Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women.

The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

Predictors of bone mineral density in aging healthy men varies by skeletal site.

Factors contributing to the pathogenesis of osteoporosis in women are well defined. However, changes in bone mineral metabolism in aging men and the role of various factors in the pathogenesis of age-related bone loss in men are less well understood. To further clarify these changes, serum and urine biochemical parameters, and lumbar spine, hip, and total body bone mineral density (BMD) were evaluated in a small sample of 45 healthy men aged 20-80 years, and multiple regression models were developed to predict age-related bone loss. Serum calcium, phosphate, albumin, creatinine clearance, osteocalcin, C-terminal propeptide of type I procollagen, log-free androgen index, dehydroepiandrosterone sulfate (DHEA-S), and androstenedione decreased with age, and serum sex hormone binding globulin and urine total and free pyridinoline increased with age. Femoral neck BMD decreased with age, but remained stable at the other sites measured. Multiple regression analysis indicated that serum phosphate, DHEA-S, and intact parathyroid hormone (PTH) predicted lumbar spine BMD. Age, serum phosphate, and PTH predicted femoral neck BMD. Urine-free deoxypyridinoline alone predicted femoral greater trochanter BMD. Weight, serum creatinine, and urine-free deoxypyridinoline predicted total body BMD. We conclude that predictor variables of bone density vary by skeletal site in healthy men. Alterations in adrenal androgens, phosphate, and PTH may be important in the pathogenesis of bone loss with aging in men.

Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data.

Hip scans of U.S. adults aged 20-99 years acquired in the Third National Health and Nutrition Examination Survey (NHANES III) using dual-energy X-ray absorptiometry (DXA) were analyzed with a structural analysis program. The program analyzes narrow (3 mm wide) regions at specific locations across the proximal femur to measure bone mineral density (BMD) as well as cross-sectional areas (CSAs), cross-sectional moments of inertia (CSMI), section moduli, subperiosteal widths, and estimated mean cortical thickness. Measurements are reported here on a non-Hispanic white subgroup of 2,719 men and 2,904 women for a cortical region across the proximal shaft 2 cm distal to the lesser trochanter and a mixed cortical/trabecular region across the narrowest point of the femoral neck. Apparent age trends in BMD and section modulus were studied for both regions by sex after correction for body weight. The BMD decline with age in the narrow neck was similar to that seen in the Hologic neck region; BMD in the shaft also declined, although at a slower rate. A different pattern was seen for section modulus; furthermore, this pattern depended on sex. Specifically, the section modulus at both the narrow neck and the shaft regions remains nearly constant until the fifth decade in females and then declined at a slower rate than BMD. In males, the narrow neck section modulus declined modestly until the fifth decade and then remained nearly constant whereas the shaft section modulus was static until the fifth decade and then increased steadily. The apparent mechanism for the discord between BMD and section modulus is a linear expansion in subperiosteal diameter in both sexes and in both regions, which tends to mechanically offset net loss of medullary bone mass. These results suggest that aging loss of bone mass in the hip does not necessarily mean reduced mechanical strength. Femoral neck section moduli in the elderly are on the average within 14% of young values in females and within 6% in males.

Site-specificity of bone mineral density and muscle strength in women: job-related physical activity.

