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.

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.

Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia.

The development of hindlimbs in tetrapod species relies specifically on the transcription factor TBX4. In humans, heterozygous loss-of-function TBX4 mutations cause dominant small patella syndrome (SPS) due to haploinsufficiency. Here, we characterize a striking clinical entity in four fetuses with complete posterior amelia with pelvis and pulmonary hypoplasia (PAPPA). Through exome sequencing, we find that PAPPA syndrome is caused by homozygous TBX4 inactivating mutations during embryogenesis in humans. In two consanguineous couples, we uncover distinct germline TBX4 coding mutations, p.Tyr113∗ and p.Tyr127Asn, that segregated with SPS in heterozygous parents and with posterior amelia with pelvis and pulmonary hypoplasia syndrome (PAPPAS) in one available homozygous fetus. A complete absence of TBX4 transcripts in this proband with biallelic p.Tyr113∗ stop-gain mutations revealed nonsense-mediated decay of the endogenous mRNA. CRISPR/Cas9-mediated TBX4 deletion in Xenopus embryos confirmed its restricted role during leg development. We conclude that SPS and PAPPAS are allelic diseases of TBX4 deficiency and that TBX4 is an essential transcription factor for organogenesis of the lungs, pelvis, and hindlimbs in humans.

Identification and Functional Evaluation of a Novel TBX4 Mutation Underlies Small Patella Syndrome.

Small patella syndrome (SPS) is a rare autosomal dominant disorder caused by mutations in TBX4 gene which encodes a transcription factor of FGF10. However, how TBX4 mutations result in SPS is poorly understood. Here, a novel TBX4 mutation c.1241C>T (p.P414L) was identified in a SPS family and series of studies were performed to evaluate the influences of TBX4 mutations (including c.1241C>T and two known mutations c.256G>C and c.743G>T). Results showed that mesenchymal stem cells (MSCs) with stable overexpression of either TBX4 wild-type (TBX4wt) or mutants (TBX4mt) were successfully generated. Immunofluorescence study revealed that both the overexpressed TBX4 wild-type and mutants were evenly expressed in the nucleus suggesting that these mutations do not alter the translocation of TBX4 into the nucleus. Interestingly, MSCs overexpression of TBX4mt exhibited reduced differentiation activities and decreased FGF10 expression. Chromatin immunoprecipitation (ChIP) study demonstrated that TBX4 mutants still could bind to the promoter of FGF10. However, dual luciferase reporter assay clarified that the binding efficiencies of TBX4 mutants to FGF10 promoter were reduced. Taken together, MSCs were firstly used to study the function of TBX4 mutations in this study and the results indicate that the reduced binding efficiencies of TBX4 mutants (TBX4mt) to the promoter of FGF10 result in the abnormal biological processes which provide important information for the pathogenesis of SPS.

The obesity indices mediate the relationships of blood lipids and bone mineral density in Chinese elders.

OBJECTIVE: It is unclear what role does obesity (OB) index play between blood lipid and bone mineral density (BMD). SUBJECTS: This study recruited a total of 4,558 Chinese elders >65 years. OB indices: waist circumference (WC), body mass index (BMI), waist-hip-ratio (WHR); blood lipid parameters: low density lipoprotein (LDL); total cholesterol (TC), triglyceride (TG), and BMDs at femur neck (FN), total hip (TH), and lumbar spine (LS) were measured. The t-test and multiple linear regression analysis were used to detect the differences of variables. Casual inference test (CIT) were performed to test potential mediators underlying the associations between blood lipid and BMD. RESULTS: The blood lipids were positively associated with BMD (p < 0.05) after adjustment of age and sex (Model 1) both in total subjects and in sex-stratified subjects. The CIT showed that OB indices had significant mediation effects on the associations between blood lipid (TG and LDL) and BMD in total subjects and males. Comparably, the correlations of TG and BMD are most likely mediated by BMI and WC. CONCLUSIONS: This study represented the first effort to report that OB indices, especially BMI and WC, served as significant mediators between blood lipid (TG and LDL) and BMD in Chinese elderly.

