 2 years in patients younger than 40 years (p = 0.01). At a mean of 5 ± 2 years after FAO, among those patients who had not undergone conversion to THA, the mean delta mHHS score for patients older than 40 was 11 ± 17, compared with 20 ± 26 for patients younger than 40 (p = 0.04). CONCLUSION: Since approximately 1 in 6 patients older than 40 years in this series who underwent FAO for FAI opted for early conversion to THA at a mean time of 2 years after the osteoplasty procedure, and the remaining patients who did not undergo THA reported lower improvement in functional outcomes, we recommend surgeons avoid this procedure in patients in this age group until or unless we can better refine our indications. This is especially true because loss to follow-up causes us to believe that, if anything, our estimates of the risk of conversion to THA are conservative. LEVEL OF EVIDENCE: Level III, therapeutic study.

Effects of types and degrees of ankylosing spondylitis hip structural damages on post-total hip arthroplasty outcome measurements.

To determine the effects of ankylosing spondylitis (AS)-associated hip damages on the outcome measurements after total hip arthroplasty (THA).The medical records of 122 patients with AS (181 hips) who underwent THA were retrospectively reviewed. The mean follow-up was 43.9 (32-129) months. The types and degrees of hip damages were evaluated by preoperative hip X-rays. The patients were grouped according to the satisfaction degree after the operation. Univariable and multivariable statistical analyses were conducted.The intraclass correlation coefficients for the assessment between the 2 reviewers in the study were 0.86 to 0.97. Cox regression showed that femoral head erosion severity had an effect on the recovery time of independent walking without crutches postoperatively (odds ratio = 1.467, 95% confidence interval: 1.050-2.409, P = .025). The mean time to recover independent walking in the severe femoral head erosion group was 7.3 ±â€Š0.9 weeks, which was 4.6 ±â€Š0.4 weeks longer than in the non-severe femoral head erosion group, as confirmed by the log-rank (Mantel-Cox) test (Chi-squared = 11.684, P = .001). The multivariable analysis showed that higher acetabular sclerosis scores correlated with lower postoperative dissatisfaction risk (odds ratio = 0.322, 95% confidence interval: 0.136-0.764). The multiple linear regression analysis showed that postoperative range of motion (ROM) improvement was affected by preoperative ROM of the hip, space narrowing degree, and ceramic-ceramic material for the weight-bearing surface (F = 179.81, P < .001), with preoperative ROM of the hip having the greatest impact.Severe femoral head erosion prolongs the recovery time of independent walking after THA. Acetabular sclerosis is not associated with poor outcomes in patients with AS-associated hip damage undergoing THA.

Degradation of subchondral bone collagen in the weight-bearing area of femoral head is associated with osteoarthritis and osteonecrosis.

BACKGROUND: The aim of the study was to evaluate the change of subchondral bone collagen and trabecular bone in the weight-bearing area of femoral head from patients with osteoarthritis (OA) or osteonecrosis of femoral head (ONFH), and discuss the effect of collagen degradation on OA and ONFH. METHODS: Femoral heads from patients with femoral neck fracture (FNF) were collected as control group. All collected samples were divided into OA group (N = 10), ONFH group (N = 10), and FNF group (N = 10). Differences of subchondral bone collagen were compared through scanning electron microscope (SEM) observation, immunohistochemistry staining, and Masson's trichrome staining. Alteration of subchondral bone was displayed through hematoxylin and eosin (H&E) staining and gross morphology. RESULTS: SEM results showed that collagen fibers in OA and ONFH group appeared to be thinner, rougher, sparser, and more wizened. Immunohistochemistry and Masson's trichrome staining results demonstrated that the content of collagen fibers in the OA and ONFH group was obviously less than the FNF group. H&E staining results showed that trabecular bone in OA and ONFH group appeared to be thinner and ruptured. Gross morphology results showed that the degeneration and destruction of cartilage and subchondral bone in OA and ONFH group were severer than FNF group. The characteristics mentioned above in ONFH group were more apparent than OA group. CONCLUSIONS: This study revealed that degradation of collagen fibers from subchondral bone in the weight-bearing area of femoral head was associated with OA and ONFH, which may help to find new therapeutic strategies of the diseases.

