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Measurement of forearm bone mineral density: comparison of precision of five different instruments.

Measurement of bone mineral density (BMD) is used for clinical estimation of fracture risk in osteoporosis. The precision of the method is important for the evaluation of true and clinical relevant changes in BMD in patients with osteoporosis. We measured BMD of the forearm in 14 young, healthy probands (10 males, 4 females), aged 24. 6 +/- 1.5 years with five different instruments using dual-energy X-ray absorptiometry (DXA), single-photon absorptiometry (SPA), and peripheral quantitative computed tomography (pQCT). Precision was expressed as the percentage coefficient of variation (CV%). In addition, the standardized CV% (sCV%) and the root mean square standard deviation (rmsSD%) was calculated for long-term precision. CV% ranged from 1.04 (SPA, distal BMD) to 2.75% (pQCT, trabecular BMD) for short-term precision and from 1.49 (DXA, QDR 1000, 1/3-distal BMD) to 4.33% (SPA, ultradistal) for long-term precision, respectively. The results for the rmsSD% were higher but correlated well with the CV%. A change that exceeds 2 radical2 CV% has been considered as being significant. On this basis, 24.0 +/- 5.1% (mean +/- SEM) of the participants in our study would be expected to have a significant change in BMD without any correlation to the time-delay between the two measurements. Measurements of BMD were done at two locations with all five instruments: ultradistal and middistal BMD using DXA and SPA and total and trabecular BMD using pQCT, respectively. Coefficients of correlation for "between-instrumental" correlation were greater than 0.5 for almost all instruments. Distal and ultradistal BMD measured by SPA and trabecular and total BMD measured by pQCT correlated better with ultradistal BMD measured by DXA. Correspondingly, "within-instrumental" correlation was better for pQCT and SPA than for DXA. The coefficients of correlation between the different DXA methods were greater than 0.95 when corresponding locations were compared. We conclude that the clinical value of monitoring bone loss by measurement of forearm BMD is compromised by the low precision which was seen for DXA methods as well as for SPA and even pQCT in young healthy controls.

Absorptiometry, Photon↗

The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss.

The effect of percutaneous estradiol alone and combined with natural progesterone on postmenopausal bone loss was studied. A total of 57 women who had experienced a natural menopause 6 months to 3 years previously entered the study. After an initial examination the women were allocated in a blinded pattern to treatment with 3 mg of percutaneous estradiol or placebo. The code was broken after 1 year of treatment, and the women receiving estradiol continued with a cyclic addition of progesterone, whereas those receiving placebo continued with placebo. The women were examined every 3 months during the 2 years of treatment. Measurement of the bone mineral content in the forearms (single photon absorptiometry) and the spine and total skeleton (dual photon absorptiometry) showed a significant decrease of 5% to 7% in the placebo group during the 2 years of treatment, whereas it remained constant in all bone compartments in the estradiol group. Addition of progesterone did not influence the results. Biochemical estimates of calcium metabolism changed toward a premenopausal level in the estradiol group but remained unchanged in the placebo group. We conclude that percutaneous estradiol is effective as preventive therapy of postmenopausal bone loss and that addition of progesterone does not influence bone or calcium metabolism.

Administration, Cutaneous↗

Bone mineral content in early-postmenopausal and postmenopausal osteoporotic women: comparison of measurement methods.

To investigate associations among methods for noninvasive measurement of skeletal bone mass, we studied 40 healthy early postmenopausal women and 68 older postmenopausal women with osteoporosis. Methods included single- and dual-energy quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the lumbar spine, single-photon absorptiometry (SPA) of the distal third of the radius, and combined cortical thickness (CCT) of the second metacarpal shaft. Lateral thoracolumbar radiography was performed, and a spinal fracture index was calculated. There was good correlation between QCT and DPA methods in early postmenopausal women and modest correlation in postmenopausal osteoporotic women. Correlations between spinal measurements (QCT or DPA) and appendicular cortical measurements (SPA or CCT) were modest in healthy women and poor in osteoporotic women. Measurements resulting from one method are not predictive of those by another method for the individual patient. The strongest correlation with severity of vertebral fracture is provided by QCT; the weakest, by SPA. There was a high correlation between single- and dual-energy QCT results, indicating that errors due to vertebral fat are not substantial in these postmenopausal women. Single-energy QCT may be adequate and perhaps preferable for assessing postmenopausal women. The measurement of spinal trabecular bone density by QCT discriminates between osteoporotic women and younger healthy women with more sensitivity than measurements of spinal integral bone by DPA or of appendicular cortical bone by SPA or CCT.

