Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the pathophysiology of SCI by altering microglial responses. The mice were anesthetized with pentobarbital (75 mg/kg i.p.) and were subjected to a contusion injury (70 kdyn) at the 10th thoracic level using an Infinite Horizons Impactor (Precision Systems Instrumentation). For flow cytometry, the samples were stained with the antibodiesand analyzed using a FACS Aria II flow cytometer and the FACSDiva software program (BD Biosciences). We retrospectively identified 528 SCI patients admitted to the Department of Orthopaedic Surgery at the Spinal Injuries Center (Fukuoka, Japan) between June 2005 and May 2011. The patients' data were obtained from their charts. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kB (NF-kB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.
The incidence of osteonecrosis was significantly lower in the anti-vasospasm agent group (32%) than that in the control group (75%). Vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis. A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. It has recently been reported that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) is considered to be involved in the possible pathogenesis of various cardiovascular disorders as well as cerebral vasospasm. We examined the effects of fasudil (Rho-kinase inhibitor), an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits.Summary Statement
Introduction
The objective of this study was to verify the long-term outcome of transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) in young patients with systemic lupus erythematosus (SLE). Consecutive series of 21 symptomatic ONFH patients with SLE (33 hips), aged 20 to 40 years, underwent ARO between 1980 and 1988. We reviewed the cases of 16 patients (25 hips), which represents a 76% rate of follow-up. Patients included 4 men and 12 women who had a mean age of 29 years at the time of surgery. A Kaplan-Meier curve was used for the survivorship analysis of ARO. Patients with surviving hips were evaluated by the modified Oxford hip score and the Medical Outcomes Study Short Form 36 (SF-36).Introduction
Methods
Transtrochanteric curved varus osteotomy is one of the effective joint-preserving operations for osteonecrosis (ON) of the femoral head. We correlated various factors with the radiological outcome of this procedure. We reviewed 74 hips in 63 patients who had a minimum follow-up of 5 years after transtrochanteric curved varus osteotomy for the treatment of ON. There were 28 men and 35 women who had a mean age of 33 years (range, 15 to 68 years) at the time of surgery. Clinical assessment was made based on the Harris hip score (HHS). Radiographically, we investigated various factors; affected lesion, stage and type (localization of the necrotic lesion) of ON, varus degree, post-operative intact ratio, progression of collapse, and joint-space narrowing. On the basis of postoperative radiographs, the hips were divided into 2 groups (Group I: either the progression of collapse or joint-space narrowing, Group II: neither progression of collapse or joint-space narrowing). The related factors with radiological outcome were analyzed by using multivariate analysis (Stepwise discriminant analysis).Introduction
Methods
Subchondral insufficiency fracture of the femoral head (SIF) is a recently proposed concept. It is generally seen in elderly people, however, some young adults have also been reported to suffer from this fracture. The purpose of this study was to investigate the clinical results of a transtrochanteric anterior rotational osteotomy (ARO) performed in young adults with SIF. This study focused on young SIF cases (age range from 10 to 29 years). Five patients were diagnosed to have SIF at our institution and conservative treatment was initially performed. The symptoms resolved in 1 case while the other 4 cases showed progression of a collapse. In these 4 cases, ARO was performed, since the fractured area was located in the anterosuperior portion of the femoral head. The average age of the patients was 22 years (range, 16 to 29 years) at the time of surgery, consisting of 2 men and 2 women.Introduction
Methods
Subchondral insufficiency fracture of the femoral head (SIF) often occurs in osteoporotic elderly patients. Patients usually suffer from acute hip pain without any obvious antecedent trauma. Radiologically, a subchondral fracture is seen mainly in the superolateral portion of the femoral head. The T1-weighted magnetic resonance (MR) images show a low-intensity band in the subchondral area of the femoral head, which tends to be irregular, disconnected, and convex to the articular surface. This low-intensity band in SIF was histologically proven to correspond to the fracture line with associated repair tissue. Some cases of SIF resolve after conservative treatment, while others progress until collapse, thereby requiring surgical treatment. The prognosis of SIF remains unclear. This study investigated the risk factors that influence the prognosis of SIF based on the progression of the collapse. Between June 2002 and June 2008, seventeen patients diagnosed as SIF were included in this study. Sequential radiographs were evaluated for the presence of progression of the collapse. The clinical profiles, including the age, body mass index (BMI), follow-up period and Singh index were examined. The morphological characteristics of the low intensity band on the T1-weighted magnetic resonance images were also examined, with regard to the band length, band thickness and band length ratio; which is defined as a proportion of the band length to the weight-bearing portion of the femoral head.Introduction
Methods
Subchondral insufficiency fracture (SIF) needs to be differentiated from osteonecrosis. The purpose of this study was to evaluate the imaging and histopathological findings of patients 60 years or older with radiological evidence of subchondral collapse of the femoral head. We reviewed 77 consecutive hips in 56 patients aged 60 years or older, which showed subchondral collapse on radiographs. According to the shapes of low-intensity bands on T1-weighted images of magnetic resonance imaging (MRI), the patients were divided into 2 groups. Group A showed a concavity of the articular surface: characteristic appearances of osteonecrosis, and Group B showed an irregular convexity of the articular surface: characteristic appearances of SIF.Introduction
Methods
The objective of this study was to investigate the incidence of steroid-induced osteonecrosis (ON) among male and female rabbits. Forty-seven adult rabbits (male, n = 24; female, n = 23) were injected once intramuscularly into the right gluteus medius muscle with 20 mg/kg of methylprednisolone acetate. Hematological examinations were performed just before and at 1 and 2 weeks after the corticosteroid injection. Two weeks after the injection, both femora and humeri were histopathologically examined for the presence of ON, and the bone marrow fat cells were examined morphologically.Introduction
Methods
We have studied the effect of hydroxyapatite (HA) coating in 15 ovariectomised and 15 normal rats which had had a sham procedure. Twenty-four weeks after operation, HA-coated implants were inserted into the intramedullary canal of the right femur and uncoated implants into the left femur. The prostheses were removed four weeks after implantation. Twelve specimens in each group had mechanical push-out tests. Sagittal sections of the other three were evaluated by SEM. The bone mineral density (BMD) of the dissected left tibia was measured by dual-energy x-ray absorptiometry. The difference in BMD between the control and ovariectomised tibiae was 35.01 mg/cm2 (95% CI, 26.60 to 43.42). The push-out strength of the HA-coated implants was higher than that of the uncoated implants in both groups (p <
0.0001), but the HA-coated implants of the ovariectomised group had a reduction in push-out strength of 40.3% compared with the control group (p <
0.0001). Our findings suggest that HA-coated implants may improve the fixation of a cementless total hip prosthesis but that the presence of osteoporosis may limit the magnitude of this benefit.
