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.

Background and Objectives: Total hip arthroplasty (THA) following pelvic osteotomy for developmental dysplasia of the hip (DDH) is technically challenging due to altered acetabular morphology. This study aimed to compare radiographic cup position and perioperative characteristics of THA after three common pelvic osteotomies-periacetabular osteotomy (PAO), shelf procedure, and Chiari osteotomy-with primary THA in Crowe type I DDH. Methods: A retrospective review identified 25 hips that underwent conversion THA after pelvic osteotomy (PAO = 12, shelf = 8, Chiari = 5) and 25 primary THAs without prior osteotomy. One-to-one matching was performed based on sex (exact match), age (within 5 years), and BMI (within 2 kg/m2) without the use of propensity scores. Cup inclination, radiographic anteversion, center-edge (CE) angle, and cup height were measured on standardized anteroposterior radiographs (ICC = 0.91). Operative time, estimated blood loss, and use of bulk bone grafts or reinforcement rings were reviewed. One-way ANOVA with Dunnett's post hoc test and chi-square test were used for statistical comparison. Results: Cup inclination, anteversion, and CE angle did not differ significantly among groups. Cup height was significantly greater in the PAO group than in controls (29.0 mm vs. 21.8 mm; p = 0.0075), indicating a more proximal hip center. The Chiari and shelf groups showed upward trends, though not significant. Mean operative time tended to be longer after PAO (123 min vs. 93 min; p = 0.078). Bulk bone grafts and reinforcement rings were more frequently required in the PAO group (17%; p = 0.036 vs. control), and occasionally in Chiari cases, but not in shelf or control groups. Conclusions: THA after PAO is associated with higher cup placement and greater need for reconstructive devices, indicating increased technical complexity. In contrast, shelf and Chiari conversions more closely resemble primary THA. Preoperative planning should consider hip center translation and bone-stock restoration in post-osteotomy THA.

This study investigated whether a composite consisting of octacalcium phosphate (OCP) and porous poly(lactide-co-glycolide) (PLGA) involving recombinant stromal-derived factor-1 (SDF-1) can be used to repair severe orthopedic bone defects. Four experiments were conducted: 1) analysis of loading and release of a model protein for SDF-1, cytochrome c for OCP/PLGA; 2) observation of the effect of SDF-1 on migration of mesenchymal stem cells (MSCs) in the presence of OCP/PLGA in vitro; 3) histomorphometry and immunohistochemistry of bone regeneration of OCP/PLGA/SDF-1 by its implantation into a 3 mm diameter rat femoral transcortical defect for 4 weeks; and 4) micro-CT analysis of the tissue and Fourier transform infrared (FTIR) spectroscopy using undecalcified specimens. The binding effects of cytochrome c and SDF-1 on 40 wt % OCP/PLGA were compared using OCP/PLGA with SDF-1 or cytochrome c prepared under saturated (S) and supersaturated (SS) conditions, containing low or high calcium and phosphate ion concentrations. The loading rates were higher in OCP/PLGA regardless of SS conditions than in PLGA, while the release rate was higher in OCP/PLGA loaded under SS conditions throughout the time, up to 168 h. MSC migration was most enhanced in the OCP/PLGA and loaded under SS conditions for up to 48 h. Bone regeneration was enhanced in OCP/PLGA loaded under SS conditions followed by S conditions and no SDF-1 loading of the OCP/PLGA for up to 4 weeks. Micro-CT and FTIR analyses suggested the material's biodegradation and new bone replacement, which was consistent with the histomorphometry. Osteocalcin-positive cells, tartrate-resistant acid phosphatase-positive cells, and C-X-C motif chemokine receptor type 4 positive cells were localized around the OCP/PLGA under SS conditions, corresponding to higher resorption of the OCP granules. The results suggest that OCP/PLGA involving SDF-1 may repair severe orthopedic bone defects.

Dialysis patients who develop degenerative hip disease or femoral neck fractures may require total hip arthroplasty, and their comorbidities predispose them to complications. This study aimed to evaluate whether dialysis was associated with early postoperative complications using a large database of Japanese. In this cohort study, using the Japanese National Administrative Diagnosis Procedure Combination database on THA for patients on hemodialysis or not from December 2011 to March 2023, we assessed the surgical-related complications, medical complications, and mortality during hospitalization after propensity score matching by age, sex, BMI, and comorbidities. A total of 2,111 pairs of patients on hemodialysis and non-dialysis were included. In THA for patients on hemodialysis, the significant odds ratios for various complications were as follows: dislocation (2.616, 95% CI: 1.282 to 5.338, p < 0.01), reoperation (2.104, 95% CI: 1.222 to 3.623, p < 0.01), deep vein thrombosis (0.407, 95% CI: 0.286 to 0.579, p < 0.01), cerebrovascular events (4.426, 95% CI: 1.495 to 13.10, p < 0.01). These findings help identify postoperative THA risks for patients on dialysis, suggesting that more attention should be paid to preoperative planning and postoperative care.

