Determinants of Gait Parameters in Patients With Severe Hip Osteoarthritis.

OBJECTIVE: To investigate the characteristics and symptoms of patients with hip osteoarthritis that are associated with spatiotemporal gait parameters, including their variability and asymmetry. DESIGN: A retrospective, cross-sectional study. SETTING: University hospital. PARTICIPANTS: The study analyzed the gait analysis data of 155 patients (N=155) with hip osteoarthritis who were admitted to a university hospital for total hip replacement and were able to walk on a treadmill without a handrail. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The dependent variables were gait parameters during treadmill walking. These included gait speed, stride length, cadence, coefficient of variation of stride length and stride time, swing time symmetry index, and step symmetry index. Single and multiple regression analyses were conducted using independent variables of the characteristics and symptoms of the patients, including age, sex, height, pain, leg-length discrepancy, and muscle strength of the affected and normal sides measured with a hand-held dynamometer (iliopsoas, gluteus medius, and quadriceps). RESULTS: In the analysis, gait speed and stride were the dependent variables, whereas age, height, and muscle strength on the affected side were the significant independent variables (P<.05). Additionally, pain demonstrated a marginal association with gait speed (P=.053). Only the leg-length discrepancy correlated with cadence. When the coefficient of variation of the stride length was the dependent variable, age and muscle strength on the affected side were significant. For the swing time symmetry index, only the muscle strength on the affected side was significant. Furthermore, the step symmetry index only correlated with leg-length discrepancy. The muscle strength on the affected side was the only significant independent variable for the coefficient of variation of the stride time. CONCLUSIONS: The results revealed that each of the frequent clinical symptoms of hip osteoarthritis, such as pain, muscle weakness, and leg-length discrepancy, can explain different aspects of gait performance.

Relationship between hip joint proximity area and sagittal balance parameters: an upright computed tomography study.

PURPOSE: A close relationship between sagittal spinal alignment and hip osteoarthritis (OA) has been documented. This study aimed to examine the relationship between hip joint proximity area and sagittal balance parameters in healthy subjects. METHODS: This prospective study enrolled 47 healthy volunteers who underwent 320-detector row upright computed tomography. Acquired data were reconstructed in a virtual three-dimensional space. The proximity area was determined by < 1 mm of the Hausdorff distance between the acetabulum and the femoral head. Volunteers were divided into the anterior and posterior proximity groups depending on the position of the closest area. Sagittal balance parameters [sagittal vertical axis (SVA), T1 spinopelvic inclination (T1-SPi), T1-pelvic angle, pelvic tilt, sacral slope, pelvic incidence, lumbar lordosis, thoracic kyphosis), offset distance between the centre of the acoustic meati (CAM) and C7 plumb line (CAM-C7-offset), and offset distance between the CAM and hip axis (HA) (CAM-HA-offset)] were compared between the two groups using independent sample t test. RESULTS: The anterior proximity group (n = 24) had higher SVA (p = 0.016) and T1-Spi (p = 0.015) than the posterior proximity group (n = 23). CAM-HA-offset was higher in the posterior than in the anterior proximity group (p < 0.000). There was no difference in other parameters (p > 0.05). CONCLUSION: The anterior proximity group had a positive anterior spinal balance; the posterior proximity group may have a more posterior gravity line than the hip joint centre. The anterior spinal balance may contribute to the anterior loading of the hip joint, with known relation with the initiation and onset of hip OA.

Increased migratory activity and cartilage regeneration by superficial-zone chondrocytes in enzymatically treated cartilage explants.