Adult↗

In vitro study of the accuracy of bone mineral measuring devices in Norway and Sweden.

PURPOSE: The aim of the study was to investigate the performance of +different types of equipment for bone mineral assessment in Sweden and Norway with standardised phantoms. MATERIAL AND METHODS: Measurements of the bone mineral content of 2 semianthropomorphic phantoms, one simulating the human torso and one the lower arm, at 21 hospitals in Norway and Sweden, were undertaken. The phantoms had inserts of hydroxyapatite in different concentrations and were measured together with additions of stearic acid simulating fat. The phantoms were repeatedly measured on 14 dual X-ray absorptiometry, 5 single X-ray absorptiometry, and 3 single photon absorptiometry devices and 1 quantitative CT device. RESULTS: The measurements showed a large spread in the measured hydroxyapatite concentrations among different devices. The inaccuracy was slightly lower than 10% without fat present when the results were expressed as bone mineral areal mass (BMA, g/cm2). With fat included the inaccuracy was at worst 50%. CONCLUSION: The large inaccuracy found in this study gives rise to a large overlap between healthy and osteoporotic cases and make the diagnosis of osteoporosis difficult in the individual patient.

Absorptiometry, Photon↗

The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism.

The effect on bone metabolism of an agonist analog of GnRH, nafarelin, was studied in 16 premenopausal women, who received 200 micrograms nafarelin/day for 6 months, and 9 premenopausal women, who received 400 micrograms nafarelin/day for 6 months, followed by a 6-month follow-up period. Bone mineral content in the forearm (measured by single photon absorptiometry) and in the spine (measured by dual photon absorptiometry) significantly decreased after 6 months of treatment with 400 micrograms nafarelin, but 6 months after termination of treatment all bone mineral measurements had returned to pretreatment levels. The bone mineral measurements in the 200 micrograms group did not change throughout the study. In both treatment groups the biochemical estimates of bone turnover increased significantly to postmenopausal levels. Withdrawal of treatment resulted in an abrupt decrease in the bone resorption parameters (fasting urinary hydroxyproline to creatinine and calcium to creatinine excretion ratios and serum phosphate), whereas there was a protracted fall in the bone formation parameters (plasma bone Gla protein and serum alkaline phosphatase) 6 months after termination of treatment. Our findings demonstrate that nafarelin in both doses increased biochemical indices of bone turnover, that 400 micrograms/day nafarelin resulted in a significant decrease in bone mineral content, and that these effects were reversible.

Adult↗

Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures.

The present study was performed to investigate the role of insulin-like growth factor I (IGF-I), IGF-binding protein-2 (IGFBP-2), and IGFBP-3 in age-dependent bone loss in postmenopausal Japanese women. One hundred and sixty-five Japanese women aged 43-88 years (mean age, 62) were enrolled in the cross-sectional study. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and midradius by dual-energy X-ray absorptiometry or single-photon absorptiometry. Serum levels of IGF-I, IGFBP-2, and IGFBP-3 were measured by radioimmunoassay. BMD at all sites as well as serum levels of IGF-I and IGFBP-3 declined with age, while the serum IGFBP-2 level increased with age. Serum IGFBP-3 and -2 levels were positively and negatively correlated with the serum IGF-I level, respectively. Serum IGF-I and IGFBP-3 levels showed positive correlationship with BMD at any site, particularly at the midradius, while the serum IGFBP-2 level showed negative correlation with BMD. Multiple regression analyses showed age-independent positive correlation between the serum IGF-I level and BMD at all sites as well as age-independent positive correlation between the serum IGFBP-3 level and midradius BMD. The relationship between susceptibility to osteoporotic spinal fracture and serum IGF-I, IGFBP-3, or -2 levels was examined by decade to exclude the influence of aging. Serum levels of IGF-I and IGFBP-3 were significantly lower in subjects with spinal fractures than those without fractures at any decade. No significant difference of serum IGFBP-2 level was observed between subjects with and without fractures. The present findings suggest that IGF-I and IGFBP-3 are important to maintaining bone mass quantitatively as well as qualitatively, and that the determination of serum IGF-I and IGFBP-3 levels could be clinically useful to predict the severity of osteoporosis, particularly the risk of bone fracture associated with osteoporosis.

