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PubMed1994

Reduced bone density in women with fractures: contribution of low peak bone density and rapid bone loss.

Osteoporosis is regarded as a disease of the elderly because fractures occur late in life. Although excessive bone loss during aging is likely to contribute to the deficit in bone density, patients with fractures do not consistently have more rapid bone loss, greater bone resorption or lower bone formation (measured using biochemical or histomorphometric markers of bone turnover). The pathogenesis of the low bone density and bone fragility that characterize osteoporosis may begin during the first two decades of life. There are differences in the hormonal regulation of regional growth and mineral accrual, differences in the age of onset, rate and duration of linear growth and mineral accrual of the axial and appendicular skeleton, of cortical and trabecular bone, and of proximal and distal limb segments. Illnesses, risk or protective factors, and disorders of hormonal deficiency or excess may affect longitudinal growth, mineral accrual, or both, depending on the timing of exposure. Quantitatively larger and qualitatively different effects on bone density may result when exposure occurs during growth rather than during adulthood. The magnitude of these deficits and their location are likely to establish the relevance of regional age-related and sex hormone dependent bone loss. Thus, any unifying hypothesis concerning the epidemiology and pathogenesis of osteoporosis must consider the relative contributions of low peak bone density and bone loss to the deficit in bone density in adulthood. A great deal of research is needed to examine the physiology of longitudinal growth and mineral accrual as the pathogenesis of osteoporosis is at least partly explained by events occurring during the first 20 years of life.

Age Factors↗
PubMed1997

Vitamin D stores of urban women in Taipei: effect on bone density and bone turnover, and seasonal variation.

This study was performed to survey the vitamin D nutritional status of urban Chinese women, and to define its role in determining bone metabolic rate and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D (25-OHD), the major storage form of vitamin D, and BMD, at the spine, hip, and total body skeleton, of 262 healthy Chinese women aged from 40 to 72 years, residing in Taipei city. Bone turnover markers, including serum osteocalcin, bone alkaline phosphatase isozyme, and C-terminal propeptide of type I procollagen, and a urinary bone resorption marker, N-terminal crosslinked fragment of type I collagen, were also measured. We found generally adequate vitamin D nutritional stores. The mean concentration of serum 25-OHD was 30.7 (SD = 8.2) ng/mL for all 262 subjects and there were no significant age-related changes. Those who had serum sampled during the summer showed higher serum 25-OHD levels (N = 138; mean +/- SD: 32.7 +/- 7.6 ng/mL) than those who had serum sampled during winter (N = 124; mean +/- SD: 28.5 +/- 8.3 ng/mL; Student's t-test, p < 0.001), but these two groups showed similar BMD and bone marker values. Those with serum 25-OHD concentration in the lowest or highest tertile did not show different BMD or bone marker values than those in the other tertiles. Multiple regression demonstrated no correlation between 25-OHD and any bone marker or BMD at any site. Thus, in this free-living urban Chinese population, in a subtropical region, we could not demonstrate a role of vitamin D stores in determining bone turnover rate or BMD in women aged 40-70 years.

Absorptiometry, Photon↗
PubMed1992

Use of a risk factor and dietary calcium questionnaire in predicting bone density and subsequent bone loss at the menopause.

One hundred and thirty six healthy white females within 30 months of their last menstrual period (mean age 52 years) were examined to determine the usefulness of a risk factor questionnaire in predicting bone density and subsequent loss. Bone density was assessed at baseline and at 12 monthly intervals. None of the proposed risk factor variables with the exception of nulliparity correlated with the baseline spinal or femoral bone density. As a predictor of bone loss only drinking alcohol (more than four units/day) was significant. A risk factor score derived from the questionnaire before its administration did not correlate with baseline bone density or subsequent bone loss. In most normal women questioned soon after a natural menopause, an estimate of bone density and subsequent bone loss and hence osteoporotic risk cannot be reliably made using a simple risk factor questionnaire.

Alcohol Drinking↗
PubMed1988

The relationship of peripheral to axial bone density.