Diagnostic Accuracy of Patient History in the Diagnosis of Hip-Related Pain: A Systematic Review.

OBJECTIVE: To investigate the diagnostic accuracy of patient history associated with hip pain. DATA SOURCES: A systematic, computerized search of electronic databases (PubMed, MEDLINE, Cumulative Index of Nursing and Allied Health Literature, and Web of Science), a search of the gray literature, and review of the primary author's personal library was performed. Hip-specific search terms were combined with diagnostic accuracy and subjective or self-report history-based search terms using the Boolean operator "AND." STUDY SELECTION: This systematic review was conducted and reported according to the protocol outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were: (1) patients with hip pain; (2) the statistical association of at least 1 patient history item was reported; (3) study designs appropriate for diagnostic accuracy; (4) adults aged ≥18 years; (5) written in English; and (6) used an acceptable reference standard for diagnosed hip pathology. Titles and abstracts of all database-captured citations were independently screened by at least 2 reviewers. DATA EXTRACTION: Two reviewers independently extracted information and data regarding author, year, study population, study design, criterion standard, and strength of association statistics associated with the subjective findings. DATA SYNTHESIS: For hip osteoarthritis (OA), a family history of OA (positive likelihood ratio [+LR], 2.13), history of knee OA (+LR, 2.06), report of groin or anterior thigh pain (+LR, 2.51-3.86), self-reported limitation in range of motion of 1 or both hips (+LR, 2.87), constant low back pain or buttock pain (+LR, 6.50), groin pain on the same side (+LR, 3.63), and a screening questionnaire (+LR, 3.87-13.29) were the most significant findings. For intra-articular hip pathology, crepitus (+LR, 3.56) was the most significant finding. CONCLUSIONS: Patient history plays a key role in differential diagnosis of hip pain and in some cases can be superior to objective tests and measures.

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment.

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Arthroscopic classification of intra-articular hip pathology demonstrates at best moderate interrater reliability.

PURPOSE: The purpose of this study was to report several novel classification systems for intra-articular lesions observed during hip arthroscopy, and to quantify the interrater reliability of both these novel systems and existing classifications of intra-articular lesions when tested by a group of high-volume hip arthroscopists. METHODS: Five hip arthroscopists deliberated over shortcomings in current classification systems and developed several novel grading systems with particular effort made to capture factors important to the treatment and outcomes of hip arthroscopy for labral injury. A video learning module describing the classifications was then developed from the video archive of surgeries performed by the senior author and reviewed by study participants. Following review of the module, a pilot study was completed using five randomly selected videos, after which participating surgeons met once more to discuss points of disagreement and to seek clarification. The final video collection for testing reliability was composed of 29 videos selected with the intent of capturing all sublevels of each classification scheme. Study participants recorded their assessments using each classification scheme, and interrater reliability was calculated by a study participant not involved in grading. RESULTS: The average kappa coefficients for the classification schemes ranged from 0.38 to 0.54, with the interrater reliability of all classification schemes except labral degeneration qualifying as moderate. The percent of cases with absolute agreement ranged from 17.2% to 51.7% across the classification systems. CONCLUSIONS: Even among a group of high-volume hip arthroscopists who engaged in several discussions about the proposed classification schemes, grades were found to have at best moderate interrater reliability. Moderate interrater reliability is demonstrated for novel grading systems for describing labral tear complexity, labral bruising, labral size, and extent of synovitis, and fair reliability is demonstrated for labral degeneration. Further development and refinement of multifactorial grading systems for describing labral injury are indicated. Evaluating the multifactorial nature of intra-articular lesions in the hip is an important part of intraoperative decision-making and defining reliable classifications for intra-articular lesions is a critical first step towards developing generalizable criteria for guiding treatment type. LEVEL OF EVIDENCE: Level III.

