To date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis. Human articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature. We identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA. This is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.

Objective: This study investigates the impact of age and knee osteoarthritis (OA) on the coronal plane alignment of the lower extremity in Japanese males and females, utilizing the Coronal Plane Alignment of the Knee (CPAK) classification system. Methods: A cross-sectional analysis was conducted with 150 male and 150 female patients. Participants were divided into three groups according to age and OA progression. The mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured using standard digital long-leg radiographs. Arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated, and the CPAK classification was performed to verify the distribution among the three groups. Results: The results showed increased varus alignment of the mean mLDFA correlated with OA in both genders and with aging in males. The mean mMPTA did not change in males but shifted toward varus in females with both aging and OA. Both genders demonstrated a constitutional varus alignment with the progression of osteoarthritis (males: 1.3 ± 2.4° to −3.5 ± 3.7°, p < 0.001; females: −1.2 ± 3.2° to −3.6 ± 2.9°, p < 0.001). However, this trend with aging was observed only in females (0.0 ± 2.5° to −1.2 ± 3.2°, p = 0.018). JLO maintained its apex distal position with aging and OA progression in all subjects. The study further revealed a notable transition from CPAK Type II to Type I with OA progression in both genders, additionally influenced by aging in females. Conclusions: Aging affects coronal alignment and CPAK classification differently across genders. With OA progression, there was a shift toward smaller aHKA, while JLO remained unchanged. Compared to other races, young Japanese people exhibit similar CPAK distributions, but distinct differences appear in OA-affected individuals, highlighting potential racial variations in CPAK classifications.

Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.

This study examined the association between developmental dysplasia of the hip (DDH) and disease-associated loci in a Japanese cohort. A genome-wide association study (GWAS) of 238 Japanese patients with DDH and 2044 healthy individuals was performed. As a replicate, GWAS was also conducted on the UK Biobank data with 3315 cases and matched 74,038 controls. Gene set enrichment analyses (GSEAs) of both the genetics and transcriptome of DDH were performed. Transcriptome analysis of cartilage specimens from DDH-associated osteoarthritis and femoral neck fractures was performed as a control. Most of the lead variants were very low-frequency ones in the UK, and variants in the Japanese GWAS could not be replicated with the UK GWAS. We assigned DDH-related candidate variants to 42 and 81 genes from the Japanese and UK GWASs, respectively, using functional mapping and annotation. GSEA of gene ontology, disease ontology, and canonical pathways identified the most enriched pathway to be the ferroptosis signaling pathway, both in the Japanese gene set as well as the Japanese and UK merged set. Transcriptome GSEA also identified significant downregulation of genes in the ferroptosis signaling pathway. Thus, the ferroptosis signaling pathway may be associated with the pathogenic mechanism of DDH.

Study Design: retrospective study.Purpose: This study aimed to develop an indicator of the compensatory capacity of hip joints in response to spinopelvic mismatch using standard radiographs.Overview of Literature: EOS imaging has enabled detailed analysis of hip and lower extremity compensation in sagittal malalignment. However, its high cost and limited availability hinder widespread clinical use. Currently, there are no established indicators to assess hip compensation for spinopelvic mismatch using standard radiographs.Methods: A total of 209 patients with osteoporosis and 54 with adult spinal deformities were included. Patients were divided into two groups based on pelvic incidence–lumbar lordosis (PI–LL): <20° and ≥20° groups. The sagittal vertical axis (SVA), thoracic kyphosis, PI, pelvic tilt (PT), LL, sacral slope, and pelvic femoral angle (PFA) were measured. Health-related quality of life (HRQOL) was assessed in 86 patients using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). A new index, PFA–(PI–LL), was defined as spinopelvic–hip mismatch. Correlation coefficients were calculated for each radiographic parameter, and the coefficient of determination (R2) for the relationship of each parameter with SVA was evaluated in both groups. The correlations between SVA, PT, PI–LL, PFA–(PI–LL), and JOABPEQ domain scores were also analyzed.Results: PI–LL correlated with PFA in the PI–LL <20° group (r=0.56, p<0.001) but not in the PI–LL ≥20° group. Among all parameters, PFA–(PI–LL) demonstrated the strongest association with SVA, indicating its superior ability to explain variations in sagittal alignment in both groups and across all patients (all patients, R2=0.77). Significant correlations were observed between the radiographic parameters and JOABPEQ scores across all domains.Conclusions: PFA–(PI–LL), which represented spinopelvic–hip mismatch, was a reliable indicator of hip compensatory function in terms of anterior trunk inclination and HRQOL.