PubMed Health⌕ Search

Biomedical subjects

T D Spector

Publications and source records attributed to T D Spector.

At least 127 records · Page 7Linked to original sources
PubMed1996

The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins.

Population based studies have demonstrated that having a first degree relative with a hip fracture is predictive of future hip fractures. Postmenopausal bone mineral density (BMD), ultrasound of calcaneus and hip axis length are associated with hip fracture, with the association for ultrasound and hip axis length being independent of BMD. The aim of this study was to determine the genetic component of these three important risk factors. We performed a classical twin study using 500 normal female twins, 128 identical and 122 non-identical pairs, aged 50 to 70 years. We measured bone mineral density at multiple sites, hip axis length (distance from the inner rim of the acetabulum to the greater trochanter), broadband ultrasound attenuation and velocity of sound of the calcaneus. Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.46 to 0.84. Hip axis length and velocity of sound had major genetic components with estimates of 0.62 and 0.61 respectively, which remained virtually unchanged after adjustment for bone mineral density. Broadband ultrasound attenuation had a moderate genetic component with an estimate of 0.53, which was reduced further to 0.45 after adjustment for BMD. In summary, all three bone measurements, which are independently associated with hip fracture, are independently heritable. This study suggests that a combination of different genetic factors acting on the structure, dimensions and density of bone may explain the importance of family history as a risk factor for hip fracture.

Aged↗
PubMed1996

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.

Absorptiometry, Photon↗
PubMed1996

Can biochemical markers predict bone loss at the hip and spine?: a 4-year prospective study of 141 early postmenopausal women.

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0 +/- 3.3 years, mean menopause duration 20.4 +/- 5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at -20 degrees C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was -1.41% (0.18) at the lumbar spine and -0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.

Absorptiometry, Photon↗
PubMed1996

Polymorphisms of the vitamin D receptor gene do not predict quantitative ultrasound of the calcaneus or hip axis length.

Quantitative ultrasound of the calcaneus and hip axis length are independent predictors of hip fracture and have a major genetic component. Polymorphisms of the vitamin D receptor gene (VDR) have been associated with variations in bone density in a number of studies. The aim of this study was to examine the role of VDR on other parameters associated with the risk of fracture. One hundred and eighty-nine pairs of healthy female dizygous twins were genotyped and had calcaneal ultrasound (broadband ultrasound attenuation and velocity of sound) and hip axis length measurements performed. Twin analysis using intraclass correlation coefficients and intrapair differences failed to find an association between the VDR polymorphisms and hip axis length or calcaneal ultrasound. Analysing the twins as a population, irrespective of twinning, also failed to find any association. The search for alternative genes influencing bone fragility should continue as a research priority.

Aged↗
PubMed1996

Geometric measurements of the proximal femur in UK women: secular increase between the late 1950s and early 1990s.

The aim of this study was to determine whether hip axis or femoral length has increased in women in the United Kingdom between the late 1950s and early 1990s. Such an observation would be of interest as it might explain the rise in age-specific incidence of hip fracture observed during these years. We studied two sets of antero-posterior pelvic radiographs of women aged 55-69 years taken during the course of population-based studies in the UK, one in 1958-60 and the other in 1989-91. One observer (S.G.) recorded the following measurements at the right hip: hip axis length (HAL), femoral length (FL) and femoral width (FW). Two summary ratios, HAL/FW and FL/FW were calculated to allow for differences in radiographic technique. HAL, FL and FW were greater in the 1989-91 films compared with those taken in 1958-60. Both HAL and FL expressed as a ratio to FW were also greater in the later films. FL/FW increased by 4.5% (p < 0.05); HAL/FW increased by 2.3%, though this was not statistically significant. We conclude that there has been a small apparent change in geometric measurements of the hip during the past 36 years. Cautious extrapolation suggests that such a change may explain up to one third of the increase in incidence of hip fracture observed during this period.

Age Factors↗
PubMed1996

Association of pain with radiological changes in different compartments and views of the knee joint.

The aim of this study was to examine the association between radiological patellofemoral and tibiofemoral osteoarthritis and knee symptoms in a population-based survey. Two hundred and fifty unrelated, normal individuals (500 knees) were included in the study. Anteroposterior (AP), lateral and skyline radiographs on each individual were graded for joint space narrowing and osteophytes using a standard atlas. Radiographic features were assessed on their ability to predict knee pain for 15 or more days in the last month, the last year or pain "ever'. The presence of osteophytes had the strongest association with knee pain "ever' with an odds ratio (95% Cl) for skyline osteophytes of 7.56 (3.84-14.81) and anteroposterior osteophytes of 5.00 (2.40-10.43). The presence or absence of joint space narrowing in all the radiological views (AP, lateral and skyline) was not significantly associated with knee pain, but there was a trend for an association with severity of narrowing in the lateral and skyline views. The presence of osteophytes in all knee views (AP, lateral or skyline) was best at predicting knee pain in the last year. Osteophytes predict pain more accurately than narrowing on all knee radiographic views (AP, lateral or skyline). Pain in the last year (defined as two or more episodes of pain, each lasting for at least 15 days and not related to recent trauma) is predicted more accurately than pain in the last month or ever having had an episode of knee pain and is a useful symptom for inclusion in population studies.

