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PubMed2000

Normalized BMD as a predictor of bone strength.

RATIONALE AND OBJECTIVES: In the noninvasive evaluation of bone quality, bone mineral density (BMD) has been shown to be the single most important predictor of bone strength and osteoporosis-related fracture. Among the methods of measuring BMD, dual x-ray absorptiometry (DXA) has widespread acceptance due to its low radiation, low cost, and high precision. However, DXA measures area BMD instead of true volumetric density; thus, a larger bone will tend to have a high BMD than will a smaller bone. Therefore, the comparison of BMDs of bones of different sizes can be misleading. In this study, the authors tried to compensate for the size effect by normalizing the area BMD with bone size as measured from a standard pelvic radiograph. MATERIALS AND METHODS: The overall method for calculation of normalized BMD included conventional area-based BMD from DXA and the extraction of geometric measures from pelvic radiographs. The database for analysis included 34 femoral neck specimens. Regression analysis was performed between the normalized volumetric BMD, measured from femoral neck region, and the mechanical properties obtained from trabecular bone cubes machined from the same region. RESULTS: After normalization of the area BMD, the coefficient of determination increased from 0.30 to 0.43 for the Young modulus and from 0.27 to 0.37 for bone compressive strength. CONCLUSION: A noninvasive method of normalizing BMD can improve the prediction of bone mechanical properties and has potential in monitoring changes in growing skeletons and in the clinical evaluation of bone quality.

Absorptiometry, Photon↗
PubMed1999

Effect of age, exercise and growth rate on bone mineral density (BMD) in third carpal bone and distal radius of Dutch Warmblood foals with osteochondrosis.

This study aimed a the determining bone mineral density (BMD) in the 3rd carpal bone and distal radius of foals age 5 and 11 months that had been subjected to different exercise regimens from birth until age 5 months. It was hypothesised that BMD would be greater in older animals, and that differences in exercise regimens before age 5 months would be associated with differences in BMD at both age 5 and 11 months. Epiphyseal bone tissue was available from 5 and 11 month old Warmblood foals bred from sires known to have radiographic evidence of osteochondrosis (OC). The foals were in a clinical trial which assessed the effect of exercise up to age 5 months on osteochondrosis (OC). Until age 5 months, foals were either box confined, box confined and sprint trained daily, or kept at pasture. Half the horses in each group were then confined together in a large stall, with access to pasture for 2 h daily, from age 6 to 11 months. BMD was assessed by dual x-ray absorptiometry in 4 areas of interest (AOIs) of excised third carpal bone (C3) and 5 in the distal radius. Volumetric BMD was determined in C3, only surface BMD was analysed in the radius. Across age groups, exercise had an effect on BMD in the mediodorsal and mediopalmar areas of C3. In the 5-month-old animals, the training exercise had similar effect to constant pasture exercise. In all AOIs, BMD was significantly greater in 11-month than in 5-month-old animals. Between age groups there was a difference in effect of exercise regimen before 5 months, in mediodorsal C3 and medial aspect of the radius, and the difference observed between exercise groups at age 5 months was no longer present in horses age 11 months, indicating no residual effect of early exercise. BMD was lower in the group with high OC scores. In the group of horses with the most severe OC, monthly growth rate did not fall uniformly with age over the first 5 months, as it did in groups with lower OC scores. It was concluded that exercise influenced significantly BMD at 5 months, suggesting that carefully designed training programmes to increase bone mineral could be employed in young animals. There was no residual effect at 11 months.

Absorptiometry, Photon↗
PubMed2005

Femoral neck bone loss predicts fracture risk independent of baseline BMD.