BACKGROUND: Biomechanical effect on hip joint stability between the transverse interportal capsulotomy and the longitudinal capsulotomy in arthroscopy has not been fully investigated. PURPOSE: To evaluate whether rotational stability and distraction resistance differ between the 2 capsulotomy directions using fresh-frozen cadavers. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve hips of 6 fresh-frozen cadavers, including intact femur and pelvis, were tested in 3 conditions: intact, capsulotomy, and repaired. Two capsulotomy patterns were made: a 4-cm transverse capsular resection based on a transverse interportal capsulotomy, and longitudinal capsulotomy. Six hips were transverse capsulotomy and 6 hips were longitudinal capsulotomy. The pelvis was fixed to a wooden plate, and the intramedullary nail was inserted into the femur. To evaluate rotational stability, internal and external torques of 5 N·m were applied at 15° of hip extension and 0°, 15°, 30°, 45°, and 60° of hip flexion, respectively. To test for distraction, the specimens were axially loaded from 0- to 150-N distraction forces at different flexion angles (0°, 30°, 45°, 60°). RESULTS: The external rotation laxity increased significantly after the transverse capsulotomy at all flexion angles and longitudinal capsulotomy only at 0°. The separation distance increased significantly after the transverse and longitudinal capsulotomies. The change in external rotation laxity was significantly greater in transverse capsulotomy at 15° of hip extension and 0° than longitudinal capsulotomies in unrepaired conditions compared with intact conditions. With distraction loads, the transverse capsulotomy resulted in a significantly greater separation distance than the longitudinal capsulotomy at all flexion angles with 100 N, and at 0° and 60° with 50 N. Significant differences were observed after capsular repaired compared with intact for external rotation angle at 15° extension and 0°, and separation distance at 60° flexion with 150 N and 100 N between capsulotomy directions. CONCLUSION: This cadaveric study demonstrated that the hips with the longitudinal capsulotomy resulted in less external rotation laxity, especially at 15° extension and 0°, and less distraction laxity compared with those with the transverse capsulotomy; and these differences remained after repair of capsulotomy. CLINICAL RELEVANCE: Either capsulotomy direction is effective if the capsular repair is performed properly because the standard capsular repair improves capsular stability. However, surgeons should note that the longitudinal incision tends to be more stable at lower levels of hip flexion.

BACKGROUND: Stress shielding (SS) after total hip arthroplasty (THA) leads to proximal femoral bone loss and increases the risk of complications such as implant loosening and periprosthetic fracture. While various low-stiffness stems have been developed to prevent SS, they often compromise mechanical stability. A novel femoral stem composed of Ti-33.6Nb-4Sn (TNS) alloy offers a gradually decreasing Young's modulus from proximal to distal regions, potentially improving load distribution and reducing SS. This study aimed to evaluate the mid-term clinical and radiographic outcomes of the TNS stem, with a particular focus on its effectiveness in suppressing SS. METHODS: A prospective clinical study was conducted involving 35 patients who underwent THA using the TNS stem, with a minimum follow-up of 7 years. Twenty-one patients with Ti6Al4V metaphyseal-filling stems served as controls. Clinical outcomes were assessed using Japanese Orthopaedic Association (JOA) scores, and radiographic SS was graded using Engh's classification and analyzed in Gruen zones. Inter-examiner reliability and statistical comparisons between groups were performed using appropriate tests. RESULTS: The TNS group showed significantly higher preoperative JOA scores than the control group, but no significant difference in final scores. Both groups demonstrated significant improvement postoperatively. Third-degree SS occurred in the TNS group, although the overall SS grade distribution was significantly lower than in the control group (p = 0.03). SS frequency was significantly reduced in Gruen Zones 2, 3, and 6 in the TNS group. CONCLUSIONS: The TNS stem demonstrated a significant reduction in SS progression compared to conventional titanium stems over a 7-year period, with comparable clinical outcomes. However, the occurrence of third-degree SS indicates that material optimization alone may be insufficient, highlighting the need for further design improvements.

Background: Total hip arthroplasty (THA) is a widely used surgical intervention for hip osteoarthritis (HOA), with a rising demand driven by an aging population. Osteoporosis is associated with increased risks of bone loss and implant loosening after THA. While medications such as bisphosphonates and denosumab have shown promise in mitigating these risks, the impact of preoperative osteoporosis treatment on postoperative outcomes remains unclear. This study investigates the effect of preoperative osteoporosis treatment intervention on stress shielding and clinical outcomes in THA patients. Methods: This retrospective study included 107 patients who underwent cementless THA between April 2019 and March 2022. Patients under 60 years old, with a follow-up period of less than one year, or with prior hip surgery were excluded. Participants were divided into two groups: a treatment group receiving osteoporosis medication preoperatively and a non-treatment group. The outcomes assessed included preoperative bone metabolism markers, Bombelli classification, stress shielding grade, and clinical scores. Statistical analysis was performed using the Mann-Whitney U test and Chi-squared test, with significance set at p < 0.05. Results: The preoperative osteoporosis treatment intervention rate was 28.9%. Stress shielding grades were significantly lower in the treatment group (p = 0.001). However, no significant differences were observed in clinical scores one year postoperatively. Conclusion: Preoperative osteoporosis treatment significantly reduced stress shielding incidence, potentially influencing long-term outcomes by preventing bone atrophy-related pain and fractures. Preoperative bone density assessment and osteoporosis treatment intervention are recommended to improve THA outcomes. Larger studies are needed for further validation.

PURPOSE: The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse. METHODS: The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated. RESULTS: There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse. CONCLUSIONS: Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.

