Regression to the mean using the disease activity score in eligibility and response criteria for prescribing TNF-alpha inhibitors in adults with rheumatoid arthritis.

OBJECTIVES: When patients with rheumatoid arthritis (RA) are selected to start TNF-alpha inhibitors on the basis of high disease activity scores (DAS), some of the fall in DAS will be due to regression to the mean (RTM). We have assessed the extent to which such RTM explains DAS improvements on TNF-alpha inhibitors in routine clinical practice. METHODS: We retrospectively evaluated DAS28 scores that had been recorded as part of routine assessment for two RA cohorts. (i) Thirty-five patients receiving TNF-alpha inhibitors who had been assessed when starting TNF-alpha inhibitors, 9-21 months prior and 1.5-6 months post-treatment. (ii) One hundred and seventy-seven clinic patients assessed twice, a year apart in the years immediately before the introduction of TNF-alpha inhibitors. RESULTS: In patients receiving TNF-alpha inhibitors, mean DAS fell 1.8 (95% confidence interval [CI] 1.3, 2.3) from baseline but only 0.9 (95% CI 0.4, 1.4) from the previous routine assessment. Twenty-four (69%) patients showed a fall in DAS of >1.2 from baseline but only 17 (49%) from the previous assessment. Regression analysis of results from the pre-biological era estimated that as much as 0.6 of the 1.8 apparent DAS response to TNF-alpha inhibitors might be accounted for by RTM. CONCLUSIONS: Assessing change in DAS from commencement of biological therapy may overestimate response, due to the impact of RTM and fluctuation in disease. Adequacy of response might be better assessed by serial assessments and a wider range of patient-centred outcomes.

The relation between progressive osteoarthritis of the knee and long term progression of osteoarthritis of the hand, hip, and lumbar spine.

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.

Touch-screen computer systems in the rheumatology clinic offer a reliable and user-friendly means of collecting quality-of-life and outcome data from patients with rheumatoid arthritis.

OBJECTIVES: To investigate the feasibility of collecting rheumatoid arthritis (RA) patient self-administered outcome data using touch-screen computers in a routine out-patient clinic. METHODS: Forty patients with RA completed the touch-screen and paper Rheumatoid Arthritis Quality of Life Questionnaire (RAQol) in the clinic and rated ease of use and preference. Forty-five others completed the Stanford Health Assessment Questionnaire (HAQ) and visual analogue scales (VASs) for pain, fatigue and global arthritis activity on touch screen and paper and a joint assessment on touch screen. They rated ease of use and willingness to complete the assessment again. Joints were independently assessed, and completion times and technical problems recorded. RESULTS: No technical problems were encountered. The touch-screen RAQol took no longer to complete, was preferred by 64% (33% had no preference) and was rated significantly higher for ease of use (two-tailed P=0.003, n=40) even by computer naïve patients (two-tailed P=0.031, n=24). Intraclass correlation coefficients between methods were high for RAQol (0.986) and tender joint counts (0.918), and as high for the pain, fatigue and global activity (0.855, 0.741, 0.881) as for test-retest of the paper versions (0.865, 0.746, 0.863). Ninety-eight per cent rated the touch screen very/quite easy for HAQ and VAS, and 90% for joint assessment. Ninety-six per cent stated a willingness to complete the touch-screen assessment in clinic again. CONCLUSIONS: Touch-screen questionnaires in the clinic can produce comparable results to paper, eliminate the need for data entry and afford immediate access to results. It is an acceptable, and in many cases a preferable, option to paper, regardless of age and previous experience of computers.

A simple extension to the Rheumatoid Arthritis Quality of Life Questionnaire (RAQol) to explore individual patient concerns and monitor group outcome in clinical practice.