We proposed that there are significant correlations between muscle strength and bone mineral density in premenopausal women and that these correlations are site-specific. To test this hypothesis, we examined the relationships among site-specific bone mineral density, physical activity, and muscle strength in a group of 96 healthy premenopausal Caucasian women. Bone mineral density was measured at the lumbar spine and at three sites in the proximal femur (trochanter, femoral neck, and Ward's triangle) with dual-energy x-ray absorptiometry and at the mid-radius with single-photon absorptiometry. The muscle strength of hip and spinal muscle groups was determined with a strain gauge isodynamometer, and grip strength was measured with the JAMAR dynamometer. The strength of shoulder girdle muscle groups was evaluated with the use of free weights. Physical activity was determined by surveying the subjects and by using a standardized scale. Data analysis revealed significant linear correlations of muscle strength with bone mineral density at the mid-radius (r = 0.31; P = 0.002) and at the hip (r = 0.26; P = 0.01). Grip strength was significantly correlated with bone mineral density of both the spine and the femur (r = 0.24, r = 0.34; P < 0.05 for both). Back extensor strength correlated with bone mineral density of the hip (Ward's triangle; r = 0.23; P = 0.023). However, there was no significant positive correlation between the strength of the spinal flexor or extensor muscles and the site-related bone mass (lumbar spine). Only one of the three components of the physical activity score (job) positively correlated with vertebral bone mineral density (r = 0.21; P = 0.04). Physical activity negatively correlated with age (r = 0.24; P = 0.02). We conclude that in premenopausal women, the effect of muscle strength on bone mass is more systemic than site-specific. A positive correlation between vertebral bone mass and components of physical activity demonstrates that even job-related physical activity is an important factor in maintaining adequate bone mass.

Updated data on proximal femur bone mineral levels of US adults.

This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III, 1988-94), and updates data previously presented from phase 1 only. The data were collected from 14,646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements.

Bone mass and muscle strength in female college athletes (runners and swimmers).

OBJECTIVE: To determine whether female college athletes had increased muscle strength and bone mass in comparison with age-matched nonathletic female subjects and, if so, whether participation in weight-bearing versus non-weight-bearing exercise made a difference. MATERIAL AND METHODS: We performed a comparative statistical analysis of the bone mineral density (BMD) of the total body, lumbar spine, and femoral neck, maximal oxygen uptake (VO2max), muscle strength, and level of physical activity in 21 runners, 22 swimmers, and 20 control subjects. The study participants were female college students, 18 to 24 years old, who had had more than 8 normal menstrual cycles during the past year. RESULTS: Statistical analyses showed significantly higher VO2max in the two athletic study groups than in the control subjects (P < 0.0001). No significant difference in BMD was noted among the three groups. Total body BMD (r = 0.30; P = 0.02) and femoral neck BMD (r = 0.39; P = 0.002) were positively correlated with weight-bearing activity but not with non-weight-bearing activity. VO2Max (an index of physical fitness) was positively correlated with femoral neck BMD (r = 0.33; P = 0.009) and trochanteric BMD (r = 0.29; P = 0.021). Shoulder muscle strength (determined by isokinetic dynamometry) was positively correlated with total body BMD (r = 0.34; P = 0.007) and lumbar spine BMD (r = 0.28; P = 0.028). Swimmers had higher muscle strength in the back and upper extremities than did runners and control subjects. Hip girdle muscle strength was not significantly different among the three groups. Total body BMD had a positive correlation with percentage of body fat and height. Lumbar spine BMD was higher in subjects who had previously used oral contraceptives. The athletes had a lower percentage of body fat, were less likely to have used oral contraceptives, and had fewer years of normal menses than did the control subjects. CONCLUSION: Our study shows that (1) total body BMD and femoral neck BMD were significantly higher in the study group that performed weight-bearing exercises than in control subjects, (2) swimming exercise had no effect on BMD, and (3) although swimming is not a bone-building exercise, it can significantly improve shoulder, back, and grip muscle strength.

Prevalence of low femoral bone density in older U.S. adults from NHANES III.

