Is the increase in the number of total hip arthroplasties in Japan due to an aging society?

BACKGROUND: The number of total hip arthroplasty (THA) is increasing globally, including Japan. The Japanese Orthopaedic Association has been conducting a registry of joint replacement surgery, but there may be a gap between the reported numbers of THA in the registry and the actual number. This study aimed to investigate the exact number of THA and assess the trends in Japan using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). METHODS: We downloaded data from 2014 to 2019 from the NDB Open Data. Data on primary THA were extracted, and we calculated the annual number and number for each 10-year age group and sex. We also compared the number and trends between elderly and non-elderly groups. RESULTS: During the study period, number of THAs increased by approximately 20,000, showing a continuous upward trend. The highest number of THAs were performed on patients in their 60s, except for the years 2014 and 2019. Comparison of the numbers in 2014 and 2019 by age group showed an increase in the number in patients in their 90s (by 2.05 times). There were significantly a greater number of elderly patients (P < 0.001). The number of THAs performed was higher in women than in men (P < 0.001). CONCLUSION: The number of THAs in Japan increased substantially from 2014 to 2019, despite a decrease in population. Significantly higher number of THAs were performed on elderly patients in Japan, which might be due to an aging society. The NDB data is highly valuable for epidemiological research in Japan, as it might enable the early detection of issues occurring during THA, facilitating their prompt integration into daily clinical practice.

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium.

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.

Influence of broach surface design of a fully hydroxyapatite coated, double tapered stem on periprosthetic bone mineral density after total hip arthroplasty: a study based on the morphology of the proximal femur.

INTRODUCTION: This study aimed to compare the impact of different broach surface designs on post-operative clinical outcomes, bone reactions and changes in bone mineral density (BMD) in patients who underwent total hip arthroplasty (THA) using a fully hydroxyapatite coated and double tapered stem with either compaction shape (COM) or hybrid shape (HYB) broaches. MATERIALS AND METHODS: A retrospective analysis was conducted on 76 patients (100 hips) who underwent primary THA using the Avenir complete stem®. Patients were divided into two groups: the COM broach group (50 hips) and HYB broach group (50 hips). We evaluated clinical outcomes using the Japanese Orthopaedic Association hip scores one month before the surgery, and 12 and 24 months after the surgery. Radiographic findings, including stem alignment angles, radiolucent lines, spot welds, and cortical hypertrophy, were assessed. BMD around the stem in Gruen zones 1-7 was evaluated using dual-energy X-ray absorptiometry (DEXA) at 7 days, 12, and 24 months post-operatively. The Dorr classification was used to assess femoral morphology. RESULTS: There were no significant differences in clinical outcomes, radiographic findings, or BMD changes between the COM and HYB broach groups in the overall patient cohort. However, in Dorr type A femurs, the COM broach group demonstrated superior BMD superior preservation in zones 1 and 7 after 12 months and in zones 1, 6 and 7 after 24 months. Additionally, in Dorr type B femurs, significant BMD preservation was observed in zone 3 at 24 months in the COM broach group. CONCLUSIONS: This study suggests that the broach surface design of fully hydroxyapatite coated stems may influence periprosthetic BMD changes, especially in Dorr type A and B femurs. Surgeons should consider broach selection based on patient-specific femoral morphology to optimize BMD preservation in THA procedures using fully hydroxyapatite coated stems.

Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight.

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes ß-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25-29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.

Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis.

The pathophysiology of early-stage hip osteoarthritis (EOA) is not fully understood. Although a previous study in an age-unmatched cohort reported that the number of macrophages was increased in knee EOA compared to late OA (LOA), it remained unclear whether increased macrophages in EOA accurately reflect EOA pathology. We investigated the differences in CD14 expression levels between EOA and LOA using age-unmatched and -matched cohorts. Synovial tissues were obtained from 34 EOA (Tönnis grades 0 and 1) and 80 LOA (Tönnis grades 2 and 3) patients. To correct for differences in demographics between patients with LOA and EOA, we also created propensity score-matched cohorts (16 EOA and 16 LOA). CD14 expression and its association with pain was estimated in LOA and EOA before and after propensity matching. We performed flow cytometry on tissues from the 16 patients, with 8 from each group, to assess for CD14+ subsets in the cells. The CD14 expression in EOA was higher than that in LOA both before and after propensity matching. The proportion of CD14high subsets in EOA was higher than that in LOA. The CD14 expression was associated with pain in EOA before matching. However, no difference was observed between the pain and CD14 expression after matching in EOA. The increased CD14 expression and the proportion of CD14high subsets may be important features associated with hip EOA pathology. To accurately compare early and late OA, the analysis of a propensity score-matched cohort is necessary.