Bone measurements were made in young normal women (n = 125) using single-photon absorptiometry (SPA with 125I) of the radius shaft and ultradistal radius, dual-photon absorptiometry (DPA with 153Gd) of the lumbar spine and the proximal femur, and 125I-based quantitative computed tomography (QCT) of the distal radius. Measurements of the appendicular and axial sites also were made in 21 women with spinal osteoporosis. The standard error of estimate in predicting axial densities from peripheral measurements was about 0.11 g/cm2 (10-13%) with all methods. The osteoporotic-normal difference was 21% for SPA of the radius shaft and 125I-QCT of the distal radius, 30% for the lumbar spine and 34% for the femoral neck. Prediction of spine and femur density, and diagnostic sensitivity, with 125I-QCT were equivalent to that obtained with conventional SPA, but the precision of 125I-QCT (0.8%) was 2-3 times better than both SPA and DPA.

Adult↗
PubMed2005

Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma.

OBJECTIVE: Untreated hyperthyroidism and treatment with high doses of thyroid hormone are associated with osteoporosis. However, their effect on bone turnover, their contribution to bone mineral density (BMD) in the context of other clinical risk factors for osteoporosis and the prevalence of vertebral fractures is not well documented. DESIGN: Cross-sectional study. METHODS: We studied 59 patients receiving L-thyroxine suppressive therapy for differentiated thyroid carcinoma (DTC). BMD of the hip was measured by dual X-ray absorptiometry (DXA) and lateral DXA pictures of the lumbar and thoracic vertebrae were performed. Bone resorption was measured by C-telopeptides of type I collagen (ICTP) and bone formation by procollagen type I N-propeptide (PINP). Clinical risk factors for osteoporosis were evaluated using a questionnaire. RESULTS: Z-scores of BMD were similar as the NHANES (National Health and Nutrition Examination Survey) III reference group in women and men, also after long-term (> 10 years) suppression therapy. Patients in the lowest and highest quartile of BMD showed significant differences in the presence of clinical risk factors. ICTP levels were significantly higher than in age-matched controls, PINP levels were not different. We found four patients with a prevalent vertebral fracture. CONCLUSIONS: We conclude that patients with well-differentiated thyroid carcinoma are not at increased risk of developing low bone mass nor have a higher prevalence of vertebral fracture at least when treated with relatively low doses of L-thyroxine.

Absorptiometry, Photon↗
PubMed2002

Nonassociation of interleukin-1 receptor antagonist genotypes with bone mineral density, bone turnover status, and estrogen responsiveness in Korean postmenopausal women.

Interleukin-1 receptor antagonist (IL-1ra), a natural inhibitor of interleukin-1 (IL-1), completely inhibits the stimulatory effects of IL-1 on bone resorption. Bioactivity of IL-1 increases in the estrogen-deficient state with an increased IL-1:IL-1ra ratio and decreases after estrogen replacement therapy with a decreased IL-1:IL-1ra ratio. An association was found between an 86 basepair variable number tandem-repeat (VNTR) polymorphism of the IL-1ra gene and an increased production of IL-1ra in a cultured monocyte system. The IL-1ra VNTR polymorphism, therefore, is an attractive candidate gene for osteoporosis susceptibility as well as hormone responsiveness after estrogen replacement. We examined the association of this VNTR polymorphism with bone mass, bone turnover, and the change of bone mineral density (BMD) after 1 year of hormone replacement therapy (HRT). The frequencies of the five alleles were as follows: A1, 90.8% (410 bp, four repeats); A2, 7.2% (240 bp, two repeats); A3, 1.6% (500 bp, five repeats); A4, 0.4% (326 bp, three repeats); and A5, 0% (595 bp, six repeats), in 714 healthy ethnically Korean postmenopausal women, aged 41-74 years (55.2 +/- 6.3 years mean +/- SD). Spine (L2-4) and femoral neck BMD were not significantly different among IL-1ra genotypes, and no significant genotypic differences were found in bone markers. There were no differences in genotypic proportions when we categorized the subjects into a high-loss group and a normal-loss group with regard to levels of bone marker. No significant genotypic differences were found in changes in lumbar and femoral neck BMD and those in bone markers before and after 1 year of HRT in 312 women. Our data suggest that these IL-1ra polymorphisms are not associated with BMD, bone turnover, or the change of BMD after 1 year of HRT in Korean women.