Most estimates of osteoporosis in older U.S. adults have been based on its occurrence in white women, even though it is known to affect men and minority women. In the present study, we used dual-energy X-ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) to estimate the overall scope of the disease in the older U.S. population. Specifically, we estimate prevalences of low femoral BMD in women 50 years and older and explore different approaches for defining low BMD in older men in that age range. Low BMD levels were defined in accordance with an approach proposed by an expert panel of the World Health Organization and used BMD data from 382 non-Hispanic white (NHW) men or 409 NHW women ages 20-29 years from the NHANES III dataset. For women, estimates indicate 13-18%, or 4-6 million, have osteoporosis (i.e., BMD > 2.5 standard deviations [SD] below the mean of young NHW women) and 37-50%, or 13-17 million, have osteopenia (BMD between 1 and 2.5 SD below the mean of young NHW women). For men, these numbers depend on the gender of the reference group used to define cutoff values. When based on male cutoffs, 3-6% (1-2-million) of men have osteoporosis and 28-47% (8-13 million) have osteopenia; when based on female cutoffs, 1-4% (280,000-1 million) have osteoporosis and 15-33% (4-9 million) have osteopenia. Most of the older U.S. adults with low femur BMD are women, but, regardless of which cutoffs are used, the number of men is substantial.

Three-year controlled, randomized trial of the effect of dose-specified loading and strengthening exercises on bone mineral density of spine and femur in nonathletic, physically active women.

The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.

Correlation of back extensor strength with thoracic kyphosis and lumbar lordosis in estrogen-deficient women.

Aging and osteoporosis have been associated with skeletal changes. Back extensor strengthening exercises are highly recommended for management of back pain, especially back pain related to osteoporosis. To our knowledge, the correlation of thoracic kyphosis, lumbar lordosis, and sacral inclination with back extensor strength, physical activity, and bone mineral density has not been critically studied in healthy, active, estrogen-deficient women. In a study of 65 such women (ages 48-65 yr), back extensor strength, bone mineral density, and physical activity score were evaluated and measured. These factors were then correlated with radiographic factors: (1) vertebral body ratios (anterior/posterior height) calculated for each vertebra from T-4 through L-5; (2) kyphosis index determined by adding the anterior heights of each vertebral body, T-4 through T-12, and then dividing the total by the corresponding sum of the posterior heights of each vertebral body; (3) thoracic kyphosis; (4) lumbar lordosis; and (5) sacral inclination. Back extensor strength had a significant negative correlation with thoracic kyphosis (r = -0.30, P = 0.019) and a positive correlation with lumbar lordosis (r = 0.26, P = 0.048) and sacral inclination (r = 0.34, P = 0.009). However, bone mineral density and physical activity score did not show any significant correlations with the radiographic factors. The results indicate that the stronger the back extensor, the smaller the thoracic kyphosis and the larger the lumbar lordosis and sacral inclination. We conclude that back extensor strength is an important determinant of posture in healthy women. However, prescribing back extensor strengthening exercises alone may also increase lumbar lordosis, which is not desirable.

Changes in quantitative bone histomorphometry in aging healthy men.