BACKGROUND: Clinical outcomes of Chiari pelvic osteotomy for acetabular dysplasia, including conversion to total hip arthroplasty (THA), have not been adequately explored. The purpose of this study was to examine the long-term results and clinical outcomes of Chiari pelvic osteotomy as the primary outcome and to analyze its prognostic factors as the second outcome. METHODS: This study was a multicenter, retrospective cohort study. Ninety-seven patients underwent Chiari pelvic osteotomy at three hospitals between March 1975 and October 1997. The long-term clinical outcomes of Chiari pelvic osteotomy, including conversion to THA and hip pain, were analyzed using the Kaplan-Meier method. In addition, the prognostic factors for conversion to THA after Chiari pelvic osteotomy were evaluated with clinical variables and radiographic parameters. RESULTS: The study included 51 hips in 45 patients (4 men and 41 women) with long-term follow-up. The survival rates assessed by Kaplan-Meier analysis with conversion to THA as an endpoint, were 90.2% (95% confidence interval (CI) 82.0-98.4%) at 20 years and 73.5% (95% CI 61.1-86.0%) at 30 years. In contrast, the Kaplan-Meier survival rates with the Japanese Orthopaedic Association hip score for pain ≤20 as an endpoint, were 86.3% (95% CI 76.8-95.7%) at 20 years and 65.6% (95% CI 52.3-79.0%) at 30 years. Only older age at osteotomy was the significantly poor prognostic factor for conversion to THA, with a hazard ratio of 1.11/year, 95% CI 1.06 to 1.18, (p < 0.01). CONCLUSION: Chiari pelvic osteotomy may still be a good alternative to bony reconstructive surgery for acetabular dysplasia especially in young patients. Only older age at the osteotomy was related to the poor prognosis of preserving hip function.

BACKGROUND: In upright standing, spinopelvic mismatch is compensated by hip extension. However, few studies have investigated the reciprocal relationship between the sagittal alignment of the hip joints and spinopelvic mismatch during upright standing in humans. Our study aims to investigate (I) the relationship between spinopelvic mismatch and hip extension and (II) whether insufficient hip extension against spinopelvic mismatch, i.e., pelvic incidence (PI)-lumbar lordosis (LL), affects trunk inclination in upright standing. METHODS: This study was a retrospective cross-sectional study. We included 398 consecutive female patients treated for osteoporosis at our outpatient department between November 2017 and June 2022. Patients with any of the following were excluded from the study: (I) those whose plain whole-spine radiographs did not cover the femurs, (II) those with fractures in the vertebrae or lower extremities, (III) those with a history of surgery of the spine or of the lower extremities, (IV) those with scoliosis with a Cobb angle ≥10° in the anteroposterior radiograph, and (V) those with transitional vertebrae. Sixty-two patients were divided into normal and malalignment groups based on their sagittal spinal alignment. The patients underwent plain whole-spine radiography as a routine examination. A linear approximation between the pelvic femoral angle (PFA), representing hip extension, and PI-LL was obtained in both groups. The optimal PFA of each patient was obtained by substituting the PI-LL into the linear approximation of the normal group. The difference between the optimal and measured PFA was defined as the ΔPFA for each patient. The correlation between the ΔPFA and sagittal vertical axis (SVA) was evaluated in both groups. RESULTS: The PFA and PI-LL were correlated in both groups. The malalignment group had a significantly greater ΔPFA than the normal group. ΔPFA was correlated with SVA only in the malalignment group. CONCLUSIONS: The magnitude of the ΔPFA indicated insufficient hip extension to compensate for the spinopelvic mismatch during upright standing.

BACKGROUND: The difference between Young's moduli of the femur and the stem causes stress shielding (SS). TiNbSn (TNS) stem has a low Young's modulus and strength with gradient functional properties during the change in elastic modulus with heat treatment. The aim of this study was to investigate the inhibitory effect of TNS stems on SS and their clinical outcomes compared to conventional stems. METHODS: This study was a clinical trial. Primary THA was performed using a TNS stem from April 2016 to September 2017 for patients in the TNS group. Unilateral THA was performed using a Ti6Al4V alloy stem from January 2007 to February 2011 for patients in the control group. The TNS and Ti6Al4V stems were matched in shape. Radiographs were obtained at the 1- and 3-year follow-ups. Two surgeons independently checked the SS grade and appearance of cortical hypertrophy (CH). The Japanese Orthopaedic Association (JOA) scores before and 1 year after surgery were assessed as clinical scores. RESULTS: None of the patients in the TNS group had grade 3 or 4 SS. In contrast, in the control group, 24% and 40% of patients had grade 3 and 4 SS at the 1- and 3-year follow-ups, respectively. The SS grade was lower in the TNS group than in the control group at the 1- and 3-year follow-ups (p < 0.001). The frequencies of CH in both groups were no significant difference at the 1- and 3-year follow-ups. The JOA scores of the TNS group significantly improved at 1 year after surgery and were comparable to control group. CONCLUSION: The TNS stem reduced SS at 1 and 3 years after THA compared to the proximal-engaging cementless stem, although the shapes of the stems matched. The TNS stem could reduce SS, stem loosening, and periprosthetic fractures. TRIAL REGISTRATION: Current Controlled Trials. ISRCTN21241251. https://www.isrctn.com/search?q=21241251 . The date of registration was October 26, 2021. Retrospectively registered.