Hip-to-calcaneus alignment differs from hip-to-talus alignment in patients with genu varum deformity.

PURPOSE: To (1) compare the weight-bearing line (WBL) ratios of the knee joints measured using the conventional (hip-to-talus radiographs, HTRs) and novel (hip-to-calcaneus radiographs, HCRs) orthoradiograms, (2) compare the hip-knee-ankle (HKA) angle between cases with < 5% and > 5% differences in WBL ratios between two orthoradiograms, and (3) investigate the optimal cutoff value (COV) of the HKA angle causing inconsistency in the orthoradiograms. METHODS: Sixty limbs of 31 patients with HTR and HCR records were retrospectively reviewed. After drawing the mechanical axis on each radiograph, the WBL ratios of the knees were calculated and compared between the conventional and novel orthoradiograms. In subgroup analysis, cases with < 5% and > 5% differences in WBL ratios between two orthoradiograms were classified as consistent and inconsistent groups, respectively. Receiver operating characteristic curve based on the HKA angles of the lower limbs was used to identify the COV causing the inconsistency between the orthoradiograms. RESULTS: Inter- and intra-rater reliabilities of all radiologic measurements were > 0.75. The WBL ratios showed no significant difference between the two orthoradiograms. However, the HKA angle was significantly larger in the inconsistent group than in the consistent group (7.0° ± 1.8° vs. 4.4° ± 2.5°; P < 0.001). The COV of the HKA angle that caused inconsistency in the two orthoradiograms was 4.0° (area under the curve, 0.774). CONCLUSION: The hip-to-calcaneus alignment differed significantly from the hip-to-talus alignment in patients with genu varum deformity. HCR measurement can be a complementary method for planning corrective osteotomy for patients with genu varum deformity. LEVEL OF EVIDENCE: IV.

Clinical Assessment and Treatment Options for Posterior Hip Pain.

BACKGROUND: Diagnosis and treatment of posterior hip pain has increased due to advancements in clinical, anatomical, biomechanical, and related pathological understandings of the hip. Due to its complexity and close anatomical relationship with many osseous, neurovascular, and musculotendinous structures, posterior hip pain must be appropriately categorized based on its origin. Therefore, it is crucial that clinicians are able to determine whether patient complaints are of extra-articular or intra-articular nature so that they can implement the optimal treatment plan. In the current review article, we discussed posterior hip pain with an emphasis on the main differential diagnoses of deep gluteal syndrome, ischiofemoral impingement, and hamstring tear/hamstring syndrome. For the appropriate diagnosis and etiology of posterior hip pain, a thorough and conclusive clinical history is imperative. Physicians should rule out the possibility of spinal involvement by physical examination and if necessary, by magnetic resonance imaging (MRI). Furthermore, because of the vicinity to other, non-orthopedic structures, an obstetric and gynecologic history, general surgery history, and urologic history should be obtained. Following the collection of patient history clinicians should adhere to an established and efficient order of evaluation starting with standing then to seated, supine, lateral, and prone testing. Imaging assessment of posterior hip pain begins with a standard anterior-posterior pelvic radiograph, in addition to frog-leg lateral. MRI is pivotal for assessing soft tissue-related extra-articular causes of hip in patients with posterior hip pain. Non-surgical treatment is preferred in most cases of deep gluteal syndrome, ischiofemoral impingement, pudendal nerve entrapment, and proximal hamstring pathologies. Surgical treatment is saved as a last resort option in cases of failed non-surgical treatment.

Changes in the macroscopic morphology of hip muscles in low back pain.

