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1.  The relation between progressive osteoarthritis of the knee and long term progression of osteoarthritis of the hand, hip, and lumbar spine 
Annals of the Rheumatic Diseases  2005;65(5):623-628.
Background
The association between progression of knee osteoarthritis and progression of osteoarthritis at sites distant from the knee is unclear because of a lack of multisite longitudinal progression data.
Objective
To examine the association between radiological progression of knee osteoarthritis and osteoarthritis of the hands, hips, and lumbar spine in a population based cohort.
Methods
914 women had knee x rays taken 10 years apart, which were read for the presence of osteophytes and joint space narrowing (JSN). Progression status was available for hand, hip, and lumbar spine x rays over the same 8 to 10 year period. The association between progression of knee osteoarthritis and osteoarthritis at other sites was analysed using odds ratios (OR) and 95% confidence intervals (CI) in logistic regression models.
Results
89 of 133 women had progression of knee osteoarthritis based on osteophytes, and 51 of 148 based on JSN definition. Progression of JSN in the knee was predicted by progression in lumbar spine disc space narrowing (OR = 2.9 (95% CI 1.2 to 7.5)) and hip JSN (OR = 2.0 (1.0 to 4.2)). No consistent effects were seen for hand osteoarthritis. The associations remained after adjustment for age and body mass index.
Conclusions
Progression of knee osteoarthritis is associated with progression of lumbar spine and hip osteoarthritis. This may have implications for trial methodology, the selection of patients for osteoarthritis research, and advice for patients on prognosis of osteoarthritis.
doi:10.1136/ard.2005.038414
PMCID: PMC1798151  PMID: 16219710
osteoarthritis; knee; lumbar spine; outcome
2.  Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population. 
Annals of the Rheumatic Diseases  1991;50(7):467-470.
The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.
PMCID: PMC1004459  PMID: 1877852
4.  Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis. 
Annals of the Rheumatic Diseases  1994;53(2):117-121.
OBJECTIVE--To examine the relationship between disease severity and bone density as well as vertebral fracture risk in patients with ankylosing spondylitis (AS). METHODS--Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS. BMD was measured at the hip (femoral neck -FN), lumbar spine (L1-L4-LS) and for the whole body using a hologic-QDR-1000/W absorptiometer. An algorithm based on normal female ranges of vertebral heights was used to define a fracture as occurring when two vertebral ratios were each three standard deviations below the calculated mean of the controls. RESULTS--Patients with AS had significantly lower FN-BMD in proportion to disease severity (based on a Schober index) and disease duration. LS-BMD was also reduced in early disease, but in patients with advanced AS it had increased considerably. Nine vertebral fractures (10.3%) were identified which was considerably higher than expected when compared with a fracture of 1.9% in a control population of 1035 females of a similar age range. Patients with AS with fractures were significantly older, more likely to be male, had longer disease duration and more advanced spinal limitation with less mobility. There was no significant reduction in lumbar spine or femoral neck bone density in the fracture group. CONCLUSIONS--Vertebral fractures that result from osteoporosis are a feature of longstanding AS. BMD used as a measure of osteoporosis of the spine in advanced AS is unreliable probably as a result of syndesmophyte formation and does not predict the risk of vertebral fracture. Alternative sites such as the neck of the femur should be used for sequential assessment of BMD in AS.
PMCID: PMC1005263  PMID: 8129456
5.  Definition of osteoarthritis of the knee for epidemiological studies. 
Annals of the Rheumatic Diseases  1993;52(11):790-794.
