Clinical Outcomes Evaluation of Combined Valgus and Chiari Osteotomy Inconsistent with Patient Satisfaction.

The Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire, which is tailored to Japanese lifestyles, has recently been developed in Japan as a patient-reported outcome measure. In this study, combined valgus and Chiari osteotomy were evaluated using the JHEQ and JOA scores. The subjects were 42 hips of 39 patients with a mean age at surgery of 45.3 years. The mean follow-up period was 95.3 months. Radiological osteoarthritis stage, preoperative and postoperative JOA scores, JHEQ score at final follow-up, and patient dissatisfaction with hip joint status rated on a visual analog scale were evaluated. The factors that affected patient dissatisfaction were also identified using multiple regression analysis. Radiological osteoarthritis stage at final follow-up was either maintained or improved in 85.7%. The mean JOA score improved from 57.2 preoperatively to 78.7 at final follow-up. The JHEQ score at final follow-up, however, was low, at 43.3 points. Patients who were comparatively satisfied accounted for 47.6%. Of the JHEQ subscales, movement had the lowest scores, and this was the subscale that had the greatest effect on patient dissatisfaction. The present results suggest that the results of JOA score are inconsistent for postoperative patients' satisfaction after CVCO, and patient-based evaluation tool must also be used.

Double-bundle anterior cruciate ligament reconstruction improves tibial rotational instability: analysis of squatting motion using a 2D/3D registration technique.

BACKGROUND: The anterior cruciate ligament-deficient (ACLD) knee requires appropriate treatment for the patient to return to sports. The purpose of this study was to clarify the kinematics of the anterior cruciate ligament-deficient knee in squatting motion before and after double-bundle anterior cruciate ligament reconstruction (DB-ACLR) using a 2D/3D registration technique. METHODS: The subjects of this study were 10 men with confirmed unilateral ACL rupture who underwent DB-ACLR. Computed tomography (CT) of the knee joints was performed before DB-ACLR. Fluoroscopic imaging of the knee motion in squatting before and after DB-ACLR was also performed. The 2D/3D registration technique is a method of calculating positional relationships by projecting the 3D bone model created from the CT data onto the image extracted from the fluoroscopic images. The tibial anteroposterior (AP) and rotational positions were analyzed with reference to the femur. RESULTS: The tibial AP position of the ACLD knees was significantly anterior to the contralateral knees (p = 0.015). The tibial rotational position of the ACLD knees was significantly internally rotated compared to the contralateral knees (p < 0.001). Both tibial AP and rotational positions improved after DB-ACLR (p < 0.001), with no significant differences compared to the contralateral knees. CONCLUSION: DB-ACLR improved not only tibial AP instability but also tibial rotational instability at knee flexion with weight-bearing. DB-ACLR appears to be a useful technique for normalizing the knee joint kinematics of ACLD knees.

Steroid changes adipokine concentration in the blood and bone marrow fluid.

Our previous study has shown that plasminogen activator inhibitor 1 (PAI-1) gene expression and secretion from bone marrow adipocytes increased markedly with dexamethasone administration. The purpose of the present study was to measure the secretion of various adipokines from human bone marrow and blood, and investigate how adipokine secretion changes in a steroid environment. Human blood and bone marrow fluid were collected from a steroid treatment group and a control group during hip replacement surgery, and an enzyme-linked immunosorbent assay (ELISA) was used to measure the adiponectin, leptin, and PAI-1 levels. Adiponectin and leptin showed no significant differences between bone marrow and blood levels, but PAI-1 was significantly higher in bone marrow. The steroid treatment group had higher levels of leptin and PAI-1 in both the blood and bone marrow than the control group. PAI-1 was present at high concentrations in the bone marrow and increased by steroid treatment. High levels of PAI-1 in bone marrow may influence intraosseous hemodynamics and may induce necrotic bone disorders.

Total Hip Arthroplasty Using the S-ROM-A Prosthesis for Anatomically Difficult Asian Patients.

BACKGROUND: The S-ROM-A prosthesis has been designed for the Asian proximal femur with a small deformed shape and narrow canal. In this study, the clinical and radiological results using the S-ROM-A prosthesis for Japanese patients with severe deformity due to dysplasia and excessive posterior pelvic tilt were examined. METHODS: 94 hips were followed up for a mean of 55 months, with a mean age at surgery of 61 years. The primary diagnoses were 94 coxarthritis cases, including 51 dysplasia and 37 primary OA, 1 avascular necrosis, 2 traumatic arthritis, and 3 Perthes disease. Thirty-one hips had been treated with osteotomy of the hip joints. Preoperative intramedullary canal shapes were stovepipe in 23 hips, normal in 51 hips, and champagne-flute in 5 hips. The maximum pelvic inclination angle was 56°. RESULTS: The mean JOA score improved from 46 points preoperatively to 80 points at final follow-up. On radiological evaluation of the fixation of the implants according to the Engh classification, 92 (97%) hips were classified as "bone ingrown fixation." CONCLUSION: In primary THA, using the S-ROM-A prosthesis for Asian patients with proximal femoral deformity, even after osteotomy and with posterior pelvic tilt, provided good short- to midterm results.