Previous research has found that octacalcium phosphate (OCP) increases macrophage accumulation and alters the initial inflammatory response. However, the role of the immune response induced by OCP in osteogenesis remains unknown. This study investigated the behavior of macrophages and bone regeneration capacity during the early inflammatory stage of OCP-mediated osteogenesis. To assess the change in macrophage polarization and osteogenic capacity, we used a standardized rat defect model filled with OCP or calcium-deficient hydroxyapatite (CDHA)-a material obtained through the hydrolysis of the original OCP. OCP or CDHA granules were incubated with RAW264 cells for 5 days to investigate the effect of physicochemical characteristics on macrophage cytokine/chemokine expression in vitro. Our in vivo results show that due to the OCP implantation, macrophages in the rat tibial defect area tend to polarize to the M2 phenotype (anti-inflammatory) and inhibit the formation of the M1 phenotype (pro-inflammatory). In comparison to CDHA, OCP exhibited superior bone regeneration potential due to its rapid promotion of cortical bone healing and stimulation of macrophage-related growth factors. Furthermore, our in vitro results have shown that OCP regulates the expression of macrophage chemokines over time. Compared to incubation with CDHA, incubation with OCP caused changes in the ionic microenvironment. These findings suggest that the OCP-mediated macrophage polarization and secretion profile not only regulate immune function but also positively affect osteogenesis.

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.

BACKGROUND: Bone grafting is widely used to treat large bone defects. A porous composite of a bioactive octacalcium phosphate material with gelatin sponge (OCP/Gel) has been shown to biodegrade promptly and be replaced with new bone both in animal models of a membranous bone defect and a long bone defect. However, it is unclear whether OCP/Gel can regenerate bone in more severe bone defects, such as a critical-size transcortical defect. QUESTIONS/PURPOSES: Using an in vivo rat femur model of a standardized, transcortical, critical-size bone defect, we asked: Compared with a Gel control, does OCP/Gel result in more newly formed bone as determined by (1) micro-CT evaluation, (2) histologic and histomorphometric measures, and (3) osteocalcin staining and tartrate-resistant acid phosphatase staining? METHODS: Thirty-four 12-week-old male Sprague-Dawley rats (weight 356 ± 25.6 g) were used. Gel and OCP/Gel composites were prepared in our laboratory. Porous cylinders 3 mm in diameter and 4 mm in height were manufactured from both materials. The OCP/Gel and Gel cylinders were implanted into a 3-mm-diameter transcortical critical-size bone defect model in the left rat femur. The OCP/Gel and Gel were randomly assigned, and the cylinders were implanted. The biological responses of the defect regions were evaluated radiologically and histologically. At 4 and 8 weeks after implantation, CT evaluation, histological examination of decalcified samples, and immunostaining were quantitatively performed to evaluate new bone formation and remaining bone graft substitutes and activity of osteoblasts and osteoclast-like cells (n = 24). Qualitative histological evaluation was performed on undecalcified samples at 3 weeks postimplantation (n = 10). CT and decalcified tissue analysis was not performed blinded, but an analysis of undecalcified specimens was performed under blinded conditions. RESULTS: Radiologic analysis revealed that the OCP/Gel group showed radiopaque regions around the OCP granules and at the edge of the defect margin 4 weeks after implantation, suggesting that new bone formation occurred in two ways. In contrast, the rat femurs in the Gel group had a limited radiopaque zone at the edge of the defect region. The amount of new bone volume analyzed by micro-CT was higher in the OCP/Gel group than in the Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 6.1 ± 1.6 mm 3 versus 3.4 ± 0.7 mm 3 , mean difference 2.7 [95% confidence interval (CI) 0.9 to 4.5]; p = 0.002; intraclass correlation coefficient [ICC] 0.72 [95% CI 0.29 to 0.91]; 8 weeks after implantation: OCP/Gel versus Gel: 3.9 ± 0.7 mm 3 versus 1.4 ± 1.1 mm 3 , mean difference 2.5 [95% CI 0.8 to 4.3]; p = 0.004; ICC 0.81 [95% CI 0.47 to 0.94]). Histologic evaluation also showed there was a higher percentage of new bone formation in the OCP/Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 31.2% ± 5.3% versus 13.6% ± 4.0%, mean difference 17.6% [95% CI 14.2% to 29.2%]; p < 0.001; ICC 0.83 [95% CI 0.53 to 0.95]; 8 weeks after implantation: OCP/Gel versus Gel: 28.3% ± 6.2% versus 9.5% ± 1.9%, mean difference 18.8% [95% CI 11.3% to 26.3%]; p < 0.001; ICC 0.90 [95% CI 0.69 to 0.97]). Bridging of the defect area started earlier in the OCP/Gel group than in the Gel group at 4 weeks after implantation. Osteocalcin immunostaining showed that the number of mature osteoblasts was higher in the OCP/Gel group than in the Gel group at 4 weeks (OCP/Gel versus Gel: 42.1 ± 6.5/mm 2 versus 17.4 ± 5.4/mm 2 , mean difference 24.7 [95% CI 16.2 to 33.2]; p < 0.001; ICC 0.99 [95% CI 0.97 to 0.99]). At 4 weeks, the number of osteoclast-like cells was higher in the OCP/Gel composite group than in the Gel group (OCP/Gel versus Gel: 3.2 ± 0.6/mm 2 versus 0.9 ± 0.4/mm 2 , mean difference 2.3 [95% CI 1.3 to 3.5]; p < 0.001; ICC 0.79 [95% CI 0.35 to 0.94]). CONCLUSION: OCP/Gel composites induced early bone remodeling and cortical bone repair in less time than did the Gel control in a rat critical-size, transcortical femoral defect, suggesting that OCP/Gel could be used as a bone replacement material to treat severe bone defects. CLINICAL RELEVANCE: In a transcortical bone defect model of critical size in the rat femur, the OCP/Gel composite demonstrated successful bone regeneration. Several future studies are needed to evaluate the clinical application of this interesting bone graft substitute, including bone formation capacity in refractory fracture and spinal fusion models and the comparison of bone strength after repair with OCP/Gel composite to that of autologous bone.