OBJECTIVES--There are no agreed criteria for osteoarthritis (OA) of the knee in population studies. The radiographic scoring system of Kellgren and Lawrence has been the system most used in the past and although other methods have been developed, comparisons have not been performed. Therefore these grading systems were compared in radiographs from a general population sample. METHODS--Anteroposterior weightbearing radiographs of 1954 knees from 977 women aged 45-64 years from the Chingford population study were read by a variety of methods, including quantitative measures of minimum joint space, qualitative measures of osteophytes and of joint space, and a qualitative Kellgren and Lawrence global score. All qualitative methods used standardised atlases. Intra-observer and interobserver reproducibility was tested on a subgroup of 100 films using three observers and two readings. Variables were dichotomised at the tenth and second centiles to define OA. Odds ratios were calculated for each method for the association of OA with knee pain, obesity, and with each of the other methods. RESULTS--Most methods had high intraobserver and interobserver reproducibility, except for measurements of lateral joint space. The best predictors of knee pain were the presence of osteophytes and the Kellgren and Lawrence grade. Methods measuring narrowing performed less well, with measurements of lateral joint space being particularly poor. Similar results were achieved in the comparison with obesity and in the comparisons between methods. CONCLUSIONS--These data suggest that the presence or absence of a definite osteophyte read by a single observer with an atlas is the best method of defining OA of the knee for epidemiological studies in women. Assessment of narrowing may be better used in evaluating severity.
PMCID: PMC1005190  PMID: 8250610
6.  C reactive protein and immunoglobulin G in synovial fluid and serum in joint disease. 
C reactive protein (CRP) and immunoglobulin G (IgG) were measured in synovial fluid and serum of 72 patients (29 with rheumatoid arthritis (RA), 17 with osteoarthritis, 11 with crystal synovitis, seven with undifferentiated arthritis, and eight with seronegative arthritis). The synovial fluid:serum (SF:S) ratios were compared with those calculated from the SF:S ratios of transferrin, caeruloplasmin, and alpha 2 macroglobulin, using the binomial test within groups and the Mann-Whitney test between groups. In RA synovial fluid CRP concentrations were lower than expected and IgG concentrations higher than expected. In osteoarthritis CRP concentrations were higher than expected. In seronegative arthritis IgG concentrations were raised. The ratio of CRP:IgG was depressed in RA. These findings are consistent with a role for CRP in the inflammatory process of RA, while the CRP:IgG ratio may be of value in the differential diagnosis of joint disease.
PMCID: PMC1004321  PMID: 1704698
7.  Cardiac tumours simulating collagen vascular disease. 
British Heart Journal  1986;55(6):592-595.
Cardiac tumours can mimic collagen vascular disease and they are often accompanied by profound systemic upset. Both benign and malignant tumours may present in this way. Three cases of cardiac tumour, two malignant and one benign, are reported with just such a presentation. A review of fifteen similar case reports showed that a spectrum of different collagen vascular diseases was diagnosed and treated before the true diagnosis emerged. In half of these cases the cardiac tumour was only diagnosed at necropsy. The diagnosis of collagen vascular disease should not be made in the absence of corroborative laboratory data. In cases of malignant cardiac tumour, and less commonly with atrial myxoma, M mode and cross sectional echocardiography may not exclude the diagnosis. There may be a good response to steroid treatment in cases of suspected but not confirmed collagen vascular disease in which the true diagnosis is cardiac tumour.
PMCID: PMC1236767  PMID: 3718799
9.  Sausage digit due to radish bacillus. 
We wish to draw attention to a very characteristic but little known syndrome. An elderly woman presented with a 'sausage finger', rheumatological jargon used to describe diffuse swelling of the digit. This proved to be a proliferative tenosynovitis caused by an atypical mycobacterium, Mycobacterium terrae, or the radish bacillus.
PMCID: PMC1000665  PMID: 7469531
10.  An articular index for the assessment of osteoarthritis. 
An articular index was devised for the sequential assessment of patients with osteoarthritis (OA). Forty-eight joint units, chosen to reflect the characteristic pattern of the disease, were scored for tenderness on pressure or movement on a 4-point scale. Four observers examined patients to assess inter- and intraobserver error. The index was highly reproducible both within and between observers; intraobserver error was, however, significantly smaller. In a double-blind, cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic. It is likely to be a useful addition to current methods of measurement in osteoarthritis.
PMCID: PMC1000661  PMID: 7008713
11.  Renal disease in rheumatoid arthritis. 
British Medical Journal  1976;1(6010):611-612.
