Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

Safety and feasibility of in-hospital autonomous transportation using a driverless mobility for patients with musculoskeletal disorders: preliminary clinical study to achieve mobility as a service in medical care.

BACKGROUND: Recent advancements in and the proliferation of autonomous mobility technology, such as intelligent wheelchairs, have made it possible to provide mobility services for patients with reduced mobility due to musculoskeletal disorders. In the present study, we conducted a preliminary clinical study to assess the safety and feasibility of in-hospital autonomous transportation using a driverless mobility (wheelchair) for patients with musculoskeletal disorders. METHODS: From January to February 2022, 51 patients with musculoskeletal disorders exhibiting gait disturbance who presented to our institution were included in the present study. Driverless mobility rides were conducted over a straight-line distance of 100 m from the orthopaedic outpatient reception to the payment counter after the outpatient consultation. We assessed the quality of life using an EQ-5D-5 L index and pain using a VAS score before riding the mobility to investigate the patient's condition. After the ride, a questionnaire survey was conducted to assess patient satisfaction on a 5-point scale. In addition, adverse events during the mobility ride were investigated. RESULTS: Overall satisfaction levels showed that 44 out of 51 (86%) patients rated the level as 3 or higher. There were no significant differences in the level of satisfaction based on the cause of disorders or EQ-5D-5 L Index. Among 19 patients who rated the level of satisfaction as 2-3, the ratio of postoperative patients and those with pain tended to be higher (p < 0.05). While 26 of 51 (51%) patients reported moments of feeling unsafe during the mobility ride, no actual adverse events, such as collisions, were observed. CONCLUSIONS: An in-hospital autonomous transportation service using a driverless mobility for patients with musculoskeletal disorders demonstrated high satisfaction levels and was safe with no severe adverse events observed. The expansion of autonomous mobility deployment is expected to achieve mobility as a service in medical care.

Effect of platelet-rich plasma on the acceleration of graft bone catabolism in lateral lumbar interbody fusion in a short-term assessment.

This study aimed to demonstrate whether impregnating the graft bone with platelet-rich plasma (PRP) accelerates graft bone catabolism in lateral lumbar interbody fusion (LLIF). Consecutive patients who underwent LLIF were assessed. Of the two spaces for bone grafts in the intervertebral cage, one space was filled with graft bone impregnated with PRP, and the other was filled with graft bone without PRP, which divided the graft bones into PRP and non-PRP groups. The mean Hounsfield units (HU) of the graft bone at the center of the cage space in the coronal and axial slices were measured using computed tomography (CT) images 1 week and 6 months after surgery. The delta value of HU from 1 week to 6 months after surgery was calculated for the PRP and non-PRP groups. We compared the delta values of the HU between the two groups. The PRP and non-PRP groups comprised 16 bone grafts. In the coronal slices, the HU value in the PRP group (delta value: 526.1 ± 352.2) tended to have a greater decrease at 6 months after surgery compared with that in the non-PRP group (delta value: 217.6 ± 240.4) (p = 0.065). In the axial slices, the HU value in the PRP group (delta value: 501.3 ± 319.6) was significantly decreased at 6 months after surgery compared with that in the non-PRP group (delta value: 159.2 ± 215.3) (p = 0.028). Impregnating the graft-bone with PRP accelerated graft bone catabolism in LLIF within 6 months after surgery.

Joint effusion at 3 months after anterior cruciate ligament reconstruction is associated with reinjury.