BACKGROUND: This study examined the biomechanics of preventing excessive internal hip joint rotation related to the hip flexion angle. METHOD: An intramedullary nail with a circular plate equipped with a protractor was installed in the femur of nine normal hips. The circular plate was pulled by 3.15 Nm of force in the internal rotation direction. The external rotators were individually resected, finally cutting the ischiofemoral ligament. The cutting order of the external rotators differed on each side to individually determine the internal rotation resistance. The external rotators were resected from the piriformis to the obturator externus in the right hips and the reverse order in the left hips. Traction was performed after excising each muscle and ischiofemoral ligament. Measurements were taken at 0°, 30°, and 60° of hip flexion, and the differences from baseline were calculated. RESULTS: For the right hip measurements, the piriformis and ischiofemoral ligament resection significantly differed at 0° of flexion (p = 0.02), each external rotator and the ischiofemoral ligament resections significantly differed at 30° of flexion (p < 0.01), and the ischiofemoral ligament and piriformis and inferior gemellus resections significantly differed at 60° of flexion (p = 0.04 and p = 0.02, respectively). In the left hips, the ischiofemoral ligament and obturator externus, inferior gemellus, and obturator internus resections significantly differed at 0° of flexion (p < 0.01, p < 0.01, and p = 0.01, respectively), as did each external rotator and the ischiofemoral ligament resections at 30° of flexion (p < 0.01). CONCLUSION: The ischiofemoral ligament primarily restricted the internal rotation of the hip joint. The piriformis and obturator internus may restrict internal rotation at 0° and 60° of flexion.

BACKGROUND: This study was performed to investigate the mid-term results of Ti-Nb-Sn (TNS) alloy stem with a low Young's modulus. METHODS: This study was a multicenter prospective cohort study. A total of 40 primary total hip arthroplasties performed between April 2016 and September 2017 was enrolled in this study. With the unique functional gradient properties by heating treatment, the strength of the proximal portion was enhanced, while the distal portion maintained a low Young's modulus. The surgeries were performed through the posterolateral approach using the TNS alloy stems. Radiographs were taken from immediately after surgeries until 3 years, and stress shielding and subsidence of the stems were evaluated. The incidences of the stem breakage were also assessed. Clinical assessments were performed using Japanese Orthopaedic Association (JOA) and Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) scores. RESULTS: Among the 40 enrolled patients, 36 patients were female and 4 were male. At 3 years after surgery, there were no radiologic signs of loosening, subsidence, or breakage of the stem. Stress shielding was observed in 26 hips (65%). Of 26 hips, 16 hips (40%) were grade 1 and 10 hips (25%) were grade 2. There was no advanced stress shielding. The JOA and JHEQ scores significantly improved compared with the preoperative scores. CONCLUSION: The current study using a new TNS alloy femoral stem showed good clinical outcomes at 3-year follow-up. Radiologically, there was no loosening or subsidence of the stem. The mild stress shielding was observed in 65% of patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21241251 . The date of registration was October 26, 2021. Retrospectively registered.

The microstructure of biomaterials influences the cellular and biological responses in the bone. Octacalcium phosphate (OCP) exhibits higher biodegradability and osteoconductivity than hydroxyapatite (HA) during the conversion process from OCP to HA. However, the effect of the microstructure of OCP crystals on long tubular bones has not been clarified. In this study, two types of OCPs with different microstructures, fine-OCP (F-OCP) and coarse-OCP (C-OCP), were implanted in rat tibia for 4 weeks. F-OCP promoted cortical bone regeneration compared with C-OCP. The osteoclasts appearance was significantly higher in the C-OCP group than in the control group (defect only) at 1-week post-implantation. To investigate whether the solubility equilibrium depends on the different particle sizes of OCPs, Nano-OCP, which consisted of nanometer-sized OCPs, was prepared. The degree of supersaturation (DS) tended to decrease modestly in the order of C-OCP, F-OCP, and Nano-OCP with respect to HA and OCP in Tris-HCl buffer. F-OCP showed a higher phosphate ion concentration and lower calcium ion concentration after immersion in the buffer than C-OCP. The crystal structures of both OCPs tended to be converted to HA by rat abdominal implantation. These results suggest that differences in the microstructure of OCPs may affect osteoclastogenesis and result in osteoconductivity of this material in long tubular bone by altering dissolution behavior.