OBJECTIVES: To find out if the RAQol, if extended by a qualifying question on the level of concern associated with each item, can function both as a group outcome measure and as a useful tool to identify the concerns of individual patients. METHODS: Thirty-seven rheumatoid arthritis (RA) patients completed the questionnaire before and after starting a biological therapy. One hundred and forty-five others receiving routine care completed it at baseline, weeks 12 and 13 with EuroQol VAS and questions on global arthritis impact and any other concerns. Reproducibility was assessed in all 59 participants whose condition remained stable between weeks 12 and 13. RESULTS: The RAQol score was highly reproducible (intraclass correlation coefficient 0.986, n=59), reflected global RA impact (P = 0.000, n=140), negatively correlated with EuroQol VAS (Spearman coefficient=-0.639, two-tailed significance=0.000, n=142), responsive to biological therapy (two-tailed P= 0.000) and to increased global RA impact over 12 weeks (two-tailed P=0.012, n=37), and had high internal consistency (Cronbach's alpha=0.94, n=143). The number of issues of great concern and their percentage contribution to the RAQol score were related to global arthritis impact (P=0.000 for both) and reduced by a biological therapy (two-tailed P=0.000 and 0.001 respectively). The mean kappa for consistency in identifying each item as a concern was 0.801 (range 0.633-0.921). CONCLUSIONS: Use of the 'extended' RAQol in clinical practice could provide a valid and sensitive score for monitoring group outcome and a comprehensive and consistent list of an individual's main issues of concern to assist assessment of needs in routine clinical practice.

Risk factors for progression of lumbar spine disc degeneration: the Chingford Study.

OBJECTIVE: Few data exist concerning the natural history of lumbar spine disc degeneration and associated risk factors. We therefore undertook this study to examine the radiographic progression of lumbar spine disc degeneration over the course of 9 years in a population-based inception cohort of women from the Chingford Study. METHODS: Seven hundred ninety-six paired lumbar spine radiographs were read by a single reader for anterior osteophytes (AO) and disc space narrowing (DSN) using the Lane atlas at each lumbar disc space (L1-5). Disc degeneration was defined using thresholds of AO and DSN grade 1+ in one or more vertebrae (L1-5) within a subject. Progression was defined as an increase in grade in an affected year-1 vertebra. Potential risk factors were assessed using odds ratios and 95% confidence intervals adjusted for age, body mass index (BMI), and other potential confounders in logistic regression models using the STATA statistical package. RESULTS: The mean +/- SD age at baseline was 53.8 +/- 6.0 years, and mean +/- SD BMI was 25.4 +/- 4.1 kg/m(2). Progression rates for AO and DSN were 4% per annum and 3% per annum, respectively. Progression of DSN was predicted by age, back pain, and radiographic hip and knee osteoarthritis (OA). Progression of AO was predicted by age and radiographic hip OA, with borderline significance for BMI >30 kg/m(2). No significant effects were seen for smoking, physical activity, hormone replacement therapy use, multiparity, or hand OA. CONCLUSION: This is the first population-based longitudinal study to assess progression of the individual radiographic features of AO and DSN in lumbar spine disc degeneration. We demonstrated progression rates of 3-4% per annum, with important risk factors for progression, including age, back pain, and radiographic OA at the hip and knee.

Multisite quantitative ultrasound: Colles' fracture discrimination in postmenopausal women.

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles' fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenopausal Colles' fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07-2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06-3.23] for the phalanx and 1.74 [1.12-2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34-2.85] for the lumbar spine, 2.21 [1.43-3.40] for the femoral neck and 2.62 [1.69-4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer's ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21-3.33], for the radius and metatarsal 1.67 [1.05-2.67], for the phalanx and metatarsal 1.86 [1.11-3.08] and for the radius, phalanx and metatarsal 1.81 [1.07-3.06]. Combinations of DXA sites gave 2.22 [1.44-3.41] for the lumbar spine and femoral neck and 2.41 [1.57-3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles' fracture patients, although the odds ratios were lower than with spine and femur BMD.

Does the Stanford Health Assessment Questionnaire have potential as a monitoring tool for subjects with rheumatoid arthritis?