PURPOSE: To evaluate whether joint effusion at 3 months after anterior cruciate ligament (ACL) reconstruction is associated with ACL reinjury. METHODS: The medical records of 227 consecutive patients who underwent single-bundle ACL reconstruction between 2015 and 2018 were reviewed in this retrospective single-center study. Demographic data such as sex and age at surgery, as well as data on preinjury Tegner activity scale score, time from injury to surgery, presence of meniscus and cartilage injuries, and the occurrence of ACL reinjury within 2 years, were collected. Joint effusion was defined as grade 3 (range 0-3) according to the ACL Osteoarthritis Score by magnetic resonance imaging at 3 months postoperatively. Multivariate logistic regression analysis was performed to control for potential confounders. RESULTS: A total of 176 patients (mean age 22.5 ± 9.9 years) were included. Among these patients, 18 (10.2%) had ACL reinjury. At the multivariate logistic regression analysis, higher Tegner activity scale (odds ratio [OR] 3.12; 95% confidence interval [CI] 1.61-6.04; p < 0.001) and presence of joint effusion (OR 34.5; 95% CI 6.63-179.7; p < 0.001) increased the odds of ACL reinjury, and older age (OR 0.68; 95% CI 0.51-0.92; p = 0.012) decreased the odds of ACL reinjury. CONCLUSIONS: Joint effusion with a larger fluid volume at 3 months postoperatively was one of the risk factors for ACL reinjury independent of confounders, such as age and activity level. This result suggests the possibility of postoperative intervention for ACL reinjury. LEVEL OF EVIDENCE: III.

An exploratory clinical trial for concentrated autologous bone marrow aspirate transplantation in the treatment of osteonecrosis of the femoral head.

PURPOSE: This study evaluated the efficacy and safety of a novel treatment for osteonecrosis, in which concentrated autologous bone marrow aspirate transplantation (CABMAT) is followed by low-intensity pulsed ultrasound (LIPUS) stimulation for 3 months. The study was designed as a prospective, uncontrolled, open-label phase II clinical study. METHODS: This study included 16 cases of osteonecrosis of the femoral head (ONFH), including 26 hips. Patients were transplanted with concentrated bone marrow and periodically evaluated for infection and neoplasm development. Moreover, clinical and radiological examinations were conducted to confirm the treatment efficacy. RESULTS: No infections were observed during the course of this study nor tumours developed at the treatment site 24 months after transplantation. At a mean 48 (30-56) months post-transplantation, the onset or progression of collapse was noted in four hips, of which one hip underwent total hip arthroplasty. CONCLUSION: Treatment with CABMAT combined with 3-month LIPUS stimulation was safe, and further randomised clinical studies are needed to determine the efficacy and feasibility of this treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000020940, 9/2/2016).

Characterization of bone remodeling of two different porous types of ß-tricalcium phosphates: a quantitative site-by-site analysis using computed tomography.

This study compared the process of bone remodeling using spherical porous ß-tricalcium phosphate (SPTCP) and unidirectional porous ß-tricalcium phosphate (UDPTCP) by quantitative computed tomography (CT) analysis. We retrospectively analyzed the data of 16 patients (4 men, 12 women; age, 43-78 years) who underwent medial opening wedge high tibial osteotomy (MOWHTO) and were followed up for 1 year postoperatively. Nine patients used SPTCP spacers and seven patients used UDPTCP spacers. CT was performed at 1 week, 6 months, and 1 year postoperatively. CT attenuation values were measured at three sites on the axial slice and sagittal slice, i.e., the superior, center, and inferior sites and the lateral, center, and medial sites for UDPTCP and SPTCP, respectively. CT attenuation values were lower for UDPTCP than for SPTCP in all sites at 6 months and 1 year postoperatively (p < 0.05). CT attenuation values decreased in the superior and inferior sites for UDPTCP (p < 0.05), and CT attenuation values decreased in the lateral site for both SPTCP and UDPTCP (p < 0.05). The process of bone remodeling differed between the two over a short-term follow-up of 1 year postoperatively.

Unidirectional porous beta-tricalcium phosphate and hydroxyapatite artificial bone: a review of experimental evaluations and clinical applications.