BACKGROUND: Limited chondrocyte migration and impaired cartilage-to-cartilage healing is a barrier in cartilage regenerative therapy. Collagenase treatment and delivery of a chemotactic agent may play a positive role in chondrocyte repopulation at the site of cartilage damage. This study evaluated chondrocyte migratory activity after enzymatic treatment in cultured cartilage explant. Differential effects of platelet-derived growth factor (PDGF) dimeric isoforms on the migratory activity were investigated to define major chemotactic factors for cartilage. METHODS: Full-thickness cartilage (4-mm3 blocks) were harvested from porcine femoral condyles and subjected to explant culture. After 15 min or 60 min of actinase and collagenase treatments, chondrocyte migration and infiltration into a 0.5-mm cartilage gap was investigated. Cell morphology and lubricin, keratan sulfate, and chondroitin 4 sulfate expression in superficial- and deep-zone chondrocytes were assessed. The chemotactic activities of PDGF-AA, -AB, and -BB were measured in each zone of chondrocytes, using a modified Boyden chamber assay. The protein and mRNA expression and histological localization of PDGF-ß were analyzed by western blot analysis, real-time reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry, and results in each cartilage zone were compared. RESULTS: Superficial-zone chondrocytes had higher migratory activity than deep-zone chondrocytes and actively bridged the cartilage gap, while metachromatic staining by toluidine blue and immunoreactivities of keratan sulfate and chondroitin 4 sulfate were detected around the cells migrating from the superficial zone. These superficial-zone cells with weak immunoreactivity for lubricin tended to enter the cartilage gap and possessed higher migratory activity, while the deep-zone chondrocytes remained in the lacuna and exhibited less migratory activity. Among PDGF isoforms, PDGF-AB maximized the degree of chemotactic activity of superficial zone chondrocytes. Increased expression of PDGF receptor-ß was associated with higher migratory activity of the superficial-zone chondrocytes. CONCLUSIONS: In enzymatically treated cartilage explant culture, chondrocyte migration and infiltration into the cartilage gap was higher in the superficial zone than in the deep zone. Preferential expression of PDGF receptor-ß combined with the PDGF-AB dimeric isoform may explain the increased migratory activity of the superficial-zone chondrocytes. Cells migrating from superficial zone may contribute to cartilage regeneration.

Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice.

Skeletal muscle is known to regulate bone homeostasis through muscle-bone interaction, although factors that control this activity remain unclear. Here, we newly established Smad3-flox mice, and then generated skeletal muscle-specific Smad2/Smad3 double conditional knockout mice (DcKO) by crossing Smad3-flox with skeletal muscle-specific Ckmm Cre and Smad2-flox mice. We show that immobilization-induced gastrocnemius muscle atrophy occurring due to sciatic nerve denervation was partially but significantly inhibited in DcKO mice, suggesting that skeletal muscle cell-intrinsic Smad2/3 is required for immobilization-induced muscle atrophy. Also, tibial bone atrophy seen after sciatic nerve denervation was partially but significantly inhibited in DcKO mice. Bone formation rate in wild-type mouse tibia was significantly inhibited by immobilization, but inhibition was abrogated in DcKO mice. We propose that skeletal muscle regulates immobilization-induced bone atrophy via Smad2/3, and Smad2/3 represent potential therapeutic targets to prevent both immobilization-induced bone and muscle atrophy.

Impact of musculoskeletal disorders on healthy life expectancy in Japan.

BACKGROUND: Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. METHODS: Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. RESULTS: There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0-0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1-0.4) and slightly decreased years with activity limitation (0.1-0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3-1.5 years) and decreased years with activity limitation (0.3-1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0-0.8 years) and non-ADL limitations (0.0-0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7-1.1 years) and non-ADL limitations (0.3-0.4). CONCLUSIONS: These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Is Up-Regulated and Involved in Hyaluronan Degradation in Human Osteoarthritic Cartilage.

Hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), also called cell migration-inducing protein (CEMIP; alias KIAA1199), plays a key role in the degradation of HA in skin and arthritic synovial fibroblasts, but its functions in osteoarthritic (OA) cartilage remain elusive. Here, we investigated the expression and roles of HYBID in human OA cartilage. HYBID was highly expressed by chondrocytes in the HA-depleted area of OA cartilage, and HYBID immunoreactivity was correlated with Mankin score, the histopathologic severity of OA lesions of cartilage. Real-time quantitative PCR indicated that HYBID expression was significantly higher in OA cartilage than in control cartilage. In addition, OA chondrocytes exhibited HA-degrading activity, which was abolished by knock-down of HYBID by siRNAs. Although OA chondrocytes also expressed certain levels of hyaluronidases 1 and 2 and CD44, knock-down of these molecules exhibited negligible effects on HA degradation. Double immunostaining of HYBID and clathrin heavy chain revealed that HYBID was localized in the clathrin-coated vesicles, and HA was endocytosed within the vesicles of OA chondrocytes. Among eight factors including cytokines and growth factors examined, only tumor necrosis factor α stimulated OA chondrocytes to overexpress HYBID. These data are the first to demonstrate that HYBID is up-regulated in OA cartilage, and suggest that tumor necrosis factor α-stimulated HYBID plays a role in HA degradation in OA cartilage.

Insulin-like growth factor-I is required to maintain muscle volume in adult mice.

Insulin-like growth factor-I (IGF-I) is a peptide with diverse functions, among them regulation of embryonic development and bone homeostasis. Serum IGF-I levels decline in the elderly; however, IGF-I function in adults has not been clearly defined. Here, we show that IGF-I is required to maintain muscle mass in adults. We crossed Igf-I flox'd and Mx1 Cre mice to yield Mx1 Cre/Igf-Iflox/flox (IGF-I cKO) mice, and deleted Igf-I in adult mice by polyIpolyC injection. We demonstrate that, although serum IGF-I levels significantly decreased after polyIpolyC injection relative to (Igf-Iflox/flox) controls, serum glucose levels were unchanged. However, muscle mass decreased significantly after IGF-I down-regulation, while bone mass remained the same. In IGF-I cKO muscle, expression of anabolic factors such as Eif4e and p70S6K significantly decreased, while expression of catabolic factors MuRF1 and Atrogin-1 was normal and down-regulated, respectively, suggesting that observed muscle mass reduction was due to perturbed muscle metabolism. Our data demonstrate a specific role for IGF-I in maintaining muscle homeostasis in adults.

Laser Resonance Frequency Analysis: A Novel Measurement Approach to Evaluate Acetabular Cup Stability During Surgery.

Artificial joint acetabular cup stability is essential for successful total hip arthroplasty. However, a quantitative evaluation approach for clinical use is lacking. We developed a resonance frequency analysis (RFA) system involving a laser system that is fully contactless. This study aimed to investigate the usefulness of laser RFA for evaluating acetabular cup stability. First, the finite element method was performed to determine the vibration mode for analysis. Second, the acetabular cup was press-fitted into a reamed polyurethane cavity that replicated the human acetabular roof. The implanted acetabular cup was vibrated with pulse laser irradiation and the induced vibration was detected with a laser Doppler vibrometer. The time domain signal from the vibrometer was analyzed by fast Fourier transform to obtain the vibration frequency spectrum. After laser RFA, the pull-down force of the acetabular cup was measured as conventional implant fixation strength. The frequency of the first highest amplitude between 2 kHz and 6 kHz was considered as the resonance peak frequency, and its relationship with the pull-down force was assessed. The peak frequency could predict the pull-down force (R2 = 0.859, p < 0.000). Our findings suggest that laser RFA might be useful to measure acetabular cup stability during surgery.

Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.