OBJECTIVE: To assist in the interpretation of the Stanford Health Assessment Questionnaire (HAQ) score changes for individual patients with rheumatoid arthritis (RA), by determining the minimum size of score change that can confidently be considered to reflect a significant change in disability from the patient's perspective. METHOD: HAQ score changes were calculated for 40 clinic patients with RA who had reported no change to health in general over two months. These were considered to reflect both inconsistencies in questionnaire completion and any true but minor changes not considered significant enough by the patients to represent a change to their health in general. HAQ score changes over one year were also calculated for 207 clinic patients with RA. RESULTS: The range within which 95% of score changes would be expected to lie in the absence of significant change was estimated as +/-0.48 points (+/-2SD of the score changes) and 80% within +/-0.31 points (+/-1.29SD). A chi(2) test showed no significant association between an HAQ score increase of >0.31 over one year and decline in health related to arthritis reported by the patient over the same period. CONCLUSION: As a general guideline, an HAQ score needs to change by 0.48 points or more for 95% confidence that it reflects significant change (0.31 for 80% confidence). Although the value of HAQ as a group outcome measure is well established, this study questions the usefulness of monitoring individual HAQ scores in a clinical setting.

The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.

The links between joint damage and disability in rheumatoid arthritis.

OBJECTIVE: The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. METHODS: MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). RESULTS: Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. CONCLUSIONS: Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.

Family history of appendicular fracture and risk of osteoporosis: a population-based study.

Family and twin studies demonstrate a strong genetic component to osteoporosis, suggesting that a positive family history for this disease may be an important clinical risk factor. We have therefore explored the extent to which a history of wrist fracture in a female first-degree relative was associated with an increased risk of prevalent fracture at both appendicular and vertebral sites in a cross-sectional study design. One thousand and three Caucasian women (age range 45-64 years) were studied from a UK population cohort. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Appendicular fractures (wrist and hip) were recorded by questionnaire and validated from radiographs and hospital records. Vertebral fractures were assessed using radiologic survey of the thoracolumbar spine and semi-automated morphometric analysis. A positive family history of osteoporotic fracture (hip and/or wrist) in either a mother and/or sister was reported in 138 of the 1003 women. When compared with those with a negative family history of fracture, BMD was significantly reduced in those with a positive history at both the spine (p = 0.02) and the hip (p = 0.02). In total, there were 63 validated fragility fractures found in the 1003 women (16 wrist, 6 hip and 41 vertebral). Family history of osteoporotic fracture was associated with an increased total risk for osteoporotic fracture, with an odds ratio (95% confidence interval) of 2.02 (1.02, 3.78). Site-specific analysis showed that a positive family history of wrist fracture was associated with a considerably elevated risk of wrist fracture, with an odds ratio of 4.24 (1.44, 12.67). These increases in risk remained after adjustment for BMD, suggesting that other genetic factors account for the familial risk of osteoporosis and fracture.

Incidence and risk factors for radiographic knee osteoarthritis in middle-aged women: the Chingford Study.

OBJECTIVE: To examine the natural history, role of risk factors, and incidence of knee osteoarthritis (OA) in a prospective study of women from a population cohort. METHODS: Women from the Chingford Study who had been recruited in 1989 were followed up with knee radiographs 4 years later. A total of 715 paired radiographs (71% of the original sample) were graded for osteophytes and 644 for joint space narrowing (JSN). Women whose radiographs had been graded as 0 in 1989 and as > or =14 years later were classified as having incident disease. Incident cases were compared with controls for associations with a number of risk factors. RESULTS: Eighty-one women (12.6%) developed JSN of the knee, equating to an incidence of 3.1% per year. No clear risk factors for JSN were identified. Reproducibility of measures of joint space is poor, however, leading to inaccuracy of definition. Incident knee osteophytes developed in 95 women (133%), equating to an incidence of 3.3% per year. Compared with controls, women with incident knee osteophytes were older, heavier, and had more hand OA and knee symptoms. Women in the top tertile of obesity (body mass index >26.4) had a significantly increased risk of incident knee osteophytes (odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.29-4.39). Incident knee osteophytes increased by 20% per 5-year age increase. A nonsignificant protective effect for incident knee osteophytes was seen with current estrogen replacement therapy (ERT) (OR 0.41, 95% CI 0.12-1.42). No effect was associated with smoking, physical activity, hysterectomy, or previous knee injury. CONCLUSION: Obesity and aging are associated with a high risk of new knee OA developing in women. Evidence of a protective effect of ERT was seen. No clear association was found for incident JSN, suggesting that different etiologic mechanisms are operating or that standard radiographs are an inaccurate measure of incident narrowing.

Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women.