In Japan, where allograft bone transplantation is not widespread, prospects for artificial bones are very high. Therefore, artificial bones with various compositions, porous structures, and porosities have been developed and employed for clinical use. Both Affinos® and Regenos® (made of beta-tricalcium phosphate and hydroxyapatite, respectively) are artificial bones with a unique unidirectional porous structure, in which pores with a diameter suitable for tissue penetration (25-300 µm) are aligned in one direction. The unidirectional porous structure allows rapid penetration of blood deep into the materials by a capillary effect. In animal experiments, Affinos® showed well-balanced resorption and was replaced with the host's own bone from an early stage after implantation and new bone formation and remodeling were observed in the cortical bone and medullary cavity. When implanted for clinical situation, resorption from an early stage and good replacement with the patient's own bone were also observed. Regenos® has an internal osteon-like material and a vascular-like structure that is maintained within the pores even after long-term implantation, as noted in an animal experiment. When implanted for clinical situation, good osteoconductivity was observed from an early stage of implantation. In addition, the material was observed to be slowly absorbed over time in some cases. We have discussed the beneficial effects of combining teriparatide and platelet-rich plasma impregnation and the potential prospects of these artificial bones.

Rehabilitation training using a single-joint type hybrid assistive limb for the knee after anterior cruciate ligament reconstruction: an initial case report indicating safety and feasibility.

[Purpose] The aim of this report was to describe the safety, feasibility, and efficacy of rehabilitation by knee extension and flexion training using the knee single-joint hybrid assistive limb in a patient after anterior cruciate ligament reconstruction. [Participant and Methods] A 33 year-old male underwent an arthroscopic procedure for anatomic single-bundle anterior cruciate ligament reconstruction with a semitendinosus tendon autograft. Rehabilitation training using the knee single-joint hybrid assistive limb was initiated at postoperative week 18 and repeated weekly for 3 weeks. The patient performed five sets of the knee single-joint hybrid assistive limb-assisted knee-extension-flexion exercises per session at a frequency of 10 exercises/set. [Results] The peak extension torque at all velocities with the limb symmetry index was higher after the hybrid assistive limb intervention (post-intervention) than before using it (pre-intervention). Peak flexion torques at 60°/s and 300°/s of limb symmetry index were higher post-intervention than pre-intervention. The range of motion in extension and flexion improved from -2° (pre-intervention) to -1° (post-intervention) and from 124° to 133°, respectively. The Lysholm score increased from 58 (pre-intervention) to 94 (post-intervention). [Conclusion] The knee single-joint hybrid assistive limb can be used safely for anterior cruciate ligament reconstruction training, without any adverse events. Our results indicate that the knee single-joint hybrid assistive limb training may improve muscle function, effectively overcoming dysfunction.

Posterolateral lumbar spine fusion with unidirectional porous beta-tricalcium phosphate in a canine model.

We investigated the use of the autologous iliac bone and unidirectional porous beta-tricalcium phosphate (UDPTCP) in posterolateral lumbar spine fusion (PLF). Ten canine PLF models were prepared. Using only the autologous bone as the control group, 100%, 75%, 50%, and 25% groups were prepared according to the mixing ratios of UDPTCP. Radiological evaluation and histological analysis were performed 12 weeks after surgery. Bone fusion was evaluated according to anteroposterior plain X-rays and coronal reconstruction CT views using four grades: 0 = no osteogenesis, 1 = only slight discontinuous osteogenesis between transverse processes, 2 = discontinuous osteogenesis between transverse processes, and 3 = continuous osteogenesis between transverse processes. Bone fusion determined by X-ray was 2.8 ± 0.5 in the control group, 0 in the 100% UDPTCP group (p = 0.02), 1.8 ± 0.5 (p = 0.03) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. The bone fusion score was significantly lower in the 75% and 100% UDPTCP groups than in the control group. Bone fusion determined by CT was 2.8 ± 0.5 in the control group, 1.0 ± 0.8 (p = 0.01) in the 100% UDPTCP group, 2.0 ± 0.0 (p = 0.02) in the 75% UDPTCP group, 2.5 ± 0.6 (p = 0.54) in the 50% UDPTCP group, and 2.8 ± 0.5 (p = 1.0) in the 25% UDPTCP group. Similar to the bone fusion determination by X-ray, the bone fusion score was significantly lower in the 75% and 100% UDPTCP groups. These data suggest that, in a canine PLF model, the appropriate mixing ratio of UDPTCP is 50% or less.