Crocin promotes osteogenesis differentiation of bone marrow mesenchymal stem cells.

Crocin has plentiful pharmacological effects, but its role in osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) is unexplored. This study explored the effect of crocin on osteogenesis differentiation, in order to provide evidence for its clinical application. In cell experiments, human BMSCs (hBMSCs) were induced by osteogenesis differentiation medium or crocin. In animal experiments, steroid-induced osteonecrosis of the femoral head (SANFH) rat models was established using lipopolysaccharide (LPS) plus methylprednisolone (MPS), and then treated with crocin. The osteogenesis differentiation capacity of hBMSCs was analyzed by alkaline phosphatase (ALP) and alizarin red S staining. Histopathological changes in rat femoral head tissues were observed by hematoxylin and eosin (H&E) staining. The expression levels of RUNX2, COL1A1, OCN, and GSK-3ß in hBMSCs and rat femoral head tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) analysis. ALP and alizarin red S staining demonstrated that LAP activity and calcium nodules were increased in hBMSCs treated with crocin. From H&E staining results, femoral head tissues of SANFH models showed typical osteonecrosis, which could be ameliorated by crocin. WB and qRT-PCR assays detected that the expression levels of RUNX2, COL1A1, and OCN in hBMSCs and femoral head tissues of models were obviously increased after crocin treatment, while GSK-3ß phosphorylation was reduced. In general, the action of crocin was concentration-dependent. Crocin might be beneficial to the recovery of SANFH through accelerating osteogenesis differentiation of BMSCs, which might be a novel therapy for related diseases.

Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers.

(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg-1). The birds in group H were injected intramuscularly with MP (20 mg·kg-1·d-1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

Effect of a Specific Questionnaire Sheet on Subclassification of Osteonecrosis of the Femoral Head.

BACKGROUND This study examined whether use of a specific questionnaire sheet for nontraumatic osteonecrosis of the femoral head (ONFH) could affect the subclassification of ONFH compared with a conventional medical interview. MATERIAL AND METHODS Study participants consisted of 400 patients with ONFH who visited our hospital between February 2011 and March 2015. Data on history of systemic steroid therapy and habitual alcohol intake were obtained during a conventional medical interview at the first visit and were re-evaluated using a specific questionnaire sheet at another visit. Patients were subclassified into 4 groups: steroid-associated, alcohol-associated, steroid/alcohol-associated, or idiopathic ONFH. RESULTS Use of the specific questionnaire sheet resulted in a 4.0% increase in the proportion of patients with a history of systemic steroid therapy, from 57.3% (n=229) to 61.3% (n=245), and a 14.3% increase for history of habitual alcohol intake, from 35.0% (n=140) to 49.3% (n=197). The proportion of patients with steroid/alcohol-associated ONFH increased from 2.5% (n=10) to 17.8% (n=71), while the proportion in the other 3 groups decreased: steroid-associated ONFH from 54.8% (n=219) to 43.5% (n=174); alcohol-associated ONFH from 32.5% (n=130) to 31.5% (n=126); and idiopathic ONFH from 10.2% (n=41) to 7.2% (n=29). Ninety-six patients (24.0%) were classified into a different subgroup based on the specific questionnaire sheet. CONCLUSIONS The use of a specific questionnaire sheet can change the distribution of ONFH subclassifications compared with use of a conventional medical history interview. Use of a specific questionnaire sheet can allow for more detailed self-reporting regarding potential causative factors for nontraumatic ONFH, especially habitual alcohol intake.

Comparison of surgical dislocation and impacting bone graft and surgical dislocation and rotational osteotomy for the treatment of ARCO III femoral head necrosis.