OBJECTIVES: Few data are available on the effects of combination therapy for the treatment of osteoporosis. The aim of this study was to compare the effects of intermittent cyclical etidronate (E) therapy alone with a combination of cyclical etidronate and calcitriol (E + C) on spine and femoral neck bone mineral density (BMD) at one year. METHODS: Postmenopausal women with at least one non-traumatic vertebral fracture or z score < -1.5 were randomly allocated to an E group (each cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily for 76 days) or an E + C group (as for E plus oral calcitriol 0.5 microgram daily). Lumbar spine and femoral neck BMDs were measured by dual energy x ray absorptiometry at baseline and at one year. The study design did not contain a placebo group. RESULTS: The mean % increase in lumbar spine BMD was 5.2% (95% CI = 3.4 to 7.0) in the E + C group (n = 24), which was significantly greater than the 2.7% (95% CI = 1.3 to 4.1) increase in the E group (n = 23) (p < 0.05). The femoral neck BMD in the E + C group increased by 2.0% (95% CI = 0.8 to 3.2), which was significantly different from the E group where there was a -0.4% (95% CI = -2.4 to 1.6) change (p = 0.046). CONCLUSIONS: These data show that a combination of cyclical etidronate and calcitriol is better than cyclical etidronate alone in terms of changes in BMD at both spine and femoral neck sites. Although further data are needed on fracture efficacy, this study suggests that combination therapies have additive therapeutic potential that may exceed that expected from their theoretical mode of action.

Is hormone replacement therapy protective for hand and knee osteoarthritis in women?: The Chingford Study.

OBJECTIVES: To explore whether hormone replacement therapy (HRT) has a protective role for osteoarthritis (OA) of the hand and knee in a cross sectional study of women in the general population. METHODS: 1003 women aged 45-64 (mean age 54.2) from the Chingford Study were asked details of HRT use. Standard anteroposterior radiographs of hands, knees were taken and scored according to the methods of Kellgren and Lawrence (grade 2+ positive for OA), and using individual features of osteophytes and joint space narrowing. Analysis compared ever use (> 12 months) versus never use, and current use (> 12 months) versus never use. Only 606 definitely postmenopausal women were included in the analysis. Odds ratios and 95% confidence intervals were calculated using logistic regression for risk of user versus non-user at each site, adjusted for age, height and weight, menopausal age and for bone mineral density of the femoral neck. RESULTS: For current users (n = 72) there was a significant protective effect of HRT for knee OA (defined by Kellgren and Lawrence grade or osteophytes 0.31 (95% CI 0.11, 0.93), and a similar but not significant effect for moderate joint space narrowing of the knee, 0.41 (95% CI 0.05, 3.15) and for distal interphalangeal OA 0.48 (95% CI 0.17, 1.42). No clear effect was seen for the carpometacarpal joint, CMC OA 0.94 (95% CI 0.44, 2.03). When analysing ever users (n = 129) the protective effect was reduced. For ex-users of > 12 months (mean duration 40.7 months), there was no overall protective effect of HRT for OA. Additional adjustment for hysterectomy, physical activity, social class, and smoking made little difference to the results. CONCLUSIONS: These data show an inverse association of current HRT use and radiological OA of the knee suggestive of a protective effect. The effect was weaker in the hand joints. The mechanism of the protection is unclear but has important implications for aetiopathogenesis.

Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease.

OBJECTIVE: To examine the role of low-grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee. METHODS: We used a new, high-sensitivity, automated monoclonal antibody immunoassay for the classic acute-phase protein, C-reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44-67) on entry into a population-based study of OA in Chingford, North London. In those defined radiologically as "cases," the knee radiographs were repeated after 4 years. RESULTS: Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren-Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0-5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3-1.8) (P < 0.001). Median levels of CRP were higher in the 31 women whose disease progressed at least 1 Kellgren-Lawrence grade (median 2.6 mg/liter, IQR 1.9-4.6), compared with the 39 whose disease did not (median 1.3 mg/liter, IQR 0.6-2.4) (P = 0.006) . The significance of these differences persisted after adjustment for age, weight, height, smoking, knee pain, or injury. Classifying disease by the presence of joint space narrowing or osteophytes alone produced similar results. CONCLUSION: CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.

