Osteoarthritis hip joints in Japan: involvement of acetabular dysplasia.

BACKGROUND: We conducted a nationwide epidemiologic study regarding hip osteoarthritis (OA) in Japan, and a previous report found these patients to be unique in comparison to Caucasians. This report focused on the data regarding each hip joint, and the involvement of acetabular dysplasia with hip OA was analyzed. METHODS: Seven hundred twenty OA hips were examined. Sixty-five joints with osteonecrosis of the femoral head and 215 non-OA contralateral joints of the unilateral patients were examined as controls. The revised system of stage classification for hip OA of the Japanese Orthopedic Association (JOA) was used according to the reproducibility in order to ensure reliable data from the multiple institutions. The acetabular dysplasia indexes were also chosen according to the reproducibility and measured in the radiograph of bilateral hip joints. The clinical score was assessed using the JOA scoring system. The relative risk of the grade of acetabular dysplasia indexes for hip OA was calculated as the odds ratio and the 95% confidence interval. RESULTS: The stage of the OA joints deteriorated with increasing age. The clinical scores also decreased. The grade of the acetabular dysplasia indexes of the OA joints was significantly higher than that of the control joints. Each index of acetabular dysplasia demonstrated significantly increased odds ratios for hip OA. Among the OA joints, the deterioration of the OA stage was found to be significantly associated with an increasing grade of acetabular dysplasia. The odds ratio for OA deterioration in the acetabular dysplasia index was also obtained. The joints of females tended to have a higher grade and prevalence of acetabular dysplasia than those of males. CONCLUSIONS: These findings confirmed a high prevalence of acetabular dysplasia in hip OA joints in Japan. Acetabular dysplasia was one of the most important factors associated with hip OA.

Subchondral insufficiency fracture of the femoral head may be associated with hip dysplasia: a pilot study.

BACKGROUND: Subchondral insufficiency fracture of the femoral head occurs mainly in elderly patients with osteoporosis. Spontaneous resolution is observed after nonoperative treatment in some patients whereas other show progressive joint destruction requiring THA. Several studies report the occurrence of subchondral insufficiency fracture of the femoral head in dysplastic hips. QUESTIONS/PURPOSES: We asked whether the extent of hip dysplasia or osteoporosis was greater in patients with subchondral insufficiency fracture of the femoral head than in normal control subjects. PATIENTS AND METHODS: We compared the clinical and imaging findings of 13 patients with subchondral insufficiency fractures of the femoral head and 12 patients scheduled for TKA with asymptomatic hips. Age, gender, and body mass index were comparable in the two groups. RESULTS: Higher mean Sharp angles, lower acetabular head indices, lower center-edge angles, and higher acetabular roof angles in patients with subchondral insufficiency fracture of the femoral head than in those with asymptomatic hips suggested a greater degree of hip dysplasia. Bone mineral density and serum levels of Type I collagen cross-linked N-telopeptide and bone alkaline phosphatase were similar in the two groups. CONCLUSIONS: We speculate an excessive amount of stress on the acetabular edge from dysplasia may be associated with the occurrence of subchondral insufficiency fracture of the femoral head.

Contrast-enhanced MR imaging of subchondral insufficiency fracture of the femoral head: a preliminary comparison with that of osteonecrosis of the femoral head.

INTRODUCTION: Subchondral insufficiency fracture of the femoral head (SIF) may be confused with osteonecrosis of the femoral head (ON) due to clinical and imaging similarities. MATERIALS AND METHODS: Contrast-enhanced MR images in patients with SIF (ten hips in ten patients) were retrospectively reviewed and compared with those from patients with ON (ten hips in six patients). RESULTS: Low-signal intensity bands on T1-weighted images were present within the femoral head in all hips examined. The segment proximal to the band was contrast-enhanced following IV gadolinium administration in nine of ten hips (90%) with SIF and in none of the 10 hips with ON. CONCLUSION: These results suggest that the presence of contrast enhancement in the segment proximal to the low-signal intensity band in the femoral head may serve as a supplemental diagnostic measure for the differentiation of SIF from ON.

