Factors associated with diagnostic stage of hip osteoarthritis due to acetabular dysplasia among Japanese female patients: a cross-sectional study.

BACKGROUND: In Japan, the majority of hip osteoarthritis (OA) was caused by acetabular dysplasia, and about 90 % of patients were female. The present study focused on Japanese female patients with hip OA due to acetabular dysplasia, and examined the associated factors with OA staging at diagnosis, in special reference to body weight. METHODS: Study subjects were 336 Japanese women who were newly diagnosed with hip OA caused by acetabular dysplasia at 15 hospitals in 2008. The self-administered questionnaire elicited patients' body weight at age 20 and at OA diagnosis. Four ranked OA staging according to radiographic findings of the hip joint (pre-OA, initial stage, advanced stage or terminal stage) was regarded as the outcome index. Proportional odds models in logistic regression were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for severer stage of OA. RESULTS: At diagnosis, 45 % of patients suffered from terminal stage of OA, whereas 13 % and 14 % were categorized into pre-OA and initial stage, respectively. After adjustment for potential confounders, weight gain since age 20 revealed the increased ORs for severer OA stage at diagnosis (OR 2.02; 95 % CI, 1.07-3.80). Other significant characteristics were age (67+ vs. 20-49 years, OR 12.4), lower education (junior high school vs. junior college or higher, OR 4.00), parity (OR 2.19), lower acetabular head index (<60.0 vs. 71.1+, OR 2.36), and longer duration since symptom onset (6.0+ vs. <1.0 year, OR 2.94). CONCLUSIONS: Weight gain since age 20 might be involved in mechanisms of OA development, which is independent of age or severity of acetabular dysplasia.

Relationship of acetabular dysplasia in females with osteoarthritis of the hip to the distance between both anterior superior iliac spines.

BACKGROUND: Acetabular dysplasia (AD) is the main cause of hip osteoarthritis in Japan. A simple method to evaluate acetabular dysplasia would be helpful for early treatment or prevention of hip osteoarthritis. Acetabular dysplasia is reported to be associated with pathological transverse growth of the pelvis, indicating that the distance between the 2 anterior superior iliac spines might be useful for screening and detection of acetabular dysplasia. The purpose of this study was to determine if the acetabular dysplasia radiographic parameters are related to the distance between the 2 anterior superior iliac spines in patients with hip osteoarthritis. MATERIAL AND METHODS: In this study, data obtained in a previous multi-institutional examination of patients with hip osteoarthritis in Japan were evaluated. The anterior superior iliac spine distances of 176 female patients (mean age, 54 years; range, 18-85 years) were measured by physical examination. The relationship between the anterior superior iliac spine distance and acetabular dysplasia was analyzed, and the anterior superior iliac spine distances of the patients with acetabular dysplasia who were at relatively high risk for hip osteoarthritis were compared with that of the patients at lower risk. RESULTS: A statistically significant relationship between the anterior superior iliac spine distance and all of the acetabular dysplasia parameters was observed. The anterior superior iliac spine distances of the acetabular dysplasia patients with a relatively high risk for radiographic acetabular dysplasia parameters were significantly smaller than those of patients at lower risk. Even after adjustment for age, height, and weight, significantly increased relative risk for having high risk AD was found in patients with an ASIS distance of less than 24.5 cm. CONCLUSIONS: There was a significant relationship between the anterior superior iliac spine distance and the degree of acetabular dysplasia.

Clinical and radiographic evaluation of total hip arthroplasties using porous tantalum modular acetabular components: 5-year follow-up of clinical trial.

OBJECTIVES: Porous tantalum is a biomaterial newly applied for artificial joints. We present here 5-years follow-up report of a multicenter clinical trial of total hip arthroplasties (THA) with porous tantalum modular acetabular component (modular PTC). METHODS: Study participants received 82 hips in 79 cases, with 61.2 months follow-up on average. Age at operation was 60.9 years. Clinical results were evaluated using Merle d'Aubigne Postel score. Presence of implant loosening, periacetabular radiolucency, osteolysis, and gap filling were examined for radiographic results. RESULTS: Merle d'Aubigne Postel score improved from 10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year, with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm; however, all showed bone filling within 12 months. PTC with oversized reaming was significantly less likely to have a gap. No implant failure was noted related to modularity. Resulting survival rate of modular PTC was 100% at 5 years. CONCLUSIONS: Modular PTC showed excellent results at 5-years of follow-up. Some hips showed periacetabular gaps, which were filled with bone within 1 year. Further follow-up was needed to determine long-term efficacy.