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study.

BACKGROUND: Idiopathic osteonecrosis of the femoral head (ONFH) occurs at a relatively younger age. It is therefore important to prevent the resultant femoral head collapse and requirement of total hip arthroplasty in these patients. In 2003, we initiated concentrated autologous bone marrow aspirate transplantation (CABMAT), a joint-preserving treatment for ONFH, at our institution. Here, we report the long-term results of CABMAT treatment. METHODS: We retrospectively collated and analyzed the demographic and treatment data of 69 patients (109 hips) with idiopathic ONFH treated with CABMAT between April 2003 and April 2008. RESULTS: Totally, 44 patients (21 men, 23 women, 80 hips) completed the 10-year follow-up. The follow-up rate was 73.4%, and the mean follow-up period was 12.0 (range, 10.0-15.4) years. The mean age of the patients was 42.2 (range, 16.3-70.5) years. Using the Association Research Circulation Osseous (ARCO) classification system for preoperative analysis, 12, 31, 32, and 5 hips were classified as stages 1, 2, 3, and 4, respectively. The overall rate of conversion to total hip arthroplasty (THA) was 34% (27/80 hips). In a multivariate regression analysis, the preoperative stage of ONFH and the body mass index were found to correlate significantly with conversion to THA. Totally, 43 hips (of 80) were classified as belonging to the pre-collapse stage (i.e., stages 1 or 2). The overall collapse rate and the THA-conversion rate of these hips were estimated to be 49% (21/43) and 14% (6/43), respectively. CONCLUSIONS: On the basis of our long-term findings, the minimally invasive and feasible CABMAT therapy can be utilized as one of a joint-preserving treatment for ONFH.

Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial.

Intra-articular platelet-rich plasma (PRP) injection has been found to be effective for treating osteoarthritis in patients from Western countries; however, the safety and efficacy of PRP have not been sufficiently investigated in Japanese patients. The present study aimed to evaluate the safety and feasibility of intra-articular PRP injection in Japanese patients with knee osteoarthritis. PRP without white blood cells was prepared using a single-spin centrifuge (PRGF-Endoret; BTI Biotechnology Institute, Vitoria, Spain). A 6-mL PRP volume was injected in the knee joint three times at 1 week intervals. All patients were prospectively evaluated before intervention and at 1, 3, and 6 months after the treatment. Adverse events, the Visual Analog Scale (VAS) pain score, Japanese Knee Osteoarthritis Measure (JKOM) score and Japanese Orthopedic Association score were evaluated. Ten patients (all women; average age, 60.6 years) were treated. Only minor adverse events after injection were noted, and symptoms resolved within 48 hours after the injection. The average VAS pain scores were 71.6 mm and 18.4 mm at baseline and the 6-month follow-up, respectively (P < 0.05). At the 6-month follow-up, 80% of patients had a decrease in the VAS pain score of 50% or more. The average JKOM scores were 35.2 and 14.3 at baseline and at the 1-month follow-up, respectively (P < 0.05). Intra-articular PRP injection likely represents a safe treatment option for Japanese patients with mild-to-moderate knee osteoarthritis, and has the potential to relieve pain for up to 6 months, but further study is needed to verify the efficacy.

Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: An experimental study in the rabbit model.