Changes in bone mineral metabolism with aging in healthy men and the roles of various factors in the pathogenesis of age-related changes in quantitative bone histomorphometry in men are poorly defined. To clarify these changes and factors, serum and urinary biochemical parameters and iliac crest bone biopsies were evaluated in 43 healthy men, aged 20-80 yr. The static histomorphometric parameters, cancellous bone volume and osteoblast-osteoid interface, decreased by 40.0% and 19.2%, respectively, between 20-80 yr of age. The dynamic histomorphometric parameters, double and single labeled osteoid, also decreased by 18.6% and 18.0%, respectively, over this period. None of the other static or dynamic histomorphometric parameters changed with age in this population sample of healthy men. Univariate analysis of static bone histomorphometric parameters and biochemical parameters revealed significant correlations between osteoid surface and intact PTH (r = 0.37; P = 0.015); osteoclast surface and serum total testosterone (r = 0.36; P = 0.016), estradiol (r = 0.40; P = 0.009), and FSH (r = 0.49; P = 0.001); osteoblast-osteoid interface and serum phosphate (r = 0.31; P = 0.046); and cortical thickness and serum total calcium (r = 0.38; P = 0.013). Univariate analysis of dynamic bone histomorphometric parameters and biochemical parameters revealed correlations between mineral apposition rate and serum total testosterone (r = 0.32; P = 0.037); total volume-referent bone formation rate and serum osteocalcin (r = 0.43; P = 0.004), total testosterone (r = 0.47; P = 0.001), estradiol (r = 0.35; P = 0.023), and dehydroepinadrosterone sulfate (r = 0.31; P = 0.045); and mean wall thickness and serum total calcium (r = 0.36; P = 0.019) and creatinine clearance (r = 0.42; P = 010). Mineralization lag time and serum phosphate (r = -0.39; P = 0.012) and urinary total pyridinoline (r = 0.36; P = 0.023), and mean wall thickness and urinary total pyridinoline (r = -0.38; P = 0.013), were inversely correlated. Multiple regression analysis using all-subset analysis comparing cancellous bone volume to serum and urinary biochemical parameters in these men indicated that the log free androgen index and body weight best predicted the age-related decline in iliac crest cancellous bone volume (r2 = 0.19; P = 0.015). Multiple regression analysis by the same method, comparing bone density at different skeletal sites to bone histomorphometric parameters, indicated that lumbar spine bone mineral density (BMD) was best predicted by cancellous bone volume and mineral apposition rate (r2 = 0.31; P = 0.001), femoral neck BMD by cancellous bone volume and osteoid surface (r2 = 0.19; P = 0.020), femoral greater trochanter BMD by cortical thickness and single labeled osteoid surface (r2 = 0.13; P = 0.060), and total body BMD by cancellous bone volume and surface-based bone formation rate (r2 = 0.31; P = 0.001). In summary, cancellous bone volume, osteoblast-osteoid interface, and double and single labeled osteoid decreased with age in this sample of healthy men. The lack of detectable change in bone density at some skeletal sites in these men may be due to the small sample size or other confounding factors. Multivariate analysis suggests that different combinations of histomorphometric parameters predict bone density at different skeletal sites, and that cancellous bone volume predicts bone density at the lumbar spine, femoral neck, and total body, but not at the femoral greater trochanter. We conclude that alterations in several biochemical parameters are important in the pathogenesis of age-related bone loss in healthy men.

Dietary protein intake and bone mass in women.

Population-based strategies to combat osteoporosis are urgently needed. The role of nutrition in such strategies has been particularly contentious. We examined the relationship among six key nutrients that are thought to affect bone metabolism and bone mineral density in the axial and appendicular skeleton using data from a population-based study in the northern United States. Data on the dietary intake of calcium, phosphorus, vitamin D, protein, fat, and total energy were obtained from a 7-day dietary record. Bone density measurements were made by dual photon absorptiometry in the lumbar spine and proximal femur, and by single photon absorptiometry in the distal and midradius. Among the 72 premenopausal women studied, there was a statistically significant positive association between protein intake and bone mineral in the distal radius and proximal femur, which was not altered by adjustment for age, weight, and physical activity. Among 218 postmenopausal women, no such relationship was found between protein intake and bone mineral, and the only significant findings in this group were negative associations between fat consumption and bone density in the lumbar spine and radius. Our results suggest that dietary protein intake may be a determinant of the peak bone mass attained by premenopausal white women. The relevance of this finding for the design of population strategies to maximize skeletal growth requires further investigation.

Filtered technetium-99m-sulfur colloid evaluated for lymphoscintigraphy.