Low back pain is a major health issue affecting the lumbopelvic muscles. Morphological changes in hip muscles, such as alterations in the muscle cross-sectional area and muscle volume, may occur in patients with low back pain. This systematic review was conducted to investigate whether patients with low back pain have macroscopic changes in their hip muscle morphology compared with asymptomatic, healthy individuals, based on current evidence. The electronic databases of PubMed/Medline, Ovid, Scopus, Embase® , and Google Scholar were searched from the inception to August 31, 2018. We only included full texts of original studies regarding macroscopic morphological alterations, including atrophy and fat infiltration, in hip muscles of patients with low back pain compared with asymptomatic controls. The quality of the included studies was determined using an assessment tool based on the Newcastle-Ottawa Scale. The scale was modified for the purposes of this study. Sixteen comparative observational studies were found eligible to be included in this review. Eleven were classified as high quality and four as moderate quality. The morphological changes in the psoas major, gluteus maximus, gluteus medius, gluteus minimus, and piriformis muscles were assessed in the primary studies. All selected studies were considered B level of evidence studies. The strength of conclusions for the psoas major, gluteal, and piriformis muscles was moderate. The results revealed that there is substantial controversy about the morphological changes in hip muscles in patients with low back pain; however, the majority of high-quality studies concluded that atrophy of hip muscles is evident in patients with low back pain. The psoas major muscle was the most commonly investigated hip muscle for morphological changes. Major methodological limitations of the included studies were identified and discussed. The present systematic review does not include a formal meta-analysis because of very significant differences in the primary studies in terms of study populations and methodologies. Finally, in clinical practice, it is recommended that physical therapists develop exercise programs to improve hip muscle function in patients with low back pain.

Increased hip circumference in individuals with metabolic syndrome affects serum nesfatin-1 levels.

BACKGROUND: This case-control study was conducted to investigate the relationship between serum nesfatin-1 levels and nutritional status and blood parameters in patients diagnosed with metabolic syndrome. METHODS: Thirty patients (case) diagnosed with metabolic syndrome according to National Cholesterol Education Program-Adult Treatment Panel III criteria were included. Thirty healthy subjects (control) matched with patients with metabolic syndrome in terms of age, gender and body mass index were included. Three-day food consumption records were obtained. Anthropometric indices were measured and body composition was determined by bioelectrical impedance method. Biochemical parameters and serum nesfatin-1 levels were measured after 8 hours of fasting. RESULTS: Serum nesfatin-1 levels were 0.245±0.272 ng/mL in the case group and 0.528±0.987 ng/mL in the control group (p>0.05). There was a positive significant correlation between serum nesfatin-1 levels and body weight, waist and hip circumferences in the case group (p<0.05). Each unit increase in hip circumference measurement affects the levels of nesfatin by 0.014 times. In the control group, there was a positive significant correlation between body weight and serum nesfatin-1 levels (p<0.05). A significant correlation was detected between HbA1c and serum nesfatin-1 levels in the case group (p<0.05). A significant relationship was detected between dietary fibre intake and the serum nesfatin-1 levels in the case group (p<0.05). CONCLUSIONS: Anthropometric indices and blood parameters were correlated with serum nesfatin-1 levels in patients with metabolic syndrome. More clinical trials may be performed to establish the relationship between serum nesfatin-1 levels and nutritional status.

Sonoanatomy and Pathology of the Gluteus Minimus Tendon.

Gluteus minimus disorders are a potential source of greater trochanteric or anterior hip pain. Disorders of the gluteus minimus tendon most commonly occur in conjunction with gluteus medius tendon abnormalities but can also occur in isolation. Understanding the sonoanatomy of the gluteus minimus muscle-tendon unit is a prerequisite for recognizing and characterizing gluteus minimus tendon disorders, which, in turn, guides treatment for patients with greater trochanteric or anterior hip pain syndromes.