Effect of the simultaneous hydrolysis of octacalcium phosphate (OCP) and poly (lactic-co-glycolic acid) (PLGA) was investigated on its osteoconductivity. PLGA soaked in phosphate buffered saline with 0%, 20%, and 40% OCP at 37°C for eight weeks indicated that when the OCP dose was increased, 1) the weight loss of PLGA increased, 2) the glass transition temperature of the PLGAs decreased, 3) the saturation degree in the saline moved to nearly saturated condition with respect to hydroxyapatite (HA) but was undersaturated with respect to OCP, and 4) OCP tended to convert to HA by X-ray diffraction and Fourier transform infrared spectroscopy. OCP/PLGA composites of 20% and 40% with more than 92% porosity were produced by combining OCP granules with 1,4-dioxane-solubilizing PLGA followed by lyophilization and then subjected to four- and eight-week in vivo implantation tests in 3 mm diameter rat femora defects. Microfocus X-ray computed tomography, histochemical and histomorphometric analyses showed that while bone formation was very limited with PLGA implantation, the extent of repair tended to increase with increasing OCP content in the PLGA, coupled with PLGA degradation, and bridge the defects with trabecular bone. Tartrate-resistant acid phosphatase-positive osteoclast-like cells were accumulated four weeks after implantation, while osteocalcin-positive osteoblastic cells appeared later at eight weeks, especially in 40% OCP/PLGA. These results suggest that OCP hydrolysis, with phosphate ion release, enhances PLGA hydrolysis, probably through the acid catalysis function of the protons supplied during the hydrolysis of OCP, thereby inducing PLGA biodegradation and new bone formation in the femoral defects. STATEMENT OF SIGNIFICANCE: Octacalcium phosphate (OCP) enhances osteoblasts and osteocytes differentiations during its hydrolysis accompanying inorganic ions exchange in this material. The present study found that the advancement of OCP hydrolysis under physiological conditions had an effect on poly (lactic-co-glycolic acid) (PLGA) degradation through its chemical environmental change around OCP, which was ascertained by the decreases in weight loss and glass transition temperature of PLGA with increasing the dose of OCP co-present. Rat femur-penetrated standardized severe defects were found to repair through bridging the cortical region defect margin. PLGA degradation could be enhanced through an acid catalyst function by protons derived from inorganic phosphate (Pi) ions through OCP hydrolysis under bone forming condition, resulting in showing a prominent bone regenerative capacity in OCP/PLGA composite materials.

INTRODUCTION: This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies. MATERIALS AND METHODS: This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO), and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months. RESULTS: At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012). CONCLUSION: Denosumab treatment might be effective for the inhibition of bone erosion progression in the patients with RA, and it potentially contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with switching treatment from bisphosphonate.

BACKGROUD: Exercises and vitamin D interventions have shown to improve muscle function and balance, and prevent falls in postmenopausal healthy women and in patients with osteoporosis. However, the effects of eldecalcitol on these factors remain undetermined. The present open-label, randomized, controlled study aimed to investigate the effects of eldecalcitol treatment in reducing falls in postmenopausal women, and improving muscle function and balance. METHODS: The study population included 226 Japanese postmenopausal women with osteoporosis. Patients were randomly divided into two groups on the basis of treatment with or without eldecalcitol (0.75 μg/day). Treatment continued for 6 months. Participants in both groups were instructed to perform back extensor muscle exercise. Isometric back extensor and leg extensor strength, grip power, ten-meter walking speed, timed up and go test and time of single leg standing were measured at baseline and 24 weeks. Patients were asked to record the number of falls during the 24-week period. RESULTS: The percentage increase in average bilateral quadriceps muscle strength was significantly higher in the eldecalcitol group compared with the non-eldecalcitol group (right, p = 0.041; left, p = 0.042). In contrast, there were no significant differences in the strength of back muscles and grip power and the parameters of balance and walking abilities between the groups. There was no significant difference in the number of falls between the groups. CONCLUSIONS: A 24-week intervention of eldecalcitol improves the strength of the quadriceps muscles in postmenopausal women with osteoporosis. However, eldecalcitol neither improve balance and walking abilities nor reduce the number of falls.

BACKGROUND: Glucocorticoid-induced osteoporosis and vertebral fracture are common complications in patients on glucocorticoid treatment for rheumatological diseases. The present study aimed to identify the risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis. METHODS: This study included 225 Japanese women with glucocorticoid-induced osteoporosis and 72 patients with postmenopausal osteoporosis. All participants were treated with bisphosphonate or denosumab for osteoporosis with active form of vitamin D for at least 3 years. The differences of clinical parameters, including age, disease duration, body mass index (BMI), bone mineral density (BMD), and the dose and treatment duration of glucocorticoid were assessed between patients with and without vertebral fracture. Multivariate logistic regression analysis was also performed to evaluate the association of vertebral fracture with clinical parameters. RESULTS: The significant differences related to age, BMD of the hip, disease duration, glucocorticoid treatment duration between patients with and without vertebral fractures were demonstrated. The present study indicated that disease duration, BMI, and the total hip BMD were independent risk factors for vertebral fractures in patients with glucocorticoid-induced osteoporosis. CONCLUSIONS: Prolonged disease duration, low BMI, and low total hip BMD could be risk factors of vertebral fracture in patients on glucocorticoid treatment for rheumatological diseases.