The association between osteoarthritis and osteoporotic fracture: the Chingford Study.

Studies of the association between the presence of osteoarthritis (OA) and the risk of osteoporotic fractures have produced conflicting results. To address this question further, we have examined the association between self-reported, validated fractures and radiological OA at multiple sites in a large population of normal Caucasian women aged 45-65 yr. Despite having increased bone mineral density (BMD) of 5.3%, subjects with hip OA had a significantly increased risk of fracture [odds ratio (OR) 2.38, 95% CI 1.06-5.35] compared to controls. Subjects with lumbar spine OA, however, had a significantly reduced risk of fracture (OR 0.45, 95% CI 0.23-0.80) compared to controls. This association was not explained by differences in BMD, weight, sex hormones or physical activity. No clear association was seen with fracture for hand or knee OA. These data suggest that the increased risk of fracture in subjects with OA of the hip is most likely to be due to mechanical and locomotor factors, such as the risk of falling.

Relation between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in the general population: the Chingford study.

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.

Generalized osteoarthritis in women: pattern of joint involvement and approaches to definition for epidemiological studies.

OBJECTIVE: To ascertain whether clustering between joint sites in osteoarthritis (OA) is more common than would be expected simply from the rising prevalence of the disorder with age, and to explore a definition of generalized OA (GOA) by determining the pattern of joint group involvement, in a population sample of peri and postmenopausal women. METHODS: Radiographs of the hands, knees, and hips were obtained in a population sample of 702 women aged 45 to 64 years. Distal interphalangeal, proximal interphalangeal, carpometacarpal, knee, and hip OA were assessed using the Kellgren-Lawrence grading system. Logistic regression was used to test for overall clustering of OA between joint sites, and log linear models were used to study the patterns of association between different sites. RESULTS: Multiple involvement of the 5 joint groups studied occurred significantly more frequently than could be expected by chance alone (chi 2 = 52.3, df = 5, p < 0.001), and this clustering remained significant after age adjustment (chi 2 = 26.1, df = 5, p < 0.001). Thresholds could be defined for the number of involved joint groups that distinguished a polyarticular subset of OA. These thresholds varied with age and the radiographic cutoff at which OA was assigned. Thus, for grade 2+ disease, GOA could be defined by involvement of 2 or more joint groups at age 45-47 years, but required involvement of all 5 joint groups at age 60-64 years. Symmetry within joint groups was the most pronounced feature in the pattern of joint involvement in the sample as a whole, with associations between different joint groups being substantially weaker than those for symmetrical bilateral involvement of a particular joint. CONCLUSION: There is a clear tendency towards polyarticular OA among women aged 45-64 years. However, there is no single threshold number of joint sites that can be used to define GOA. The pattern of joint involvement in OA is primarily symmetrical, and this pattern strongly suggests a systemic etiology in this subset of postmenopausal women.

The effect of weight-bearing exercise on bone mineral density: a study of female ex-elite athletes and the general population.

The aim of this retrospective cohort study was to estimate the changes in bone mineral density (BMD) as a consequence of exercise in female ex-athletes and age-matched controls. Eighty-three ex-elite female athletes (67 middle and long distance runners, 16 tennis players, currently aged 40-65) were recruited from the original records of their sporting associations. Controls were 585 age-matched females. The main outcome measures were BMD of lumbar spine (LS), femoral neck (FN), and forearm, estimated by dual-energy X-ray absorptiometry (DXA) scan. Levels of physical activity were assessed using a modified Allied Dunbar Fitness Survey scale and classified as (a) ex-athletes, (b) active controls (> or = 1 h of vigorous physical activity currently and in the past), (c) low activity controls with inconsistent or intermediate levels of activity, and (d) inactive controls (< 15 minutes of exercise per week). After adjustment for differences in age, weight, height, and smoking, athletes had greater BMDs than controls: 8.7% at the LS (95% confidence interval [CI] 5.4-12.0; p < 0.001) and 12.1% at FN (CI 9.0-15.3; p < 0.001). The benefits of exercise appeared to persist after cessation of sporting activity. Active controls (n = 22) had greater BMDs than the inactive group (n = 347): 7.9% LS (CI 2.0-13.8; p = 0.009) and 8.3% FN (CI 2.7-13.8; p = 0.004). The low activity controls (n = 216) had an intermediate BMD. Tennis players had greater BMDs compared with runners: 12.0% LS (CI 5.7-18.2; p = 0.0004) and 6.5% FN (CI -0.2-13.2; p = 0.066). The BMD of tennis players' dominant forearms were greater than their nondominant forearms. In conclusion, regular vigorous weight-bearing exercise of 1 h or more per week is associated with an increase in BMD within a normal population. This study confirms long-term weight-bearing exercise as an important factor in the regulation of bone mass and fracture prevention.

