Michael G. Yeates

Genetic determinants of bone mass in adults. A twin study.

The relative importance of genetic factors in determining bone mass in different parts of the skeleton is poorly understood. Lumbar spine and proximal femur bone mineral density and forearm bone mineral content were measured by photon absorptiometry in 38 monozygotic and 27 dizygotic twin pairs. Bone mineral density was significantly more highly correlated in monozygotic than in dizygotic twins for the spine and proximal femur and in the forearm of premenopausal twin pairs, which is consistent with significant genetic contributions to bone mass at all these sites. The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist. This is the first demonstration of a genetic contribution to bone mass of the spine and proximal femur in adults and confirms similar findings of the forearm. Furthermore, bivariate analysis suggested that a single gene or set of genes determines bone mass at all sites.

Physical fitness is a major determinant of femoral neck and lumbar spine bone mineral density.

The relationship between physical fitness and bone mass in the femoral neck, lumbar spine, and forearm was studied in 84 normal women. Femoral neck and lumbar spine bone mineral density and forearm bone mineral content were estimated by absorptiometry. Fitness was quantitated from predicted maximal oxygen uptake. Femoral neck and lumbar bone mineral density were significantly correlated with fitness as well as age and weight. In the 46 postmenopausal subjects, fitness was the only significant predictor of femoral neck bone mineral density, and both weight and fitness predicted the lumbar bone mineral density. These data represent the first demonstration of a correlation between physical fitness, and, by implication, habitual physical activity, and bone mass in the femoral neck; they also support the previous reported correlation between lumbar bone mass and physical activity. The data suggest that increased physical fitness may increase bone mass at the sites of clinically important fractures in osteoporosis.

Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids.

Fear of inducing generalised osteoporosis is one reason why corticosteroids are withheld in patients with rheumatoid arthritis (RA). No studies, however, have directly measured bone density in such patients at clinically relevant sites. To assess this risk we measured bone mineral density in the lumbar spine and femoral neck by dual photon absorptiometry in 84 patients with RA, 44 of whom had been treated with low dose prednis(ol)one (mean dose +/- SE 8.0 +/- 0.5 mg/day; mean duration of treatment 89.6 +/- 12.0 months). There were significant reductions in bone mineral density in patients treated with corticosteroids (lumbar 9.6%, p less than 0.001; femoral 12.2%, p less than 0.001) and in those who had not received corticosteroids (lumbar 6.9%, p less than 0.01; femoral 8.9%, p less than 0.001), but the differences between the two groups were not significant. We conclude on the basis of these studies that low dose oral corticosteroids do not increase the risk of generalised osteoporosis in patients with rheumatoid arthritis.

Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.

Effects of tobacco use on axial and appendicular bone mineral density.

Tobacco use has been identified as being a risk factor for the development of osteoporosis. While some data have suggested an effect on peripheral bone mass there are little previous data examining the role of tobacco use in axial skeletal bone loss. We examined tobacco use in relation to lumbar spine and proximal femur bone mineral density and forearm bone mineral content in 203 women. Data from identical twin pairs, comprising a subgroup of the larger group as well as a small number of male twin pairs, was also analyzed. The data show a difference in lumbar and proximal femur BMD of 0.03 and 0.06 g/cm2 respectively between smoking and nonsmoking identical twins. There was however no difference in the cross-sectional studies and no significant deleterious effect detected of tobacco use on forearm bone mineral content. The effect of smoking on lumbar and proximal femur bone mineral density, in identical twins discordant for tobacco use, was equivalent on average to 3 to 4 years of normal postmenopausal bone loss.

Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18±0.06 U (scan 1) and 0.17±0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R=0.76), interscan reproducibility (SD) was 0.03 U (R=0.62), and overall reproducibility (SD) was 0.04 U (R=0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n=29) studied previously in this department. A change of ≥0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF ≤ 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.