Ryosuke Yamaguchi

Morphological analysis of collapsed regions in osteonecrosis of the femoral head

In order to investigate the mechanisms of collapse in osteonecrosis of the femoral head, we examined which part of the femoral head was the key point of a collapse and whether a collapsed region was associated with the size of the necrotic lesion. Using 30 consecutive surgically removed femoral heads we retrospectively analysed whole serial cut sections, specimen photographs, specimen radiographs and histological sections. In all of the femoral heads, collapse consistently involved a fracture at the lateral boundary of the necrotic lesion. Histologically, the fractures occurred at the junction between the thickened trabeculae of the reparative zone and the necrotic bone trabeculae. When the medial boundary of the necrotic lesion was located lateral to the fovea of the femoral head, 18 of 19 femoral heads collapsed in the subchondral region. By contrast, when the medial boundary was located medial to the fovea, collapse in the subchondral region was observed in four of 11 femoral heads (p = 0.0011). We found that collapse began at the lateral boundary of the necrotic lesion and that the size of the necrotic lesion seemed to contribute to its distribution.

Incidence of nontraumatic osteonecrosis of the femoral head in the Japanese population

OBJECTIVE To estimate the incidence rate of nontraumatic osteonecrosis of the femoral head (ONFH) in the Japanese population. METHODS A survey was conducted to ascertain newly identified patients with nontraumatic ONFH in the Specified Disease Treatment Research Program of Fukuoka Prefecture (population 5 million) between 1999 and 2008. Distributions of age and sex in this population were investigated. Crude incidence rates of nontraumatic ONFH were calculated, and age-adjusted incidence rates were estimated by adjusting the crude values against those for the Japanese standard population in each year. RESULTS In Fukuoka Prefecture, 1,244 newly identified patients with nontraumatic ONFH were recruited into the Japanese subsidy program over the span of 10 years. The ratio of men to women was 1.6, comprising 758 men (61%; mean age 48 years) and 486 women (39%; mean age 56 years). The crude incidence rate of nontraumatic ONFH in the 10-year period was 2.58 cases per 100,000 person-years (range 1.54-3.66). The mean age-adjusted incidence rate was 2.51 cases per 100,000 person-years. CONCLUSION This study showed that the incidence rate of nontraumatic ONFH was 2.51 cases per 100,000 person-years in the Japanese population.

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.

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.

Contralateral osteonecrosis of the femoral head newly developed after increasing the dose of corticosteroids

Nontraumatic osteonecrosis of the femoral head (ONFH) is a debilitating disorder that commonly affects 30to 50-year-old individuals, with corticosteroid use being one of the major causative factors [1]. Although the precise pathogenesis of corticosteroid-induced ONFH remains unclear, both high-dose oral corticosteroid therapy and corticosteroid pulse treatment have been reported to be risk factors, highlighting the importance of the dose of corticosteroids in the development of corticosteroid-induced osteonecrosis [2–7]. Corticosteroid-induced osteonecrosis often affects both femoral heads (50–70 %), and bilateral ONFH is considered to develop concurrently [1, 2]. In contrast, in patients with unilateral ONFH, it is rare that new osteonecrotic lesions subsequently develop in the contralateral femoral head. To our knowledge, there are no reports in the literature regarding the development of new corticosteroidinduced ONFH lesions on the contralateral side. Here we report the case of a patient who developed new ONFH in the contralateral hip after increasing the dose of corticosteroids for a different underlying disease. We clearly indicate that written informed consent for publication was obtained from the patient. Case report

MRI-detected double low-intensity bands in osteonecrosis of the femoral head

Abstract When treating osteonecrosis of the femoral head (ONFH), it is important to define the site and size of necrotic lesions, in general based on the detection of the demarcating area. Although a plain radiograph is routinely performed, it does not always make the lesion clear, especially in early stage cases. On the other hand, magnetic resonance (MR) imaging usually detects the necrotic lesion more clearly even at the early stage [1, 2], and therefore MR imaging is widely used in both the diagnosis and the selection of treatment for ONFH [3, 4].