P.D. Ross

A critical review of bone mass and the risk of fractures in osteoporosis.

SummaryThe usefulness of various bone mineral measurement techniques is a subject of current controversy. In order to explore whether disparate conclusions may have arisen from differences in analytic methodology, data from published reports of bone mass and nonviolent fractures have been reanalyzed in terms of fracture risk. In the large majority of studies, reduced bone mass was associated with an increased risk of fractures. However, the magnitude of the relationship varied much more among cross-sectional studies than among prospective studies, suggesting that bias related to subject selection and/or postfracture bone loss may have strongly influenced the cross-sectional findings. We conclude that more emphasis should be given to the results of prospective studies, and that more attention should be paid to subject selection in all investigations. Analyzing and presenting results in terms of fracture risk would probably reduce the level of confusion in the field and provide more clinically relevant information. These issues are also applicable to studies of potential fracture risk factors other than bone mass, such as bone structure and bone quality.

Predicting vertebral deformity using bone densitometry at various skeletal sites and calcaneus ultrasound

We investigated the usefulness of bone density measurements from multiple skeletal sites and calcaneus ultrasound for evaluating the probability of vertebral deformation. Bone mineral density (BMD) was measured at the second metacarpal and middle phalanges using radiographic absorptiometry of hand radiographs, and at the lumbar spine using dual-energy x-ray absorptiometry. Distal radius and proximal radius were measured using single-energy x-ray absorptiometry (SXA), expressed as bone mineral content (BMC, grams per centimeter), and as BMD (grams per square centimeter). The calcaneus was measured using both SXA (BMD) and broadband ultrasound attenuation (BUA). Among the women in this study (mean age 74, SD = 5), 84 women developed new vertebral deformations (57 cases with one and 27 cases with two or more deformations), which were identified on serial radiographs during an average of 9 years prior to the measurements of bone density. Logistic regression analysis was used to calculate odds ratios for risk of deformation corresponding to a 1-SD difference in density or ultrasound, adjusted for age. All bone measurements were significantly associated with vertebral deformation, with odds ratios (95% confidence intervals) ranging from 1.40 (1.10, 1.78) for proximal radius BMD to 1.88 (1.45, 2.44) for calcaneus BMD measurements. Measurements of calcaneal BUA, calcaneal BMD, and hand BMD generally remained significant when included simultaneously with another measurement in the same model, suggesting that spine or radius BMD may not provide much additional information about risk of deformation. It appears that all of the measurements of bone density and ultrasound provide useful information regarding the probability of deformation. These findings await confirmation in a prospective study.

Users of low-dose glucocorticoids have increased bone loss rates: A longitudinal study

Although high doses of glucocorticoids are believed to cause bone loss, the effects of low glucocorticoid doses are still controversial. Our study examined the effects of low-dose glucocorticoids on the rate of bone loss at three appendicular bone sites. The study population was a cohort of elderly Japanese-Americans, 1094 women and 1378 men. The women were all postmenopausal. At the baseline examination the mean age of the women was 64 years (range 45–81), and the mean age of the men was 68 years (range 61–82). Glucocorticoid users (19 women and 21 men) had used oral systemic or inhaled glucocorticoids on a regular schedule for more than 1 month (mean use was 2.1 years for the women and 1.9 years for the men). The most common dose was equivalent to 5 mg/day of prednisone; fewer than 15% of users had taken doses equivalent to 10 mg/day or more. Changes in bone mass at the calcaneus, distal radius, and proximal radius were documented using bone densitometry at 1 to 2-year intervals over an 8-year period. The initial bone mass of the glucocorticoid users and controls was similar at the baseline examination. The subsequent loss rates among females during glucocorticoid use, however, were approximately double that of the controls. Among males, bone loss rates during glucocorticoid use were 2–3 times that of controls for the calcaneus and radius sites. The differences between glucocorticoid users and controls persisted after adjusting for confounding variables such as age and use of thiazides and estrogens. We conclude that users of low-dose glucocorticoids have increased rates of bone loss at appendicular sites among both elderly women and men.

