Objectives-To assess the relative contribution of genetic and environmental factors to common forms ofosteoarthritis ofthe hands and knees.Design-Classic twin study with unselected twins who were screened radiologically for osteoarthritis.Subjects-130 identical and 120 non-identical female twins aged recruited from a London based twin register and through a national media campaign.Main outcome measures-Similarity in identical compared with non-identical twin pairs for radiographic changes at the interphalangeal and first carpometacarpal joints of the hands and the tibiofemoral joint and patellofemoral joint of the knee expressed as intraclass correlations.Results-The intraclass correlations of radiographic osteophytes and narrowing at most sites and the presence of Heberden's nodes and knee pain were higher in the identical pairs. The intraclass correlation of the total radiographic osteoarthritis score in identical pairs (rMZ) was 0-64 (SE 0.05) compared with 0-38 (0.08) in non-identical pairs.The proportion of genetic variance of total osteoarthritis score (osteophytes and narrowing) with modelling techniques was estimated at 0*54 (95% confidence interval 0 43 to 0 65) and ranged from 0 39 to 0-65 for different sites and features (P< 0.001) after adjustment for age and weight.Conclusions-These results demonstrate for the first time a clear genetic effect for radiographic osteoarthritis of the hand and knee in women, with a genetic influence ranging from 39-65%, independent of known environmental or demographic confounders. The results of this study should lead to further work on isolating the gene or genes involved in the pathogenesis ofthis common disabling disease.

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.

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.

Objective-To assess the reproducibility of different methods of radiological assessment of pateliofemoral 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 pateliofemoral joint OA.The reproducibility for osteophytes was high (K > 0-8) and that for joint space narrowing moderate (K > 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 ; 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 ofpain. It has been shown that symptomatic knee OA may often be related to patellofemoral disease that is not revealed by conventional anteroposterior radiographs and is difficult to grade reproducibly.3 Although one small clinical study has shown the skyline view to give better results than the lateral view,6 the optimal method for assessing this joint site radiologically requires confirmation, particularly for use in population based surveys. This is important in understanding the epidemiology and natural history of knee OA. The aim of this study was to determine the optimal method for assessing patellofemoral OA in a population based survey. Methods SELECTION OF CASESThis was a population based study of 252 unrelated, middle aged women who were randomly selected from a group of 504 as part of a twin study of OA. The participation rate in the twin study was 83%. Only one twin of each twin pair was randomly included. Compared with another population based sample of middle aged women described previously,7 this group did not differ in prevalence of OA or risk factors for OA. The analyses performed in this report refer to the (504) knee joints, examined as separate units.Each subject was interviewed with a standard questionnaire for arthritis and joint symptoms, and the joints were examined in a systematic way using previously validated and reproducible techniques.7 The following radiographic views of the patellofemoral joint were obtained: a standing lateral (mediolateral) view in 30°flexion; a skyline (inferosuperior) view in 450 flexion using a Perspex positioning wedge with the subject supine. Lateral radiographs were available on all knees (n = 504) from the onset of the study, but skylin...

The objective of this study was to examine the relative contribution of genetic and environmental factors in determining pain perception in a classical twin study. Dolorimeter measurements of pressure pain threshold (PPT) were recorded in 609 healthy female-female twin pairs of whom 269 pairs were monozygotic (MZ) and 340 were dizygotic (DZ). There was a strong correlation (R) in PPT in both MZ and DZ pairs (R(MZ) = 0.57, 95% confidence interval (CI): [0.49, 0.65]; R(DZ) = 0.51, 95% CI: [0.42, 0.59]). The slight excess in intraclass correlation observed in MZ when compared with DZ twins corresponds to a heritability for PPT of only 10% and is not statistically significant. Neither estimate of intraclass correlation was substantially altered after adjusting for a range of potential confounding variables including age, current tobacco and alcohol use, current analgesic use, psychological status assessed by the general health questionnaire, and social class. The dolorimeter measurements were shown to be reliable (between observer agreement R = 0.66; within observer agreement R = 0.70-0.76) and stable over time. In conclusion, these data suggest that there is no significant genetic contribution to the strong correlation in PPT that is observed in twin pairs. These findings reinforce the view that learned patterns of behaviour within families are an important determinant of perceived sensitivity to pain.