Absorptiometry, Photon↗

Bone mineral density, muscle strength and physical activity. A population-based study of 332 subjects aged 15-42 years.

The aim of this population-based study was to find out whether differences in levels of physical activity have an influence on bone mass quantity and whether quadriceps muscle strength is a reliable determinant of bone mass. Included were 175 men and 157 women, aged 15-42 years. Bone mineral density (BMD) was measured at various sites by dual X-ray absorptiometry (DXA) and single photon absorptiometry (SPA). Muscle strength was assessed using an isokinetic muscle force meter. A questionnaire was used to estimate the level of physical activity. We found a positive correlation between physical activity and BMD for boys at the distal forearm and for girls at the trochanter (age group 15-16 years). Active men (age group 21-42 years) had up to 9% higher BMD levels at the hip than those who were less active. Quadriceps muscle torque was not an independent predictor of BMD. Our data suggest that a higher level of physical activity-within the limits of a "normal life style"-may have a positive effect on BMD in the proximal femur of young adults, which in turn may lessen the subsequent risk of fracture.

Absorptiometry, Photon↗

[Comparative bone density measurements in healthy women and women with osteoporosis].

To compare methods of noninvasive measurement of bone mineral content, 40 healthy early postmenopausal women and 68 postmenopausal women with osteoporosis were studied. The methods included mono- and dual-energy quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the lumbar spine, single-photon absorptiometry (SPA) of the distal third of the radius, and combined cortical thickness (CCT) of the second metacarpal shaft. Lateral thoracolumbar radiographic studies were performed and the spinal fracture index calculated. There was good correlation between QCT and DPA methods in early postmenopausal women and moderate correlation in postmenopausal osteoporotic women. Correlations between spinal measurements (QCT or DPA) and appendicular cortical measurements (SPA or CCT) were moderate in healthy women and poor in osteoporotic women. Measurements resulting from one method were not predictive of measurements obtained by another method for individual patients. The strongest correlation with severity of vertebral fracture was provided by QCT and the weakest by SPA. There was good correlation between single- and dual-energy QCT results. Osteoporotic women and younger healthy women can be distinguished by the measurement of spinal trabecular bone density using QCT, and this method is more sensitive than the measurement of spinal integral bone by DPA or of appendicular cortical bone by SPA or CCT.

Adult↗

Effects of weight lifting on bone mineral density in premenopausal women.

A group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual-photon absorptiometry and of the os calcis with single-photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gamma-carboxyglutamic acid (Gla). Subjects were given a daily 500 mg supplement of elemental calcium. There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a paired t-test revealed a significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated population.

Adult↗

Relationship between local and total bone mineral in patients with rheumatoid arthritis and normal subjects.

Total body bone mineral (TBBM) measured by dual photon absorptiometry and local bone mineral (BMC) measured by single photon absorptiometry were determined in 55 patients with definite or classical rheumatoid arthritis. All of them had been on a steady dose of anti-inflammatory drugs for at least 12 months, and furthermore, 13 patients were on glucocorticoids. The results were compared with 49 normal persons matched for sex, age and menopausal state. A highly significant correlation was found between BMC and TBBM in the patients (r = 0.84, SEE = 13.0%) as well as in the controls (r = 0.77, SEE 10.5%). Moreover, the intercepts and the slopes were virtually of the same order. Subdividing the patients according to glucocorticoid treatment the same high correlations were shown in the two subgroups. As a group the patients on glucocorticoids had a highly significant generalized osteopenia (a reduction of TBBM of 26% compared to normals). The patients on other anti-inflammatory drugs had a significant, but less pronounced generalized osteopenia (a reduction of TBBM by 11% compared to normals). It is concluded, that BMC of the forearm can be used as a valid estimate of total body calcium in groups of patients with rheumatoid arthritis and in normal subjects.

Activation Analysis↗

Bone density of the radius, spine, and hip in relation to percent of ideal body weight in postmenopausal women.