N-Acetyl-beta-D-glucosaminidase (NAG) is a sensitive indicator of renal damage. When the urinary NAG levels of 60 patients with rheumatoid arthritis (RA) were measured a highly significant difference was detected between the mean urinary NAG excretion of the patients with RA (341 +/- 294-92 nmol h-1 mg creatinine-1) and that of 60 matched controls (67-53 +/- 16-93 nmol h-1 mg creatinine-1). In 10 patients studied no correlation could be shown between the urinary NAG levels and levels in either serum or synovial fluid. A significant positive correlation was noted between urinary NAG excretion and disease activity as estimated by the Lansbury activity index, the Ritchie articular index, and the haemaglobin level. An abnormally raised urinary NAG excretion was detected in eight out of 20 previously untreated patients with RA, which suggested that the rheumatoid process may affect renal function.
PMCID: PMC1639063  PMID: 1252848
12.  Relation between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in the general population: the Chingford study. 
Annals of the Rheumatic Diseases  1996;55(12):870-874.
OBJECTIVE: To assess the association between serum insulin-like growth factor-I (IGF-1) concentrations and osteoarthritis, and bone mineral density, and fractures in a large group of middle aged women from the general population. METHODS: 761 women aged 44-64 years from the Chingford study had serum IGF-I concentrations measured; hand, hip, spine, and anteroposterior weight bearing knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the hip and spine. X rays were scored using the Kellgren and Lawrence system. In addition knee x rays were scored using a standard atlas for individual features of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations were adjusted for the effects of age. RESULTS: In the osteoarthritis analysis results were compared to a constant group of 155 subjects with no evidence of osteoarthritis at any site. There was no significant difference in serum IGF-I between these subjects and 606 subjects with osteoarthritis at any site. When individual sites were analysed, serum IGF-I was higher in those cases with more severe bilateral knee osteoarthritis and in those with distal interphalangeal (DIP) joint disease. There was no significant association between serum IGF-I and other forms of osteoarthritis or milder forms of knee osteoarthritis. There was no correlation between IGF-I concentrations and bone mineral density at the spine or hip, nor any difference between IGF-I concentrations in subjects with and without a history of non-traumatic fracture [22.8 (SD 6.6) v 23.1 (SD 6.6) nmol litre-1, P = 0.6] CONCLUSIONS: There is a modest association between IGF-I concentrations and the development of DIP osteoarthritis and more severe or bilateral knee joint osteoarthritis in women from the normal population, but no association with other forms of osteoarthritis, bone density, or fractures.
PMCID: PMC1010336  PMID: 9014579
13.  Spiking of the tibial tubercles--a radiological feature of osteoarthritis? 
Annals of the Rheumatic Diseases  1996;55(2):105-108.
OBJECTIVE: To determine whether 'spiking' or angulation of the tibial tubercle is associated with other radiographic markers of osteoarthritis (OA) or pain in the knee joint, and could be taken as a reliable marker for early OA, in a large general population sample. METHODS: A total of 950 women from the Chingford general population survey underwent anteroposterior extended weight bearing radiography of the knees. Angulation of the tip of the medial and lateral tubercles, and height of the tubercles above the tibial plateau were measured. These measures were compared with standard radiographic indices including qualitative Kellgren and Lawrence global score, individual scores of osteophytes and joint space narrowing, and pain score. Intraobserver and interobserver reproducibility for assessment of spiking was tested in a subgroup of 50 films using two observers and two readings. Tibial spiking (angulation and height) was defined for this study as the top 10th centile for the whole population. Patients with normal radiographs (Kellgren and Lawrence grade 0) were allocated to quartile groups on the basis of spiking to define severity. Odds ratios were then calculated for the association of spiking and knee pain. RESULTS: The majority of the measures of tibial spiking were highly reproducible. There was a significant correlation between tibial spike angulation and the presence of osteophytes, but not joint space narrowing. The correlations for spike height with osteophytes and joint space narrowing were poor. There was an association between spike angulation at the lateral tubercle and reported knee pain (odds ratio 1.45 (95% confidence interval 1.03 to 2.03)) after adjustment for age, body mass index, and Kellgren and Lawrence score. There was no association between medial spike angulation or spike height and pain. Among the 950 women, 683 (72%) had normal radiographs (Kellgren and Lawrence = 0); in this group there was a similar association between pain and lateral spike angulation, but not medial spike angulation or spike height. CONCLUSIONS: Tibial spiking is associated with the presence of knee osteophytes and is reproducible, but does not have a strong independent relationship with knee pain. In patients with normal radiographs there is no useful correlation between tibial spiking and pain. Isolated tibial spiking is not a reliable sign of early knee OA, and should not routinely be reported.