UNLABELLED: Several 99mTc-labeled radiopharmaceuticals have been developed for lymphoscintigraphy of the extremities. In the United States, however, these agents are not widely used clinically. This study evaluates the use of smaller particle sizes ( < 0.1 micron) of 99mTc-sulfur colloid (99mTc-SC) for lymphoscintigraphy. METHODS: The 99mTc-SC was prepared by kit, and the final preparation was filtered through a sterile 0.1-micron filter. The radiochemical purity (RCP) of the filtered 99mTc-SC was determined before administration. Nineteen patients with suspected lymphedema were injected with 18.5 MBq (500 muCi) filtered 99mTc-SC intradermally in each foot, and whole-body images were obtained immediately and 1, 3, 6 and 24 hr later. Local views over the inguinal or axillary lymph nodes were also obtained every 5 min for the first hour. RESULTS: The average RCP value was 93.4% +/- 4.2% (n = 19), and the RCP difference pre- and postfiltration of the 99mTc-SC preparation was -1.7% +/- 1.4% (n = 40). Evaluation of the particle size with the polycarbonate filter showed that 89.9% +/- 4.5% (n = 28) of particles were less than 50 nm, and the particle size was further determined by electron microscopy to be 38.0 +/- 3.3 nm (n = 202). The mean particle sizes of two peaks measured by laser light scattering techniques were 7.5 and 53.9 nm (major peak). Clinical studies with filtered 99mTc-SC demonstrated similar lymphoscintigrams compared with those obtained with 99mTc antimony sulfide colloid (99mTc-ATC). Filtered 99mTc-SC showed a faster transport rate to the inguinal lymph nodes and lower radiation dosimetry for liver, spleen and whole body compared with 99mTc-ATC. CONCLUSION: Filtered 99mTc-SC can be easily prepared and is readily available for routine clinical use in lymphoscintigraphic studies.

Prevalence of low femoral bone density in older U.S. women from NHANES III.

Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to approximately 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal femur bone mineral levels of US adults.

This paper describes bone mineral levels in the proximal femur of US adults based on a nationally representative sample of 7116 men and women aged 20 years and older. The data were collected in phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in five selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter, Ward's triangle and total. These variables are provided separately by age and sex for non-HIspanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). BMD and BMC in the five ROI tended to decline with age, whereas area did not. BMD and BMC were highest in NHB, intermediate in MA and lowest in NHW, but areas were highest in NHW, intermediate in NHB and lowest in MA. Men had greater BMD, BMC and area than women in all three race/ethnic groups. Differences by age, sex or race/ethnicity tended to be the largest in Ward's triangle, followed by the femur neck; patterns in the trochanter, intertrochanter and total ROI were reasonably similar to each other. This report provides extensive data on femur bone mineral levels of adults from one of the largest samples available to date and should be valuable as reference data for other studies which examine this skeletal site in adults.

Quality control of bone densitometry in a national health survey (NHANES III) using three mobile examination centers.

A quality control (QC) program for bone mineral measurements at the proximal femur by dual-energy x-ray absorptiometry (DXA) was designed for the osteoporosis component of the Third National Health and Nutrition Examination Survey (NHANES III). Major elements of the QC program are (1) a QC center for review of all scans, (2) setup procedures for and continuous monitoring of daily QC procedures, (3) reference standards for cross-calibration, (4) longitudinal studies for assessment of instrument stability, (5) monitoring of technologist performance, and (6) training. This report describes the results of the QC program of the first half of this 6 year study, which began in 1988. Measurements were performed on 7376 subjects in three mobile examination centers, which traveled to a new location about every 3 months, a total of 44 locations. A small percentage (3.5%) of all scans were rejected, mostly because of patient motion during scanning, but 33% of the remaining scans required reanalysis at the QC center to refine the location of the regions of interest. Precision in spine and hip phantoms was below 1% at all ROIs. In 535 subjects with duplicate scans, age 20-91 of both sexes, examined in a blinded review, precision for BMD at the femur neck ROI was 3.2% (CV) and 5.1% for Ward's triangle BMD. The central review improved scan quality, increased the number of usable scans, and reduced significantly the range of the mean percentage difference in the duplicate scans. Minor alterations in machine function were observed and corrected. QC results on phantoms were similar to those obtained with stationary instruments in dedicated laboratories. Retrospective analysis of the regression slopes from QC records did not show a need for correction of the data base, indicating that the instruments were stable during the course of the study.

Continuing loss of vertebral mineral density in renal transplant recipients.