The purpose of this study was to investigate whether the chemical condition of osteoporotic serum affects the chemical stability of octacalcium phosphate (OCP) and its osteoconductive property. The in vitro chemical dissolution in osteoporotic ovariectomized (OVX)-simulated conditions was analyzed. OCP and its composite form with gelatin (OCP/Gel), containing specific amounts of OCP (either 17% or 44% by weight), were used as experimental materials. The degrees of supersaturation (DS) of the OVX-simulated buffer solutions, containing distinct inorganic phosphate (Pi) ion concentrations, after immersing OCP or OCP/Gel, were determined. The rod-shaped OCP/Gel was then implanted into the OVX and Sham rat tibia defects, exhibiting a similar shape and size, and assessed at 4, 8, and 12 weeks. Increasing Pi concentration in OVX-simulated buffer solution increased the DS, with respect to OCP, upon the introduction of OCP and 44% OCP/Gel, but decreased the DS to a slightly saturated condition with 17% OCP/Gel, indicating that increasing the OCP in the Gel matrix tends to inhibit the hydrolysis of OCP into hydroxyapatite (HA). Histomorphometric analyses of bone formation and the appearance of osteoblasts and osteoclast-like cells, together with OCP resorption, confirmed that while 44% OCP/Gel showed higher bone formation than 17% OCP/Gel at intramedullary bone defect sites in Sham rat tibia, both OCP/Gels tended to enhance cortical bone formation in the OVX group, concomitant with the higher resorption of OCP within 17% OCP/Gel. The appearance of osteoclast-like cells in the OVX group increased as the OCP dose decreased from 44% to 17% in the Gel matrix, with an approximately 4 times higher bone formation rate, 8-12 weeks after the implantation. Additional in vitro assays showed that bone marrow mesenchymal stem cells isolated from OVX and wild-type (WT) rats treated with OCP had similar proliferation and differentiation rates, up to 21 days. These results show that OCP can enhance cortical bone repair even in osteoporotic bone if suitable thermodynamic metastable dissolution conditions are provided in relation to the mass of OCP.

Effect of octacalcium phosphate/gelatin composite (OCP/Gel) on angiogenesis was studied by its implantation in rat calvaria critical-sized defect in relation to bone regeneration for 2 and 4 weeks. The implantation of OCP/Gel disks was analyzed by radiomorphometry using a radiopaque material perfusion (Microfil®) method and histomorphometry by hematoxylin and eosin-staining before and after the decalcification. Effect of the OCP dose in the range up to 4 mg per well on the capillary-like tube formation by human umbilical vein endothelial cells (HUVECs) was also examined in a transwell cell culture. The results showed that the blood vessels formation by OCP/Gel group was significantly higher at 2 weeks than other groups but decreased at 4 weeks during the advancement of new bone formation. The capillary-like tube formation was highest in an OCP dose of 1 mg per well while other OCP doses above or below 1 mg did not show such a stimulatory effect. The results established both in vivo and in vitro confirmed that OCP has a positive effect on angiogenesis during bone regeneration in a suitable dose ranges, suggesting that the angiogenesis stimulated by OCP could be involved in the OCP/Gel-enhanced bone regeneration. STATEMENT OF SIGNIFICANCE: We have reported that octacalcium phosphate (OCP) materials display stimulatory capacities on the bone tissue-related cells. However, the effect of OCP on the angiogenesis and its relation to the OCP-enhanced bone regeneration is unknown. This study confirmed the capacity of OCP on angiogenesis before increasing the new bone mass after the implantation of a composite of OCP and gelatin (OCP/Gel). The blood vessels formation took place associated with the area beginning of the new bone formation, which finally decreased together with development of bone formation. Because OCP was ascertained stimulating the capillary-like tube formation in HUVEC culture with a certain OCP dose, the present study is the first report showing the capacity of OCP on angiogenesis during the OCP/Gel-enhanced bone regeneration.

Three-dimensional (3-D) cell culture can better mimic physiological conditions in which cells interact with adjacent cells and the extracellular matrix than monolayer culture. We have developed a 3-D cell culture device, the Oxy chip, which can be used to generate and supply oxygen to cell spheroids to prevent hypoxia. Here, we used the Oxy chip to generate hybrid spheroids comprising calcium phosphate (CaP) particles (hydroxyapatite (HA), β-tricalcium phosphate (β-TCP) or octacalcium phosphate (OCP)) and mesenchymal stem cells (MSCs, C3H10T1/2 cells or D1 cells) that can be used to analyze cell differentiation mechanisms. We showed that the 3-D cell-cell and cell-material interactions and oxygenation offered by the Oxy chip promoted osteoblastic differentiation of MSCs. We also used histomorphometric analysis of hematoxylin and eosin staining, quality analyses by μCT and collagen orientation observation with picrosirius red staining in bone regeneration following implantation of three CaPs in a critical-sized defect in mouse calvaria. The in vivo bone formation capacity of the three tested CaP materials was OCP ≥ β-TCP > HA: the newly formed bone by OCP had a structure relatively close to that of the calvaria intact bone. When MSCs were 3-D cultured with the CaP materials using the Oxy chip, the in vitro osteogenic capacity of these materials was highly similar to trends observed in vivo. The in vitro alkaline phosphatase activity of D1 cells had the highest correlation with in vivo bone volume (R = 0.900). Chemical and FTIR spectroscopic analyses confirmed that differentiation of D1 cells could be associated with amorphous calcium phosphate (ACP) precipitation concomitant with OCP hydrolysis. Taken together, hybrid spheroid cultures using the Oxy chip can be used to screen and predict bone forming potential of bone substitute materials. STATEMENT OF SIGNIFICANCE: An oxygen permeable-culture chip (Oxy chip) can be used to induce formation of cell spheroids by mesenchymal stem cells (MSCs). Use of the Oxy chip avoids hypoxia in the spheroid core and enhances MSC osteoblastic differentiation relative to conventional spheroid culture methods. The present study showed that the Oxy chip mimics the in vivo environment associated with bone formation and can be used to generate hybrid spheroids consisting of calcium phosphates and MSCs that are useful for analyzing cell differentiation mechanisms. Bone formation analysis following implantation of calcium phosphate materials in mouse calvaria defects showed positive correlation with the in vitro results. We propose that hybrid spheroids cultured on the Oxy chip can be used to screen and predict the bone forming potential of bone substitute materials.

