PubMed Health⌕ Search

Biomedical subjects

T D Spector

Publications and source records attributed to T D Spector.

At least 163 records · Page 9Linked to original sources
PubMed1994

Methodological problems in the epidemiological study of osteoarthritis.

In conclusion, though there are numerous opportunities and different approaches to studying the epidemiology of OA, we have concentrated on some of the methodological problems and difficulties inherent in these methods. We think it is important that researchers are aware of these problems before undertaking such studies. In addition, readers of published studies need to be aware of these potential pitfalls before being able to make valid judgements on research papers. We hope, however, that stressing these problems does not dissuade present and future investigators from participating in this area of research. Despite difficulties inherent in the epidemiology of chronic diseases and OA in particular, studies may uncover modifiable risk factors for the development and progression of OA which could lead to important preventive strategies.

Case-Control Studies↗
PubMed1994

The relationship between osteoarthritis and osteoporosis in the general population: the Chingford Study.

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.

Bone Density↗
PubMed1994

Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity.

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.

Body Mass Index↗
PubMed1994

Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE).

Despite its obvious benefits, many physicians are reluctant to prescribe HRT to patients with SLE. We have performed a retrospective study in 60 postmenopausal women with SLE including 30 HRT users and 30 never users. The patients were studied for 12 months after the initiation of HRT. The two groups were well matched for disease characteristics. The HRT users experienced significant improvements in general well being, libido and depression. There was no significant difference in any other parameter measured. There was no increase in the number of thrombo-embolic events in the user group despite 7 patients having a positive thrombophilia screen. In conclusion, in stable postmenopausal SLE HRT appears well tolerated and safe.

Adult↗
PubMed1993

Inflammation-induced cartilage degradation in female rodents. Protective role of sex hormones.

OBJECTIVE: To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation. METHODS: We used an in vivo model of inflammation-induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin-1 (IL-1) production by granulomatous tissue, and its effects on female mouse articular cartilage. RESULTS: Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL-1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagonized the effects of IL-1 on both proteoglycan loss and proteoglycan synthesis. CONCLUSION: These data suggest that sex steroids have an important influence on inflammation-induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.

Animals↗
PubMed1993

The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women.

OBJECTIVE: To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. METHODS: One hundred ninety-five postmenopausal patients with RA were compared with 597 post-menopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). RESULTS: Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4-10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0-13.0%) and by 7.4% at the hip (95% CI 1.2-13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = -0.23, P < 0.01; whole-body BMD r = -0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = -0.32, P < 0.01; whole-body BMD r = -0.72, P < 0.01). CONCLUSION: Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.

Absorptiometry, Photon↗
PubMed1993

Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: the Chingford Study.

A population survey was performed to estimate the prevalence of vertebral fractures in women aged 45-69 and to determine their relationship to bone density and symptoms. Subjects were 1035 women aged 45-69 (mean 55.4 years, response rate 77%) from the age-sex register of a large 11,000-person general practice in Chingford, London. Thoracic and lumbar spine x-rays were read by a semiautomated quantitative method. Vertebral fractures were diagnosed using a variety of morphometric methods, including a new method we recently developed and the published methods of Melton and Eastell. These methods all detect abnormal ratios between anterior, central, or posterior vertebral height and between observed posterior vertebral height and values predicted from the posterior height of adjacent vertebrae. Bone mineral density (BMD) of lumbar spine L1-4 and neck of femur was measured by dual-energy x-ray absorptiometry (DXA). Using our method, 147, 14.2% (95% CI 12.0-16.2%) of the 1035 women, had minor fractures (at least two vertebral ratios 2-2.99 SD below the mean) and 20, 1.9% (95% CI 1.2-3.0%) of the total, had severe fractures (at least two ratios more than 3 SD below the mean). In the 147 women with minor fractures, bone density of the spine was not significantly lower than in the other 868 women, and reported back pain or loss of height was no more common. Women with multiple minor fractures did have lower bone density, by 0.4 SD. In the 20 women with severe fracture, bone density was significantly lower, by 0.6 SD.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

The assessment of vertebral deformity: a method for use in population studies and clinical trials.

