Background. Smoking is recognized as a risk factor for vertebral, fore
arm, and hip fractures. Since bone density is an important determinant
of bone strength, we conducted a study to ascertain whether a deficit
in bone density is associated with tobacco use and, if so, to identif
y the responsible mechanisms. Methods. We conducted a cross-sectional
study of bone density at the lumbar spine and the femoral neck and sha
ft in 41 pairs of female twins (21 monozygotic pairs), 27 to 73 years
of age (mean, 49), who were discordant for at least 5 pack-years of sm
oking (mean, 23; maximum, 64). Bone density was measured by dual-photo
n absorptiometry. The difference in bone density between the members o
f a pair was expressed as a percentage of the mean value for the pair.
Results. For every 10 pack-years of smoking, the bone density of the
twin who smoked more heavily was 2.0 percent lower at the lumbar spine
(P = 0.01), 0.9 percent lower at the femoral neck (P = 0.25), and 1.4
percent lower at the femoral shaft (P = 0.04). These results were not
confounded by measured lifestyle factors. In the 20 pairs who were di
scordant by 20 or more pack-years (mean, 35), the (mean +/- SE) within
-pair differences in bone density at the three sites were 9.3 +/- 3.1
percent (P = 0.008), 5.8 +/- 2.9 percent (P = 0.06), and 6.5 +/- 3.2 p
ercent (P = 0.05), respectively. Smoking was associated with higher se
rum concentrations of follicle-stimulating hormone (P = 0.02) and lute
inizing hormone (P = 0.03) and lower serum concentrations of parathyro
id hormone (P = 0.05). Differences in spinal bone density between memb
ers of a pair were associated with differences in the serum concentrat
ions of parathyroid hormone (P = 0.01) and calcium (P = 0.05) and urin
ary pyridinoline excretion (P = 0.06), a marker of bone resorption. Co
nclusions. Women who smoke one pack of cigarettes each day throughout
adulthood will, by the time of menopause, have an average deficit of 5
to 10 percent in bone density, which is sufficient to increase the ri
sk of fracture.