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T D Spector

Publications and source records attributed to T D Spector.

At least 145 records · Page 8Linked to original sources
PubMed1996

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.

Arthrography↗
PubMed1995

Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain.

OBJECTIVES: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. DESIGN: Cross sectional twin study. SETTING: Twin population based in Britain. SUBJECTS: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. MAIN OUTCOME MEASURES: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. RESULTS: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. CONCLUSIONS: The findings that in postmenopausal women in Britain bone density-particularly at the hip and spine-is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.

Absorptiometry, Photon↗
PubMed1995

Osteoporosis in rheumatoid arthritis. A monozygotic co-twin control study.

OBJECTIVE: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study. RESULTS: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites. CONCLUSION: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.

Arthritis, Rheumatoid↗
PubMed1995

Markers of bone metabolism in postmenopausal women with rheumatoid arthritis. Effects of corticosteroids and hormone replacement therapy.

OBJECTIVE: To investigate bone metabolism in postmenopausal women with rheumatoid arthritis (RA) treated with or not treated with corticosteroids, and the response to hormone replacement therapy (HRT). METHODS: One hundred six RA patients were divided into those taking low-dose steroids (RA+; n = 35) and those not (RA-; n = 71) and randomly allocated to receive HRT or calcium for 2 years. Bone formation markers included serum osteocalcin (OC) and bone-specific alkaline phosphatase, and resorption markers included urinary deoxypyridinoline (DPyr) and CrossLaps (XL). Bone mineral density (BMD) was measured annually using dual x-ray absorptiometry. RESULTS: OC levels were significantly lower in both the RA+ and RA- groups compared with 112 healthy control subjects (P < 0.01 and P < 0.05, respectively), but were similar in the 2 RA groups. DPyr and XL levels were elevated in the RA+ group compared with the RA- group (P < 0.05) but were similar between the RA- group and controls. OC was negatively correlated with parameters of disease activity (P < 0.05). After HRT, XL excretion decreased significantly in the overall RA group. Three-month changes in XL correlated with 2-year changes in spinal BMD (P < 0.01). CONCLUSION: Bone metabolism may be uncoupled in chronic RA. Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption is increased only in steroid users. HRT reduces resorption in RA irrespective of steroid usage, emphasizing its value in the treatment of postmenopausal women with RA.

Absorptiometry, Photon↗
PubMed1995

The classification and assessment of osteoarthritis.

Osteoarthritis is the commonest rheumatic disease, but despite its high prevalence in the elderly, associated disability and public health costs, there is little understanding of the aetiology of the disease. Questions still remain unanswered: 'what do we mean by the term osteoarthritis?; how do we define it?; how do we classify patients with the disease?; how do we differentiate between cases for population studies, and clinically relevant disease the physician wishes to treat?'. This chapter has demonstrated the considerable advances that have been made over the last thirty years in solving these issues, but we are still lacking a universal definition and classification of the disease. Defining and classifying OA is not an easy task, as it is not a single disease, but rather a spectrum of diseases that are the end result of a number of different processes. However, in order to understand the aetiology and natural course of the disease, and to devise appropriate treatment strategies, correct definition of OA at distinct sites is vital. Radiological site-specific definition of the disease is now recognized as the major tool available in defining OA. There is general consensus that the grading of osteophytes and joint space narrowing at the major sites using validated atlases is an important step forward.

Arthrography↗
PubMed1995

A population study of the screening potential of assessment of trabecular pattern of the femoral neck (Singh index): the Chingford Study.

The trabecular pattern of the femoral neck (Singh index) has been used as a measure of osteopenia and fracture risk but the value of this method is controversial. This study assessed the usefulness of the Singh index (SI) by using dual energy X-ray absorptiometry (DXA) as the "gold standard". 659 Caucasian women (45-70 years) from an age-sex register of a general practice had their femoral neck and lumbar spine bone densities measured by DXA and had antero-posterior hip X-rays performed which were then categorized into six osteopenia grades using the SI method. The intraobserver and interobserver reproducibility of this method was good (kappa = 0.64 and 0.61, respectively). The SI grades correlated significantly with body mass index (r = 0.35) and age (r = 0.17) (p < 0.001). The mean femoral neck and lumbar spine bone densities were significantly higher with increasing SI grade even after adjustment for age and body mass index (p < 0.001). The proportion of subjects below the fracture threshold (2 SD below mean peak bone mass) decreased with increasing SI grade, ranging from 100% in SI grade 2 to 16.8% in SI grade 6. There was, however, wide overlap of bone densities between the grades. Using the criteria "osteoporosis < or = SI grade 4", the sensitivity and specificity of the SI method diagnosing low bone mass was 35.1% and 90.0%, respectively. These data suggest that the SI is a reproducible tool which may detect differences in bone mass between populations or subgroups within populations, although caution should be used in classifying individual patients because of the wide variation in bone density. The method has a low sensitivity but a relatively high specificity in diagnosing low bone mass.