Effects of tacrolimus (FK506) on the development of osteonecrosis in a rabbit model.

The present study examined the effects of tacrolimus (FK506) on the development of osteonecrosis in rabbits. In Experiment A, rabbits were given FK506, and also given a single dose of steroid. Control rabbits were given the same dose of steroid only. In Experiment B, rabbits were given FK506 and a reduced dose of steroid. The results showed that addition of FK506 did not change the number of rabbits with osteonecrosis when an identical steroid dose was given. When the steroid dose was reduced, the osteonecrosis incidence significantly decreased (p < 0.01). These results suggest that the clinically reported decrease in the osteonecrosis incidence following the introduction of FK506 is most likely attributable to the lower doses of steroids.

[Anesthesia in a patient with alkaptonuric ochronosis for total hip arthroplasty].

Alkaptonuric ochronosis, caused by a deficiency of homogentisate 1,2-dioxygenase, is a rare, autosomal recessive, metabolic disorder. Accumulation of homogentisate acid (HGA) at the connective tissue destructs the spine and large joints, and cardiac valvular disease is prominent. In this report, we describe a case of alkaptonuric ochronosis for anesthetic management. A 75-year-old female patient with the disease was scheduled for a total-hip arthroplasty. We avoided applying general anesthesia for her valvular regurgitations. Spinal anesthesia was achieved successfully, and resulted in a hypesthesia level at T12. Although a epidural catheter was indwelled with no leak of cerebrospinal fluid, an accidental dural puncture appeared later during the surgery, suggesting a subdural catheterization. She had an uneventful perioperative course without any symptoms. In the patient of alkaptonuric ochronosis, the dura and arachnoid membrane could be damaged made vulnerable by HGA. In addition, since the clinical findings resemble ankylosing spondylitis, degenerative changes such as a narrowing of the disk space and spine fusion would make the regional technique unsuccessful. In term of anesthesia, alkaptonuric ochronosis requires ingenuity since there are a number of factors associated with prevention of untoward complications. Each case is to be evaluated individually and managed carefully.

Ochronotic arthropathy: pathological evidence of acute destruction of the hip joint.

Alcaptonuria is a hereditary disease, also known as black hip, where there is an accumulation of homogentisic acid pigmentation in joint cartilages. We describe a 74-year-old woman who showed acute destruction of her left hip joint. She received a total hip arthroplasty on her right side in July 2000, and was diagnosed with ochronosis. Her postoperative follow-up was at our institutions outpatient department. She first complained of increasing groin pain in July 2005, after which she had a left total hip arthroplasty in October 2005. Histopathologically, samples from this patient showed "fragmentation and cleft formation" in the cartilage of the femoral head. In addition, the samples revealed a remarkable degradation of proteoglycan, which is the secondary most abundant constituent of extra cellular matrix. These findings suggested that "cleft formation", where cracks develop toward the center, caused an acute destructive arthropathy with morphological fragility suggestive of ochronosis.

[Animal models for steroid-induced osteonecrosis].

We describe that high-dose methylprednisolone (20 mg/kg) can induce multifocal osteonecrosis (ON) in conjunction with thrombocytopenia, hypofibrinogenemia, and hyperlipemia. Detailed clinical and laboratory evaluations of coagulation system are recommended in those patients who develop manifestations of an abnormal lipid metabolism shortly after high-dose corticosteroid therapy. Moreover, we investigated the effects of the combination treatment with an anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on prevention of steroid-induced osteonecrosis (ON) in this animal model. The incidence of ON in warfarin plus probucol (5%) was significantly lower than that observed in the control group (70%) (p <0.0001). Our results experimentally showed that the combined use of an anticoagulant and a lipid-lowering agent helps prevent steroid-induced ON in rabbits.

Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro.