Bone mineral content (BMC) and bone mineral density (BMD) of the spine (L2-L4) and hip (at femoral neck, Ward's triangle, and greater trochanter sites) were determined by dual-photon absorptiometry (DPA), and of the radius by single-photon absorptiometry (SPA) in healthy postmenopausal women aged 40-70 years. The relationships of BMC and BMD to years since menopause were examined separately in 97 women who were above 115% of ideal body weight (IBW) and in 128 women below. The heavier women had significantly greater mean BMC and BMD at each site than did the normal-weight women. In the normal-weight women, there was a significant negative correlation between BMD and years since menopause at each measurement site except the greater trochanter. In the obese women, BMD decreased with increasing years since menopause at the radius site only and BMC declined with increasing years after menopause at the hip (femoral neck and Ward's triangle region) as well as the radius. Thus, body size is a significant determinant of BMD in this population. The pattern of loss of BMD from Ward's triangle and femoral neck regions of hip are similar to that of the spine. The BMC and BMD findings in the hip suggest that remodeling occurs at this weight-bearing site which has a favorable effect on bone strength.

Adult↗

Bone mineral density and skeletal fractures in familial benign hypercalcemia (hypocalciuric hypercalcemia).

To determine whether familial benign hypercalcemia, or familial hypocalciuric hypercalcemia (FHH), has adverse effects on the skeleton, we measured bone mineral density (BMD) in 31 affected persons from 14 families (16 women and 15 men), ranging in age from 19 to 68 years. Forearm BMD was measured by single-photon absorptiometry, and spinal BMD was measured by dual-photon absorptiometry. In addition, we systematically queried 82 hypercalcemic and 52 normocalcemic family members about skeletal fractures. Both men and women with FHH had normal BMD (expressed as grams per square centimeter) in the lumbar spine, distal radius, and midradius. Osteoporotic-type fractures (vertebrae, hip, and distal radius) were virtually absent in both affected and unaffected family members. Detailed evaluation of larger numbers of of older affected persons may be necessary to resolve this issue definitively, but we conclude provisionally that FHH has no important adverse effects on skeletal health.

Adult↗

Lactation history and bone mineral density among perimenopausal women.

To examine the relation between lactation and bone mineral density, we conducted a cross-sectional study among white, nonsmoking, perimenopausal women age 40-54. Three hundred fifty-two women completed a questionnaire covering medical and reproductive histories, physical activity, and diet. We measured the bone density of lumbar vertebrae 2-4 with dual photon absorptiometry, and the midradius and distal radius with single photon absorptiometry. Women with a history of lactation had 41 mg per cm2 higher lumbar bone mineral density than women with no lactation (95% confidence interval = 8-74 mg per cm2), controlling for parity, body mass, physical activity, and menopausal status. We found no important increase at mid- or distal radius.

Adult↗

Insulin-like growth factors I and II: aging and bone density in women.

Serum concentrations of insulin-like growth factors (IGF) were measured by RIA in 57 normal women, ages 30 - 90 yr, and in 29 untreated women with postmenopausal osteoporosis and vertebral compression fractures, ages 55 - 75 yr. These values were correlated with bone mineral density (BMD) of the distal and midradius assessed by single photon absorptiometry and of the lumbar spine assessed by dual photon absorptiometry as well as serum and urinary calcium, phosphorus, creatinine, alkaline phosphatase, immunoreactive PTH, urinary hydroxyproline, and creatinine clearance. Serum IGF-I levels declined markedly with age (r = -0.47, P less than 0.001). Serum IGF-II levels decreased only slightly with age, and this decrease was not statistically significant. Although BMD at all three scanning sites also declined significantly with age, neither serum IGF-I nor II concentrations correlated with BMD when age was held constant. In women with postmenopausal osteoporosis, serum IGF-I and II did not differ from the concentrations in normal women of similar age and did not correlate with BMD. In neither group was a correlation between serum IGF-I or II and serum or urinary proteins or cations found. Thus, there was no evidence that impaired synthesis of IGF-I and II contributes to pathogenesis of the syndrome of Type I (postmenopausal) osteoporosis, which is characterized by accelerated loss of trabecular bone and vertebral compression fractures. The possibility remains, however, that decreasing concentrations of serum IGF-I play a role in the more gradual loss of bone with aging (Type II osteoporosis) in which impared bone formation at the cellular level has been demonstrated.

Adult↗

Lower vertebral bone density in male long distance runners.