PMCID: PMC1010103  PMID: 8712859
14.  Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity. 
Annals of the Rheumatic Diseases  1994;53(9):565-568.
OBJECTIVES--The natural history of knee osteoarthritis (OA) is poorly understood. The principal aim was to assess the rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease and to identify the major factors that influence this rate. METHODS--Fifty eight women aged (45-64) from a general population study cohort were identified with unilateral knee OA diagnosed radiologically (Kellgren and Lawrence 2+) (K&L). Follow up AP films were obtained at 24 months and compared with the baseline for K&L grade and individual features of osteophytes and joint space. RESULTS--Twenty women (34%) developed incident disease in the contralateral knee (based on K&L 2+ or osteophyte changes) and 22.4% (n = 13) of women progressed radiologically in the index joint. Obesity at baseline was the most important factor related to incident disease, 47% of women in the top BMI tertile developed OA, compared with 10% in the lowest tertile: relative risk 4.69 (063-34.75). No clear effect was seen for age, physical activity, trauma or presence of hand OA. CONCLUSIONS--Over one third of middle aged women with unilateral disease will progress to bilateral knee OA within two years and a fifth will progress in the index joint. Obesity is a strong and important risk factor in the primary and secondary prevention of OA. These natural history data provide a useful estimate for planning therapeutic intervention trials.
PMCID: PMC1005406  PMID: 7979593
15.  The relationship between osteoarthritis and osteoporosis in the general population: the Chingford Study. 
Annals of the Rheumatic Diseases  1994;53(3):158-162.
OBJECTIVE--A total of 979 women from the Chingford general population survey were studied to examine the hypothesis that osteoarthritis (OA) and osteoporosis are inversely related. METHODS--All women had radiographs of the hands and knees. A total of 579 also had AP radiographs of the lumbar spine which were graded for the presence of osteophytes. All women had bone densitometry performed at the lumbar spine (L1-L4) and femoral neck. Mean bone densities (BMD) were compared between those with disease and those with no disease at any other sites. All results were adjusted for age and body mass index (BMI). RESULTS--All OA groups had significantly higher bone density than controls at the lumbar spine. For distal interphalangeal (DIP) OA (n = 140) the difference was +5.8% (+3.0, +8.6), for carpometacarpal (CMC) OA (n = 160) +3.0% (+0.1, +5.9), for knee OA (n = 118) +7.6% (+4.3, +10.9), and lumbar spine OA (LSOA) (n = 194) +7.8% (+6.0, +8.8). Those with generalised OA (GOA n = 22), a combination of knee, DIP and CMC OA had an increase of +9.3 (+2.0, +16.6). For the femoral neck BMD was also increased significantly ranging from +2.5% for the CMC, +6.2% for the knee and +6.3% in the lumbar spine OA group. The risk of knee OA for women in the top tertile of BMD was 2.13 (1.15-3.93). Additional adjustment for other confounders such as smoking, alcohol, exercise, HRT, social class and spine osteophytes did not alter the results. CONCLUSIONS--These results suggest that small increases in BMD are present in middle aged women with early radiological OA of the hands, knees and lumbar spine. These data support the hypothesis that the two conditions are inversely related, although the mechanisms remain unclear.
PMCID: PMC1005278  PMID: 8154931

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