UNLABELLED: Whereas low BMD is known to be a risk factor for fracture, it is not clear whether loss of BMD is also a risk factor. In elderly women, greater loss of BMD at the femoral neck was associated with increased risk of fracture, independent of baseline BMD and age. INTRODUCTION: Baseline measurement of BMD predicts fracture risk. However, it is not clear whether short-term bone loss is an independent risk factor for fractures. This study was designed to investigate the relationship between changes in BMD and fracture risk in elderly women in the general population. MATERIALS AND METHODS: A total of 966 women > or = 60 years of age (mean, 70 +/- 6.7 [SD] years), who had been followed for an average of 10.7 years, were studied. Atraumatic fracture of the proximal femur (hip), symptomatic vertebral fracture, and other major fractures, excluding pathological fractures or those resulting from severe trauma, were recorded and confirmed by radiographs. Femoral neck and lumbar spine BMD was measured by DXA. RESULTS: During the follow-up period, 224 had sustained a fracture (including 43 hip, 71 symptomatic vertebrae, 37 proximal humerus, 46 forearm and wrist, and 27 rib and pelvis fractures). The annual rate of change in BMD in fracture women (-2.1 +/- 4.2%) was significantly higher than that in nonfracture women (-0.8 +/- 2.8%; p = 0.005). In the multivariable Cox's proportional hazards analysis, the following factors were significant predictors of fracture risk: femoral neck bone loss (relative hazard [RH], 1.4; 95% CI, 1.1-1.8 per 5% loss), baseline femoral neck BMD (RH, 2.0; 95% CI, 1.7-2.7 per SD), and advancing age (RH, 1.2; 95% CI, 1.1-1.4). The proportion of fractures attributable to the three factors was 45%. For hip fracture, the attributable risk fraction was approximately 90%. CONCLUSION: Bone loss at the femoral neck is a predictor of fracture risk in elderly women, independent of baseline BMD and age.

Absorptiometry, Photon↗
PubMed2006

Reduced peripheral nerve function is related to lower hip BMD and calcaneal QUS in older white and black adults: the Health, Aging, and Body Composition Study.

UNLABELLED: Bone tissue is innervated, and peripheral nerve function may impact BMD. Older black and white men and women (N = 2200) in the Health, Aging, and Body Composition Study with worse sensory and motor peripheral nerve function had lower hip BMD and calcaneal BUA independent of lean mass, strength, physical ability, and diabetes. Poor peripheral nerve function may directly affect bone. INTRODUCTION: Bone tissue is innervated, yet little is known about the impact of nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD and higher fracture risk, particularly in those with diabetic neuropathy. MATERIALS AND METHODS: The Health, Aging, and Body Composition (Health ABC) Study included annual exams in white and black men and women 70-79 years of age recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel broadband ultrasound attenuation (BUA), and total fat and lean mass were measured 1 year later (QDR 4500A, Sahara QUS; Hologic). RESULTS: Participants (N = 2200) were 48% men and 37% black. Poor nerve function (lower monofilament detection, higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4-5.7% lower BUA and significant for all but NCV, adjusted for demographics, diabetes, body composition, and physical ability. Results were similar for adjusted hip BMD, with 1.0-2.9% lower BMD, significant for monofilament and CMAP testing. When considering the components of BMD, total hip area was 1.8-4.9% higher in those with the worst nerve function, although BMC showed little difference. Lower monofilament detection and CMAP were independently associated with lower heel BUA (p < 0.01), and monofilament detection was associated with lower hip BMD (p < 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications. CONCLUSIONS: Poor peripheral nerve function may directly related to lower BMD, likely through an increase in bone area in older adults, independent of lean mass, strength, physical ability, and diabetes. Whether those with impaired nerve function are at higher risk for fracture independent of falls needs to be studied.

Aged↗
PubMed2007

Large-scale genome-wide linkage analysis for loci linked to BMD at different skeletal sites in extreme selected sibships.

UNLABELLED: Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. INTRODUCTION: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. MATERIALS AND METHODS: We performed a genome-wide scan involving 3093 siblings 25-64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. RESULTS: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. CONCLUSIONS: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants.

Asian People↗
PubMed1998

[Bone mineral density (BMD) distribution in edentulous mandible--a measuring system for bone mineral content with computed radiography (CR)].