Hip preserving procedures are still a challenge in late-stage osteonecrosis of femoral head (ONFH) patients. We aimed to compare the clinical outcomes of surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy for treatment of ONFH in Association Research Circulation Osseous (ARCO) stage III patients.We retrospectively reviewed 30 ARCO stage III patients (33 hips) who had surgical dislocation and impaction bone graft or surgical dislocation and rotational osteotomy in our center from June 2012 to December 2017. Baseline characteristics, clinical evaluation using Harris score and radiologic evaluation up to 12 months after surgery were recorded and compared.Fifteen patients (17 hips) were in the surgical dislocation and impaction bone graft group and 15 patients (16 hips) were in the surgical dislocation and rotational osteotomy group. No significant differences in age, gender, etiology, ARCO stage, duration of illness, operation time, and length of hospitalization were observed between the 2 groups. Compared to preoperation Harris score, the Harris score of 6 months postoperation and 12 months postoperation significantly improved. At 12 months postoperation, the excellent and good rate was 76.5% in the impaction bone graft group and 87.5% in the rotational osteotomy group. No significant difference in Harris scores was detected in the 2 groups.Surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy had satisfactory 1-year efficacy for ARCO III ONFH patients. Surgical dislocation and rotational osteotomy had better short-term efficacy than surgical dislocation and impaction bone graft.

The effect of the necrotic area on the biomechanics of the femoral head - a finite element study.

BACKGROUND: Femoral head collapse is the key to the progress of osteonecrosis of the femoral head (ONFH), but the causes of collapse are not completely clear. The better understanding of the progress of femoral head collapse will guide the treatment strategy for ONFH patients. The purpose of this study was to evaluate the biomechanical influence of necrosis area on the collapse of the femoral head by finite element analysis. METHODS: CT and MRI data from the hip joint of a healthy volunteer were collected to establish a finite element (FE) model of a normal hip. Subsequently, five categories of osteonecrosis FE models were established by using the normal model and computer software according to China-Japan Friendship Hospital (CJFH) classification for ONFH. The CJFH system includes five types based on the size and location of necrosis lesions in the femoral head (type M, C, L1, L2, and L3) and the stage of ONFH. The collapse indices of each model were analyzed by FE method, including the displacement, peak von Mises stress and stress index of the simulated necrotic area as well as the lateral pillar contact area of the femoral head to acetabular. RESULTS: (1) The displacement increments in the simulated necrotic areas of type M, C, L1, L2, and L3 models were 3.75 µm, 8.24 µm, 8.47 µm, 18.42 µm, and 20.44 µm respectively; the peak von Mises stress decrements were 1.50 MPa, 3.74 MPa, 3.73 MPa, 4.91 MPa, and 4.92 MPa respectively; and the stress indices were 0.04, 0.08, 0.08, 0.27, and 0.27 respectively. (2) The displacement increments in the lateral pillar contact areas of five type models were significantly different (P < 0.001) and increased in sequence as follows: 1.93 ± 0.15 µm, 5.74 ± 0.92 µm, 5.84 ± 1.42 µm, 14.50 ± 3.00 µm, and 16.43 ± 3.05 µm. The peak von Mises stress decrements were also significantly different (P < 0.001) and increased in sequence as follows: 0.52 ± 0.30 MPa, 0.55 ± 0.12 MPa, 0.67 ± 0.33 MPa, 4.17 ± 0.59 MPa, and 4.19 ± 0.60 MPa. (3) The collapse indices including the displacement increments and peak von Mises stress decrements of type L2 and L3 models were markedly higher than those of type M, C, and L1 models (P < 0.001). CONCLUSIONS: The collapse indices of the femoral heads of type L2 and L3 FE models were significantly higher than those of type M, C, and L1. Different areas of necrosis result in varied impact on the femoral head collapse.

Changes in the mechanical properties of femoral cartilage tissue in advanced osteoarthritis.

