Yoshio Enyo

Prevalence of radiographic knee osteoarthritis and its association with knee pain in the elderly of Japanese population-based cohorts: The ROAD study

OBJECTIVE We investigated the prevalence of radiographic knee osteoarthritis (OA) and knee pain in the Japanese elderly using a large-scale population of a nationwide cohort study, Research on Osteoarthritis Against Disability (ROAD), and examined their association. METHODS From the baseline survey of the ROAD study, 2,282 participants > or =60 years (817 men and 1,465 women) living in urban, mountainous and seacoast communities were analyzed. The radiographic severity at both knees was determined by the Kellgren/Lawrence (KL) grading system. KL> or =2 and KL> or =3 knee OA were examined separately to assess osteophytosis and joint space narrowing (JSN). RESULTS The prevalence of KL> or =2 OA (47.0% and 70.2% in men and women, respectively) was much higher than that of previous studies in Caucasians, while that of KL> or =3 OA was not much different in men. Age, BMI, female sex and rural residency were risk factors for radiographic knee OA, knee pain and their combination. The prevalence of knee pain was age-dependent in women, but not in men. Knee pain was more strongly associated with KL> or =3 OA than with KL=2, and the association was higher in men than in women. Female sex was a strong risk factor even in the subgroup without radiographic knee OA (KL=0/1). CONCLUSION The present cross-sectional study revealed a high prevalence of radiographic knee OA in the Japanese elderly. Knee pain was strongly associated with JSN especially in men, while women tended to have knee pain even without radiographic OA.

Prevalence of radiographic lumbar spondylosis and its association with low back pain in elderly subjects of population-based cohorts: the ROAD study

Objectives: Although lumbar spondylosis is a major cause of low back pain and disability in elderly people, few epidemiological studies have been performed. The prevalence of radiographic lumbar spondylosis was investigated in a large-scale population study and the association with low back pain was examined. Methods: From a nationwide cohort study (Research on Osteoarthritis Against Disability; ROAD), 2288 participants aged ⩾60 years (818 men and 1470 women) living in urban, mountainous and coastal communities were analysed. The radiographic severity at lumbar intervertebral levels from L1/2 to L5/S was determined by Kellgren/Lawrence (KL) grading. Results: In the overall population the prevalence of radiographic spondylosis with KL⩾2 and ⩾3 at the severest intervertebral level was 75.8% and 50.4%, respectively, and that of low back pain was 28.8%. Although KL⩾2 spondylosis was more prevalent in men, KL⩾3 spondylosis and low back pain were more prevalent in women. Age and body mass index were risk factors for both KL ⩾2 and KL⩾3 spondylosis. Although KL = 2 spondylosis was not significantly associated with low back pain compared with KL = 0 or 1, KL⩾3 spondylosis was related to the pain only in women. Conclusions: This cross-sectional study in a large population revealed a high prevalence of radiographic lumbar spondylosis in elderly subjects. Gender seems to be distinctly associated with KL⩾2 and KL⩾3 lumbar spondylosis, and disc space narrowing with or without osteophytosis in women may be a risk factor for low back pain.

Association of radiographic and symptomatic knee osteoarthritis with health-related quality of life in a population-based cohort study in Japan: the ROAD study

OBJECTIVE Knee osteoarthritis (OA) is a major public health issue causing chronic pain and disability. However, there is little information on the impact of this disease on quality of life (QOL) in Japanese men and women. The objective of the present study was to clarify the impact of radiographic and symptomatic knee OA on QOL in Japan. METHODS This study examined the association of radiographic and symptomatic knee OA with QOL parameters such as the Medical Outcomes Study Short Form-8 (SF-8), EuroQOL (EQ-5D) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic knee OA was defined according to Kellgren/Lawrence (KL) grades, and symptomatic knee OA was defined as KL=3 or 4 with knee pain. We also examined the independent association of symptomatic knee OA and grip strength with QOL. RESULTS From the 3040 participants in the Research on Osteoarthritis Against Disability (ROAD) study, the present study analyzed 2126 subjects older than 40 years who completed the questionnaires (767 men and 1359 women; mean age, 68.9+/-10.9 years). Subjects with KL=3 or 4 had significantly lower physical QOL as measured by the physical component summary (PCS) score of the SF-8 and pain domains of the WOMAC, whereas mental QOL, as measured by the mental component summary (MCS) score of the SF-8, was higher in subjects with KL=3 or 4 than KL=0 or 1. Symptomatic knee OA was significantly more likely than radiographic knee OA without pain to be associated with physical QOL loss as measured by the PCS score and physical domains of the WOMAC. Symptomatic knee OA and grip strength were independently associated with physical QOL. CONCLUSION This cross-sectional study revealed that subjects with symptomatic knee OA had significantly lower physical QOL than subjects without it.

Prevalence of falls and the association with knee osteoarthritis and lumbar spondylosis as well as knee and lower back pain in Japanese men and women

There is little information on falls by sex and age strata in Japan, and few factors associated with falls have been established. However, the association between bone and joint diseases and falls remains unclear. We examined prevalence of falls by sex and age strata, determined its association with radiographic osteoarthritis (OA) of the knee and lumbar spine, and determined knee and lower back pain after single and multiple falls.