This study aimed to evaluate the nerve regenerative effect and behavior of Schwann cells (SCs) on local administration of autologous platelet-rich plasma (PRP). METHODS: Twenty-eight Japanese white rabbits were used. A 15-mm sciatic nerve defect was created on the left limb. The resected nerve was used as a reverse autologous nerve. The rabbits were randomly divided into two groups. In group A (n = 10), only nerve grafting was performed. In group B (n = 18), nerve grafting was performed with local PRP administration. Right limbs were used as control (group C, n = 28). The rabbits in each group were equally divided into two subgroups based on the evaluation period of 4 and 12 weeks after grafting. Electrophysiological evaluation, muscle wet-weight, histological evaluation, and multiple immunofluorescence staining were performed to investigate the regenerative effect of PRP. RESULTS: The mean regenerative axon diameter of the graft portion in group B (2.02 ± 0.22-µm) was significantly larger than that in group A (1.89 ± 0.16-µm) at 4 weeks. The regenerative axon number at the distal portion showed a greater increase in group B (9017 ± 2224/mm2 ) than in group A (4955 ± 3117/mm2 ) at 12 weeks. Electrophysiological evaluation and muscle wet-weight revealed no significant differences. On immunohistological evaluation, the number of activated SCs increased to a larger extent in group B (188 ± 90/mm2 ) than in group A (117 ± 51/mm2 ). CONCLUSIONS: Local PRP administration increases the regenerative axon diameter and the regenerative axon number at the distal portion. PRP accelerates SC proliferation in vivo.

Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

PURPOSE: We had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). This study aimed to evaluate the effects of CABMAT as a hip-preserving surgical approach, preventing conversion to total hip arthroplasty (THA) and femoral head collapse in patients with systemic lupus erythematosus (SLE). METHODS: Since 2003, 52 SLE patients (8 male, 44 female, 92 hips, mean age 35.3 (16-77) (years) were treated with CABMAT. The mean follow-up period was 5.5 (0.7-14) years. Conversion rate to THA and its predicting factors were analyzed. RESULTS: The overall conversion rate to THA was 29% (27/92). Conversion rate to THA was 0% (0/3), 0% (0/4), 22% (9/41), and 41% (18/44) in types A, B, C1, and C2, respectively. Conversion rate to THA was 26% (5/19), 26% (6/23), 28% (11/39), 44% (4/9), and 50% (1/2) in stages 1, 2, 3A, 3B, and 4, respectively. In multivariate logistic regression analysis, sex, body mass index (BMI), pre-operative type, and pre-operative stage were significantly correlated with conversion to THA. CONCLUSION: The conversion rate to THA was lower than that in the natural course and core decompression, but was higher than that seen in other bone marrow transplantation and osteotomy. Since sex, pre-operative type, and pre-operative stage were significantly correlated with conversion to THA, it is suggested that the higher proportion of women, advanced stage (stage 3A or above), and advanced type (type C or above) in this study affected the THA conversion rate.

SDF-1 improves wound healing ability of glucocorticoid-treated adipose tissue-derived mesenchymal stem cells.

Glucocorticoids cause the delayed wound healing by suppressing inflammation that is required for wound healing process. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) play an important role for wound healing by their cytokine productions including stromal derived factor 1 (SDF-1). However, it has not been clear how glucocorticoids affect the wound healing ability of AT-MSCs. In this study, we found that glucocorticoid downregulated SDF-1 expression in AT-MSCs. In addition, glucocorticoid-treated AT-MSCs induced less migration of inflammatory cells and impaired wound healing capacity compared with glucocorticoid-untreated AT-MSCs. Of note, prostaglandin E2 (PGE2) synthesis-related gene expression was downregulated by glucocorticoid and PGE2 treatment rescued not only SDF-1 expression in the presence of glucocorticoid but also their wound healing capacity in vivo. Furthermore, we found SDF-1-overexpressed AT-MSCs restored wound healing capacity even after treatment of glucocorticoid. Consistent with the results obtained from glucocorticoid-treated AT-MSCs, we found that AT-MSCs isolated from steroidal osteonecrosis donors (sAT-MSCs) who received chronic glucocorticoid therapy showed less SDF-1 expression and impaired wound healing capacity compared with traumatic osteonecrosis donor-derived AT-MSCs (nAT-MSCs). Moreover, the SDF-1 level was also reduced in plasma derived from steroidal osteonecrosis donors compared with traumatic osteonecrosis donors. These results provide the evidence that concomitant application of AT-MSCs with glucocorticoid shows impaired biological modulatory effects that induce impaired wound healing.