Adult↗
PubMed2001

Bone densities and bone size at the distal radius in healthy children and adolescents: a study using peripheral quantitative computed tomography.

Peripheral quantitative computed tomography (pQCT) has the ability to improve the diagnostic utility of densitometry in children and adolescents, because bone size and volumetric bone mineral density (vBMD) can be measured independently. Nevertheless, detailed reference data are lacking. We therefore performed pQCT (XCT-2000 scanner, Stratec, Inc., Pforzheim, Germany) at the distal radius in 371 healthy children, adolescents, and young adults (185 males and 186 females, ages 6-23 years) and in 107 of their parents (19 men and 88 women, ages 29-40 years). Total vBMD, trabecular, and "cortical + subcortical" vBMD as well as cross-sectional area (CSA) were determined at the "4% site" of the distal radius. This location was defined as the site whose distance to the most distal portion of the growth plate or to the radial articular surface corresponded to 4% of the forearm length. In both genders, total vBMD remained stable between 6 and 15 years of age and then increased by 30% in girls and by 46% in boys. Regarding pubertal development, total vBMD remained almost constant throughout pubertal stages 1-4 and thereafter increased in both genders. Trabecular vBMD did not change with age in girls, whereas in boys an increase with age of about 10% was noted after 15 years of age. Males had higher trabecular vBMD than females. This gender difference increased from 6% in prepubertal children to 23% in adults. The variation with age and pubertal stage in "cortical + subcortical" vBMD-cort was similar to that of total vBMD. CSA roughly doubled between 6 and 15 years of age in both genders. In conclusion, the availability of this reference material will provide a basis for the use of pQCT in the assessment of pediatric bone diseases.

Absorptiometry, Photon↗
PubMedDate not supplied

Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials.

BACKGROUND: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women. METHODS: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. RESULTS: Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). CONCLUSIONS: Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.

Bone Density↗
PubMed2006

Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: the SOF study.

Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was measured at an initial exam and after an average of 5.9 years of follow-up. Hip BMD was measured at an initial exam and after 3.7 years of follow-up. Baseline spine BMD and hip structural parameters were measured. Incident hip fractures were confirmed by review of radiographic reports; follow-up was greater than 98% complete. Incident vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. The frequencies of the NOS3 Glu298Asp genotypes were Glu/Glu=46.2%, Glu/Asp=42.7%, and Asp/Asp=11.1%. There were no significant associations between NOS3 genotypes and initial calcaneal BMD, hip BMD, or rate of change in hip or calcaneal BMD. None of the hip structural parameters differed substantially by genotype. NOS3 genotype was not significantly associated with either incident or prevalent radiographic vertebral fractures. Women with the heterozygous Glu/Asp genotype had a borderline statistically significantly lower rate of hip fracture than either the Glu/Glu genotype (HR=0.87, 95% CI: 0.74, 1.01) or the Asp/Asp genotype (HR=0.78, 95% CI: 0.62, 0.98). In conclusion, the Glu298Asp polymorphism does not contribute substantially or consistently to indices of bone strength in this sample of older white women, although our findings suggest allelic variation at the NOS3 locus maybe associated with hip fracture risk. Confirmation of these findings is needed in other populations and with additional markers within and flanking the NOS3 gene region.

Age Factors↗
PubMed2006

Comparison of the femoral neck bone density, quantitative ultrasound and bone density of the heel between dominant and non-dominant side.