Definition of a spine fracture threshold based upon prospective fracture risk

Assessment of fracture threshold (FT) could have important clinical application in determining which individuals should be treated preventively, and what level of therapy to prescribe, if suitable treatment regimens can be developed. We propose that FT be defined as the bone mineral content (BMC) at which the risk of fracture doubles, relative to premenopausal women, as determined by logistic regression analysis of spine fracture incidence in a prospective study of 408 postmenopausal women. The observed values for the FT agree well with those reported by others, based upon more arbitrary definitions. More than 90% of individuals with new nonviolent spine fractures have BMC below the fracture threshold, while fewer than 10% of younger women (age 30-45) are below this value. Although not all women with BMC below the FT have had fractures, they are at increased risk of fracture. Women with BMC equivalent to the FT have at least a 5% chance of fracture over a 10-year period, and the probability of fracture rises rapidly as BMC decreases. BMC appears to be a much stronger predictor of fracture risk than age or body size (height or weight). Thus, use of a BMC fracture threshold to categorize individual risk could provide a more objective basis for clinical decision making.

Characteristics of respondents and nonrespondents in a prospective study of osteoporosis

During 1981-1982, a cohort of elderly Japanese Americans living in Hawaii was recruited for an epidemiologic study of osteoporosis. The male subjects were simultaneously being examined for an epidemiologic study of heart disease. Baseline data collected from both the men and women at a previous heart disease examination were used to compare responders vs nonresponders. The target population for the osteoporosis study consisted of 1685 men and 1594 women. Of these, 1379 men (81.8%) and 1105 women (72.0%) participated in the initial osteoporosis examination. For each sex, nonrespondents were older and had higher systolic blood pressure levels than did the respondents. Male nonresponders had a higher stroke prevalence and more frequent recent use of vasodilator medicine. Female nonresponders had a less frequent history of having ever taken female hormones than did the responders. The responders and nonresponders were reasonably similar in other respects, as indicated by the comparison of more than 40 other variables. This suggests that nonresponse bias is probably not a major influence in exposure-disease associations in this osteoporosis cohort. We believe this is the first published report dealing with nonresponse characteristics in a cohort study of osteoporosis.

The peak bone mass of Hawaiian, Filipino, Japanese, and white women living in Hawaii

Our study compares the bone mass of Hawaiian, Filipino, Japanese, and white women living in Oahu, Hawaii. Eligible women ranged in age from 25 to 34; all had bone mass measurements at the spine, calcaneus, and proximal and distal radius. Their average bone mineral density (BMD) remained stable with age at all four bone sites, indicating that the age range 25–34 may represent the peak bone mass. Bone mass varied, however, between ethnicities; differences in BMD up to 11% were observed. The Hawaiian women had the greatest BMD, and whites had the second greatest BMD at the spine and calcaneus. The Japanese most frequently had the lowest BMD. Differences in body size partly explained the differences; most ethnic differences were reduced or eliminated after adjusting for height and weight. At the spine, the ethnic differences for BMD were also apparent with BMC and with vertebral area. Hawaiian and white women had greater values than Japanese or Filipino women. Differences at the proximal radius resembled the spine, except that whites had the widest proximal widths. The results were more complex for the distal radius. At the distal radius whites had the lowest BMD of the four ethic groups. The difference between whites and Hawaiians derived from the greater bone mineral content (BMC) of the Hawaiian women. By contrast, the difference between whites and the Japanese and Filipinos derived from the wider distal widths of the white women. Compared with the Japanese and Filipino women, the white women appeared to disperse their BMC at the distal radius across a wider bone width. Such differences in bone distributions might lead to an altered risk of distal radius (wrist) fractures. Within ethnicities there was marked variation among individuals in bone mass. At the extremes, women differed by 50–100% or more within all four ethnic groups.