Absorptiometry, Photon↗
PubMed1995

Osteoarthritis in the aged. Epidemiological issues and optimal management.

Osteoarthritis (OA) is the most common of the arthropathies. The prevalence increases significantly with age, with as many as 68% of women and 58% of men aged 65 years or older having radiological evidence of disease. With an aging population, OA will represent an increasingly significant healthcare burden. The current treatment of patients with OA is purely symptomatic. As yet, there is no evidence that treatment changes the course of the disease. The current optimal treatment involves a combined approach which includes modification of risk factors, particularly obesity, and nonpharmacological treatments such as physiotherapy. If drugs are required in the treatment of OA, full dose regular paracetamol (acetaminophen) should be the first line of analgesic therapy. There is little evidence that the current over-reliance on long term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is justified. If NSAIDs are used, it is necessary to regularly review their use and to be aware of their potential toxicity, particularly in the older age group.

Aged↗
PubMed1995

Patterns of joint involvement in osteoarthritis of the hand: the Chingford Study.

OBJECTIVE: The hand is the major site of joint involvement in osteoarthritis (OA), but the clustering of this condition at different joint sites within the hand as part of an entity known as generalized OA remains contentious. We examine this issue in a population sample of 967 peri and postmenopausal women. METHODS: The pattern of radiographic involvement of hand joints was examined using the Kellgren and Lawrence system in a sample of women aged 45-64 years, selected from the general population in Chingford, East London. Log linear modelling techniques were used to examine clustering of OA in different joint sites and to examine whether this clustering remained significant after age adjustment. RESULTS: There was clear evidence of clustering in joint involvement: Thus 20 women had 4 or more affected joints compared with only 2 expected (chi 2 = 72.0, 4df, p < 0.001). The risk of multiple distal interphalangeal (DIP) joint involvement, after age adjustment, in a woman with a single affected DIP joint was significantly increased (OR 10.0, 95% CI 7.3-13.7) and was substantially greater than the corresponding risk for proximal interphalangeal joint (OR 3.1, 95% CI 1.4-6.8) involvement. Symmetry was the strongest determinant of pattern with an OR 38.8 (95% CI 14.5-103.5) for corresponding DIP joint involvement in the contralateral hand. CONCLUSION: These data provide clear evidence for a polyarticular subset of hand OA in women. There are 3 major determinants of the pattern of polyarticular involvement; symmetry, clustering by row and clustering by ray, in descending order of importance.

Female↗
PubMed1995

The epidemiology of osteoarthritis of the hand.

The hand is a common site of osteoarthritis. Defining hand OA, particularly for epidemiological studies, has undergone reassessment and revision over the last few years. Although many studies to date have used a system of grading radiographic severity that was developed by Kellgren and Lawrence, there are significant problems with this system. In this paper we consider a number of alternative methods for grading hand OA including a scale which grades the individual joint features separately. Patterns of hand OA as well as the natural history and risk factors are also discussed.

Adult↗
PubMed1995

Association between metabolic factors and knee osteoarthritis in women: the Chingford Study.