Bone density in 13 male long distance runners (28.7 +/- 1.2 yr, 67.6 +/- 2.0 kg) and 11 male nonrunners (26.8 +/- 1.3 yr, 71.0 +/- 2.2 kg) was compared. Bone was measured at the lumbar spine and mid-tibia using dual photon absorptiometry and at the mid-radius using single photon absorptiometry. Runners (mean weekly training 92.2 +/- 6.3 km) had significantly lower (P less than 0.05) vertebral bone mineral density (1.12 +/- 0.03 g.cm-2) than nonrunners (1.24 +/- 0.04 g.cm-2). Tibial and radial bone mineral density did not differ between the groups. Daily calcium intake for runners (1,373 +/- 486 mg) and nonrunners (1,267 +/- 236 mg) exceeded the RDA. The results of this study suggest that long distance running may lead to decreased vertebral bone mineral density. The hormonal changes that occur with endurance training may contribute to this decrease.

Adult↗

Calcitriol treatment is not effective in postmenopausal osteoporosis.

STUDY OBJECTIVE: To determine if calcitriol is an effective treatment in postmenopausal osteoporosis. DESIGN: Double-blind, randomized clinical trial of 2 years' duration. SETTING: University medical center with patients recruited by media announcements. PATIENTS: Eighty-six postmenopausal women with vertebral compression fractures. INTERVENTIONS: Patients were treated with calcitriol or placebo. Mean dose was 0.43 micrograms/d. Dietary calcium was 1000 mg/d (24.9 mmol/d). The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia. MEASUREMENTS AND MAIN RESULTS: No significant differences between placebo and control groups were seen in the percent change in total body calcium (0.4% +/- 1.0 compared with 0.0% +/- 0.9), single photon absorptiometry (-0.5% +/- 1.2 compared with -3.1% +/- 0.9) or dual photon absorptiometry (0.0% +/- 1.7 compared with -1.0% +/- 2.2). New fractures were seen in 16% of the placebo group and 26% of the calcitriol groups, so the difference in percent fractures was 10% (95% CI, -5.7% to 25.7%). Bone biopsies did not show changes in either group. The calcitriol group had significantly higher serum and urine calcium values, but renal function was not worse than in the placebo group. CONCLUSIONS: Calcitriol is not an effective treatment for established postmenopausal osteoporosis.

Aged↗

Total and local bone mineral during estrogen treatment: a placebo controlled trial.

103 healthy postmenopausal women with a natural menopause 0.5-2 years previously were randomized to either estrogen (n = 52) or placebo (n = 51) treatment. Total body bone mineral (TBBM) was measured by dual photon absorptiometry and forearm bone mineral content (BMC) by single photon absorptiometry before and after one year. Both TBBM and forearm BMC fell significantly (P less than 0.001) in the placebo group, but were unchanged after estrogen treatment. The loss of bone mineral in the placebo group during one year was 5% (TBBM) and 3% (forearm BMC). A significant correlation (r = 0.53; P less than 0.001) was found between the fractional percent change in forearm BMC and TBBM. It is concluded, that both the forearm BMC and the TBBM measurements are suitable for following changes in bone mass postmenopausally. The almost equal relative amount of cortical bone in the total skeleton and in the forearm BMC may explain that longitudinally performed forearm BMC measurements are indicative of average changes in the total skeletal status.

Bone and Bones↗

Bone density of the radius, spine, and proximal femur in osteoporosis.

Bone mineral density (BMD) was measured in 140 normal young women (aged 20 to 39 years) and in 423 consecutive women over age 40 referred for evaluation of osteoporosis. Lumbar spine and proximal femur BMD was measured using dual-photon absorptiometry (153Gd), whereas the radius shaft measurement used single-photon absorptiometry (125I). There were 324 older women with no fractures, of which 278 aged 60 to 80 years served as age-matched controls. There were 99 women with fractures including 32 with vertebral and 22 with hip fractures. Subsequently, another 25 women with hip fractures had BMD measured in another laboratory; their mean BMD was within 2% of that of the original series. The mean age in both the nonfracture and fracture groups was 70 +/- 5 years. The BMD in the age-matched controls was 20% to 25% below that of normal young women for the radius, spine, and femur, but the Ward's triangle region of the femur showed even greater loss (35%). The mean BMD at all sites in the crush fracture cases was about 10% to 15% below that of age-matched controls. Spinal abnormality was best discriminated by spine and femoral measurements (Z score about 0.9). In women with hip fractures, the BMD was 10% below that of age-matched controls for the radius and the spine, and the BMD for the femoral sites was about 25% to 30% below that of age-matched control (Z score about 1.6). Femoral densities gave the best discrimination of hip fracture cases and even reflected spinal osteopenia. In contrast, neither the spine nor the radius reflected the full extent of femoral osteopenia in hip fracture.

Adult↗