The absence of specific criteria for the definition of vertebral fracture has major implications for assessing the apparent prevalence and incidence of vertebral deformity. Also, little is known of the effect of using different criteria for new vertebral fractures in clinical studies. We therefore developed radiological criteria for vertebral fracture in women for assessing both the prevalence and the incidence of vertebral osteoporosis in population and in prospective studies and compared these with several other published methods. Normal ranges for vertebral shape were obtained from radiographs in 100 women aged 45-50 years. These included ranges for the ratios of anterior/posterior, central/posterior and posterior/predicted posterior vertebral heights from T4 to L5. The predicted posterior height was calculated from adjacent vertebrae. In contrast to other methods, our definition of fracture required the fulfillment of two criteria at each vertebral site, and was associated with a lower apparent prevalence of fracture in the control women due to a lower false positive rate. The prevalence and incidence of vertebral deformity using different criteria were then compared in a series of women with skeletal metastases from breast cancer in whom radiographs were obtained 6 months apart. The prevalence of vertebral deformity and the specificity for deformity varied markedly with differing criteria. Using a cut-off of 3 standard deviations the prevalence of vertebral deformity in the women with breast cancer was 46%. Using other methods, the prevalences of deformity ranged from 33% to 74%. Over a 6-month interval 25% of patients with breast cancer sustained 61 deformities using our method, of which only 8% resulted from errors in reproducibility. The number of patients sustaining new deformities was increased twofold when assessed by other methods (45%-53%), but errors of reproducibility may have accounted for 21% of the new deformities. The magnitude and distribution of these errors have important implications for the apparent therapeutic efficacy of agents in clinical trials of osteoporosis. The rapid semi-automated technique for assessing vertebral deformities on lateral spine radiographs that we have developed has a high specificity, and reduces the impact of errors of reproducibility on estimates of prevalence and incidence. The method should prove a value in assessing vertebral deformity both in population studies and in prospective clinical trials.

Adult↗
PubMed1993

Increased levels of urinary collagen crosslinks in females with rheumatoid arthritis.

Bone loss is a feature of RA, but the exact mechanisms involved are not clear. The collagen crosslinks deoxypyridinoline (DPYR) and pyridinoline (PYR) are specific indices of 'mature' collagen breakdown and reflect increased bone turnover. The aims of the study were to examine crosslink levels in RA and their association with disease activity and the effect of steroids. Urinary crosslinks corrected for creatinine were measured on morning fasting samples by HPLC in 70 postmenopausal women with rheumatoid arthritis (RA) aged 45-65 and compared with 169 postmenopausal healthy age-matched controls from the population. Mean levels of PYR were significantly higher in RA cases than in controls (52.4 versus 37.5 nmols/mmolCr) although mean levels of DPYR did not differ significantly. A weak correlation was found with ESR and PYR (r = 0.35) but not with other markers of disease activity. Thirteen of the RA cases were current steroid users and their levels of DPYR and PYR even with low doses, were significantly elevated above those of non-users, ex-users and controls. The finding of raised urinary PYR but not the bone specific DPYR in nonsteroid using RA cases suggests that the increased collagen breakdown does not primarily come from bone but from other sources such as cartilage and synovium. The large increases in collagen excretion in low dose steroid users, may reflect the higher risk of osteoporosis in this group.

Aged↗
PubMed1993

Epidemiology of the rheumatic diseases.

Emerging osteoarthritis studies suggest that certain occupations are associated with a high risk for development of hip and knee osteoarthritis, at least in men. The main activities identified are regular lifting for the hip and knee bending for the knee. Obesity is a well-known risk factor for the knee, and it has been suggested that this risk can be halved by losing weight. Studies of the natural history of knee osteoarthritis suggest that many individuals do not develop osteoarthritis, although precise prognostic indicators are lacking at present. No new etiologic information on rheumatoid arthritis has appeared recently, although hormonal and reproductive factors in women continue to be studied with variable results. Agreement is slowly being reached on how to define vertebral fractures for epidemiologic study, which should produce more consistent results. In a study from Rochester, Minnesota, US incidence rates were produced for clinically diagnosed vertebral fracture (117/100,000) that are similar to hip rates, although they occur at an earlier age. Continued study of risk factors continues to show them to be of little use in screening. In systemic lupus erythematosus, hair dyes have not been confirmed as a risk factor, although there may be a link with domestic pets. There are conflicting data on the roles of obesity and occupational factors in carpal-tunnel syndrome.

Arthritis, Rheumatoid↗
PubMed1993

Definition of osteoarthritis of the knee for epidemiological studies.

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.

Bone and Bones↗
PubMed1993

Cigarette smoking and risk of osteoarthritis in women in the general population: the Chingford study.