Association of occupational activity with radiographic knee osteoarthritis and lumbar spondylosis in elderly patients of population-based cohorts: a large-scale population-based study.

OBJECTIVE To investigate the risk of radiographic knee osteoarthritis (OA) and lumbar spondylosis associated with occupational activity in elderly Japanese subjects using the large-scale population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study. METHODS From the baseline survey of the ROAD study, 1,471 participants age > or =50 years (531 men and 940 women) living in mountainous and seacoast communities were analyzed. Information collected included a lifetime occupational history and details of specific work place physical activities. Radiographic severity at the knee and lumbar spine was determined by the Kellgren/Lawrence (K/L) grading system. RESULTS The prevalence of K/L grade > or =2 knee OA and lumbar spondylosis among agricultural, forestry, and fishery workers was significantly higher than among clerical workers and technical experts in the overall population. For occupational activities, sitting on a chair had a significant inverse association with K/L grade > or =2 knee OA and lumbar spondylosis. Standing, walking, climbing, and heavy lifting were associated with K/L grade > or =2 knee OA, but were not associated with K/L grade > or =2 lumbar spondylosis. Kneeling and squatting were associated with K/L grade > or =3 knee OA. CONCLUSION This cross-sectional study using a population-based cohort suggests that sitting on a chair is a significant protective factor against both radiographic knee OA and lumbar spondylosis in Japanese subjects. An occupational activity that includes heavy lifting appears to have a greater effect on knee OA than on lumbar spondylosis.

The effects of bone morphogenetic protein and basic fibroblast growth factor on cultured mesenchymal stem cells for spine fusion.

Study Design. Posterolateral lumbar transverse process fusion was carried out using cultured mesenchymal stem cells with or without bone morphogenetic protein (BMP) and basic fibroblast growth factor (FGF). Objectives. To determine the ability of BMP and basic FGF to enhance the efficacy of bone marrow-derived mesenchymal stem cells in lumbar arthrodesis. Summary of Background Data. Our previous study hypothesized that it would be important to differentiate into osteogenic cells and to implant a large number of cells for achieving solid spinal fusions. Methods. Thirty-six adult rabbits underwent single-level bilateral posterolateral intertransverse process fusions at L4–L5. Animals were divided into 5 groups, each according to the material implanted: (1) autologous bone (autograft; n = 8); (2) mesenchymal stem cells (n = 7); (3) mesenchymal stem cells with recombinant human bone morphogenetic protein (rhBMP)-2 (mesenchymal stem cell-BMP; n = 7); (4) mesenchymal stem cells with basic FGF (mesenchymal stem cell-FGF; n = 7); and (5) mesenchymal stem cells with rhBMP-2 and basic FGF (mesenchymal stem cell-BMP-FGF; n = 7). Fresh bone marrow cells from the iliac crest of each animal were cultured in a standard medium for 2 weeks. For an additional week, the mesenchymal stem cells (1 × 106cells/mL) were cultured in 10−8M dexamethasone, type I collagen gel and porous hydroxyapatite particles with or without rhBMP-2 (2 &mgr;g/mL) and basic FGF (5 &mgr;g/mL). Animals were killed 6 weeks after surgery. Radiograph, manual palpation, and histology were used to evaluate spinal fusions. Results. Fusion rates were 5/7 in the autograft group, 0/7 in the mesenchymal stem cell group, 2/7 in the mesenchymal stem cell-BMP group, 3/7 in the mesenchymal stem cell-FGF group, and 6/7 in the mesenchymal stem cell-BMP-FGF group. The histology in some of both mesenchymal stem cell-BMP and mesenchymal stem cell-FGF groups demonstrated that fibrous tissues and cartilages remained in grafted areas. In the mesenchymal stem cell-BMP-FGF group, each grafted fragment was connected with new bone ingrowths. Conclusions. This study showed that bone marrow-derived mesenchymal stem cells cultured with rhBMP-2 and basic FGF act as a substitute for autograft in lumbar arthrodesis. This technique may yield a more consistent quality of fusion bone as compared to that with autograft.

Health-Related Quality of Life in Subjects With Low Back Pain and Knee Pain in a Population-Based Cohort Study of Japanese Men: The Research on Osteoarthritis Against Disability Study