PURPOSE: The main goal of this article was the analysis of the changes of mechanical properties, thickness and histology of the cartilage in different regions of the femur head in advanced stage of the osteoarthritis. METHODS: The study material consisted of cylindrical specimens (9.7 mm) prepared form proximal epiphysis of the human femur bone after hip arthroplasty. The thickness was determined from the reconstruction of the specimen from microtomography (SkyScan 1172, Bruker®) images. Mechanical properties of the cartilage tissue were identified in static indentation test conducted the use of MTS® Synergie 100 testing machine. Histological study enabled us to determine cartilage total thickness as well as location and orientation of the collagen fibers. RESULTS: Depending on the region of the head, the cartilage tissue thickness was in the range (0.74-2.23 mm). The lowest thickness values were obtained for the R5 region and the lowest for R4. Samples from R1-R4 regions differ by 24%. Measurements of cartilage tissue indentation, determined with the help of Hayes' formula, showed that the values of mechanical parameters in regions R1, R2, R3 and R5 have similar values (the difference between them is about 5.5%). Region R4, which had the smallest thickness, also had the lowest values of mechanical parameters. CONCLUSIONS: Using κ coefficients, proposed by Hayes, enabled us to obtain similar values of mechanical parameters in the regions R1, R2, R3 and R5, despite differences in cartilage tissue thickness. The R4 region, which had the weakest mechanical parameters, was characterized by the strongest reduction of the articular cartilage tissue, which was accompanied by an unformed mass of cartilage residue originating from the abraded surface and bursa fluid.

Bone Mineral Density in Patients Suffering from Ménière's Disease.

INTRODUCTION: Previous studies have reported an association between reduced bone mineral density and the occurrence of benign paroxysmal positional vertigo, balance impairment, and saccular dysfunction. Furthermore, the results of recent animal studies have raised the possibility that vestibular dysfunction could affect bone remodeling and bone mass. The goal of the study was to compare bone mineral density of patients suffering from definite Ménière's disease to that of a matched control group. METHODS: We conducted a case-control cross-sectional study in a tertiary referral center. The study group included 23 patients suffering from definite Ménière's disease, and the control group was comprised of 23 patients matched in their race, gender, and age parameters in whom no vestibular pathology could be found. Dual energy X-ray absorptiometry of the femoral head was used for the assessment of bone mineral density. The T and Z scores of the femoral heads' bone mineral density were compared. RESULTS: The average T scores were -1.53 ± 1.08 in the study and -0.39 ± 0.72 (p = 0.016) in the control groups, and the Z scores were -0.4 ± 0.63 and 0.33 ± 0.31 (p = 0.018), respectively. Seventeen patients (74%) of the study group and 9 (39%) of the control group had T scores less than -1.0, indicating osteopenia/osteoporosis (p = 0.036). CONCLUSIONS: The results showed a significant association between Ménière's disease and reduced bone mineral density of the femoral head. Bone mineral density studies of the weight-bearing bones are warranted in Ménière's disease for the early diagnosis and treatment of osteopenia/osteoporosis on the one hand and possible benefit of this treatment for the evolution of Ménière's disease on the other hand.

Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.

In this study, we aimed to identify a candidate drug that can activate endogenous Angiopoietin 1 (Ang1) expression via drug repositioning as a pharmacological treatment for avascular osteonecrosis. After incubation with 821 drugs from the Food and Drug Administration (FDA)-approved drug library, Ang1 expression in U2OS cell culture media was examined by ELISA. Metformin, the first-line medication for treatment of type 2 diabetes, was selected as a candidate for in vitro and in vivo experimental evaluation. Ang1 was induced, and alkaline phosphatase activity was increased by metformin treatment in U2OS and MG63 cells. Wound healing and migration assay showed increased osteoblastic cell mobility by metformin treatment in U2OS and MG63 cells. Metformin upregulated expression of protein markers for osteoblastic differentiation in U2OS and MG63 cells but inhibited osteoclastic differentiation in Raw264.7 cells. Metformin (25 mg/kg) protected against ischemic necrosis in the epiphysis of the rat femoral head by maintaining osteoblast/osteocyte function and vascular density but inhibiting osteoclast activity in the necrotic femoral head. These findings provide novel insight into the specific biomarkers that are targeted and regulated by metformin in osteoblast differentiation and contribute to understanding the effects of these FDA-approved small-molecule drugs as novel therapeutics for ischemic osteonecrosis.