A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. Constitutively activated mutants of a bone morphogenetic protein (BMP) receptor, ALK2, have been identified in patients with FOP. Recently, a novel ALK2 mutation, L196P, was found in the most benign case of FOP reported thus far. In the present study, we examined the biological activities of ALK2(L196P) in vitro. Over-expression of ALK2(L196P) induced BMP-specific activities, including the suppression of myogenesis, the induction of alkaline phosphatase activity, increased BMP-specific luciferase reporter activity, and increased phosphorylation of Smad1/5 but not Erk1/2 or p38. The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP. ALK2(L196P) was equally or more resistant to inhibitors in comparison to ALK2(R206H). These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in patients with this mutation.

Epidemiology of hip fractures in Okinawa, Japan.

This study investigated the current incidence of hip fractures in Okinawa prefecture and compared the data with those obtained in our previous study, which was conducted using similar methods in 1987/1988. All patients, aged 50 years or older and residing in Okinawa, admitted to Okinawa hospitals in 2004 for a fresh hip fracture were identified from hospital registries. Details were obtained from the medical records and radiographs of all patients and classified according to fracture type (cervical or trochanteric), age, sex, and fracture location. Subtrochanteric fractures and pathological fractures were excluded. A total of 1,349 patients (242 men and 1,107 women) were admitted for a fresh hip fracture in 2004. Their average age was 76.9 years for men and 82.4 years for women. There were 671 cervical fractures, 654 trochanteric fractures, and 24 unclassified proximal femoral fractures. Comparing the data from 1987/1988 to those from 2004, the total number of hip fractures increased by 188%, from 469 to 1,349. The age-adjusted incidence rates per 100,000, standardized to the 2000 US population, were 75.7 and 296.1 in 1987/1988 and 123.6 and 420 in 2004 for men and women, respectively. The incidence rates in all age groups (at 5-year intervals) were higher in 2004 than in 1987/1988, indicating that people 50 years of age or older became more susceptible to hip fractures. Accordingly, the accretion of the hip fracture incidence rate was greater than that which could be explained purely by changes in population size and structure.

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.

Analysis of interobserver reliability for radiographic staging of coxarthrosis and indexes of acetabular dysplasia: a preliminary study.

BACKGROUND: We are planning a multicenter survey on coxarthrosis and acetabular dysplasia in Japan. To collect reliable data, we performed a preliminary study to elucidate the observer agreement on assessment items. METHODS: We collected radiographs of hip joints in eight patients with various findings of coxarthrosis. Twelve registered orthopedic specialists evaluated them regarding the roentgenographic stage of coxarthrosis and five indexes of acetabular dysplasia (acetabular angle, center-edge angle, acetabular roof obliquity, acetabular head quotient, approximate acetabular quotient). To assess observer agreement, we calculated the value of the kappa statistic for stages and the coefficient of variation for the indexes. The same 12 specialists then assessed the coxarthritis stage on the same radiographs 1 month after the first evaluation based on our own descriptions of the roentgenographic stages. RESULTS: For the first evaluation of the roentgenographic stage, the value of the kappa statistic was 0.448; and for the second evaluation it was 0.600. The results of the coefficient of variation for the indexes of acetabular dysplasia, ranked in ascending order, were as follows: acetabular angle, acetabular head quotient, acetabular roof obliquity, center-edge angle, approximate acetabular quotient. CONCLUSIONS: For the upcoming multicenter survey, clear descriptions of the stages of coxarthrosis and selection of appropriate indexes can be helpful for collecting dependable results.

A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic bone formation in muscle tissues. A common mutation among FOP patients has been identified in ALK2, ALK2(R206H), which encodes a constitutively active bone morphogenetic protein (BMP) receptor. Recently, a unique mutation of ALK2, ALK2(G356D), was identified to be a novel mutation in a Japanese FOP patient who had unique clinical features. Over-expression of ALK2(G356D) induced phosphorylation of Smad1/5/8 and activated Id1-luc and alkaline phosphatase activity in myoblasts. However, the over-expression failed to activate phosphorylation of p38, ERK1/2, and CAGA-luc activity. These ALK2(G356D) activities were weaker than those of ALK2(R206H), and they were suppressed by a specific inhibitor of the BMP-regulated Smad pathway. These findings suggest that ALK2(G356D) induces heterotopic bone formation via activation of a BMP-regulated Smad pathway. The quantitative difference between ALK2(G356D) and ALK2(R206H) activities may have caused the phenotypic differences in these patients.

Factors associated with functional limitations in the daily living activities of Japanese hip osteoarthritis patients.

