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.

Trends in hip preservation surgery in Japan from 2014 to 2019 with a focus on hip arthroscopic surgery.

Secondary hip osteoarthritis due to hip dysplasia is common among Japanese populations. This study aimed to investigate the number of hip preservation surgeries performed in Japan and assess trends, by age and sex, from 2014 to 2019, focusing on hip arthroscopic surgery, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). We downloaded the files 'Number of calculations by division, sex, and age group' under 'operation (code K)' from 2014 to 2019 from the NDB Open Data Japan database. Data on hip preservation surgeries were extracted, including the number for each surgical procedure and its incidence per year, calculated as the number of surgeries performed for each 10-year age group and by sex, regarding hip arthroscopic surgery. Overall, 14 891 hip preservation surgeries were performed in Japan over the study period, with pelvic osteotomy being the most common procedure. Although the incidence of hip preservation surgeries decreased from 2014 to 2019, there was a specific 1.54-fold higher incidence in hip arthroscopic procedures in 2019 compared to 2014. Hip arthroscopic labral repair was performed more frequently than synovectomy. The highest incidence of hip arthroscopic surgery was in the 40- to 49-years age group, with no difference in incidence between sexes (P = 0.951). In Japan, pelvic osteotomy was performed more often as a hip preservation surgery than hip arthroscopic surgery. Although hip arthroscopic surgery was developed in Japan, its use has not increased from 2017 to 2019.

A systematic review and meta-analysis of antibiotic-loaded bone cement for prevention of deep surgical site infections following primary total joint replacement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) as a mean for preventing deep surgical site infections (SSI) after total joint replacement is controversial. Therefore, we have conducted a meta-analysis to evaluate the prophylactic effect of ALBC for SSI prevention in patients undergoing arthroplasty. This study was conducted to revise treatment guidelines for MRSA infections in Japan. METHODS: PubMed (Medline), Scopus, Embase, Web of Science and Cochrane library were searched for relevant articles comparing preventive effect of ALBC for patients undergoing primary total joint arthroplasty by August 2022. Primary outcome was the incidence of deep SSI. Subgroup analyses by type of surgery (total hip (THA) or knee (TKA) arthroplasty) and by causative pathogen (methicillin-resistant Staphylococcus aureus (MRSA)) were performed. RESULTS: Of the 3379 studies identified for screening, six studies involving 5745 patients were included. The use of ALBC significantly reduced the incidence of deep SSI in overall patients (risk ratio [RR] 0.60, 95% confidential interval [CI] 0.39-0.92), but the evidence level was very low. There was no significant preventive effect for ALBC compared with non-ALBC in both THA and TKA (THA, RR 0.52, 95% CI 0.23-1.16; TKA, RR 0.64, 95% CI 0.38-1.06), and for preventing MRSA-SSI (RR 0.27, 95% CI 0.03-2.41). CONCLUSIONS: Although the overall preventive effect of ALBC was significant, the evidence level was very low. Thus, the routine use of ALBC as a mean to prevent SSI in arthroplasty may not be suggested.

A novel primary stability test method for artificial acetabular shells considering vertical load during level walking and shell position.

Uncemented acetabular shell primary stability is essential for optimal clinical outcomes. Push-out testing, rotation testing, and lever-out testing are major evaluation methods of primary stability between the shell and bone. However, these test methods do not consider shell loads during daily activity and shell installation angle. This study proposes a novel evaluation method of acetabular shell primary stability considering load during level walking and acetabular installation angles such as inclination and anteversion. To achieve this, a novel primary stability test apparatus was designed with a shell position of 40° acetabular inclination and 20° anteversion. The vertical load, corresponding to walking load, was set to 3 kN according to ISO 14242-1, which is the wear test standard for artificial hip joints. The vertical load was applied by an air cylinder controlled by a pressure-type electro-pneumatic proportional valve, with the vertical load value monitored by a load cell. Torque was measured when angular displacement was applied in the direction of extension during the application of vertical load. For comparison, we also measured torque using the traditional lever-out test. The novel primary stability test yielded significantly higher primary stabilities; 5.4 times greater than the lever-out test results. The novel primary stability test failure mode was more similar to the clinical failure than the traditional lever-out test. It is suggested that this novel primary stability test method, applying physiological walking loads and extension motions to the acetabular shell, better reflects in vivo primary stability than the traditional lever-out test.