Risk of osteoarthritis associated with long-term weight-bearing sports: a radiologic survey of the hips and knees in female ex-athletes and population controls.

OBJECTIVE: To estimate the risk of osteoarthritis (OA) of the hip and knee due to long-term weight-bearing sports activity in ex-elite athletes and the general population. METHODS: A retrospective cohort study was conducted of 81 female ex-elite athletes (67 middle- and long-distance runners, and 14 tennis players), currently ages 40-65, recruited from original playing records, and 977 age-matched female controls, taken from the age-sex register of the offices of a group general practice in Chingford, Northeast London, England. The definition of OA included radiologic changes (joint space narrowing and osteophytosis) in the hip joints, patellofemoral (PF) joints, and tibiofemoral (TF) joints. RESULTS: Compared with controls of similar age, the ex-athletes had greater rates of radiologic OA at all sites. This association increased further after adjustment for height and weight differences, and was strongest for the presence of osteophytes at the TF joints (odds ratio [OR] 3.57, 95% confidence interval [95% CI] 1.89-6.71), at the PF joints (OR 3.50, 95% CI 1.80-6.81), narrowing at the PF joints (OR 2.97, 95% CI 1.15-7.67), femoral osteophytes (OR 2.52, 95% CI 1.01-6.26), and hip joint narrowing (OR 1.60, 95% CI 0.73-3.48), and was weakest for narrowing at the TF joints (OR 1.17, 95% CI 0.71-1.94). No clear risk factors were seen within the ex-athlete groups, although the tennis players tended to have more osteophytes at the TF joints and hip, but the runners had more PF joint disease. Within the control group, a small subgroup of 22 women who reported long-term vigorous weight-bearing exercise had risks of OA similar to those of the ex-athletes. Ex-athletes had similar rates of symptom reporting but higher pain thresholds than controls, as measured by calibrated dolorimeter. CONCLUSION: Weight-bearing sports activity in women is associated with a 2-3-fold increased risk of radiologic OA (particularly the presence of osteophytes) of the knees and hips. The risk was similar in ex-elite athletes and in a subgroup from the general population who reported long-term sports activity, suggesting that duration rather than frequency of training is important.

Assessment of osteopenia from spine radiographs using two different methods: the Chingford Study.

Two methods for diagnosing radiological osteopenia in thoracic (TS) and lumbar (LS) spine radiographs were assessed: a subjective conventional method (A) and a semiquantitative method (B), by comparing them with bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA), in a population of "normal" women aged 45-70 years (n = 818). For both methods there was good intraobserver and interobserver reproducibility. BMDs were significantly lower with increasing radiological osteopenia grades (p < 0.001), and remained lower after adjustment for age and body mass index (p < 0.01). The proportion of subjects with DEXA-defined osteoporosis rose with increasing radiological osteopenia grades for both methods. The worst osteopenia categories identified 29.7-55.3% of women with DEXA-defined osteoporosis, compared with 6.1-11.7% in the "normal" categories. Both methods, however, showed a large degree of overlap of BMDs between the various radiological osteopenia grades. The sensitivity and specificity of method A in diagnosing osteoporosis were 45.3% and 78.4%, respectively, for the TS and 19.0% and 94.3%, respectively, for the LS. For method B the sensitivities and specificities were 8.8% and 96.1%, respectively (TS), and 10.2% and 95.6%, respectively (LS). Although both methods have poor sensitivities, "definite" or "high" grade osteopenia should be an indication for bone densitometry. The high specificities suggest that a "normal" (no osteopenia) X-ray is unlikely to have a significantly low BMD.