Larsen Grade Research Articles

Involvement of fibroblast growth factor-2 in joint destruction of rheumatoid arthritis patients.

To investigate the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patients with different severities of joint destruction on osteoclastogenesis and bone resorption. Synovial fluid was harvested from the knee joints of 59 RA patients and 37 ostcoarthritis (OA) patients. RA patients with Larsen's knee grade 1-3 were classified as mild RA (n = 30) and those with grade 4 or 5 as severe RA (n = 29). Cytokine concentrations in synovial fluid were measured by ELISA. Osteoclastogenesis was measured by tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in a co-culture of mouse osteoblastic cells and bone marrow cells, and bone resorption by 45Ca release from pre-labelled cultured neonatal mouse calvariae. The synovial fluid of severe RA patients significantly stimulated TRAP-positive MNC formation and 45Ca release compared to those of mild RA and OA patients. Among the bone-resorptive cytokines fibroblast growth factor-2 (FGF-2), tumour necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6 and soluble IL-6 receptor (sIL-6R), only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. The increase in endogenous FGF-2 levels in the synovial fluid of RA patients may play a role in the joint destruction by inducing osteoclastogenesis.

Larsen grades in evaluating the first carpometacarpal joint

Objective: To illustrate different Larsen grades for CMC I. Methods: In the Heinola Follow-up Survey of Arthritis 103 seropositive patients with rheumatoid arthritis (RA) were followed prospectively over 20 years. Hand radiographs were taken at onset and at 1, 3, 8, 15, and 20 years from entry. One female patient was selected to demonstrate Larsen grades for CMC I, as she presented all the different grades of destruction during the progression of RA. Interobserver and intraobserver errors in grading of CMC I were tested. Results: Radiographs of the different grades with schematic presentation are illustrated. Interobserver and intraobserver errors were in the Weighted Kappa test 0.75 and 0.82, respectively. Conclusion: We emphasise the importance of following the destruction of CMC I separate from the entire carpus during the course of RA.

Association between hypoxanthine concentration in synovial fluid and joint destruction in patients with rheumatoid arthritis

To evaluate the significance of augmented levels of hypoxanthine in synovial fluids in patients with rheumatoid arthritis (RA), the hypoxanthine level in the synovial fluid was investigated in association with joint damage. Concentrations of hypoxanthine, xanthine and uric acid in synovial fluids from knee joints of 45 patients with RA, six patients with gout and five patients with osteoarthritis were determined by high performance liquid chromatography. Relationships between these oxypurines and markers for joint inflammation or Larsen grade of knee joint X-ray film were analyzed. Hypoxanthine levels were significantly elevated in patients with RA and with gout but not in those with osteoarthritis. In RA patients, levels of synovial fluid hypoxanthine were correlated with matrix metalloproteinases MMP-3 (r=0.510), but not with C-reactive protein nor synovial fluid cytokines. Among various biological factors in synovial fluid (including cytokines and metalloproteinases) only hypoxanthine levels were significantly (P<0.05) positively correlated with Larsen’s grade of knee joint. In conclusion, augmented levels of synovial hypoxanthine can indicate joint damage in patients with RA and might be a useful marker in a clinical context.

Association between hypoxanthine concentration in synovial fluid and joint destruction in patients with rheumatoid arthritis

To evaluate the significance of augmented levels of hypoxanthine in synovial fluids in patients with rheumatoid arthritis (RA), the hypoxanthine level in the synovial fluid was investigated in association with joint damage. Concentrations of hypoxanthine, xanthine and uric acid in synovial fluids from knee joints of 45 patients with RA, six patients with gout and five patients with osteoarthritis were determined by high performance liquid chromatography. Relationships between these oxypurines and markers for joint inflammation or Larsen grade of knee joint X-ray film were analyzed. Hypoxanthine levels were significantly elevated in patients with RA and with gout but not in those with osteoarthritis. In RA patients, levels of synovial fluid hypoxanthine were correlated with matrix metalloproteinases MMP-3 (r=0.510), but not with C-reactive protein nor synovial fluid cytokines. Among various biological factors in synovial fluid (including cytokines and metalloproteinases) only hypoxanthine levels were significantly (P<0.05) positively correlated with Larsen’s grade of knee joint. In conclusion, augmented levels of synovial hypoxanthine can indicate joint damage in patients with RA and might be a useful marker in a clinical context.