Risk Factors for Contralateral Slipped Capital Femoral Epiphysis: A Meta-analysis of Cohort and Case-control Studies.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is an important cause of hip pain and disability in pediatric patients. SCFE occurs bilaterally in 12% to 80% of cases, and the risk of contralateral SCFE is noted to be 2335 times higher than the index SCFE. Several studies have reported risk factors for contralateral SCFE; however, these studies have not been systematically analyzed. The purpose of this systematic review and meta-analysis was to review and analyze risk factors for subsequent contralateral SCFE and identify the strongest risk factors for a subsequent slip. METHODS: A systematic review was performed of all observational studies focusing on risk factors for subsequent contralateral SCFE indexed in Medline, Embase, and Cochrane databases. Data extraction was performed and summarized using descriptive statistics. Meta-analysis was performed for risk factors with sufficient constituent study data. Quality assessment was performed using the Newcastle-Ottawa Scale, and funnel plots were generated to assess publication bias. RESULTS: The initial search strategy identified 226 references, and after exclusions, 20 studies were included in this analysis. Demographic risk factors included age, sex, weight, body mass index, ethnicity, and urban/rural residence; clinical risk factors included endocrine abnormality, duration of symptoms, slip stability, and slip chronicity; and radiographic risk factors included slip angle, triradiate cartilage, alpha angle, posterior sloping angle (PSA), physeal sloping angle, modified Oxford score, and bone age. Younger patient age, body mass index≥95th percentile, presence of an endocrine abnormality, higher PSA of the unaffected hip, and lower modified Oxford score have been noted to be significant risk factors for contralateral SCFE. Meta-analysis showed that younger age (-0.9; confidence interval, -1.1, -0.6), and higher PSA (4.7 degrees; 95% confidence interval, 3.3-6.2 degrees) of the unaffected hip were predictive of subsequent contralateral SCFE. The majority of studies were of good quality. CONCLUSION: There are several risk factors for subsequent contralateral SCFE. On the basis of the available data, younger patients with a high PSA of the unaffected hip would most likely benefit from prophylactic fixation of the unaffected hip. LEVEL OF EVIDENCE: Level II.

ß-Angles of hips with femoroacetabular impingement versus asymptomatic normal hips in a Japanese population: A CT-based observational clinical study.

BACKGROUND: The beta angle (ß-angle)-although used to assess femoroacetabular impingement (FAI)-has not been well evaluated. This study aimed to measure the ß-angle on multiradial computed tomography (CT) slice images of both hips with symptomatic FAI and asymptomatic normal hips to determine its optimal cutoff value for detecting FAI in a Japanese population. METHODS: CT was performed with each subject supine. The ß-angle was measured on seven radial slices (designated R0, R15, R30, R45, R60, R75, R90) that were generated at 15° intervals from the oblique axial slice through the center of the femoral neck. An a priori power analysis was performed. The measurements were made in 20 FAI hips (FAI group) and 23 asymptomatic normal hips (ANH group). Cutoff values were evaluated using receiver operating characteristic curves. RESULTS: The mean ß-angles of the FAI and ANH groups at R0, R15, R30, R45, R60, R75, and R90° were, respectively, 73.6° and 84.2°, 66.0° and 79.3°, 57.2° and 69.2°, 48.1° and 63.1°, 46.7° and 62.5°, 50.0° and 63.7°, and 53.7° and 65.9°. For all slices, the ß-angle was significantly smaller in the FAI group than the ANH group. The optimal ß-angle cutoff values for diagnosing FAI at R0, R15, R30, R45, R60, R75, and R90 were 73.9°, 70.2°, 61.4°, 55.7°, 53.6°, 59.4°, and 60.9°, respectively. The respective specificities and sensitivities of the cutoff values at R0, R15, R30, R45, R60, R75, and R90 were 78.3% and 65.0%, 82.6% and 70.0%, 73.9% and 60.0%, 73.9% and 75.0%, 95.7% and 75.0%, 69.6% and 95.0%, and 78.3% and 80.0%. CONCLUSIONS: In all radial slices, the ß-angle was significantly smaller in the hips with symptomatic FAI than in the asymptomatic normal hips. The most useful cutoff value for diagnosing FAI was a ß-angle of 53.6° at R60.

Predicting the mechanical hip-knee-ankle angle accurately from standard knee radiographs: a cross-validation experiment in 100 patients.