Central sensitization inventory scores correlate with pain at rest in patients with hip osteoarthritis: a retrospective study.

BACKGROUND: Patients with persistent pain due to osteoarthritis (OA) complain of multiple symptoms that cannot be explained solely by structural changes. A poor correlation exists between structural and inflammatory changes in OA and pain levels. Central sensitization (CS) has been identified as a factor that induces chronic pain in patients with OA. Although it is important to identify osteoarthritis patients with CS components, the prevalence and characteristics of CS, especially those in patients with hip OA, are not well understood. Thus, we aimed to determine the prevalence and characteristics of CS in patients with hip OA, in this study. METHODS: The CS Inventory (CSI), used as a non-invasive routine clinical tool to evaluate the presence of CS 1 month before surgery in 100 patients with hip OA, was measured at our outpatient clinic, and the data were retrospectively reviewed. We determined the number of patients with a CSI score of 40 points or higher and assessed the relationships between the CSI score and clinical factors (including age, duration of hip pain, degree pain at rest and on activity, by using the visual analogue scale [VAS] and the Harris Hip Score) using the Spearman's correlation coefficient. RESULTS: The mean age of participants was 63.9 ± 11.6 years, and there were 15 men and 85 women. All patients had hip OA, categorised as advanced and terminal stage (Tönnis grade 2-3) on preoperative plain radiography. The mean duration of hip pain was 4.2 ± 4.4 years. The mean CSI score was 19.5 ± 11.3 and 5 (5.0%) of the patients had a score of 40 or more points. CSI scores correlated significantly only with VAS pain at rest (r = 0.348, P < 0.001). CONCLUSION: In this study, 1 out of every 20 hip OA patients had CS components. CSI scores were significantly correlated with pain at rest in hip OApatients. CS approaches to hip OA may be one of the treatment options for pain at rest.

CD39+CD55- Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee.

Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45-CD31-CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55- and CD39-CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55- Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39-CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55- Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39-CD55+ Fb. CD39-CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states ('RA', 'TNF signaling pathway', 'IL-17 signaling pathway'). The proportion of CD39+CD55- Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55- Fb. In contrast, there was no correlation between the proportion of CD39-CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55- cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55- synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.

Correlation between CD163 expression and resting pain in patients with hip osteoarthritis: Possible contribution of CD163+ monocytes/macrophages to pain pathogenesis.

Expression of CD163, a scavenger receptor specifically expressed by monocytes and macrophages, is elevated in the synovial tissue of patients with knee osteoarthritis (OA) compared with healthy controls. However, the association between CD163 expression in the synovium and pain in OA patients is unclear. We investigated the correlation between synovial CD163 expression and resting and active pain levels in patients with hip osteoarthritis (HOA). To investigate the possible contribution of CD163+ subsets to pain pathogenesis, we compared pain-related cytokine expression and M1/M2 macrophage marker expression in CD163+ and CD163- cells. We performed flow cytometric analysis to study the CD163+ cell population. We also examined pain-related cytokine expression and M1/M2 macrophage marker expression on CD163+ CD14high and CD163+ CD14low cells using cell sorting. Synovial CD163 expression significantly correlated with resting pain levels (p = 0.006; R = 0.321), but not active pain levels (p = 0.155; R = 0.169). Expression of the M1 macrophage marker CD80 was significantly higher in CD163+ than CD163- cells (p = 0.010), as was the expression of M2 macrophage markers CD206 and IL10 (CD206, p = 0.014; IL10, p = 0.005), and TNFA and IL1B (TNFA, p = 0.002; IL1B, p = 0.001). TNFA expression was significantly higher in CD163+ CD14low than CD163+ CD14high cells, while IL1B, IL10, and CD206 expression were comparable among these subsets. Our findings suggest that CD163 expression is associated with higher resting pain scores. As TNF-α plays a role in the pain process, CD163+ CD14low cells expressing TNFA may be a potent contributor to the pathogenesis of resting pain in HOA.

Differences in outcomes after total hip arthroplasty for osteoarthritis between patients with and without central sensitivity syndromes other than fibromyalgia.