Our study was initiated to evaluate whether there are differences between the two sides, depending on hand dominance, in densitometry values and quantitative ultrasound parameters (QUS) of the lower limb. One hundred and six women and 44 men were involved. The hand dominance was determined by interview. The bone mineral density (BMD) of the left and the right femoral necks and the calcanei were measured by dual-energy X-ray absorptiometry (DXA). The QUS examination consisted of measuring the attenuation (BUA), the speed of the ultrasound (SOS) and quantitative ultrasound index (QUI) transversing the left and right calcanei. The density of the neck of femur of the non-dominant side did not differ from that of the dominant side. On the other hand, BMD, BUA and the QUI of the calcaneus were higher on the non-dominant side in both genders (p<0.05 for each parameter). No similar differences were seen for the SOS values. Our study has confirmed the side-to-side differences of the calcaneus in both genders, lower values were found on the dominant side. No similar differences were seen on the femur. The AUC values seemed to be higher on the dominant side, however, these differences were not strictly significant. In the case of peripheral site (heel) measurements, the practical significance of our observations is that they raise the possibility of performing peripheral DXA and QUS examinations of the calcaneus on the dominant side of the patient according to handedness.

Absorptiometry, Photon↗
PubMed1997

Assessment of fracture risk by bone density measurements.

Bone densitometry in its various applications has become an established tool for the diagnosis of osteoporosis. Bone density has been shown to be significantly associated with the risk of future fracture in many prospective studies. From long-term prospective studies, it can be concluded that peak bone density and bone loss are important predictors of subsequent fracture, and that fracture can be predicted over a longer period. Bone density predicts fracture even in elderly persons aged 80 years and older. However, in this population some fractures, such as the cervical hip fracture, may be more strongly influenced by other risk factors. The differences between the various densitometric techniques in predicting future osteoporotic fracture of any type is marginal. However, it seems that bone density measurements at the site of fracture do perform better than measurements at other sites. There is no evidence that measuring a second site improves the diagnostic capability of bone densitometry. The association between bone density and future fracture is partly independent of age and other significant predictors of fracture such as falls, cognizance, and mobility. Quantitative ultrasonic measures of bone quality have been shown to have a predictive capability that is comparable to that of bone density. From the perspective that bone densitometry and quantitative ultrasound independently predict fractures, these measures actually seem complementary rather than competitive. Simple geometric measures of the bones such as hip axis length and vertebral depth may be derived from images of bone densitometry scans and are also predictive of hip fracture or vertebral fracture independently of bone density. Using the current knowledge of the association between bone density, quantitative ultrasound, geometric properties, and fractures as well as clinical risk factors, new models for fracture prediction can be developed for future application in clinical practice for the benefit of the individual patient.

Adult↗
PubMed1996

[Measurement of bone density by ultrasound bone densitometer in normal pregnant women].

The bone mineral density in reproductive aged and pregnant women was measured with an ultrasound bone densitometer (Achilles, Luner Co, USA). Both parameters of bone density on Os calsis, sound of speed (SOS) and broad ultrasound attenuation (BUA) were significantly correlated with bone mineral density in lumbar2-4 measured by dual energy X-ray absorptiometry (DXA) (p < 0.01) in reproductive aged women (mean age; 24.5 +/- 2.3, n = 30). The changes in bone density during pregnancy and at delivery were studied. In a cross-sectional study, no significant changes in SOS, BUA and stiffness were observed, but in a longitudinal study (n = 21), all of these parameters decreased as pregnancy advanced. The markers of bone turnover (serum Ca, alkaline phosphatase, procollagen type 1-C peptide, urinary Ca/Cr and deoxypyridinoline/Cr) did not change during pregnancy. Ten pregnant women with low bone density (less than-1.5 SD mean value) were found. There was no significant difference between the markers of bone turnover in pregnant women with low and normal bone density. The clinical usefulness of the screening of bone density of reproductive aged and pregnant women to detect osteopenia is suggested.

Adult↗
PubMed2003

Relevance of bone mineral density, bone quality and falls in reduction of vertebral and non-vertebral fractures.