This study examined the effects of intermittent hydrostatic pressure (IHP) and transforming growth factor-beta 3 on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. Chondrogenic gene expression was determined by quantifying mRNA signal levels for SOX9, a transcription factor critical for cartilage development and the cartilage matrix proteins, aggrecan and type II collagen. Extracellular matrix production was determined by weight and histology. IHP was applied to hMSCs in pellet culture at a level of 10 MPa and a frequency of 1 Hz for 4 h per day for periods of 3, 7, and 14 days. hMSCs responded to addition of TGF-beta 3 (10 ng/mL) with a greater than 10-fold increase (p < 0.01) in mRNA levels for each, SOX9, type II collagen, and aggrecan during a 14-day culture period. Applying IHP in the presence of TGF-beta 3 further increased the mRNA levels for these proteins by 1.9-, 3.3-, and 1.6-fold, respectively, by day 14. Chondrogenic mRNA levels were increased with just exposure to IHP. Extracellular matrix deposition of type II collagen and aggrecan increased in the pellets as a function of treatment conditions and time of culture. This study demonstrated adjunctive effects of IHP on TGF-beta 3-induced chondrogenesis and suggests that mechanical loading can facilitate articular cartilage tissue engineering.

Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro.

This study examined effects of varying magnitudes of intermittent hydrostatic pressure (IHP) applied for different times on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. hMSCs were exposed to 0.1, 1, and 10 MPa of IHP at a frequency of 1 Hz for 4 h/day for 3, 7, and 14 days in the presence of transforming growth factor (TGF-beta3). Chondrogenesis was characterized by gene expression, macromolecule production, and extracellular matrix deposition. Exposure of hMSCs to 0.1 MPa of IHP increased SOX9 and aggrecan mRNA expression by 2.2- and 5.6-fold, respectively, whereas type II collagen mRNA expression responded maximally at 10 MPa. Production of sulfated glycosaminoglycan responded to IHP of 1 MPa and 10 MPa, whereas collagen levels increased only at 10 MPa. Morphologically, matrix condensation occurred with increased IHP, concomitant with collagen expression. This study demonstrated that different levels of IHP differentially modulate hMSC chondrogenesis in the presence of TGF-beta3. The data suggest that tissue engineering of articular cartilage through application or recruitment of hMSCs can be facilitated by mechanical stimulation.

Temporal effects of a COX-2-selective NSAID on bone ingrowth.

The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.

Bone marrow fat-cell enlargement in early steroid-induced osteonecrosis--a histomorphometric study of autopsy cases.

Some animal studies and magnetic resonance imaging studies suggest that there may exist a relationship between abnormal lipid metabolisms and osteonecrosis. The purpose of this study was to examine the size of bone marrow fat cells in the early osteonecrosis femoral head using autopsy specimens. We compared the size of bone marrow fat cells in the viable areas in the following three autopsy groups: the early osteonecrosis group (4 femoral heads); the steroid-administered group (without osteonecrosis) (n = 10), and the normal group (n = 19). In addition, after adjusting for age and sex, the size of bone marrow fat cells was compared using multiple regression analysis. The size of bone marrow fat cells was significantly larger in the early osteonecrosis group (84.7+/-5.5 microm) than in both the steroid-administered group (75.3+/-4.3 microm) and the normal group (76.3+/-4.9 microm) (p<0.01 and p<0.05, respectively). After adjusting for age and sex, the size of bone marrow fat cells in the early osteonecrosis group was significantly larger as compared with the other groups. This study suggests that in steroid-induced osteonecrosis, the size of bone marrow fat cells increases significantly at an early stage.

Periprosthetic osteolysis: induction of vascular endothelial growth factor from human monocyte/macrophages by orthopaedic biomaterial particles.