The Impact of Sarcopenia Risk on Postoperative Walking Independence in Older Adults Undergoing Total Joint Arthroplasty.

BACKGROUND AND PURPOSE: Sarcopenia is known to be associated with poor outcomes after arthroplasty; however, no study has reported the relationship between sarcopenia and postoperative walking independence. This study aimed to determine the impact of sarcopenia risk screening using the SARC-CalF questionnaire and calf circumference on the time to walk independently after total hip or knee arthroplasty in older patients. METHODS: We included 599 nonobese patients aged 65 years and older who underwent unilateral and primary total hip or knee arthroplasty. Preoperative sarcopenia risk was assessed using the SARC-CalF or calf circumference. The outcome of this study was the time to independent walking after surgery; it was calculated as the number of days from the date of surgery to the date when the patient was able to walk independently. The association between preoperative sarcopenia risk and time to independent walking after surgery was analyzed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Among the 599 patients undergoing total joint arthroplasty, 175 (29.2%) were determined to be at risk of sarcopenia using SARC-CalF and 193 (32.2%) using calf circumference. The Kaplan-Meier curve showed that sarcopenia risk assessed by SARC-CalF or calf circumference was associated with a prolonged time to independent walking in patients undergoing hip arthroplasty (log-rank test, P < .001 and P < .001, respectively). In patients undergoing hip arthroplasty, the Cox proportional hazards model showed that SARC-CalF score of 11 points and greater or a calf circumference less than the cutoff was a risk factor for delayed time to independent walking (hazard ratios: 0.55 and 0.57, P < .001 and P = .001, respectively). There was no association between preoperative sarcopenia risk and postoperative time to independent walking in patients who underwent knee arthroplasty. CONCLUSIONS: Sarcopenia screening tools, such as SARC-CalF or calf circumference, should be useful for planning postoperative rehabilitation in older adults scheduled for hip arthroplasty. However, the accuracy of SARC-CalF or calf circumference measurement in patients scheduled for knee arthroplasty may be low.

Association of affected and non-affected side ability with postoperative outcomes in patients undergoing total hip arthroplasty.

BACKGROUND: Although several reports have examined the association between preoperative function and postoperative outcomes in patients undergoing total hip arthroplasty (THA), it is unclear whether the ability of the affected or non-affected side particularly impacts on outcomes. We aimed to investigate the association between affected and non-affected side ability and walking independence. METHODS: We prospectively enrolled 721 consecutive patients who underwent THA. Preoperatively, quadriceps isometric strength (QIS) and one-leg standing time (OLST) were measured. The endpoints were walking independence within 3, 5, 7, 10, and 14 days postoperatively. The associations between preoperative abilities and outcomes were examined using multivariate Cox hazard model, and the area under the curves (AUCs) for outcomes were compared. RESULTS: We analysed 540 patients after excluding patients who met the exclusion criteria. Both affected and non-affected QIS predicted walking independence within 3 (p = 0.006 and 0.001, respectively), 5, 7, 10, and 14 (both p < 0.001) days postoperatively. For OLST, only the affected side did not predict walking independence within 3 days postoperatively (p = 0.154 and 0.012, respectively), and both sides did at days 5 (p = 0.019 and <0.001, respectively), 7, 10, and 14 (both p < 0.001). The AUCs of the non-affected side ability for walking independence were significantly greater than those of the affected side on postoperative days 3 (0.66 vs. 0.73; p = 0.021) and 5 (0.67 vs. 0.71; p = 0.040), with no significant difference after day 7. CONCLUSIONS: Both sides abilities were associated with walking independence after THA, but non-affected side was found to be particularly crucial for early walking independence.

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.

Sports activity participation and subjective health status of patients after total hip arthroplasty via the anterolateral-supine approach: a case series study.

