Ken Iwata

Multiinstitutional epidemiological study regarding osteoarthritis of the hip in Japan

Background. Osteoarthritis (OA) of the hip is a major disease that affects the healthy lifespan of a population. It is necessary to fully understand the patients’ conditions before a systematic treatment can be applied. However, a nationwide epidemiological study regarding hip OA has not yet been conducted in Japan. The present study examined the current status of patients with hip OA, including the disease etiology. Methods. This is a multiinstitutional study of new patients presenting with hip OA at the orthopedic outpatient clinics of 15 institutions in fi ve geographical areas of Japan. The collected data from each patient included the sex, age, treatment history for developmental dysplasia of the hip (DDH), the clinical score of the hip joints based on the Japanese Orthopaedic Association (JOA) scoring system, and the pelvic inclination according to anteroposterior radiographs. In addition, the etiology was determined from the following 17 options: primary OA, acetabular dysplasia, intragluteal dislocation, osteonecrosis, trauma, Perthes disease, slipped capital femoral epiphysis, infection, rheumatoid arthritis, ankylosing spondylitis, neuroarthropathy, endocrine diseases, metabolic diseases, hereditary bone diseases, synovial chondromatosis, generalized OA, and others. Results. There were a substantially larger number of female patients than male patients. This difference regarding sex was present in each generation. The mean age of the patients was 58 ± 14 years. The peak age at presentation was approximately 50 years. Most patients had no history of therapy for DDH. The older patients had lower gait and activities of daily living scores. The etiology was assessed to be acetabular dysplasia in most of the patients. A lower frequency of elderly patients demonstrated acetabular dysplasia. The patients who had a pelvic posterior inclination increased with increasing age. Conclusions. The patients with hip OA in Japan were unique in regard to age distribution, sexual heterogeneity, and disease

Osteoarthritis hip joints in Japan: involvement of acetabular dysplasia

BackgroundWe 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.MethodsSeven 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.ResultsThe 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.ConclusionsThese 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

BackgroundWe 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.MethodsWe 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.ResultsFor 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.ConclusionsFor the upcoming multicenter survey, clear descriptions of the stages of coxarthrosis and selection of appropriate indexes can be helpful for collecting dependable results.

Effects of minodronic acid and alendronate on bone remodeling, microdamage accumulation, degree of mineralization and bone mechanical properties in ovariectomized cynomolgus monkeys.

Suppression of bone remodeling by bisphosphonates leads to accumulation of microdamage in bone. If this microdamage develops due to suppressed repair of remodeling only, more potent bisphosphonates should cause more damage. In this study, we evaluated the effects of reduced bone turnover produced by a potent bisphosphonate, minodronic acid, on microdamage accumulation, the degree of mineralization and mechanical properties of bone in ovariectomized cynomolgus monkeys, and compared these effects with those of alendronate. Sixty female monkeys aged 9-17 years old were divided into five groups. The sham group and the ovariectomized group were treated daily for 17 months with lactose vehicle. The other three groups were treated daily with minodronic acid at a dose of 0.015 mg/kg or 0.15 mg/kg, or alendronate at 0.5mg/kg orally. After sacrifice, lumbar vertebrae and left femurs were subjected to histomorphometry, microdamage, mineralization analyses, and mechanical testing. Minodronic acid suppressed bone remodeling of cancellous and cortical bone in a dose-dependent manner and the higher dose of minodronic acid suppressed bone remodeling more strongly than alendronate. The lower dose of minodronic acid did not increase microdamage accumulation and compressive strength, but the higher dose of minodronic acid and alendronate resulted in similar increases in cancellous microdamage accumulation and ultimate load in lumbar vertebra. There were no significant differences among the groups in microdamage, degree of mineralization and mechanical properties in cortical bone of the femoral shaft; however, only alendronate showed a tendency to increase highly mineralized osteons and microdamage. These findings suggest that microdamage caused by minodronic acid is less than that expected based on the extent of remodeling suppression, in comparison with alendronate although this was not reflected in any significant change of mechanical properties.