Background and purpose - Being able to predict the hip-knee-ankle angle (HKAA) from standard knee radiographs allows studies on malalignment in cohorts lacking full-limb radiography. We aimed to develop an automated image analysis pipeline to measure the femoro-tibial angle (FTA) from standard knee radiographs and test various FTA definitions to predict the HKAA. Patients and methods - We included 110 pairs of standard knee and full-limb radiographs. Automatic search algorithms found anatomic landmarks on standard knee radiographs. Based on these landmarks, the FTA was automatically calculated according to 9 different definitions (6 described in the literature and 3 newly developed). Pearson and intra-class correlation coefficient [ICC]) were determined between the FTA and HKAA as measured on full-limb radiographs. Subsequently, the top 4 FTA definitions were used to predict the HKAA in a 5-fold cross-validation setting. Results - Across all pairs of images, the Pearson correlations between FTA and HKAA ranged between 0.83 and 0.90. The ICC values from 0.83 to 0.90. In the cross-validation experiments to predict the HKAA, these values decreased only minimally. The mean absolute error for the best method to predict the HKAA from standard knee radiographs was 1.8° (SD 1.3). Interpretation - We showed that the HKAA can be automatically predicted from standard knee radiographs with fair accuracy and high correlation compared with the true HKAA. Therefore, this method enables research of the relationship between malalignment and knee pathology in large (epidemiological) studies lacking full-limb radiography.

Why SNP rs227584 is associated with human BMD and fracture risk? A molecular and cellular study in bone cells.

A large number of SNPs significant for osteoporosis (OP) had been identified by genome-wide association studies. However, the underlying association mechanisms were largely unknown. From the perspective of protein phosphorylation, gene expression regulation, and bone cell activity, this study aims to illustrate association mechanisms for representative SNPs of interest. We utilized public databases and bioinformatics tool to identify OP-associated SNPs which potentially influence protein phosphorylation (phosSNPs). Associations with hip/spine BMD, as well as fracture risk, in human populations for one significant phosSNP, that is, rs227584 (major/minor allele: C/A, EAS population) located in C17orf53 gene, were suggested in prior meta-analyses. Specifically, carriers of allele C had significant higher BMD and lower risk of low-trauma fractures than carriers of A. We pursued to test the molecular and cellular functions of rs227584 in bone through osteoblastic cell culture and multiple assays. We identified five phosSNPs significant for OP (P < 0.01). The osteoblastic cells, which was transfected with wild-type C17orf53 (allele C at rs227584, P126), demonstrated specific interaction with NEK2 kinase, increased expression levels of osteoblastic genes significantly (OPN, OCN, COL1A1, P < 0.05), and promoted osteoblast growth and ALP activity, in contrast to those transfected with mutant C17orf53 (allele A at rs227584, T126). In the light of the consistent evidences between the present functional study in human bone cells and the prior association studies in human populations, we conclude that the SNP rs227584, via altering protein-kinase interaction, regulates osteoblastic gene expression, influences osteoblast growth and activity, hence to affect BMD and fracture risk in humans.

Accumulation of microdamage in subchondral bone at the femoral head in patients with end-stage osteoarthritis of the hip.

In end-stage osteoarthritis (OA) of the hip, the effect of bone metabolism with and without cartilage is unclear. In this study, we aimed to investigate histomorphology and microdamage in the subchondral bone of the femoral head in areas with and without articular cartilage in patients with end-stage OA. Nineteen femoral heads were evaluated in 10 women who underwent total hip arthroplasty for OA and in nine cadaveric controls (CNT). Chondral thickness and subchondral bone plate thickness (SBP.Th) were measured in 5-mm-wide areas where cartilage was lost (area A) or preserved (area B) in OA and in corresponding areas in the load-bearing portion of the femoral head in the CNT. Histomorphometry and microdamage in 5 × 5-mm areas of cancellous bone were assessed. SBP.Th and bone volume were significantly greater in area A than in area B or in the CNT. Osteoid volume was significantly greater in area A than in area B or in the CNT. There was no significant difference in eroded surface between area A and CNT. Microcrack density was significantly greater in area A than in area B or in the CNT. Although accumulation of microdamage was caused by concentration of stress on the subchondral bone in the cartilage loss area in end-stage OA, remodeling for microdamage repairing mechanism was not enhanced. It was considered that the subchondral cancellous bone volume was increased because of modeling, not remodeling, by stress concentration due to articular cartilage loss.