Osteoclasts and foreign body giant cells (FBGCs) are derived from common progenitors and share properties such as multi-nucleation capacity induced by cell-cell fusion; however, mechanisms underlying lineage determination between these cells remain unclear. Here we show that, under inflammatory conditions, osteoclasts are stimulated in a manner similar to M1 macrophages, while formation of FBGCs, which exhibit M2-like phenotypes, is inhibited in a manner similar to that seen in M1/M2 macrophage polarization. FBGC/osteoclast polarization was inhibited by conditional knockout of tumor necrosis factor receptor associated factor 6 (Traf6) in adults in vivo and in vitro. Traf6-null mice were previously reported to die soon after birth, but we found that Traf6 deletion in adults did not cause lethality but rather inhibited osteoclast activation and prevented FBGC inhibition under inflammatory conditions. Accordingly, basal osteoclastogenesis was significantly inhibited by Traf6 deletion in vivo and in vitro and accompanied by increased bone mass. Lipopolysaccharide-induced osteoclast formation and osteolysis were significantly inhibited in Traf6 conditional knockout mice. Our results suggest that Traf6 plays a crucial role in regulating M1 osteoclast and M2 FBGC polarization and is a potential therapeutic target in blocking FBGC inhibition, antagonizing osteolysis in inflammatory conditions, and increasing bone mass without adverse effects in adults.

Pelvic Tilt Displacement Before and After Artificial Hip Joint Replacement Surgery.

BACKGROUND: Prediction of pelvic displacement before total hip arthroplasty (THA) is important for accurate acetabular implant placement. This study aimed to evaluate the effect of contralateral joint conditions on pelvic displacement after THA. METHODS: A total of 355 cases that underwent computed tomography before and after THA for osteoarthritis due to developmental dysplasia were assessed. The pelvic plane was based on preoperative and postoperative day 1 computed tomography images. The displacement in the anteversion direction was expressed as +. Subjects with a minimal joint space <2 mm in the contralateral hip joint were in group N; subjects with ≥2 mm were in group W; subjects with THA were in group P; and subjects who underwent THA simultaneously on both sides were in group B. The Bartlett test was used when conducting the equal variance test among the groups. The F test was used for pairwise comparison. A P value <.01 was considered statistically significant. RESULTS: Groups N, W, P, and B had 49, 227, 55, and 24 cases, respectively, and their displacements were -0.2° ± 2.7°, 0.8° ± 3.9°, 0.5° ± 2.6°, and 1.1° ± 4.0°, respectively; the variance between the groups was significantly different (P = .0001). The differences between groups W and N (P = .0020), between groups W and P (P = .0003), and between groups P and B (P = .0086) were statistically significant. CONCLUSION: When the contralateral joint space is wide, the variance of the displacement is high. The contralateral joint affects pelvic displacement.

Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.

Hif1α is required for osteoclast activation and bone loss in male osteoporosis.

The number of osteoporosis patients is increasing not only in women but in men. Male osteoporosis occurs due to aging or androgen depletion therapies, leading to fractures. However, molecular mechanisms underlying male osteoporosis remain unidentified. Here, we show that hypoxia inducible factor 1 alpha (Hif1α) is required for development of testosterone deficiency-induced male osteoporosis. We found that in mice Hif1α protein accumulates in osteoclasts following orchidectomy (ORX) in vivo. In vitro, Hif1α protein accumulated in osteoclasts cultured in hypoxic conditions, but Hif1α protein rather than mRNA levels were suppressed by testosterone treatment, even in hypoxia. Administration of a Hif1α inhibitor to ORX mice abrogated testosterone deficiency-induced osteoclast activation and bone loss but did not alter osteoclast activities or bone phenotypes in sham-operated, testosterone-sufficient animals. We conclude that Hif1α protein accumulation due to testosterone-deficiency promotes development of male osteoporosis. Thus Hif1α protein could be targeted to inhibit pathologically-activated osteoclasts under testosterone-deficient conditions to treat male osteoporosis patients.

Bcl6 promotes osteoblastogenesis through Stat1 inhibition.

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in significant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-deficient mice in vivo. Altered osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.

ADAM17 regulates IL-1 signaling by selectively releasing IL-1 receptor type 2 from the cell surface.