Potentiation of osteoclastogenesis by adipogenic conversion of bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (BMSCs) are the indispensable component of the bone marrow, being the common precursors for adipocytes and osteoblasts. We show here that adipogenic differentiation resulted in increase in the production of adipocyte markers, such as adiponectin,fatty-acid binding proteins (FABP4), peroxisome proliferator-activated receptor γ (PPARγ), as well as the receptor activator of nuclear-κB ligand (RANKL). Co-culture of osteoclast precursors (OCPs) with BMSCs-derived adipocytes significantly enhanced osteoclast differentiation with low-dose RANKL, whose levels alone could not promote osteoclastogenesis. These results demonstrate for the first time that adipogenic differentiation of BMSCs plays a pivotal role in maintaining bone homeostasis.

Primary human bone marrow adipocytes support TNF-α-induced osteoclast differentiation and function through RANKL expression.

PURPOSE: In previous reports, it was demonstrated that bone marrow adipocytes were related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes. METHODS: RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA expression in bone marrow adipocytes and their regulation by TNF-α treatment were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and osteoclast precursors were performed with or without TNF-α, and osteoclast differentiation was evaluated morphologically and functionally. RESULTS: RANKL expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were stimulated by TNF-α treatment. In co-culture of bone marrow adipocytes and osteoclast precursors with TNF-α, the number of TRAP-positive multinuclear cells and resorption cavity formations of calcium phosphate film were increased. Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co-culture with non-cell-contact conditions, no TRAP-positive cells or resorption cavity formations were observed. CONCLUSIONS: TNF-α increased RANKL expression in primary human bone marrow adipocytes. TNF-α induced the ability of bone marrow adipocytes to promote osteoclast differentiation and activity in a manner directly related to RANKL expression.

Simvastatin suppresses dexamethasone-induced secretion of plasminogen activator inhibitor-1 in human bone marrow adipocytes.

BACKGROUND: Osteonecrosis of the femoral head is a common complication of high-dose glucocorticoid treatment. Intravascular thrombosis is thought to be associated with the ischemic state of the femoral head. Plasminogen activator inhibitor-1 (PAI-1) is an adipokine, which are physiologically active substances secreted from visceral and subcutaneous adipocytes. PAI-1 suppresses fibrinolysis by binding tissue-type plasminogen activator. Several reports have described the relationship between PAI-1 and steroid-induced osteonecrosis of the femoral head, and the preventive effects of lipid-lowering agents (statins) against steroid-induced osteonecrosis of the femoral head. We previously reported that adipokines and dexamethasone induced PAI-1 secretion from bone marrow adipocytes. The purpose of the present study is to examine the effects of simvastatin on PAI-1 secretion from human bone marrow adipocytes in vitro. METHODS: Primary bone marrow adipocytes were extracted from collagenase-treated bone marrow fluid obtained from the femoral necks of 40 patients (6 men, 34 women; age range, 52-81 years) undergoing hip joint replacement surgery. After suspended culture with or without dexamethasone or simvastatin, PAI-1 mRNA expression was assessed by real-time RT-PCR. Total PAI-1 protein secretion in culture medium was assessed by enzyme-linked immunosorbent assay. RESULTS: PAI-1 mRNA expression was up-regulated by 388% (P=0.002) with dexamethasone, and down-regulated by 45% (P=0.002) with simvastatin, as compared to control levels. Dexamethasone increased total PAI-1 secretion by 166% (P=0.001) and simvastatin decreased total PAI-1 secretion by 64% (P=0.002). No significant changes were observed in adiponectin mRNA expression and secretion by dexamethasone and simvastatin, while pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion by 89%, as compared to control levels. CONCLUSION: The present study confirmed the suppressive effects of simvastatin on PAI-1 expression and secretion from bone marrow adipocytes. Furthermore, pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion. Simvastatin may thus exhibit preventive effects against steroid-induced osteonecrosis of the femoral head by suppressing PAI-1 secretion.

Human bone marrow adipocytes support dexamethasone-induced osteoclast differentiation and function through RANKL expression.

The TNF-family molecule, Receptor Activator of Nuclear factor κ B Ligand (RANKL) is known as a key regulator for bone remodeling, and is essential for the development and activation of osteoclasts. In this study, we examined the regulation of RANKL in primary human bone marrow adipocytes and the relationship between bone marrow adipocytes and bone metabolism. RANKL expression and the RANKL/osteoprotegerin (OPG) mRNA ratio in marrow adipocytes increased following dexamethasone treatment. In co-cultures of human osteoclast precursors and bone marrow adipocytes with dexamethasone, osteoclast precursors differentiated to TRAP-positive multinuclear cells. Moreover, the ability of bone resorption was confirmed in co-culture in flasks coated with calcium phosphate film. Osteoclast precursor differentiation and bone resorption were blocked by RANKL antibody pretreatment. TRAP-positive multinuclear cells did not form in coculture without cell-to-cell contact conditions. We conclude that primary human bone marrow adipocytes have the ability to promote osteoclast differentiation and activities, similar to osteoblasts and other RANKL-expressing cells.