Positive FABER distance test is associated with higher alpha angle in symptomatic patients.

PURPOSE: The purpose of this study was to determine the diagnostic value of the flexion abduction external rotation (FABER) distance test (FDT) for the diagnosis of cam-type femoroacetabular impingement (FAI) as defined by alpha angle. METHODS: For this study, 603 patients with symptomatic, unilateral femoroacetabular impingement were included. Patients with symptoms of hip instability, bilateral symptoms, bilateral surgery, or bilateral alpha angles over 55 were excluded from the analysis. A positive FDT was defined as a difference of 4 cm or more between hips. A pathological cam was defined as an alpha angle of 78° or greater. RESULTS: The average age was 36.4 ± 12 years, with 344 males and 259 females. Faber distance of the injured hip was correlated with age at surgery (rho = 0.148; p < 0.001). Alpha angle on the injured hip was positively correlated with injured hip FABER distance (rho = 0.276; p < 0.001). The average alpha angle in patients with a positive FABER distance test was 74° (SD = 11°) compared to 68° (SD = 8°) in patients with a negative distance test (p = 0.001). The sensitivity of the FDT to diagnose pathological cam was 0.848 (0.79-0.89) with a negative predictive value of 86% (81-90%). CONCLUSION: This study demonstrated that the FABER distance test is correlated with the alpha angle and is a good diagnostic exam for pathological cam-type FAI as defined by and alpha angle equal to or greater than 78°. CLINICAL RELEVANCE: FABER distance test is a simple test that can be used as a screening test to decide if FAI should be suspected and further testing is needed. LEVEL OF EVIDENCE: III.

Unrecognized Osteoporosis Is Common in Patients With a Well-Functioning Total Knee Arthroplasty.

BACKGROUND: Peri-prosthetic fractures after total knee arthroplasty (TKA) are associated with poorer outcomes and high costs. We hypothesize that osteoporosis is under-recognized in the TKA population. The purpose of this study is to report osteoporosis prevalence in a healthy cohort of patients with well-functioning TKA and to compare prevalence between males and females. METHODS: This study is a cross-sectional study of 30 adults (15 males/15 females) aged 59-80 years without known bone health issues who volunteered to undergo routine dual-energy X-ray absorptiometry 2-5 years (average 3.2 ± 0.8) after primary unilateral TKA. These data plus clinical risk factors were used to estimate fracture risk via the Fracture Risk Assessment Tool and skeletal status (normal, osteopenic, osteoporotic) was determined based on the World Health Organization definition. The National Osteoporosis Foundation criteria for treatment were applied to all patients. RESULTS: Six of 30 (20%) patients had T-score ≤ -2.5. Eighteen of 30 (60%) patients had T-score between -1 and -2.5 and 6 (20%) patients had T-score ≥ -1. Five patients with normal or osteopenic bone mineral density (BMD) had occult vertebral fractures. Eleven of 30 (36.7%) patients met National Osteoporosis Foundation criteria for pharmacologic treatment. CONCLUSION: The prevalence of occult osteoporosis meeting treatment guidelines after TKA is substantial in this sample (36.7%). BMD and osteoporosis prevalence are similar between men and women. This underappreciated prevalence of osteoporosis may contribute to peri-prosthetic fracture risk. Arthroplasty surgeons and bone health specialists must be aware of post-operative changes in bone density. These data support the further study of post-operative osteoporosis and consideration of routine BMD screening after TKA. LEVEL OF EVIDENCE: III.