Estrogen and calcium supplement use among Japanese-American women: Effects upon bone loss when used singly and in combination

We examined the effects of estrogen and calcium supplementation upon bone loss among a cohort of Japanese-American women. The women averaged 64 years of age (age range 45-81) and 14 years postmenopause at their initial examination in 1981. They returned at 1-3-year intervals for subsequent examinations, most recently in 1992-1994. At each examination, bone mass was measured at the calcaneus and distal and proximal radius. The women had low average dietary calcium intakes (median intake 384 mg/day). Women taking calcium supplements reported a median supplement intake of 355 mg/day; over 75% of the women taking estrogen took the equivalent of 0.6 mg/day or more of conjugated estrogens. Women taking estrogen had uniformly slower bone loss at all three sites. Compared to women not taking estrogen, whose bone loss averaged about 1% per year, women taking estrogen had 0.75-0.85% per year decreased bone loss at the three bone sites. By contrast, women who stopped estrogen had greater than average loss rates (0.35-0.65% per year greater). Calcium supplementation also reduced bone loss, but to a lesser extent than estrogen: bone loss decreased 0.25% per year at the radius sites, but was not slowed at the calcaneus. The calcaneus is more trabecular than the radius sites, which may explain the lack of response. We also examined combined estrogen and calcium supplement use.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertebral dimension differences between Caucasian populations, and between Caucasians and Japanese

Various criteria have been proposed for using vertebral measurements to identify vertebral fractures. It is known that the normal distributions of vertebral heights and ratios vary with location within the spine. However, very little is known regarding the degree to which differences in these parameters may exist between populations. We report the vertebra-specific distributions of vertebral dimensions and ratios for Japanese-Americans, and compare these values to published data for Caucasians. The mean Japanese vertebral heights were 1 to 2 mm shorter than Caucasians, which may be due in part to the shorter stature of Japanese. However, differences in mean values were also observed between Caucasian populations. Furthermore, anterior/posterior vertebral height ratios differed between Caucasian studies, and between races. Additional studies are needed to determine to what degree these differences are due to technical and biological factors before criteria derived from one population can be used for identifying vertebral fractures in other populations of the same, or different, race.

Comparison of bone mineral content between Japan-born and US-born Japanese subjects in Hawaii

The bone mineral content (BMC) of the calcaneus, and distal and proximal radius was measured by the single photon absorptiometric technique for 2307 US-born and 172 Japan-born subjects of Japanese ancestry living in Hawaii. The bone mineral content of the US-born subjects was greater than that of their Japan-born counterparts, on the average, by 8.8% at the calcaneus, 3.5% at the distal radius and 4.5% at the proximal radius. Differences between the two groups in height, weight, thiazide use, exercise (in men), estrogen therapy (in women), and calcium and vitamin D intake accounted for much of the difference in BMC between the US-born and Japan-born women, but less so for the men. Additional studies of BMC in migrant populations are needed to characterize further the environmental factors affecting bone mineral content.

Vertebral dimension measurements improve prediction of vertebral fracture incidence.

We investigated the independent contributions of vertebral size and shape, bone density, and existing fractures for predicting the risk of new vertebral fractures among postmenopausal Japanese-American women in Hawaii. Baseline measurements of bone density at the distal and proximal radius and the calcaneus were obtained in 1981, and at the lumbar spine in 1984. Incident fractures were documented on serial radiographs during an average of 8.0 years of follow up of 840 women. A positive difference of 1 standard deviation in vertebral depth increased the risk of new vertebral fractures by approximately 1.3-fold (95% confidence interval = 1.03, 1.66) after controlling for bone density and prevalent fractures. A combination of large vertebral depth (above the 66th percentile) and low bone density (below the 33rd percentile) increased fracture risk approximately six times compared to women with high bone density (above the 66th percentile) and small vertebral depth (below the 33rd percentile). We conclude that combining information about vertebral depth, bone density, and prevalent fracture appears to be better for predicting new fractures than any single variable alone.