Previous studies have suggested that smoking might be protective against the development of osteoarthritis (OA) of the knee. A group of 1003 women aged 45-64 years (mean 54.2 years) from the Chingford general population survey were studied to examine the effect of cigarette smoking on the prevalence of radiologically confirmed OA at different sites. Standard anteroposterior radiographs of the hand and knee were available in 985 women. Disease classification was made on the basis of radiological OA and symptomatic radiological OA. Odds ratios were calculated and adjusted for age and body mass index. A total of 463 (46.2%) women were ever smokers compared with 540 (53.8%) non-smokers. Ever smokers had consumed an average of 14.9 cigarettes a day for a mean of 25.7 years. For radiological OA of the distal interphalangeal joint (DIP) (140 women), proximal interphalangeal joint (40 women), carpometacarpal joint (160 women), and knee joint (118, women) there was no reduced risk of OA in ever smokers. In the small number of subjects with generalised OA (22 women) there was a non-significant 40% reduction of radiological OA in ever smokers (odds ratio 0.63; 95% confidence interval 0.24 to 1.68). Results were similar for subjects with radiographic clinical OA, except the DIP joint which showed a positive association between smoking and Heberden's nodes (odds ratio 2.02, 95% confidence interval 1.89 to 3.42). Results were similar when analysed using current smokers against never smokers. These results do not support an inverse association between cigarette smoking and OA in women. A possible inverse relation with the small subgroup of women with generalised OA and an effect of cigarettes on disease severity cannot, however, be discounted.

Arthrography↗
PubMed1993

Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density.

The sex hormones dehydroepiandrosterone sulphate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG) were measured in 185 postmenopausal women (aged 45-65 years) with rheumatoid arthritis (RA) and related to assessments of bone mineral density at the spine and proximal femur. Compared with 518 postmenopausal control women (aged 45-65 years), DHEAS levels were below normal in the 120 patients with RA who had never taken corticosteroids and levels were further depressed in 39 patients currently using steroids. Twenty six patients who had completed steroid treatment also had lower DHEAS levels, suggesting a delayed recovery of adrenal androgen secretion. Oestradiol and SHBG levels were similar in all groups. There was no correlation between sex hormones and disease activity. Oestradiol correlated with bone mineral density at all sites. Although oestradiol correlated with DHEAS, there was no relation between DHEAS and bone mineral density. The cause of below normal levels of DHEAS in RA is unclear, whether a consequence of chronic illness, immune dysfunction, or a defect of adrenal androgen synthesis.

Aged↗
PubMed1993

Prevalence of rheumatoid arthritis and rheumatoid factor in women: evidence for a secular decline.

OBJECTIVE: To determine the current prevalence of rheumatoid arthritis (RA) and rheumatoid factor positivity in the United Kingdom middle aged female population and to compare this with previous estimates to assess whether the disease is becoming less prevalent. METHODS: A cross sectional prevalence study was undertaken. All women aged 45-64 from the age and sex register of a large 11,000 general practitioner group practice in Chingford, East London were contacted and responders examined clinically and radiographically for the presence of RA by a single observer. Blood was also taken for rheumatoid factor testing (sheep cell agglutination test (SCAT), latex, and IgG). The prevalence in non-attenders was assessed from general practitioner and local hospital records. A diagnosis of definite or classical RA according to 1958 American Rheumatism Association criteria was used, and seropositivity was defined by a SCAT rheumatoid factor of 1/32 or more. RESULTS: From the 1003 women examined (response rate of 78.8%), 12 women had definite RA (1.2%, 95% confidence interval 0.6 to 1.8). Of these, 7/12 had definite erosive changes on radiography and 3/12 had a positive SCAT (> 1/32). Three cases of RA were also found in the 284 non-responders (prevalence 1.1%) by case-finding techniques. The rate of SCAT positivity in the whole study group was 0.5%. The rates of RA and SCAT positivity currently found in this group were less than those obtained in previous surveys. In the only previous large scale United Kingdom survey, performed in the north of England between 1958 and 1960, 406 women aged 45-64 were examined and 10 cases of definite RA were found, a prevalence of 2.5%. In the patients with RA 68% had erosions and 63% positive SCAT. The population SCAT positive rate in this and other surveys sampled between 1954 and 1961 was in the range of 4-5%, since when there has been a progressive decline according to a number of other studies. CONCLUSIONS: The prevalence of RA and rheumatoid factor in middle aged women is lower than previously believed and supports a variety of other data which indicate that RA is declining in incidence and severity.

Agglutination Tests↗