BACKGROUND: No reports have been published about participation in sports activity and subjective health status after total hip arthroplasty via the anterolateral approach in the supine position (ALS-THA) in Japanese patients. This study assessed sports activity participation and subjective health status, as well as factors potential associated with these variables, in patients who underwent ALS-THA. METHODS: Of 698 patients who underwent total hip arthroplasty at our institution between 2013 and 2018, questionnaires were sent to 355 patients under 80 years old who had undergone ALS-THA and 242 responded. Patients were asked about their subjective health status, participation in sports activity, the EuroQol 5-dimensions 5-level (EQ-5D-5L), the University of California Los Angeles (UCLA) activity scale score and the Forgotten Joint Score (FJS). Patient characteristics and hospitalization information were also collected. Patients' subjective health status was categorized as "healthy" or "unhealthy". Univariate and multivariate logistic regression analyses were performed to determine factors associated with participation in sports activity after ALS-THA and a "healthy" status. RESULTS: The pre- and postoperative sports activity participation rates were 54.0% and 57.8%, respectively. Most patients (76.8%, n = 182) were considered "healthy". Age (P = .019) and UCLA activity score (P < .001) were significantly associated with sports activity after ALS-THA. FJS (P = .002) and EQ-5D-5L (P = .004) were significantly associated with a "healthy" status. CONCLUSION: Patients participating in sports activity after ALS-THA are older and have higher UCLA activity scores and patients considered "healthy" have higher FJS and EQ-5D-5L scores.

Is bone marrow oedema in patients with labral tear an indicator of hip pain?

BACKGROUND: Hip labral tear (LT) causes various degrees of hip pain, for which there are few objective measures. Bone marrow oedema (BME), characterized by a diffuse, widely spreading change in the bone marrow, is observed in some patients with LT. However, its pathological role has not been fully understood. The purpose of this study was to investigate the prevalence of BME on hip magnetic resonance imaging (MRI) in patients with LT and to determine whether BME was an objective indicator of hip pain. METHODS: In total, 84 patients with LT who underwent MRI scanning under the same conditions were included. We determined the presence or absence of BME and its size on MRI and evaluated the relationships between BME and sex, age, and pain and total scores on the modified Harris hip score (MHHS). In addition, we collected data on surgical treatments such as hip arthroscopy within a one-year follow-up period and examined whether the presence of BME affected the course of therapy. RESULTS: BME was found in 34.5% of patients. MHHS pain and total scores were significantly lower in patients with BME (MHHS pain score: non-BME vs. BME ≤ 1 cm: p = 0.022, non-BME vs. BME > 1 cm: p < 0.001; MHHS total score: non-BME vs. BME ≤ 1 cm: p = 0.131, non-BME vs. BME > 1 cm: p = 0.027). The presence of BME did not differ between patients who did and did not undergo surgery during follow-up (p = 0.563). CONCLUSION: BME on MRI in patients with LT might be an indicator of hip pain and hip joint dysfunction.

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.

Initial trough concentration may be beneficial in preventing linezolid-induced thrombocytopenia.

We assessed whether prospective therapeutic drug monitoring to optimise the therapeutic range could prevent linezolid-induced thrombocytopenia. This prospective interventional study was conducted from September 2017 to October 2020 among 37 adult patients receiving linezolid. Patients were administered one of the following two initial dosages: 600 mg twice or once daily for patients with a creatinine clearance rate of ≥50 or <50 mL/min, respectively. Linezolid dosage adjustment was performed on days 3-5 based on the trough concentration. The serum linezolid levels in 22 and 15 patients were within and above the therapeutic range (2-7 µg/mL), respectively. The incidence of thrombocytopenia was significantly lower among patients whose linezolid levels were within the therapeutic range (4.5%;1/22) than in those whose levels were above the therapeutic range (80%; 12/15). It is important to maintain the linezolid level within the therapeutic range at the first therapeutic drug monitoring to prevent thrombocytopenia.

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.

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.

Hip Dislocation After Correction for Scoliosis in an Adolescent with Angelman Syndrome: A Case Report.

CASE: Although scoliosis is common in Angelman syndrome (AS), there are no reports of hip dislocation as a complication of scoliosis surgery. We experienced a case of hip dislocation after posterior spinal instrumentation and fusion from T4 to L5 because of scoliosis progression in an adolescent girl with AS. Postoperatively, posterior dislocation of the left hip occurred; after closed reduction, instability remained. Thus, periacetabular osteotomy was performed (left hip), with good clinical outcomes. CONCLUSION: Especially in cases of abnormal muscle tone, a loss of spinal flexibility because of extensive spinal fixation may result in secondary pathologies of the hip joint.