This cross-sectional study examined bone abnormalities by digital radiography, bone densitometry and biochemical tests in 44 clinically asymptomatic renal transplant recipients 6-195 months after renal transplantation. Abnormal radiographs were obtained in 40 of the 44 patients. Dual-energy X-ray absorptiometry (DXA) performed at the lumbar spine (L2-L4)/showed a negative Z score in all patients, ranging from -1 to -1.9 in 28 patients and less than -2.0 in 16 patients. The severity of osteopenia increased with the length of time after transplantation and there was a significant correlation with parathyroid hormone values in patients with normal and low glomerular filtration rates. Our data suggest that decreased bone density values (Z score less than -2) are present in about one-third of patients with renal transplants. Bone loss appears to continue after transplantation. Steroid therapy and immunotherapy are probably the cause of this bone loss. Bone mineral measurements alone are helpful in identifying asymptomatic patients with low bone mass after transplantation.

Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis.

In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF at 75 mg/day or placebo (both groups received supplementary calcium at 1500 mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional analyses and extended observations are now available on 50 women from the NaF group followed for up to 6 years of treatment. In these women, LS-BMD increased linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because during the 4 year trial the NaF dosage was decreased (because of side effects) in 54 of the 101 women randomized to NaF, dose-response relationships could be evaluated. For the entire study population, serum F level correlated directly with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of observation were grouped by deciles of LS-BMD, VFR (per 100 person-years) decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2 g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2. Multivariate analyses and inspection of three-dimensional plots revealed a complex pattern in which VFR was influenced by interaction of several variables. When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed simultaneously, VFR was seen to decrease with increasing LS-BMD except when the higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large increase from baseline serum F. For some patients (noncompliers or nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that lower dosages of NaF produce moderate decreases in VFR.

Noninvasive evaluation of the lymphatic system with lymphoscintigraphy: a prospective, semiquantitative analysis in 386 extremities.

PURPOSE: Lymphoscintigraphy has emerged as the diagnostic test of choice in patients with suspected lymphedema. To assess the lymphatic circulation of 386 extremities in 188 patients, we prospectively recorded a semiquantitative index of lymphatic transport in addition to visual evaluation of lymphoscintigraphy image patterns. METHODS: Sixty-one male and 127 female patients were studied (mean age 48 years, range 13 to 87 years). Twenty had upper extremity swelling, and 168 had lower extremity swelling. The disease was bilateral in 60 patients. Lymphoscintigraphy was performed by injecting a mean of 503 microCi of technetium 99m-antimony trisulfide colloid subcutaneously into the second interdigital space of the extremity. Time for transport to regional lymph nodes, appearance of lymph vessels and nodes and distribution pattern were scored. These scores were compiled into a modified Kleinhans transport index (TI). To assess the venous circulation, 155 patients underwent evaluation of the venous system by impedance plethysmography, ultrasonography, or contrast venography. RESULTS: The mean TI (+/- SEM) in 79 asymptomatic extremities was 2.6 +/- 0.5, with 66 (83.5%) demonstrating normal lymphoscintigraphy pattern (TI < 5). Patients with clinical diagnosis of lymphedema (n = 124) had a mean TI of 23.8 +/- 1.5; 81.5% of these were greater than 5. Fifty-six patients (30%) had primary and 68 (36%) had secondary lymphedema. (TI of 26 +/- 3.5 and 22.1 +/- 1.9, respectively, p = NS). Patients without any lymphatic transport (TI of 45) were more likely to have cellulitis in their history (p < 0.05). Contrast lymphangiography in six patients correlated with lymphoscintigraphy. Sixty-four patients (34%) had swelling without lymphedema (venous edema, cardiac edema, lipedema, etc.; TI of 1.9 +/- 0.4, p < 0.001). Of the 41 patients with abnormal venous studies, 18 (44%) had an elevated TI. CONCLUSIONS: Semiquantitative evaluation of the lymphatic transport with lymphoscintigraphy reliably depicts abnormalities in the lymphatic circulation. Lymphoscintigraphy excluded lymphedema as a cause of leg swelling in one third of our patients.