AIM: As society ages, there is a vast number of elderly people with locomotive syndrome. In this study, the factors associated with functional limitations in daily living activities evaluated by female hip osteoarthritis (OA) patients were investigated. METHODS: This study was a cross-sectional study. The subjects were 353 female patients who were newly diagnosed with hip OA at an orthopedic clinic with no history of hip joint surgery. Outcome indices were functional limitations in two daily living activities obtained from a questionnaire completed by the patients: (i) standing up (standing from a crouched position) and (ii) stair-climbing (climbing and/or descending stairs). The odds ratios (ORs) and 95% confidence intervals (CIs) were computed for explanatory variables using the proportional odds model in logistic regression to evaluate their associations with functional limitations. RESULTS: Functional limitations in standing up were associated with heavy weight (third tertile vs. first tertile: 1.91, 1.11-3.27), participation in sports at school (0.62, 0.40-0.98), parity (vs. nullipara: 1.96, 1.08-3.56), old age and OA stage. Associations with functional limitations in stair-climbing were seen with short height (< 151.0 cm vs. ≥ 156.0 cm: 2.05, 1.02-4.12), bilateral involvement (vs. unilateral: 1.71, 1.01-2.88), old age and OA stage. CONCLUSION: Old age, OA stage, heavy weight, parity, shorter height and bilateral OA were associated with functional limitations in standing up and/or stair-climbing, whereas participation in sports such as club activities in school maintained standing up.

Characterization of dynamic three-dimensional strain fields in the canine radius.

This note describes a method to approximate the 3-D mechanical environment of a long bone during a normal daily activity. Our specific goal was to characterize the temporal and spatial strain distributions in the mid-shaft region of the canine radius during gait. Direct measurement of strains along the entire surface of in vivo bone is not feasible, so we employed a combination of experimental measurements and numerical interpolation techniques to approximate the time-varying longitudinal strain distribution. Using standard in vivo strain gauging techniques, we measured dynamic strains at nine locations (three locations on each of three cross sections, data pooled from two experimental animals) on the canine radius during trotting gait. These in vivo strain measurements were then used to approximate the time course of the strain field for the entire radius mid-shaft region using a 3-D numerical interpolation scheme using finite element basis functions. Despite limitations in the present implementation of the method, the results show that there are considerable time-dependent variations in the strain distribution occurring at different transverse sections along the length of the diaphysis with substantial anteroposterior bending and rotation of neutral axis locations during the gait cycle.

Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and by progressive heterotopic bone formation in muscle tissue. Recently, a mutation involving a single amino acid substitution in a bone morphogenetic protein (BMP) type I receptor, ALK2, was identified in patients with FOP. We report here that the identical mutation, R206H, was observed in 19 Japanese patients with sporadic FOP. This mutant receptor, ALK2(R206H), activates BMP signaling without ligand binding. Moreover, expression of Smad1 and Smad5 was up-regulated in response to muscular injury. ALK2(R206H) with Smad1 or Smad5 induced osteoblastic differentiation that could be inhibited by Smad7 or dorsomorphin. Taken together, these findings suggest that the heterotopic bone formation in FOP may be induced by a constitutively activated BMP receptor signaling through Smad1 or Smad5. Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP.

Midkine as a novel target for antibody therapy in osteosarcoma.

Osteosarcoma is a malignant tumor with poor prognosis, and lack of accurate prognostic factors is one of the reasons that make this tumor difficult to cure. The heparin-binding growth factor, midkine is involved in generation and progression of many types of tumors. However, the relationship between midkine and osteosarcoma has been unclear. We show here that midkine is overexpressed in osteosarcoma and the level of midkine expression is correlated with prognosis (P<0.05; log-rank test). Treatment with functional antibodies against midkine suppresses growth of osteosarcoma cell lines, 9N2, 3N1, Saos-2, and NOS-1, to 25-65% of untreated controls. Our results suggest that midkine is useful as a prognostic marker, and is a candidate therapeutic target for osetosarcomas.

Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome.

The C syndrome is characterized by trigonocephaly and associated anomalies, such as unusual facies, psychomotor retardation, redundant skin, joint and limb abnormalities, and visceral anomalies. In an individual with the C syndrome who harbors a balanced chromosomal translocation, t(3;18)(q13.13;q12.1), we discovered that the TACTILE gene for CD96, a member of the immunoglobulin superfamily, was disrupted at the 3q13.3 breakpoint. In mutation analysis of nine karyotypically normal patients given diagnoses of the C or C-like syndrome, we identified a missense mutation (839C-->T, T280M) in exon 6 of the CD96 gene in one patient with the C-like syndrome. The missense mutation was not found among 420 unaffected Japanese individuals. Cells with mutated CD96 protein (T280M) lost adhesion and growth activities in vitro. These findings indicate that CD96 mutations may cause a form of the C syndrome by interfering with cell adhesion and growth.