UNLABELLED: VEGF and VEGF receptor, Flt-1, expression was observed in periprosthetic tissues surrounding loosened total joint implants. Exposure of monocyte/macrophages to titanium particles resulted in increased VEGF expression, p44/42 MAPK activation, and VEGF-dependent macrophage chemotaxis. Increased levels of angiogenic factors, such as VEGF, may be critically important in wear debris-induced implant loosening after total joint arthroplasty. INTRODUCTION: Periprosthetic osteolysis after total hip arthroplasty occurs in association with formation of a vascularized granulomatous tissue in response to particulate debris. MATERIALS AND METHODS: This study examined expression of vascular endothelial growth factor (VEGF) and the VEGF receptor in 10 periprosthetic tissues from loosened prostheses and quantified effects of titanium particles on VEGF release, intracellular signaling, and VEGF-dependent chemotaxis in primary cultures of human monocyte/macrophages. RESULTS: Double immunofluorescent staining showed that VEGF and Flt-1 co-localized with cells positive for the macrophage marker, CD11b, in the periprosthetic tissues. Monocyte/macrophages challenged with titanium particles showed a dose- and time-dependent release of VEGF ranging from 2.8- to 3.1-fold and exhibited increased expression of VEGF121 and VEGF165 mRNAs, reaching levels up to 5.0- and 8.6-fold, respectively, by 48 h (p < 0.01). Exposure of monocyte/macrophages to titanium particles upregulated phosphorylated-p44/42 mitogen-activated protein kinase (MAPK) within 30 minutes. Particle-induced activation of p44/42 MAPK and release of VEGF were dose-dependently suppressed by pretreatment of cells with PD98059, a specific inhibitor of p44/42 MAPK. Monocyte/macrophages challenged with titanium particles also showed a time-dependent activation of AP-1, a transcription factor associated with VEGF expression (p < 0.01). Supernatants from particle-challenged monocyte/macrophages increased macrophage chemotactic activity by 30%, which was significantly inhibited by anti-VEGF neutralizing antibody (p < 0.01). CONCLUSIONS: This study suggests that induction of VEGF release from monocyte/macrophages in response to orthopaedic biomaterial wear debris may contribute to periprosthetic osteolysis and implant loosening.

Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles.

Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation.

Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle-induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle-mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10-mm-long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin-6, monocyte chemotactic protein-1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle-induced intramedullary inflammation may facilitate cost-effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle-mediated periprosthetic osteolysis.

Mortality after hip fracture in Japan: the role of nutritional status.

PURPOSE: To assess factors that influence 4-year mortality following hip fracture surgery in a Japanese population. METHODS: Records of 129 hips in 24 men and 103 women aged 50 to 103 (mean, 79) years who underwent surgery for femoral neck or trochanteric fractures were reviewed. Clinical data reviewed included age, gender, body mass index (BMI), side of fracture, fracture type, fracture stability, surgery type, interval from admission to surgery, length of hospital stay, number of pre-fracture comorbidities, pre-fracture ambulatory level, pre-fracture place of residence, preoperative dementia, preoperative skeletal traction, blood haemoglobin level, serum albumin level, number of postoperative complications, and postoperative delirium. Univariate and multiple logistic regression analyses were performed to identify the relative contribution of the variables to mortality. Receiver operating characteristic (ROC) curves were used to identify optimal cut-off levels. RESULTS: The 4-year mortality was 48%. Multiple logistic regression analysis showed that serum albumin level (p = 0.0004, odds ratio [OR] = 5.8541) and BMI (p = 0.0192, OR = 1.1693) significantly influenced mortality; the cut-off points were 36 g/l and 18.9 kg/m square, respectively, based on the ROC curves. Kaplan-Meier curves showed that survival rates were significantly worse in patients with values below these cut-off points. CONCLUSION: Serum albumin level and BMI on admission are predictive of mortality after hip fracture surgery.

Risk factors leading to total hip arthroplasty in patients with subchondral insufficiency fractures of the femoral head.