We investigated the differences in outcomes after total hip arthroplasty (THA) for hip osteoarthritis (HOA) between patients with and without central sensitivity syndromes (CSSs) other than fibromyalgia (FM). After excluding two patients with FM, we compared the clinical data of 41 patients with CSSs and 132 patients without CSSs. Clinical data included scores on the central sensitization inventory, visual analog scale for pain (VAS pain), and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ). VAS pain was significantly higher at 3 and 6 months after THA in patients with CSSs than in those without CSSs (3 and 6 months, P < 0.001). Satisfaction, pain, and mental JHEQ scores were lower in patients with CSSs than in those without CSSs (satisfaction, P < 0.001; pain, P = 0.011; mental, P = 0.032). Multiple regression analyses indicated that one and ≥ 2 CSS diagnoses significantly impacted the satisfaction score (one CSS, ß = - 0.181, P = 0.019; ≥ 2 CSSs, ß = - 0.175, P = 0.023). Two or more CSSs were the only factor influencing the pain score (ß = - 0.175, P = 0.027). Pain in patients with CSSs reflects central sensitization, which may adversely affect post-operative outcomes. Surgeons should pay attention to patients with a history of CSSs diagnoses who undergo THA for HOA.

NGF Expression and Elevation in Hip Osteoarthritis Patients with Pain and Central Sensitization.

Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular cartilage degeneration and chronic pain. Research into OA animal models suggests that elevated NGF levels in the synovium contribute to pain and central sensitization (CS). However, it is unclear whether synovial NGF contributes to CS in patients with OA. We investigated the association between synovial NGF expression and clinical assessments of pain and CS in hip OA (hOA) patients. We also aimed to identify which cells in the synovium of hOA patients express NGF. Sixty-six patients who received total hip replacement and a diagnosis of hOA were enrolled. We measured NGF mRNA expression in synovial samples obtained from 50 patients using qPCR and analyzed the correlation of NGF expression with the CS inventory (CSI) score and Japanese Orthopaedic Association (JOA) score, a clinical scoring system for OA. To identify the synovial cells expressing NGF, we analyzed NGF mRNA expression in CD14+ and CD14- cells, which represent macrophage-rich and fibroblast-rich fractions, respectively, extracted from 8 patients. To further identify which macrophage subtypes express NGF, we examined NGF mRNA expression in CD14high and CD14low cells sorted from 8 patients. Synovial NGF mRNA expression was negatively correlated with JOA score but positively correlated with CSI score (JOA pain, r = -0.337, P = 0.017; CSI score, r = 0.358, P = 0.011). Significantly greater levels of NGF were observed in CD14- cells compared to CD14+ cells (P = 0.036) and in CD14high cells compared to CD14low cells (P = 0.008). In conclusion, synovial NGF expression is correlated with the degree of pain and CS in hOA patients. NGF is predominantly expressed in synovial fibroblasts. Further, CD14high synovial macrophages expressed higher levels of NGF. Our results may provide a novel NGF-targeted therapeutic strategy for hOA pain.

Adverse Effects of Higher Preoperative Pain at Rest, a Central Sensitization-Related Symptom, on Outcomes After Total Hip Arthroplasty in Patients with Osteoarthritis.

BACKGROUND: In patients with hip osteoarthritis (OA), pain at rest, unlike pain on activity, is due to pain mechanisms that cannot be explained by nociceptive pain. However, it remains unclear whether central sensitization (CS) is one of the causes of exacerbated pain at rest in patients with hip OA. Therefore, we investigated the differences in causative factors and postoperative course of total hip arthroplasty (THA) between preoperative pain at rest and on activity in patients with hip OA. METHODS: In total, 120 patients (125 hips, 22 men and 98 women, aged 64.5±1.0 years) with hip OA were included. Preoperative pain at rest and on activity and CS were assessed using the visual analog scale (VAS) and CS Inventory (CSI), respectively. Postoperative assessments were evaluated using the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ); pain, satisfaction, function, and mental scores were evaluated 6 and 12 months after THA. RESULTS: Multivariate regression analysis indicated the CSI score as affecting VAS for pain at rest (ß=0.067, P=0.002) but not VAS for pain on activity (ß=0.036, P=0.073). VAS for pain at rest had a weak negative correlation with satisfaction and pain scores at both 6 and 12 months after THA (satisfaction, r=-0.309, -0.278; pain, r=-0.202, -0.22). VAS for pain on activity was not correlated with JHEQ. The CSI score had a weak or moderate negative correlation with three scores other than the function score at both 6 and 12 months after THA (satisfaction, r=-0.266, -0.213; pain, r=-0.332, -0.203, mental, r=-0.427, -0.370). The function score was weakly correlated with the CSI score only 6 months after THA (function, r=-0.231, -0.190). CONCLUSION: A higher level of preoperative pain at rest, a CS-related symptom, may affect postoperative pain persistence and dissatisfaction in patients with hip OA.