All epidemiological studies conclude that without prompt, concerted and well-designed prevention programs, the increasing cost related to osteoporotic fractures will become an unbearable burden for the community within the next fifteen years. However, the most effective way of setting up such preventive strategies is not yet unequivocally defined. Low bone mass and microarchitectural damage of bone tissue may account for a large part of the epidemiology of vertebral fractures. Extraskeletal determinants, including low muscle strength, poor balance and gait, all resulting in an increased propensity to fall, also play a major role in the occurrence of hip fracture. Depending on the localization of the fractures, the relative importance of skeletal and extraskeletal risk factors can significantly differ. For prevention of vertebral fractures, drugs affecting bone mass and skeletal architecture may provide a substantial benefit while hip fracture prevention will be more successfully targeted by multi-faceted strategies concentrating not only on the skeletal dimension of the fracture but also aiming, either pharmacologically or through multi-intervention programs, at a reduction in the incidence and in the consequences of falls in the elderly.

Journal Article↗
PubMed2001

Update on bone density measurement.

Bone densitometry is a clinically accepted technique for assessing fracture risk and evaluating skeletal change. The proper clinical use of densitometry requires an understanding of the available techniques, their appropriate application, and the potential sources of measurement error. Recent clinical guidelines recommend that all women over the age of 65 years and all postmenopausal women with risk factors should have their bone density assessed. With the advent of smaller portable devices, bone density measurements are now widely available. In particular, ultrasound techniques, which do not use radiation, have particular promise for widespread screening applications. Peripheral densitometry alone cannot adequately address all clinical questions, particularly the question of monitoring subtle changes in bone density. For this purpose, central densitometers are still preferred. For any bone density measurement to be clinically useful, it must be performed with careful attention to detail, particularly with regard to instrument calibration, patient positioning, measurement analysis, and interpretation.

Absorptiometry, Photon↗
PubMed1994

Reduced femoral neck bone density in the daughters of women with hip fractures: the role of low peak bone density in the pathogenesis of osteoporosis.

Low bone density in women with hip fractures ("senile" osteoporosis) may be due to excessive bone loss or low peak bone density. If excessive bone loss is responsible, then no reduction in bone density is expected in their daughters. If low peak bone density is responsible, then bone density should also be reduced in their daughters because genetic and family environmental factors influence the variability in bone density. Bone density was measured using dual-photon absorptiometry and expressed as a standardized deviation or Z score relative to 697 controls, adjusting for age, height, weight, and menopausal status. In 74 women with hip fractures, the Z score (mean +/- SEM) was -0.52 +/- 0.14 (P < 0.001) at the femoral neck, -1.04 +/- 0.17 (P < 0.001) at the femoral shaft, and -0.43 +/- 0.10 (P < 0.001) at the lumbar spine. In their 41 daughters, the Z score was -0.40 +/- 0.17 (P < 0.05) at the femoral neck, -0.41 +/- 0.19 (P < 0.001) at the femoral shaft, and 0.23 +/- 0.13 (NS) at the lumbar spine. We conclude that daughters of women with hip fractures are likely to be at increased risk for hip fractures themselves because they have reduced femoral neck bone density. Femoral neck fractures may not be entirely attributable to trauma; reduced bone density is likely to contribute and may be caused by the attainment of a lower peak femoral neck bone density.

Absorptiometry, Photon↗
PubMed1979

Bone densitometry using computed tomography. Part I: selective determination of trabecular bone density and other bone mineral parameters. Normal values in children and adults.

Gamma-ray computed tomography (gamma-ray CT), using a special purpose scanner, enables in-vivo quantitative analysis of bone mineralization. Trabecular bone density (TBD), the relative amount of compact bone (bone density, BD) and the total absorption (TA) for a cross-section of the radius are determined from measurements of local linear absorption coefficients. A preliminary study of normal children (n = 49) and adults (n = 34) indicated that TBD is independent of age and sex in the age range 4 to 40 years. DB remains constant throughout childhood but increases after puberty in both women and men. TA is higher for adults than for children, and also higher for men than for women. A correlation between TA and parameters relating to body size indicates a relationship between body weight and bone mass.

Adolescent↗