Interleukin (IL)-1 is one of the most evolutionarily conserved cytokines and plays an essential role in the regulation of innate immunity. IL-1 binds to two different receptors, IL-1R1 and IL-1R2, which share approximately 28% amino acid homology. IL-1R1 contains a cytoplasmic domain and is capable of transducing cellular signals; by contrast, IL-1R2 lacks a functional cytoplasmic domain and serves as a decoy receptor for IL-1. Interestingly, IL-1R2 is proteolytically cleaved and also functions as a soluble receptor that blocks IL-1 activity. In the present study, we examined the shedding properties of IL-1R2 and demonstrate that ADAM17 is de facto the major sheddase for IL-1R2 and that introducing a mutation into the juxta-membrane domain of IL-1R2 significantly desensitizes IL-1R2 to proteolytic cleavage. IL-1R1 was almost insensitive to ADAM17-dependent cleavage; however, the replacement of the juxta-membrane domain of IL-R1 with that of IL-1R2 significantly increased the sensitivity of IL-1R1 to shedding. Furthermore, we demonstrate that ADAM17 indirectly enhances IL-1 signaling in a cell-autonomous manner by selectively cleaving IL-1R2. Taken together, the data collected in the present study indicate that ADAM17 affects sensitivity to IL-1 by changing the balance between IL-1R1 and the decoy receptor IL-1R2.

Experimental assessment of a novel intramedullary nail for callus distraction by the segmental bone transport method.

BACKGROUND: Segmental bone transport (SBT) is a revolutionary method for treating extensive bone defects, and it is in wide clinical use. Although external fixation is generally used to perform SBT, it is associated with problems such as complications due to pin placement and limitations of the amount and rate of lengthening. As a way to overcome these problems we developed a novel intramedullary (IM) nail for SBT that minimizes damage to the surrounding tissue and improves the amount and rate of bone lengthening. The purpose of this study was to perform SBT in the femur of beagle dogs using the novel IM nail that we devised, and to evaluate the morphology and quality of the regenerated bone and circulation status in the surrounding tissue. We also considered the possibilities and limitations of the IM in regard to clinical application. METHODS: This experiment was conducted on six beagle dogs. The novel IM nail we devised was inserted into the marrow cavity of the femur, and a 30-mm bone defect was created. After a 7-day postoperative waiting period, a bone segment was transported by 1.0 mm per day in two 0.5-mm increments. Because the nail broke in two dogs, they received only partial elongation by 15 mm over a 15-day period, with a 15-mm defect remaining, whereas full elongation by 30 mm in 30 days was performed in the other four dogs. The elongation was followed by a 30-day bone hardening period. RESULTS: The macroscopic and histological results demonstrated that high-quality, new bone had replaced the 30-mm bone defect created in the femur of all six dogs. The density and number of blood vessels that had penetrated the elongated segment of bone from the surrounding muscles was greater than in the corresponding segment of the contralateral femur, which served as a control. The results imply that the traction stimulus induced vigorous angiogenesis in the surrounding tissue. CONCLUSION: We concluded that this method has tremendous potential for clinical application, and will overcome the limitations of conventional external fixators.

Higher Incidence of Venous Thromboembolism in Anterolateral Approach in Lateral Position Compared to Anterolateral Supine and Direct Anterior Approaches in Minimally Invasive Total Hip Arthroplasty.