Arthralgia↗
PubMed1996

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.

Body Weight↗
PubMed1996

A randomized trial of testosterone therapy in males with rheumatoid arthritis.

Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA.

Adult↗
PubMed1996

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.

Absorptiometry, Photon↗
PubMed1996

Spiking of the tibial tubercles--a radiological feature of osteoarthritis?

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.

Aged↗
PubMed1996

Choosing the best method for radiological assessment of patellofemoral osteoarthritis.

OBJECTIVE: To assess the reproducibility of different methods of radiological assessment of patellofemoral osteoarthritis (OA) and to determine which is the best view as a research tool in epidemiological studies of knee OA requiring explicit diagnostic criteria to classify the disease in the general population. METHODS: A population based study of 252 unrelated, normal individuals (504 knees) was performed. Lateral and skyline radiographs from each individual were graded for joint space narrowing and osteophytes using a standard atlas. Reproducibility was assessed by two observers on 50 knees. Radiographic features were assessed on their ability to predict knee pain. RESULTS: The skyline views performed better than the lateral views in the assessment of patellofemoral joint OA. The reproducibility for osteophytes was high (kappa > 0.8) and that for joint space narrowing moderate (kappa > 0.6) for both lateral and skyline views. Although the specificity for detecting knee pain was similar in both views, the sensitivity of skyline views in the assessment of knee pain was greater (52.8% versus 30%). The odds ratio for skyline osteophytes as a predictor of knee pain was 7.66 (95% confidence interval (CI) 3.68 to 15.90); that for osteophytes seen on lateral view was 1.83 (95% CI 0.96 to 3.49). Narrowing on both views was a poor predictor of pain. There was frequent disagreement between the lateral and skyline views for detecting osteophytes. CONCLUSION: In a community based study, skyline views performed better than lateral views in terms of reproducibility and for identifying symptomatic patellofemoral joint OA. Skyline radiographs should be the preferred method for examining the patellofemoral joint in such studies.

Female↗
PubMed1996

Genetics of osteoarthritis.

The available evidence suggests that genetic factors have a major role in osteoarthritis. It has been believed for over 50 years that a strong genetic component to certain forms of osteoarthritis is present. This genetic influence has now been estimated to be up to 65% in a recent twin study. The nature of the genetic influence in osteoarthritis is speculative and may involve either a structural defect (that is, collagen), alterations in cartilage or bone metabolism, or alternatively a genetic influence on a known risk factor for osteoarthritis such as obesity. Exciting work has showed that mutations in the collagen type 2 are important in some rare, familial forms of osteoarthritis. Further work is needed on isolating the gene or genes involved in the pathogenesis of this common, disabling condition.

Disease Susceptibility↗
PubMed1996

Genetic influence on bone turnover in postmenopausal twins.

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.

Aged↗
PubMed1996

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.

Absorptiometry, Photon↗
PubMed1996

The association of obesity with osteoarthritis of the hand and knee in women: a twin study.

OBJECTIVE: To examine the association of obesity and osteoarthritis (OA) at various sites in middle aged women and to estimate the magnitude of the weight difference associated with OA. METHODS: A co-twin control study was performed within a population based twin study of women aged 48-70. OA was defined radiologically using site specific features and a standard atlas. Twin pairs discordant for OA disease traits were analyzed. RESULTS: The mean weight differences (95% CI) within twin pairs discordant for different OA traits were: tibiofemoral osteophytes 3.75 (1.29, 6.21) kg; patellofemoral osteophytes 3.05 (0.96, 5.15) kg; carpometacarpal (CMC) osteophytes 3.06 (0.83, 5.28) kg. There was no significant difference in weight within twin pairs discordant for osteophytes at the distal interphalangeal (DIP) or proximal interphalangeal (PIP) joints or for joint space narrowing at all sites examined except the patellofemoral joint, 4.73 (1.61, 7.84) kg. For each kg increase in weight the increased likelihood of developing different OA traits [OR (95% CI)] was: tibiofemoral osteophytes 1.14 (1.01-1.28), patellofemoral osteophytes 1.32 (1.09-1.59), patellofemoral narrowing 1.15 (1.01-1.30), and CMC osteophytes 1.09 (1.02-1.17). CONCLUSION: Obesity is an important risk factor for development of OA at the tibiofemoral and patellofemoral joints of the knee and CMC joints of the hands, with significant increases of 9-13% in risk of OA per kg increase in body weight. This emphasizes the potential importance of even minor weight reduction as a preventive health measure for OA.

Aged↗