Hip Involvement in Seropositive Rheumatoid Arthritis: Survivorship analysis with a 15-year follow-up

In a prospective survey of recent arthritis 96 patients had erosive and seropositive rheumatoid arthritis (RA). Severe radiological changes in the hip joint (Larsen grade 3-5) were observed in 31 (32%) and acetabular protrusion in five (5%) patients 15 years after the onset of arthritis. At the end of follow-up Larsen score 0-100 of peripheral joints (p<0.015), HAQ (p<0.001), ESR (p<0.001), and CRP (p<0.01) were significantly higher in patients with hip joint destruction than in those without. Secondary amyloidosis was found in eight patients with and in three patients without hip involvement (p=0.002). In survivorship analysis (the Larsen 0-2 grade hips) an overall predicted rate of survival was 80% after 14 years of rheumatoid arthritis. When analyzed according to HLA-B27 the rate of radiological survival for the patients with a positive test was 62% and 87% for the others (p=0.02). In conclusion, RA patients with high number of destructive peripheral joints (Larsen score) and high ESR or CRP should be carefully monitored due to the increased risk of hip destruction.

Destruction and Arthroplasties of the Metatarsophalangeal Joints in Seropositive Rheumatoid Arthritis: A 20-year follow-up study

Destruction and arthroplasties of the metatarsophalangeal (MTP)joints and interphalangeal (IP) joint of the big toe were evaluated in 103 seropositive rheumatoid arthritis (RA) patients in a prospective follow-up study at onset and at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year follow-up and 68 attended the 20-year follow-up. Data on the forefoot synovectomies and reconstructions performed were obtained from patient documents and radiographs. The radiographs were assigned by the Larsen method; in the end point analysis the last or preoperative radiograph was used. Erosions of Larsen grade > or =2 were present in 6%/ of the investigated 1236 joints at onset and after 20 years in 62%, respectively. At the end point, 24% of the joints were severely damaged (Larsen grade 4-5). The MTP I and IP joints showed the lowest grade of destruction during follow-up, and MTP V the worst destruction. Synovectomies were performed in 24 MTP joints; a total of 75% of these joints were later resected. MTP II-V head resections were performed in 21% and the Keller procedure in 12% of the MTP I joints. Erosive changes occur early in the MTP joints, and their grade of destruction is high; therefore they should be included in radiographic criteria and scores. MTP synovectomies are insufficient treatments for RA without concomitant immunosuppression of the disease.

A 20-year Follow-up Study of Subtalar Changes in Rheumatoid Arthritis

The destruction of the subtalar joints in 103 seropositive RA patients with recent (6 months) disease was evaluated radiographically in a prospective follow-up study at onset and at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year follow-up and 68 the 20-year follow-up. The Larsen grades of the joints were evaluated and the need for surgical treatment considered. At the 15-year follow-up the mean Larsen grade was 1.2 (median 0) and at the 20-year follow-up 1.3 (median 0); at the 20-year follow-up 77 subtalar joints were still assessed as Larsen grade 0. In this series, subtalar fusions were performed in 12 patients only. Spontaneous fusions occurred in 5 hindfeet in 3 patients.The destruction rate of the subtalar joint was lower than in previous retrospective or cross-sectional studies. The need for routine radiographs of ankles in RA patients is questioned.

Does wrist fusion cause destruction of the first carpometacarpal joint in rheumatoid arthritis? 18 patients followed for 2-6 years.

We evaluated radiographic destruction of the first carpometacarpal joint (CMC I) in 18 hands with wrist fusions and compared it with the unoperated contralateral hands preoperatively and after a follow-up of a mean of 4.4 (2-6) years. Patients were obtained from a prospective 20-year follow-up study of 103 patients with seropositive rheumatoid arthritis. The degree of destruction in the CMC I-joints was evaluated with Larsen grades. The mean value of Larsen indices for CMC I was 0.9 before wrist fusion and 2.5 (p < 0.001) at the follow-up, compared to 0.8 and 1.3 (p = 0.06) in the control hands, respectively. No preoperative difference was found between the hands to be fused and the control hands, but the difference was significant (p = 0.009) after the follow-up.

Measurement of hand bone mineral content by dual energy x-ray absorptiometry: development of the method, and its application in normal volunteers and in patients with rheumatoid arthritis.