Study Design. Cross-sectional surveys of health-related quality of life (QOL) in subjects with low back pain and knee pain using a population-based cohort. Objective. The purpose of the present study was to clarify the impact of low back pain and knee pain on QOL in men. In addition, we analyzed the impacts of vertebral fracture (VFx), lumbar spondylosis, and knee osteoarthritis (OA) on the magnitude of QOL loss in men with low back pain and knee pain. Summary of Background Data. Low back pain and knee pain are major public health issues causing disability among the elderly men, but there were no population-based studies to compare the impact of low back pain on QOL with that of knee pain in Japanese men. Methods. From 3040 participants in the Research on Osteoarthritis Against Disability study, data from 767 men older than 40 years who completed questionnaires (mean age = 69.7 years) were examined. To carry out the QOL assessment, the Medical Outcomes Study Short Form 8 (SF-8) and EuroQol (EQ-5D) were used. We examined the association of low back pain and knee pain with QOL. Furthermore, we also examined the presence of VFx and the severity of lumbar spondylosis and knee OA with the magnitude of QOL loss in men with low back pain and knee pain, respectively. Results. The impact of low back pain on QOL was larger than that of knee pain. In men with low back pain, there were few associations between Kellgren-Lawrence grade and QOL, whereas VFx was associated with physical QOL. For men with knee pain, Kellgren-Lawrence grade equal to 4 knee OA was associated with QOL. Conclusion. This study revealed that low back pain has a larger impact than knee pain on QOL. Furthermore, low back pain with VFx is strongly associated with physical QOL loss.

Association of low dietary vitamin K intake with radiographic knee osteoarthritis in the Japanese elderly population: dietary survey in a population-based cohort of the ROAD study

BackgroundThe present study sought to identify dietary nutrients associated with the prevalence of radiographic knee osteoarthritis (OA) in the Japanese elderly of a population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study.MethodsFrom the baseline survey of the ROAD study, 719 participants ≥60 years of age (270 men, 449 women) of a rural cohort were analyzed. Dietary nutrient intakes for the previous 1 month were assessed by a self-administered brief diet history questionnaire. The radiographic severity at both knees was determined by the Kellgren/Lawrence (KL) system.ResultsThe prevalence of knee OA of KL ≥2 was 70.8%. Age, body mass index, and female sex were positively associated with the prevalence. Among the dietary factors, only vitamin K intake was shown to be inversely associated with the prevalence of radiographic knee OA by multivariate logistic regression analysis. The presence of joint space narrowing of the knee was also inversely associated with vitamin K intake. The prevalence of radiographic knee OA for each dietary vitamin K intake quartile decreased with the increased intake.ConclusionsThe present cross-sectional study using a population-based cohort supports the hypothesis that low dietary vitamin K intake is a risk factor for knee OA. Vitamin K may have a protective role against knee OA and might lead to a disease-modifying treatment.

Independent association of joint space narrowing and osteophyte formation at the knee with health‐related quality of life in Japan: A cross‐sectional study

OBJECTIVE To clarify the individual associations of joint space narrowing (JSN) and osteophytosis at the knee with quality of life (QOL) in Japanese men and women using a large-scale population-based cohort from the Research on Osteoarthritis Against Disability (ROAD) study. METHODS The associations of minimum joint space width (JSW) and osteophyte area in the medial compartment of the knee with QOL parameters, such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), were examined. Minimum JSW and osteophyte area in the medial compartment of the knee were measured using a computer-aided system for the diagnosis of knee osteoarthritis. RESULTS Of the 3,040 participants in the ROAD study, the present study included 2,039 participants age 40 years or older who completed the questionnaires (741 men and 1,298 women with a mean ± SD age of 68.6 ± 10.9 years). Multiple regression analysis after adjustment for age and body mass index showed that minimum JSW was significantly associated with scores on the pain domains of the WOMAC in men and women, while osteophyte area was significantly associated with scores on the physical function domains of the WOMAC in men and women. CONCLUSION The findings of this cross-sectional study using a large-scale population from the ROAD study indicate that JSN and osteophytosis are independently associated with QOL.

Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats.

Study Design. An in vivo study using a rat lumbar disc herniation model. Objectives. To evaluate the effects of sarpogrelate hydrochloride on neurogenic pain induced by nucleus pulposus translocation and to elucidate its mechanism. Summary of Background Data. Sarpogrelate, an antiplatelet agent with selective 5-hydroxytryptamine (5-HT) receptor 2A antagonist activity, has been reported to improve low back pain, sciatica, and numbness of lower extremities in patients with lumbar disc herniation. However, the efficacy of sarpogrelate for pain relief in this situation has not been established by clinical studies and its mechanism remains unknown. Methods. The autologous nucleus pulposus was placed onto the left L4 and L5 nerve roots of 30 Sprague-Dawley rats allotted to sarpogrelate (100 mg/kg, n = 15) and control (vehicle, n = 15) treatment groups. Sarpogrelate or vehicle was administered orally once daily between days 7 and 14 after surgery. Mechanical allodynia was measured before and after treatment. The right and left nerve roots and dorsal root ganglions were isolated from 5 animals in each group to assay 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine on day 5 of administration (= day 11 after surgery). Results. Sarpogrelate treatment significantly reduced mechanical allodynia on days 5 and 8 of administration. The placement of the nucleus pulposus onto nerve roots increased norepinephrine but not 5-HT and 5-HIAA contents in inflamed nerve roots or dorsal root ganglions. Sarpogrelate did not affect these levels. Conclusions. Sarpogrelate attenuated pain-related behavior induced by the nucleus pulposus in the animal model. Although further investigation is needed concerning the mechanism of action, this study supported the hypothesis that sarpogrelate is efficacious for treating the pain of lumbar disc herniation.