Hip preserving surgery with concentrated autologous bone marrow aspirate transplantation for the treatment of asymptomatic osteonecrosis of the femoral head: retrospective review of clinical and radiological outcomes at 6 years postoperatively.

BACKGROUND: We had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). The present study aimed to evaluate the effects of CABMAT as a hip preserving surgical approach, preventing femoral head collapse in asymptomatic ONFH. METHODS: In total, 222 patients (341 hips) with ONFH were treated with CABMAT between April 2003 and March 2013. Based on magnetic resonance imaging, we determined that 119 of these patients had bilateral asymptomatic ONFH (238 hips), and 38 further patients had unilateral asymptomatic ONFH (38 hips). In this series, we retrospectively examined 31 hips in 31 patients with unilateral asymptomatic ONFH treated surgically between 2003 and 2012 and followed up for more than 2 years. Clinical and radiological evaluation were performed immediately before the procedure and at the final follow-up. The two-year follow-up rate among patients with unilateral ONFH was 82% (31/38). Therefore, the present study included 31 patients (19 males and 12 females), with a mean age and follow-up period of 40 and 5.8 years, respectively. Of the 31 asymptomatic hips, 5, 6, 10, and 10 had osteonecrosis of types A, B, C1, and C2, respectively. The diagnosis, classification, and staging of ONFH were based on the 2001 Japanese Orthopaedic Association (JOA) classification. RESULTS: Secondary collapse of the femoral head was observed in 6/10 hips and 5/10 hips with osteonecrosis of types C1 and C2, respectively. Total hip arthroplasty was performed in 9.6% of patients (3/31 hips), at an average of 33 months after surgery. Clinical symptoms improved after surgery, and the secondary collapse rate at a mean of 5.8 years after CABMAT was lower than that reported in several previous studies on the natural course of asymptomatic ONFH. CONCLUSIONS: Early diagnosis of ONFH (i.e., before femoral head collapse) and early intervention with CABMAT could improve the clinical outcome of corticosteroid and alcohol-induced ONFH.

Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis.

BACKGROUND AIMS: Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model. METHODS: The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy. RESULTS: The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells. CONCLUSION: These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling.

The safety and efficacy of combined autologous concentrated bone marrow grafting and low-intensity pulsed ultrasound in the treatment of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is commonly treated with total hip arthroplasty; however, the disadvantages of this form of treatment, especially in young patients, include the need for revision arthroplasty. Here we describe a novel, combined approach to the treatment of ONFH based on autologous concentrated bone marrow grafting and low-intensity pulsed ultrasound (LIPUS). The 7 male and 7 female patients (mean age: 40 years; 22 hips) underwent autologous concentrated bone marrow grafting followed by 6 months of continuous LIPUS. The mean follow-up period was 26 months. We evaluated site-specific bacterial infection of the grafted bone marrow concentrate microbiologically and site-specific cancer by magnetic resonance imaging 24 months after grafting. All patients were assessed using the visual analogue scale (VAS) for pain and the Japanese Orthopedic Association (JOA) hip score. Clinical and plain radiographic evaluations were performed before grafting and at the most recent follow-up. Computed tomography (CT) scans were obtained before and 12 months after grafting. None of the grafted bone marrow concentrates were infected, and none of the patients developed a tumor at the treatment site. The VAS and JOA scores improved in all patients. Collapse progressed in 8 of the 22 hips, but none required total hip arthroplasty. The mean volume of new bone formation 12 months post-grafting as seen on CT was 1256 mm(3). New bone formation was observed in all patients. Our study demonstrates the safety and efficacy of autologous concentrated bone marrow grafting and LIPUS as a joint-preserving procedure for patients with ONFH.