OBJECTIVES--To develop a method of measuring hand bone mineral content (BMC) by dual energy x ray absorptiometry (DXA); to apply this method of measuring hand BMC to normal volunteers to ascertain causes of variability; and to measure hand BMC in patients with rheumatoid arthritis (RA) of varying duration and severity. METHODS--The x ray beam of the Hologic QDR 1000 dual energy x ray absorptiometer was hardened by introducing a perspex-aluminium plate and the analysis software altered to allow for the small tissue bulk of the hand compared with the torso. Ninety five volunteers (46 men age 24-81 and 49 women age 20-83) had scans of both hands. Eight volunteers were assessed repeatedly to establish reproducibility and effect of hand position. Fifty six patients (22 men, 34 women, age range 25-86 years) with RA of differing duration and severity, had hand BMC measurement by DXA. RESULTS--The precision of BMC measurement was 2.3% with no additional variation due to hand position. Hand dominance had no significant effect on BMC. In men, hand BMC correlated with height (r = 0.57, p < 0.0001), weight (r = 0.58, p < 0.0001), forearm span (r = 0.5, p = 0.0006) and hand volume (r = 0.66, p < 0.0001). In women hand BMC correlated with height (r = 0.66, p < 0.0001), weight (r = 0.4, p = 0.003), forearm span (r = 0.3, p = 0.03) and hand volume (r = 0.49, p = 0.0008). After correcting for all these variables, male volunteers had significantly higher hand BMC than female volunteers (p = 0.01) and patients with RA had lower hand BMC than normal volunteers (total hand BMC in male volunteers 90.9 gms, 95% CI 86.9-95, in male patients 81.7 gms, 95% CI 73.7-89.6, p < 0.004, total hand BMC in female volunteers 62.2 gms 95% CI 59.8-64.5, female patients 52.3 gms, 95% CI 48.1-56.5, p < 0.005). In patients with RA, the hand BMC showed an inverse correlation with age (r = -0.44, p = 0.01), disease duration (r = -0.62, p = 0.0003), Larsen's grades (r = -0.62, p = 0.0002) and modified Sharp's method score (r = -0.69, p < 0.0001) in female patients only. CONCLUSIONS--A new, sensitive and reproducible technique of measurement of hand bone mineral content by DXA, has been developed and this method has been applied to normal volunteers and patients with RA. Hand dominance had no significant effect on hand BMC. After correcting for physical size, men have higher hand BMC than women. Hand BMC inversely correlates in women patients with disease duration and other validated methods of assessing radiological outcome in RA. Longitudinal studies are needed to establish its role in monitoring disease progression.

慢性関節リウマチにおける膝関節の鏡視下滑膜切除術の術後成績

The clinical results after arthroscopic synovectomy in 24 knees of 14 RA patients with chronic synovitis were reviewed. The follow-up period ranged from 2 to 55 months, with an average of 32 months. The operated knee joints were divided into early synovectomy (Larsen's grade 0, 1, 2) and late synovectomy (Larsen's grade 3, 4, 5). Compared with preoperative findings, pain and swelling was on the whole improved. In early synovectomy, pain and swelling was improved in 11 of 13 knees and the effect was expected to remain for 3 to 5 years. In comparison, in late synovectomy, pain and swelling was improved in 5 of 9 knees (56%) within 3 years after surgery, with none achieving a good result after more than 3 years. This procedure seems to be indicated in early grade patients and appears to provide significant time saving in late grade patients.

Precision of Larsen grading of radiographs in assessing progression of rheumatoid arthritis in individual patients.

A study was designed to evaluate observer variation in the assessment of radiographic deterioration of individual patients using the Larsen grading system. Radiographs of hands and feet of 52 patients were assessed by three observers. Each patient had paired films taken one year apart which were assessed together for change in score. To assess within-observer variation each set of films was read twice by all observers. The average progression was 11.6 (SD 9.0). Analysis of the source of variation showed the single observer replication SD to be 3.7 but that for different observers to be 5.5. This may be interpreted as indicating that to achieve 95% confidence of detecting a true change an increase in Larsen score of 8 is required if the same observer assesses or up to 11 if a different observer assesses.

Discriminative Power of Larsen's Grading System for Assessing the Course of Rheumatoid Arthritis

In the classification of 18628 joints in 186 patients with rheumatoid arthritis during a follow-up of 3 to 12 years, the discriminative power of Larsen's scoring system was assessed. Obvious radiologic progression did not give rise to a change of grading in 9.5 per cent of the examinations. For investigations with a relatively short observation period, more detailed scoring systems should therefore be used.

Radiologic evaluation of the progression of rheumatoid arthritis.

The severity of rheumatoid arthritis in 20 groups of limb joints was evaluated by means of 661 skeletal radiologic examinations on 188 patients. The severity of the disease was classified by grades 0 to 5 in accordance with Larsen's grading system and was related to the duration of the condition. The result differs at several points from results in other surveys.