Dexamethasone-induced plasminogen activator inhibitor-1 expression in human primary bone marrow adipocytes.

Several studies have demonstrated the association of plasminogen activator inhibitor-1 (PAI-1) with osteonecrosis, but the underlying mechanism of osteonecrosis and its relationship with local PAI-1 is not clear. The objective of this study was to evaluate PAI-1 production by primary human bone marrow adipocytes and the effects of glucocorticoid administration. Bone marrow was obtained from 25 individuals during prosthetic insertion. Mature adipocytes were cultured for 24 h with or without dexamethasone. PAI-1, adiponectin, tumor necrosing factor-α (TNFα) expression were measured by latex photometric immunoassay or RT-PCR. Adiponectin, TNFα and PAI-1 were detected in all culture media. PAI-1 expression was significantly increased by treatment with 10(-6) mol/L dexamethasone up to 24 h in protein and mRNA levels, while the levels of other adipokines did not change by dexamethasone. These results suggest that bone marrow adipocytes may play important roles for the development of glucocorticoid-induced osteonecrotic diseases by enhancing PAI-1 expression.

Pentosan reduces osteonecrosis of femoral head in SHRSP.

Increased oxidative stress is considered one of the main causes of steroid-induced osteonecrosis of the femoral head (ONFH). The aim of this study was to evaluate the effects of a steroid hormone and pentosan polysulfate sodium (pentosan), a heparin analog, in stroke-prone spontaneously hypertensive rats (SHRSP) as a model of ONFH. One hundred twenty-three 13-week-old male SHRSP/Izm rats were divided into four groups: a control group (group C), pentosan-administered group (group P), steroid-administered group (group S), and group administered pentosan plus steroid (group PS). Methylprednisolone acetate, as the steroid hormone, at a dose of 4 mg (15 mg/kg) was administered at 15 weeks of age. Pentosan at a dose of 3 mg/day/kg was continuously administered intraperitoneally from 13 weeks of age for 4 weeks. Rats were sacrificed at 17 weeks of age, and heart blood and both femora were collected. Triglyceride levels were significantly lower in group PS than in group S, indicating that pentosan improves lipid metabolism. The incidence of histologic ONFH was significantly lower in group P, at 14.8% (10/71 femoral heads), than in group C, at 30.4% (17/56 femoral heads), and significantly lower in group PS, at 40.8% (29/71 femoral heads), than in group S, at 91.3% (42/46 femoral heads), indicating that pentosan markedly inhibits ONFH. Immunohistochemical staining for oxidative stress showed that the stainability was significantly lower in group PS than in group S. Pentosan seems to reduce the incidence of ONFH in SHRSP by improving lipid metabolism and decreasing oxidative stress.

Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation.

The purpose of this study was to examine the ability of bone marrow adipocytes to support osteoclast differentiation in vitro. The primary bone marrow adipocytes were obtained from bone marrow fluid during prosthesis insertion. NFkappa-B ligand (RANKL), Osteoprotegerin (OPG), and macrophage colony stimulating factor (M-CSF) expressions in bone marrow adipocytes with or without dexamethasone were examined. In a co-culture system with bone marrow adipocytes and osteoclast precursor cells, osteoclast differentiation was assessed by the expression of titrate-resistant acid phosphatase (TRAP) staining. RANKL, OPG, and M-CSF mRNA expressions were confirmed in all individuals. Dexamethasone significantly induced RANKL and OPG expression. The RANKL/OPG ratio was increased by dexamethasone and was significant at 10(-7) M dexamethasone. With 10(-7) M dexamethasone, osteoclast precursor cells differentiated into multinucleated TRAP-positive cells when co-cultured with bone marrow adipocytes. The present study demonstrates for the first time that bone marrow adipocytes can support osteoclast differentiation in vitro.

Osteonecrosis of femoral head in the stroke-prone spontaneously hypertensive rats, especially old rats.

The average life span of stroke-prone spontaneously hypertensive rats (SHRSP) is about eight months. Male SHRSPs at 40 weeks old were used to study the idiopathic osteonecrosis of the femoral head (ION). The control group showed about 40% old necrosis and 20% early necrosis. The group administered with steroid hormone showed an increasing degeneration of adipocyte in the bone marrow, and 20% fresh necrosis was recognized. Furthermore, we observed the adipocyte change as well as early necrosis occurring among old necrosis sites. The study of aged rats may provide further understanding into the pathogenesis of ION.