John M. Vogel

Prediction of postmenopausal fracture risk with use of bone mineral measurements

In a study of 1098 women (mean age, 63.3 years) nonspine fracture incidence and prevalence rates and spine fracture prevalence rates were compared by quintile of bone mineral content at the proximal radius, distal radius, os calcis, and lumbar spine. The risk of fracture associated with varying bone mineral content levels was explored with use of estimated odds ratios. Risk of fracture is significantly increased with diminishing quintiles of bone mineral content. Subjects in the lowest quintile of os calcis bone mineral content have a nonspine fracture risk 10 times greater than subjects in the highest bone mineral content quintile. The os calcis bone mineral content measurement is the best predictor of nonspine fracture risk and is also the best overall indicator of spine fracture risk. Therefore measurement of os calcis bone mineral content may be useful for routine risk evaluation of perimenopausal women. The ability to predict individual risk should allow for more rational preventive regimens.

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.

Thiazide Effect on the Mineral Content of Bone

The thiazide diuretics are known to cause calcium retention. In order to study the effect of thiazides on bone mineralization, we have measured the mineral content of bone at five sites (the distal radius, the distal ulna, the proximal radius, the proximal ulna, and the os calcis) in 1368 men with a mean age of 68 years, including 323 who were taking thiazides for hypertension. The results were adjusted for age and body-mass index. Thiazide users had significantly more bone mineral content at all five sites than did non-users. Untreated hypertensive patients and persons without hypertension had comparable bone mineral content, indicating that the higher mineral content found among thiazide users is related to the drug and not to the underlying hypertension. These findings suggest the possibility of a preventive or therapeutic role for thiazides in osteoporosis.

The clinical relevance of calcaneus bone mineral measurements: a review

The use of bone mineral content (BMC) measurements to assist in the management of osteoporosis has received increasing emphasis in recent years. Although the calcaneus, an essentially trabecular bone (90-95%), has been used extensively in the NASA experiments, few data relating to primary osteoporosis have appeared in the literature until recently. This paper is a review of the methods of measurement, their precision and methods of calibration, and the relationship of calcaneal mineral content to age, height, weight, other bone sites, degree of spinal osteoporosis, metabolic bone disease and the effects of therapeutic drugs. Prospectively, calcaneal BMC relates as well as spinal BMC to osteoporotic fracture risk. It is this use of BMC measurements which has the most promise for the future. The data indicate that osteoporosis is a systemic disease and trabecular bone losses are reflected in the calcaneus as well as in the spine itself.

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.

The Effects of Smoking on Bone Mass and the Rates of Bone Loss Among Elderly Japanese‐American Men

Bone density and bone loss rates were examined among Japanese‐American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow‐up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51–82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10–30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.

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.

Long-term precision of bone loss rate measurements among postmenopausal women

SummaryRepeated measurements of bone mineral content can indicate the rate of bone loss among postmenopausal women. The clinical utility of such loss rate measurements will depend upon the long-term precision of the measurements. We have analyzed the precision of appendicular bone measurements among 495 Japanese-Americans followed for an average of 5.3 years and of both appendicular and axial measurements among 70 clinical trial participants followed for 2 years. Tables were derived from these analyses to quantitate the precision of individual loss rates under varying measurement conditions that might be encountered in clinical practice. The results demonstrate that only unusually rapid loss rates could be identified with confidence within short intervals, such as 1 year or 2. Extending the length of follow-up, however, appreciably improved the measured loss rate precision. In comparisons between bone sites, appendicular sites were determined to achieve a specified precision within the shortest intervals, followed by spine dual photon absorptiometry measurements. Spine quantitative computerized tomography measurements and measurements of hip sites required considerably longer follow-up intervals to achieve comparable precision.

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.

Methodological issues in comparing genetic and environmental influences on bone mass

Measurements of bone mineral content (BMC), bone width (BW) and BMC/BW (BMA) at the proximal radius were compared for both Japanese and Japanese-American men and women, after adjusting for measurement technique differences. Within each nationality, men had greater values than women at all ages. Japanese-Americans had substantially greater values of BMC (6-10%) and BMA (16-17%), but lower BW (-12 to -15%), relative to Japanese. Adjustment for body size (height and weight) reduced the magnitude of these differences by approximately one-half for BMC, but had a smaller effect on BMA, and slightly increased the difference in BW. Comparison of these results to published data suggests that environmental factors may have influences on bone mass that are similar in magnitude to the effects of race. The need for additional studies to address potential methodological problems is discussed, using this and other reports as examples.