INTRODUCTION: Venous thromboembolism (VTE) remains a major complication after total hip arthroplasty (THA), irrespective of the surgical approach. This study investigated the incidence of VTE in patients undergoing THA through intermuscular minimally invasive surgical techniques, which included a direct anterior approach (DAA), an anterolateral approach (AL), and an anterolateral supine approach (ALS), at a single institution. METHODS: A hundred consecutive patients treated with each surgical approach were evaluated. Plasma D-dimer levels one month preoperatively and one day postoperatively, operative time, and intraoperative blood loss were recorded, and the presence of VTE was evaluated based on multidetector-row computed tomography performed the day after surgery. Student's t-test and Pearson's chi-square test or one-way analysis of variance were used in statistical analysis. RESULTS: No differences among the groups in terms of age, height, weight, operative time, intraoperative bleeding, and preoperative and postoperative D-dimer levels were observed. The overall incidence of VTE was 21%. The incidences of VTE were 30% in AL, 17% in ALS, and 16% in DAA, representing a significantly higher rate in AL than in ALS and DAA (P=0.025). The incidences of VTE on the operated side were 19% in AL, 13% in ALS, and 12% in DAA, with no statistically significant differences. The incidences of VTE on the non-operated side were 22% in AL, 9% in ALS, and 8% in DAA; these differences were statistically significant (P=0.0045). DISCUSSION: Results showed that the incidence of VTE was significantly higher in AL than in ALS and DAA, especially for the non-operated side.

Robotic-assisted total hip arthroplasty utilizing a fluoroscopy-guided system produced similar cup accuracy and precision relative to a computerized tomography-based robotic platform.

Robotic assistance for total hip arthroplasty (THA) has been demonstrated to improve accuracy of acetabular cup placement relative to manual, unassisted technique. The purpose of this investigation was to compare the accuracy and precision between a fluoroscopy-based robotic total hip arthroplasty platform (FL-RTHA) and a computerized tomography-based (CT-RTHA) platform. The study included 98 consecutive FL-RTHA and 159 CT-RTHA procedures performed via direct anterior approach (DAA). All cases were performed for a pre-operative diagnosis of osteoarthritis, avascular necrosis, or rheumatoid arthritis. Primary outcome variables included cup implantation accuracy and precision (variance). Implantation accuracy was calculated as the absolute value of the difference between pre-operative target cup angles (inclination and anteversion) and the same post-operative angles. Percentage placement in the Lewinnek safe zone was also measured for both cohorts. The FL-RTHA and CT-RTHA cohorts demonstrated a 1.2° difference in absolute values for cup inclination accuracy (4.6° ± 3.6 vs. 3.4 ± 2.7; p = 0.005), and no difference in absolute values for cup anteversion accuracy (4.7° ± 4.1 vs. 4.6 ± 3.4; p = 0.991). Cohorts demonstrated similar precision for cup inclination and anteversion placement parameters, as well as equivalent Lewinnek safe zone placement. The use of a fluoroscopy-based robotic assistance platform for primary DAA THA resulted in similar accuracy and precision of acetabular cup placement when compared to a CT-based robotic assistance system.

Bezafibrate attenuates immobilization-induced muscle atrophy in mice.

Muscle atrophy due to fragility fractures or frailty worsens not only activity of daily living and healthy life expectancy, but decreases life expectancy. Although several therapeutic agents for muscle atrophy have been investigated, none is yet in clinical use. Here we report that bezafibrate, a drug used to treat hyperlipidemia, can reduce immobilization-induced muscle atrophy in mice. Specifically, we used a drug repositioning approach to screen 144 drugs already utilized clinically for their ability to inhibit serum starvation-induced elevation of Atrogin-1, a factor related to muscle atrophy, in myotubes in vitro. Two candidates were selected, and here we demonstrate that one of them, bezafibrate, significantly reduced muscle atrophy in an in vivo model of muscle atrophy induced by leg immobilization. In gastrocnemius muscle, immobilization reduced muscle weight by an average of ~ 17.2%, and bezafibrate treatment prevented ~ 40.5% of that atrophy. In vitro, bezafibrate significantly inhibited expression of the inflammatory cytokine Tnfa in lipopolysaccharide-stimulated RAW264.7 cells, a murine macrophage line. Finally, we show that expression of Tnfa and IL-1b is induced in gastrocnemius muscle in the leg immobilization model, an activity significantly antagonized by bezafibrate administration in vivo. We conclude that bezafibrate could serve as a therapeutic agent for immobilization-induced muscle atrophy.