Kenyu Iwasaki

Prognostic factors associated with a subchondral insufficiency fracture of the femoral head.

OBJECTIVE The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF). METHODS Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singhs index, were documented. The morphological characteristics of the low-intensity band on T(1) weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre). RESULTS Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values. CONCLUSION These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF.

Radiologic Measurements Associated With the Prognosis and Need for Surgery in Patients With Subchondral Insufficiency Fractures of the Femoral Head

OBJECTIVE The objective of this study was to identify the risk factors associated with the prognosis and need for surgery of patients with subchondral insufficiency fractures of the femoral head. MATERIALS AND METHODS Twenty-nine consecutively registered patients with subchondral insufficiency fractures of the femoral head were divided into the two groups: a non-progression of collapse group, which included patients who had no collapse or 2 mm or less of collapse of the femoral head and whose symptoms resolved (14 patients), and a progression of collapse group, which included patients who had more than 2 mm of collapse, for which surgery was indicated (15 patients). Both groups received the same conservative therapy. The following radiographic measurements were obtained: Sharp angle, center edge angle, acetabular roof angle, and acetabular head index. On MR images, band length, defined as the length of a low-signal-intensity band in the coronal plane, and band length ratio, defined as the proportion of the band length relative to the weight bearing portion, were assessed for each patient. Bone mineral density measurements (T score) were available for 17 patients. RESULTS In the univariate analyses, T score, Sharp angle, center edge angle, acetabular roof angle, acetabular head index, band length, and band length ratio were found to be significant prognostic factors. Multivariate analyses of T score, acetabular head index, and band length ratio showed that both acetabular head index and band length ratio were significant predictors. CONCLUSION Both acetabular head index and band length ratio are important prognostic factors in the care of patients with subchondral insufficiency fractures of the femoral head.

Bone and cartilage metabolism markers in synovial fluid of the hip joint with secondary osteoarthritis

OBJECTIVE The aim of this study was to compare the levels of bone and cartilage metabolism markers in the synovial fluid of the hip joint between patients with secondary OA due to osteonecrosis of the femoral head (ONFH), rapidly destructive arthrosis (RDA) and developmental dysplasia of the hip (DDH). METHODS We studied 70 synovial fluid samples obtained from 57 patients with ONFH (mean age 46 years, 34 males, 23 females), 21 samples obtained from 21 patients with RDA (mean age 70 years, 2 males, 19 females) and 20 samples obtained from 20 patients with DDH (mean age 56 years, 2 males, 18 females). The levels of bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), as bone metabolism markers, and matrix metalloproteinase 3 (MMP-3) and keratan sulphate (KS), as cartilage metabolism markers, were analysed. RESULTS The levels of BAP, MMP-3 and KS were significantly higher in the ONFH group than in the RDA and DDH groups. The levels of TRACP-5b were highest in the RDA group. The levels of BAP in the ONFH group after the development of osteoarthritic changes were significantly lower than those observed in earlier stages. In comparisons between the samples obtained from each group with a terminal condition, the ONFH samples exhibited significantly higher MMP-3 and KS levels, while the TRACP-5 levels were highest in the RDA group. CONCLUSION The ONFH patients showed a relatively bone formative condition before the osteoarthritic stage and maintained a higher rate of cartilage turnover throughout several stages compared with the RDA and DDH patients. RDA patients were characterized by a significantly high osteoclast activity.