PURPOSE: To retrospectively evaluate factors leading to total hip arthroplasty (THA) in patients with subchondral insufficiency fractures (SIF) of the femoral head. METHODS. 5 men and 22 women aged 51 to 85 (mean, 72) years with SIF of the femoral head initially underwent conservative treatment. THA was later performed for 13 patients, as the hip pain became worse secondary to joint space narrowing and/ or femoral head collapse. Patient demographics and radiological variables were retrieved. Risk factors leading to THA in patients with SIF of the femoral head were identified. Receiver operating characteristic curves were used to determine optimal cut-off values for the significant risk factors. RESULTS: 2 men and 11 women aged 62 to 85 (mean, 74.9) years underwent THA and were followed up for 0.2 to 62 (mean, 13) months. The remaining 3 men and 11 women aged 51 to 81 (mean, 68) years underwent conservative treatment and were followed up for 9 to 93 (mean, 28) months. Patient age was the only risk factor for THA (p = 0.047, odds ratio = 1.13), the cutoff value being 71 years (sensitivity, 77%; specificity, 64%). The survival rate was significantly lower in patients aged 71 years or older than in those aged younger than 71 years (p < 0.05). CONCLUSION: Elderly patients with SIF of the femoral head are at higher risk of undergoing THA.

Short-term wear of Japanese highly cross-linked polyethylene in cementless THA.

INTRODUCTION: Production of polyethylene wear from acetabular liners is thought, in part, to mediate the periprosthetic osteolysis. This study examined the in vivo wear performance of Japanese highly cross-linked polyethylene (Aeonian) in cementless total hip arthroplasty. MATERIALS AND METHODS: Ninety-five hips received a highly cross-linked polyethylene liner, while 20 hips were implanted with conventional polyethylene. Two-dimensional linear wear was measured on radiographs and volumetric wear was then calculated. Both linear and volumetric wear rates were examined for the 1-year postoperative period as well as for the time frame beginning after 1 year ending with the final follow-up. RESULTS: The amount of linear wear was significantly lower in the cross-linked group at 3 and 5 years postoperatively (P < 0.01 and < 0.001, respectively). Linear and volumetric wear rates after 1 year postoperatively for hips with the cross-linked polyethylene were significantly reduced by 57 and 59%, respectively, when compared to rates for those who received conventional polyethylene (P < 0.01). A multiple logistic regression analysis revealed that cross-linking was a significant factor influencing linear wear rate after 1 year postoperatively with an odds ratio, exp(ss) = 10.033 (P < 0.001). CONCLUSION: These results suggest that the highly cross-linked polyethylene reduces penetration of the femoral head and may be an optimal bearing surface for patients receiving total hip arthroplasty.

Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits.

OBJECTIVE: Both abnormal lipid metabolisms and coagulopathy have been suggested to be associated with the development of steroid-induced osteonecrosis (ON). We examined plasma risk factors for development of steroid-induced ON in rabbits after prophylaxis with a lipid-lowering agent and/or an anticoagulant. METHODS: Seventy adult male rabbits were injected intramuscularly once with 20 mg/kg methylprednisolone acetate. Fifty-five rabbits received prophylaxis with probucol (a lipid-lowering agent; n = 20) or warfarin (an anticoagulant; n = 14) or both (n = 21). Probucol and warfarin were administered beginning 1 to 2 weeks prior to steroid injection. Two weeks after steroid injection, the bilateral femora and humeri were examined histopathologically for the presence of ON. Based on a logistic regression model, laboratory variables before steroid injection were assessed to determine whether they demonstrated any association with the risk of ON. RESULTS: Twenty-one rabbits developed ON. In the univariate analyses, significant positive associations were observed between plasma concentrations of triglyceride and low-density lipoprotein and the risk of development of ON. In the multivariate model, only the plasma triglyceride level suggested a positive association. Even after adjusting for probucol and warfarin use, the plasma triglyceride level was still suggested to be a predictor for development of ON. Rabbits with higher baseline triglyceride levels had a more pronounced triglyceride increase in their response to steroids. CONCLUSION: Our study suggests that, after prophylaxis with probucol and/or warfarin, plasma triglyceride level is associated with the development of steroid-induced ON in rabbits.