Circadian variation of growth factor levels in platelet-rich plasma.

OBJECTIVE: The influence of circadian rhythms has recently been considered in advanced studies of chronopharmacology and chronotherapeutics. Although emerging studies have reported the usefulness of platelet-rich plasma (PRP), no reports have described the diurnal variations in PRP growth factor levels. In the present study, we hypothesized that growth factor levels in PRP show a significant diurnal variation. DESIGN: Controlled laboratory study. SETTING: Institutional. PARTICIPANTS: Ten adult male volunteers (mean age, 30.0 ± 2.6 years; range, 26-34 years). INTERVENTIONS: Each subject donated a 20-mL sample of fasting blood, 4 times per day (7 AM, 11 AM, 3 PM, and 7 PM). MAIN OUTCOME MEASURES: Each blood sample was processed to produce PRP. Complete blood counts of peripheral blood (PB) and PRP, as well as quantitative determination of PRP growth factor levels (platelet-derived growth factor and transforming growth factor) were performed. Statistical analyses were conducted using a one-way repeated measures analysis of variance. RESULTS: No significant differences were observed in platelet, white blood cell, and red blood cell counts in the PB or in the PRP samples throughout the course of the day. In addition, there were no significant differences in PRP growth factor levels at the various time points. CONCLUSIONS: Significant diurnal variations in platelet counts and growth factor levels were not observed in PRP. Therefore, adjustments for diurnal variation in chronotherapy may not be important when PRP is used in clinical practice.

Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion.

The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262-27,392) mm3 total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.

Single-Joint Type Hybrid Assistive Limb for Knee Training in the Acute Postoperative Phase After Opening Wedge High Tibial Osteotomy: A Feasibility and Safety Trial.

BACKGROUND AND OBJECTIVE: Opening wedge high tibial osteotomy (OWHTO) influences the knee extensor mechanism, the range of passive motion of knee extension and persistent quadriceps, and anterior knee pain and weakness. Rehabilitation should focus on quadriceps strength and improving joint mobility. The single-joint hybrid assistive limb device (HAL-SJ) is a wearable exoskeleton cyborg. In this study, we investigated the feasibility and safety of HAL-SJ training after the early postoperative period following OWHTO and whether the use of this device can improve functional outcomes, including knee muscle extensor strength and knee extension range of motion without knee pain. METHODS: Patients who had been diagnosed with knee osteoarthritis and had undergone OWHTO were assessed for eligibility in this prospective trial conducted at our institution between June 2015 and November 2020. The participants were split into two groups, i.e., 10 patients in the hybrid assistive limb (HAL) group and eight patients in the control group. We initiated HAL-SJ therapy on postoperative day 8 and continued it until the patient's discharge. During the hospitalization period, patients engaged in HAL-SJ-assisted knee extension exercises. This exercise routine encompassed five sets, each comprising 10 repetitions, and was conducted twice a week. We conducted assessments aimed at detecting any potential adverse events that could be linked to HAL training. Assessment of the knee extension angle via the visual analog scale (VAS) and strength assessments using a hand-held dynamometer (HHD) were conducted. To compare clinical outcomes before and after OWHTO, knee extension angle, the VAS, HHD, Japanese Orthopaedics Association (JOA) score, and the Japanese Knee Osteoarthritis Measure (JKOM) were assessed at four distinct time points. RESULTS: No adverse events were observed during the study. The assessment of clinical outcomes before and after OWHTO demonstrated a gradual improvement in outcomes. CONCLUSION: The single-joint hybrid assistive limb device in patients who underwent OWHTO appears to be potentially safe. It contributed to enhanced muscle activity efficiency by reducing knee pain and improving knee extension angles in the early postoperative phase.