Subchondral insufficiency fracture of the femoral head in young adults

A subchondral insufficiency fracture of the femoral head (SIF) is generally observed in elderly women. In addition, SIF has been reported to occur in young military trainees, which are considered to be due to a fatigue stress fracture. This report reviewed five cases of SIF in young adults without any history of overexertion or antecedent trauma. The clinical findings, time to the initial radiograph, time to the initial magnetic resonance imaging (MRI), and follow-up period were investigated. Radiographs and MRI were obtained in both hips. Bone mineral density and bone scintigram were performed. Measurements of a bone mineral density indicated presence of osteopenia in three patients. MRI disclosed a discontinuous irregular-shaped low-intensity band surrounded by bone marrow edema in all cases. After conservative treatments, one patients condition resolved, while four patients underwent femoral head collapse resulting in surgical treatment. In these four patients, the diagnosis of SIF was histologically confirmed. In addition, the histological findings showed thin disconnected bone trabeculae, thus indicating the presence of some degree of osteopenia. These patients were considered to demonstrate an insufficiency fracture rather than a fatigue stress fracture based on both clinical findings and histological findings. SIF needs to be considered in patients presenting with hip pain even in young cases.

Effects of an anti-platelet drug on the prevention of steroid-induced osteonecrosis in rabbits

OBJECTIVE To investigate the effects of an anti-platelet drug (clopidogrel) on the prevention of steroid-induced osteonecrosis (ON) in rabbits. METHODS Adult male Japanese white rabbits were divided into two groups and treated as follows: one group received daily clopidogrel mixed in normal saline (AP; n = 35), the other received only normal saline (NS; n = 30). One week after the administration, all rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. Three weeks after, both the femora and humeri were examined histopathologically for the presence of ON. The platelet aggregation assay and hematological examinations were performed before and after the steroid injection. RESULTS The incidence of ON in the AP group (48.5%) was significantly lower than that observed in the NS group (73.3%). The platelet aggregations in the AP group were significantly inhibited by the administration of clopidogrel. The levels of total cholesterol and triglycerides showed no significant differences between the AP and NS group. CONCLUSION The present experimental study demonstrated that the administration of an anti-platelet drug prevented steroid-induced ON in rabbits and that platelet aggregation seems to be one of the possible factors involved in the pathogenesis of steroid-induced ON.

Preventive effects of the anti-vasospasm agent via the regulation of the Rho-kinase pathway on the development of steroid-induced osteonecrosis in rabbits

A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. We examined the effects of fasudil, an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits. One group of rabbits received 15mg/kg of fasudil intravenously, which were then injected once intramuscularly with 20mg/kg of methylprednisolone (n=33), and one received methylprednisolone alone as a control (n=28). Eight rabbits from each group were sacrificed 24h after methylprednisolone injection to analyze them by the expression of endothelinA-receptor and eNOS. Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the incidence of osteonecrosis. In addition, plasma from each of four osteonecrosis-positive or -negative rabbits was used for the proteomic analysis in the fasudil group. The incidence of osteonecrosis was significantly lower in the fasudil group (32%) than that in the control group (75%) (P<0.01). Immunohistochemically, endothelinA-receptor expressions levels were decreased in the smooth muscle of the bone marrow in the fasudil group in comparison to that in the control group. The eNOS expressions levels in both serum and bone marrow in the MF group were significantly higher than those in the M group (P<0.05). Based on the proteomic analysis, several proteins related to vasospasm, such as fibrinogen, thrombin, and apolipoprotein E, were identified in rabbits with osteonecrosis soon after steroid administration. This study indicates that vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis and that the anti-vasospasm agents seem to decrease the incidence of steroid-induced osteonecrosis.

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses

The pathogenesis of alcohol‐induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol‐treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low‐dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high‐dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low‐dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA.

Cholesterol- and lanolin-rich diets may protect against steroid-induced osteonecrosis in rabbits