OBJECTIVE: Several studies have shown an association with density and knee osteoarthritis (OA), however the role of other metabolic factors is unclear, with conflicting data in the literature. We studied the association between metabolic risk factors and k nee OA in women in the general population. METHODS: One thousand three women aged 45-64 from the Chingford population study completed risk factor questionnaires. Current blood pressure and ever hypertension were noted and fasting blood glucose, serum cholesterol, triglycerides, high density lipoprotein( HDL), and uric acid levels were measured. AP weight bearing radiographs were available in 979 women and scored using the Kellgren and Lawrence system. Grade 2+ (definite osteophytes) was used a definition of knee OA. Odds ratios (OR) and 95% confidence intervals were calculated for risk of knee OA in highest tertile versus lowest for death risk factor. All OR were adjusted for age and body mass index as potential confounders for OA. RESULTS: Radiological evidence of knee OA was found in 118 women (12%). For knee OA in either knee the variables significantly associated were raised blood glucose OR = 1.95 (1.08-3.59), and moderately raised serum cholesterol OR = 2.06 (1.06-3.98). For symptomatic women (n = 58) raised blood glucose OR = 2.77 (1.13-6.76), and use of diuretics OR = 2.27 (1.11-4.65) were significantly associated. For bilateral knee disease (n = 55) significant associations were found for ever hypertension OR = 3.02 (1.51-6.06), subjects taking diuretics OR = 2.84 (1.37-5.89), and both high and moderately raised serum cholesterol OR = 3.91 (1.07-14.25), and OR = 3.63 (1.00-13.88), respectively. In all categories of knee OA serum uric acid was nonsignificantly increased. No association was found with raised triglyceride or HDL levels or with current systolic blood pressure. Further adjustment for physical activity and social class did not affect the results. CONCLUSION: These data suggest that hypertension, hypercholesterolemia, and blood glucose are associated with both unilateral and bilateral knee OA independent of obesity, and support the concept that OA has an important systemic and metabolic component in its etiology.

Body Mass Index↗
PubMed1995

Radiographic criteria for epidemiologic studies of osteoarthritis.

For the purpose of epidemiologic studies in osteoarthritis (OA) an agreed criteria set is required that is both reliable and reproducible. A standardized method of radiologic classification will promote better reporting of epidemiologic data and consistency between centers. The radiographic scoring system of Kellgren and Lawrence has been used in OA research for over 30 years. Its deficiencies include the lack of clarity in interpretation and its reliance on the presence of the osteophyte. Recent advances suggest other pathological evidence of OA on radiographs should be measured when assessing OA. There is growing consensus that while a global score is still useful, the separate features should be recorded in a semiquantitative fashion using standardized atlases allowing different emphasis of particular features at different sites.

Guidelines as Topic↗
PubMed1994

Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids.

OBJECTIVE: To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids. METHODS: Two hundred postmenopausal women with RA (ages 45-65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 micrograms daily) or calcium supplementation (400 mg daily) for 2 years. Forty-two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months. RESULTS: In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by -0.41% (95% CI -1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by -1.19% (95% CI -2.29, -0.09) and mean BMDF by -0.56% (95% CI -2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT-treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI -1.27, +4.51). CONCLUSION: This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.

Adrenal Cortex Hormones↗
PubMed1994

Mutation analysis of coding sequences for type I procollagen in individuals with low bone density.

Mutations in one of the two genes encoding type I procollagen (COL1A1 and COL1A2) are frequently the cause of osteogenesis imperfecta (OI), a disorder characterized by brittle bones. Here we tested whether patients with low bone density also have mutations in these genes. The 26 patients studied had no apparent metabolic bone disease, but most had a positive family history of osteopenia or osteoporosis. Although a diagnosis of OI was considered by the clinician in some cases, the clinical criteria for OI were not satisfied. Our strategy for mutation analysis consisted of PCR amplification of cDNA made to fibroblast mRNA using primers specific for the coding regions of COL1A1 and COL1A2. The PCR products were then sequenced directly with primers located within each PCR product. We found that 3 of 26 patients had mutations that altered the encoded amino acid. One mutation, at position alpha 2(I)-661 has been reported (Spotila et al. 1991 Proc Natl Acad Sci USA PNAS 88:5423). The other 2 patients, who were not related to each other, had a mutation that altered the proline codon at alpha 1(I)-27 to alanine. This mutation was not found in 81 normal individuals or in 37 additional osteopenic individuals. However, its effect on the biologic function of type I collagen, as well as its role in osteopenia, is uncertain. In addition to the two mutations, we found a polymorphism in codon alpha 2(I)-459. Although this polymorphism involved an amino acid substitution, it was present with equal frequency in the patient and the normal population. By analyzing this and previously reported neutral sequence variants in the COL1A2 gene, we determined that all patients expressed both alleles of the COL1A2 gene. The 12 patients who were heterozygous for a COL1A1 neutral sequence variant also expressed both alleles. Here we present all PCR primer and sequencing primer information. The results suggest that surveying a larger group of similarly selected individuals may reveal additional mutations in the COL1A1 or COL1A2 genes.