A large amount of microdamages in the cortical bone around fracture site in a patient of atypical femoral fracture after long-term bisphosphonate therapy

A breast cancer patient developed an atypical femoral fracture after 9 years of bisphosphonate therapy for the treatment of multiple bone metastases. We histopathologically analyzed the femoral cortical bone at the fracture site and the iliac cancellous bone. Four months prior to the fracture, the patient had experienced pain in the right femur and underwent plain radiography and bone scintigraphy which revealed cortical thickening and radioisotope accumulation at each site, respectively. The patient had also experienced a non-traumatic fracture at the same site on the contralateral side 2 years earlier. Based on these findings, atypical femoral fracture was diagnosed and intramedullary nailing performed. A cortical bone specimen taken from near the fracture site during surgery showed marked microdamages, and analysis of the iliac cancellous bone specimen revealed severely suppressed bone turnover. These findings suggest that microdamage and severely suppressed bone turnover are associated with atypical femoral fracture reported in this patient with long-term bisphosphonate therapy.

Effects of suppressed bone remodeling by minodronic acid and alendronate on bone mass, microdamage accumulation, collagen crosslinks and bone mechanical properties in the lumbar vertebra of ovariectomized cynomolgus monkeys.

Collagen crosslinking is an important determinant of the quality of bone material. We have previously shown that suppressed bone turnover by high doses of minodronic acid and alendronate increases compressive strength of vertebra, but also increases microdamage accumulation, in monkey bone. The aim of this study is to examine the effects of these bisphosphonates on collagen crosslinks and intrinsic material properties, in addition to microdamage accumulation, in vertebral cancellous bone in ovariectomized cynomolgus monkeys. Sixty female monkeys aged 9-17years were divided into five groups: sham and ovariectomized groups were treated daily for 17months with lactose vehicle, and the other three groups were given minodronic acid daily at 0.015 or 0.15mg/kg or alendronate daily at 0.5mg/kg orally. After sacrifice, lumbar vertebrae were subjected to histomorphometry, microdamage measurement, analysis of collagen crosslinking and compressive mechanical tests. Minodronic acid caused dose-dependent suppression of increased bone remodeling due to ovariectomy, and low-dose minodronic acid suppressed remodeling same level as alendronate. However, low-dose minodronic acid did not change microdamage accumulation, collagen maturity and the pentosidine level, whereas high-dose minodronic acid and alendronate increased these parameters. Compressive ultimate load was increased following high-dose minodronic acid and alendronate, but no treatment altered the reduction in intrinsic material properties caused by ovariectomy. These findings suggest that deterioration of bone material and formation of pentosidine and microdamage induced by minodronic acid is less than that expected based on the extent of remodeling suppression, in comparison with alendronate, but this was not reflected in any significant change of mechanical properties.

Accumulation of microdamage at complete and incomplete fracture sites in a patient with bilateral atypical femoral fractures on glucocorticoid and bisphosphonate therapy

Atypical femoral fractures are defined in the second report by the Task Force of the American Society for Bone and Mineral Research in 2014 [1] as stress and fragility fractures caused by deterioration of bone quality resulting from suppressed bone turnover associated with exposure to bisphosphonates and/or glucocorticoids, abnormal alignment of the lower extremities because of femoral lateral bowing or genu varum, and other skeletal diseases such as hypophosphatasia, pycnodysostosis, and osteopetrosis. Odvina et al. reported that marked suppression of bone turnover by longterm bisphosphonate therapy increased the risk of atypical femoral fracture [2]. Recently, we reported accumulation of microdamage in the lateral cortical bone adjacent to an atypical femoral fracture site and marked suppression of cancellous bone turnover on an iliac bone biopsy at this site in a patient who had received long-term bisphosphonate therapy [3]. Our report indicated that the stress fracture occurred because accumulated microdamage was not repaired because of severely suppressed bone turnover. In the present study, we performed biopsy of the cortical bone around bilateral atypical femoral fractures (complete fracture of one leg and incomplete fracture of the other) in a patient with rheumatoid arthritis and neurosarcoidosis on glucocorticoid and bisphosphonate therapy for 10 years and 20 months, respectively, and herein report our pathological findings. The patient and her family provided written informed consent for data from her case to be submitted for publication.