Efficacy and safety of arthroscopic treatment for native acute septic arthritis of the hip joint in adult patients.

BACKGROUND: As septic arthritis is time-dependent and has a propensity for irreversible joint damage, early diagnosis and treatment are needed. Frequently, adult patients with septic arthritis cannot undergo invasive surgery because of comorbidities and a weakened immune system. Hip arthroscopic irrigation and debridement for native acute septic arthritis of the hip joint have been performed as the first choice of treatment for patients of all ages. This study aimed to assess the efficacy and safety of arthroscopic management for native acute septic arthritis of the hip joint in adult patients. METHODS: Five adult patients (mean age, 46.2 years; all male) were retrospectively reviewed. Immediately after diagnosis, all patients underwent hip arthroscopic irrigation, debridement with synovectomy, and drainage. Partial weight-bearing was permitted once the C-reactive protein level normalised to < 1.0 mg/dl. Preoperative comorbidities, bacterial culture results, surgical complications, duration of hospital stay, time-to-confirmed normalisation of the C-reactive protein level, and recurrence incidence were evaluated. RESULTS: All patients had comorbidities, and the cultured microorganisms differed among cases. There were no complications related to arthroscopic surgery. All patients achieved confirmed C-reactive protein normalisation within an average of 69.8 days, and there was no recurrence during the follow-up period (mean, 40.2 months; range, 16-60 months). CONCLUSION: Arthroscopic management for native acute septic arthritis of the hip joint is a safe and effective procedure in adult patients.

Management of regional bone bank during declaration of a state of emergency concerning the COVID-19 in Japan.

Bone banks are necessary for providing biological allografts for a series of orthopedic procedures. As nations cope with new realities driven by the 2019 coronavirus disease (COVID-19) pandemic, health-care providers, institutions, and patients share a particular concern about the effect of COVID-19 on organ donation and transplantation. Here, we describe the management of the Kitasato University Bone Bank during the state of emergency declared in response to COVID-19. Living donors received pre-operative screening by PCR, and allograft bone from COVID-19-negative donors was cryopreserved as transplantable tissues. The weekly rate of infection gradually increased from February 2-9 to April 5-11 in the dead donor-derived allograft bone-harvesting region covered by the Bank. It is becoming clear that the virus can be transmitted by asymptomatic patients, and that this route may have facilitated the spread of COVID-19. Therefore, the Bank stopped dead donor donation to consider the safety of medical staff. Three recipients received bone allografts following pre-operative COVID-19 screening by PCR. All patients were asymptomatic after bone allograft. Our experience may provide helpful information for the management of tissue banks.

Population Pharmacokinetic and Pharmacodynamic Target Attainment Analysis of Cefazolin in the Serum and Hip Joint Capsule of Patients Undergoing Total Hip Arthroplasty.

The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in patients undergoing total hip arthroplasty and to establish the pharmacodynamic target concentration exceeding the MIC for designing an effective dosing regimen for serum and the hip joint capsule. We analyzed 249 serum samples and 125 hip joint capsule samples from 125 individuals using a nonlinear mixed-effects model. The pharmacodynamic index target value obtained from our results indicates the probability of maintaining CFZ trough and hip joint capsule concentrations exceeding the MIC of 1 mg/liter to account for methicillin-susceptible S. aureus (MSSA). We estimated the population pharmacokinetics using a two-compartment model. The estimated population pharmacokinetic parameters were as follows: clearance (CL) (liters/h) = 1.46 × (creatinine clearance [CLcr] [ml/min]/77)0.891, volume of distribution of the central compartment (Vc) (liters) = 7.5, central-hip joint capsule compartment clearance (Q) (liters/h) = 3.38, and volume of distribution in the hip joint capsule compartment (VJC) (liters) = 36.1. The probability of achieving concentrations exceeding the MIC90 for MSSA was approximately 100% for serum and 100% for the hip joint capsule at 3 h after the initial dose. Our findings suggest that population-based parameters are useful for evaluating CFZ pharmacokinetics and that individual dosages should be determined based on the dosage regimen that achieves and maintains adequate tissue CFZ concentration.