The purpose of the current study was to retrospectively evaluate the long-term outcome of our shelf operation for acetabular dysplasia in adults and adolescents. We evaluated the outcome of shelf operation performed in 35 hips of 32 patients with acetabular dysplasia between 1978 and 1996. The mean age at the time of surgery was 30.6 years, and the mean follow-up period was 25.9 years. The pre-operative stage of osteoarthritis was Tönnis grade 0 in 12 hips and grade 1 in 23 hips. Clinical evaluation using the JOA hip score showed more than 85 of 100 points over 25 years. Radiologically, acetabular index was significantly improved after operation. Osteoarthritis deteriorated to grade 3 in 8 of 35 hips (23%) at an average 17.1 years, and accordingly 3 of those 8 hips were converted to THA. The shelf height was significantly higher in those which advanced to grade 3 than in those which did not. There were no significant differences in mean sharp angle, CE angle, AHI, and roundness index. Mean survival was 74% with grade 3 as the endpoint and 72% with THA conversion as the endpoint. Shelf operation provides satisfactory long-term outcome in adults and adolescents with acetabular dysplasia. Higher location of the shelf is a risk factor for advancement of osteoarthritis, whereas sphericity of the femoral head does not affect the long-term results. Further studies are needed to clarify the risk factors about OA progression among the patients with acetabular dysplasia, like as the assessment of three-dimensional morphology of hip joints.

BACKGROUND: The aim of this study was to assess the relationships between clinical parameters and bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE). METHODS: A total of female 136 SLE patients without menopause were retrospectively assessed to identify associations between age, disease duration, body mass index (BMI), glucocorticoid usage and disease activity and BMD based on the treatment with or without bisphosphonate. There were 71 patients treated with bisphosphonate (bisphosphonate group) and 65 patients without (non-bisphosphonate group). We evaluated the impact of age, disease duration, BMI, serologic SLE markers, glucocorticoid use on BMD of the anterior-posterior (AP) and lateral lumbar spine, total hip and femoral neck using univariate and multivariate linear regression analyses of both bisphosphonate and non-bisphosphonate groups. RESULTS: Multivariate linear regression analyses showed that in non-bisphosphonate group disease duration was negatively associated with BMD of AP spine and femoral neck, whereas in bisphosphonate group these negative associations were not present. However, multivariate linear regression analyses showed a significant relationship between BMI and BMD of the AP spine, femoral neck and total hip, regardless of bisphosphonate treatment. CONCLUSIONS: Bisphosphonate treatment eliminated the negative relationships between disease duration and the BMD of the spine and hip. AP spine and hip BMD in patients with SLE depend on BMI, regardless of bisphosphonate use. SLE serologic markers and glucocorticoid use were not negatively associated with generalized bone loss. SLE patients with low BMI have a high risk of generalized bone loss, and should be assessed and treated to prevent osteoporosis even before menopause.

The purpose of this study was to compare the biodegradation rate and quality of regenerated bone among four materials. A short time period of 8 weeks was chosen to examine early bone healing. The rod-shaped implants of commercially available two β-tricalcium phosphate (β-TCP) ceramics with porosity 60% and 71-80%, respectively, laboratory prepared octacalcium phosphate/gelatin composite (OCP/Gel), which has been proven to have a highly osteoconductive and biodegradable property in rat calvarial defect, and gelatin sponge (Gelatin) were implanted in rabbit tibia defect of 6 mm diameter and 7 mm depth for 2, 4 and 8 weeks. Analyses by μCT, histomorphometry and push-in test were carried out to evaluate the extent of the tissue regeneration and the material biodegradation in the long bone. OCP/Gel and Gelatin were completely resorbed but only OCP/Gel induced cortical bone bridge until 8 weeks that has strength compatible to that of the natural bone. β-TCP (71%-80%) and β-TCP (60%) were not completely resorbed and never induced the amount of new bone formation beyond that by OCP/Gel. The results indicate that the new bone having enough strength could be regenerated if the material shows not only higher biodegradation rate but also higher osteoconductivity. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2833-2842, 2016.