Background and purpose It remains controversial how hypercholesterolemia influences the development of steroid-induced osteonecrosis (ON). We investigated the role of hypercholesterolemia induced by a cholesterol-rich diet on the development of ON in rabbits. Methods 40 adult male Japanese white rabbits were randomly divided into 2 groups. 20 rabbits were maintained on a cholesterol-rich diet for 2 weeks before receiving steroid treatment (the CHOL group). The other 20 rabbits were maintained on a standard diet (the control (CTR) group). 2 weeks after the start of the study, all 40 rabbits were injected with methylprednisolone acetate (MPSL) into the right gluteus medius muscle (20 mg/kg body weight). 2 weeks after the steroid injection, both the femora and humeri were examined histopathologically for the presence of ON. Hematological analysis of the serum lipid levels was performed every week. Based on the same protocol, we also investigated the effects of lanolin, a primary component of a cholesterol-rich diet, in another group (the LA group). Results The incidence of ON in the CHOL group (3/20) was lower than that observed in the CTR group (15/20) (p < 0.001). During the whole experiment, the levels of total cholesterol and the ratio of low-density lipoprotein to high-density lipoprotein in the CHOL group were higher than those observed in the CTR group (p < 0.001). The LA group also had a lower incidence of ON (2/20), and the lipid levels in the LA group showed similar changes to those observed in the CHOL group. Interpretation Our findings suggest that preexisting hypercholesterolemia itself induced by a cholesterol-rich diet does not increase the risk of developing steroid-induced ON, but rather seems to diminish it. Lanolin may be the active anti-ON component of the cholesterol diet.

Common site of subchondral insufficiency fractures of the femoral head based on three-dimensional magnetic resonance imaging

ObjectivesThe objective of this study was to investigate the common sites of subchondral insufficiency fractures of the femoral head (SIF) based on three-dimensional (3-D) reconstruction of MR images.Materials and methodsIn 33 hips of 31 consecutive patients diagnosed with SIF, 3-D reconstruction of the bone, fracture, and acetabular edge was performed using MR images. These 3-D images were used to measure the fractured areas and clarify the positional relationship between the fracture and degree of acetabular coverage.ResultsThe fractured area in the anterior portion was significantly larger than in the posterior area. In 11 cases, the fractures contacted the acetabular edge and were distributed on the lateral portion. The indices of acetabular coverage (center-edge angle and acetabular head index) in these cases were less than the normal range. In the remaining 22 cases, the fractures were apart from the acetabular edge and distributed on the mediolateral centerline of the femoral head. The majority of these cases had normal acetabular coverage.ConclusionsThe common site of SIF is the anterior portion. In addition, two types of SIF are proposed: (1) Lateral type: the contact stress between the acetabular edge and lateral portion of the femoral head causes SIF based on the insufficient acetabular coverage, and (2) Central type: the contact stress between the acetabular surface and the mediolateral center of the femoral head causes SIF independent from the insufficiency of acetabular coverage. These findings may be useful for considering the treatment and prevention of SIF.

Cytochrome P4503A activity affects the gender difference in the development of steroid-induced osteonecrosis in rabbits

The aim of this study was to investigate cytochrome P4503A activity and its correlation with the development of osternecrosis (ON) among male and female steroid‐treated rabbits. Forty adult rabbits (male, n = 20; female, n = 20) were injected once with 20 mg/kg of methylprednisolone intramuscularly. Haematologically, cytochrome P4503A activity was measured by plasma 1′‐hydroxymidazolam‐to‐midazolam (1′‐OH‐MDZ/MDZ) ratio just before and 48 h after the steroid injection. We also measured the levels of oestradiol every week. Both femora and humeri were histopathologically examined for the presence of ON. Fifteen of 20 male rabbits (75%) developed ON, while 6 of 20 female rabbits (30%) did so. There was a significant difference in the rate of incidence of ON between male and female rabbits (P = 0.010). The 1′‐OH‐MDZ/MDZ ratio in female rabbits just before, as well as 48 h after the steroid injection was significantly higher than that in male rabbits (P = 0.039 and P = 0.001 respectively). In addition, 1′‐OH‐MDZ/MDZ ratio in female rabbits significantly increased in 48 h after the steroid injection (P = 0.044), while that in male rabbits did not so (P = 0.978). The levels of oestradiol in female rabbits were significantly higher than those in male rabbits during the experimental period (P = 0.008). In conclusion, this study indicates that the gender difference in cytochrome P4503A activity may be one of the important factors for the development of steroid‐induced ON, possibly due to the effects of oestradiol.