Adolescent↗
PubMed1994

The progression of radiological hand osteoarthritis over ten years: a clinical follow-up study.

The natural history of hand osteoarthritis (OA) is poorly understood. The aim of the study was to ascertain the extent and pattern of radiological progression of hand OA over a 10-year period. A follow-up study was carried out on 169 consecutive patients who initially presented with OA of the hands or knees between 1975-1977. Fifty-nine subjects (45 women and 14 men) were recontacted who had paired hand radiographs, a mean of 10 years apart, and were a mean 69 (range 53-86) years old at follow-up. X-rays were scored blind, in three joint areas--distal and proximal interphalangeal joints (DIP and PIP) and first carpo-metacarpal (CMC) joints--using the method of Kellgren and Lawrence (K&L) (0-4), and for osteophytes and narrowing (0-3). Using the highest score for right and left hands (N = 118), K&L changes at the three areas were similar with 47-50% deteriorating, 45-46% unchanged, and 6-8% improving. Similar deterioration was seen when scoring the three joint areas for osteophytes (38-39%) and narrowing (39-48%). New osteophytes appeared in 48% of DIP joints during the 10 years. There was a weak correlation between progression at the DIP and PIP joints, but no relationship between DIP and CMC, or CMC and PIP. Virtually all subjects (97%) deteriorated when the total scores of all joints were calculated. No significant differences were seen between 'severe progressors' and 'minor' in terms of age or body mass index (BMI). A nonsignificant increase in the proportion of knee progressors in the severe progressor hand group was seen and there was a higher rate of baseline DIP OA in knee progressors. These results suggest that the majority of patients with OA of the hands attending a rheumatology outpatients clinic deteriorate radiologically over a 10-year period, about half developing new changes in DIP joints. There were no obvious features distinguishing those with rapid deterioration, although DIP OA appears to be a risk factor for knee progression.

Aged↗
PubMed1994

A randomised controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis.

OBJECTIVE: To assess the effects of hormone replacement therapy (HRT) on disease activity in postmenopausal rheumatoid arthritis (RA). METHODS: Two hundred postmenopausal outpatients (aged 45-65 years) were admitted into a single blind randomised placebo controlled trial of transdermal oestradiol (50 micrograms daily) over six months. Patients continued with routine antirheumatic medications. Compliance with HRT was monitored using serum oestradiol (E2) levels. Disease activity was monitored at entry, three and six months using erythrocyte sedimentation rate (ESR), articular index (AI), visual analogue pain scale (VPS) and early morning stiffness (EMS). RESULTS: Ninety one and 77 patients completed six months treatment with placebo and HRT respectively. There were no significant differences in baseline characteristics between the groups and no overall effects of treatment. However, 35 patients (41.6%), who completed HRT, failed to achieve serum E2 levels > 100 pmol/l at either three or six months and were considered 'poor-compliers'. In the remaining HRT 'compliers' (58.4%) there were significant improvements after six months in articular index (28.9%; p < 0.01) and pain score (21.7%; p < 0.05) compared with placebo, as well as reductions in ESR (8.9%; NS) and morning stiffness (25.2%; NS). Comparisons between HRT 'compliers' and 'poor-compliers' confirmed significant improvements in articular index (p < 0.001), pain score (p < 0.05) and morning stiffness (p < 0.001) in the 'compliers'. CONCLUSIONS: This study did not show an overall effect of HRT on disease activity when used as an adjunct therapy in postmenopausal patients. A subgroup of patients, who had greater increments in serum E2 whilst taking HRT, demonstrated improvements in some parameters of disease activity, suggesting a potential beneficial effect with good compliance and higher dose HRT. Most importantly, in the treatment of RA associated bone loss, HRT can be prescribed without fear of a disease flare up.

Aged↗
PubMed1994

Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis.

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.

Adult↗