The purpose of this study was to develop a measuring system for bone mineral density(BMD) using computed radiography and to measure BMD distribution in the edentulous mandible. Nine 2-3 mm thick sequential cross-sectional bone slices were obtained from five cadaveric mandibles. Each slice in cross-sectional view on X-ray image was divided into 64 elements and BMD distribution was investigated. The results were as followed: 1. BMD measuring system: The accuracy was 1.4%(relative error) and the reproducibility was 1.1%(CV). 2. BMD distribution in edentulous mandible: 1) BMD varied from slice to slice, decreasing from anterior to posterior in both cortical and cancellous bone on the inferior and lingual side. The BMD of buccal cancellous bone was relatively higher than that of the lingual side and remained fairly constant throughout. The BMD of buccal cortical bone showed a slight posterior increase. 2) Greater individual variation of BMD was observed near mental foramen and in incisor lingual and inferior cancellous bone. Our system demonstrated excellent precision and reproducibility BMD distribution varied near regions of muscle attachment and the mandibular canal. Further, it was suggested that strong implant stability in the molar region may be obtained by installation of the fixtures in the buccal cancellous area.

Bone Density↗
PubMed1999

Bone mineral density (BMD) in obesity effect of weight loss.

It is generally believed that bone mineral density (BMD) is increased in obese subjects, but the effect of weight loss on BMD has not been well studied. Therefore, we evaluated BMD among 11 obese women (mean age 45.5 +/- 14.2 years) before and after weight loss achieved by ingesting an 800 calorie diet for 12 weeks. BMD measurements were made at baseline, 6 months and 1 year intervals. Urinary hydroxyproline:creatinine (H:Cr), calcium:creatinine (Ca:Cr) ratios were measured as indices of bone turnover. Mean weight at baseline was 103.8 +/- 15.8 kg and decreased to 83.2 +/- 12.2 at six months and was 85.8 +/- 14.2 kg at one year. Total body, hip and lumbar spine BMD were 1.12 +/- 0.07, .87 +/- 0.11, and 1.02 +/- 0.12 gm/cm2, respectively. Total body BMD was significantly lower at 12 months compared to baseline. No significant change was observed in BMD of the lumbar spine. There was also a significant decrease in hip BMD at six months and 12 months compared to baseline. H:Cr and Ca:Cr ratios did not change over time. We conclude that weight loss achieved by VLCD is accompanied by a statistically significant change in BMD, but the BMD remained in the normal range.

Body Weight↗
PubMed2000

[Influence of gluten free diet on bone mineral density (BMD) in children with celiac disease].

UNLABELLED: In children with celiac disease (CD) bone metabolism and mineralization are frequently disturbed. The present study aimed to assess the influence of gluten free diet (GFD) on bone mineral density (BMD) in 73 children with CD, mean age of 12.4 +/- 0.4 years and mean body mass index (BMI) 17.9 +/- 0.4 kg/m2 (mean +/- SEM). Diagnosis of CD was established according to ESPEGAN criteria. Compliance to the GFD was verified on the basis of interview and by estimation of antiendomysial antibodies (IgAEmA/IgGEmA) in blood serum. BMD was measured by dual energy X-ray absorptiometry (DEXA). Plasma calcium (Ca) and phosphorus (P) concentrations, alkaline phosphatase (AP) and its bone fraction (BAP) were estimated before BMD measurement. All children were divided into two groups. Group A consisted of 33 children where gluten free diet was strictly respected for 11.7 +/- 0.6 years. The second group (Group B) comprised 40 children without strictly respected GFD. Children who strictly followed GFD showed statistically higher BMI, AP-spine BMD and total body BMD in comparison with children without GFD (BMI 19 +/- 0.52 kg/m2 vs 17.3 +/- 0.4 kg/m2; p < 0.01, AP-spine BMD 0.951 +/- 0.04 g/cm2 vs 0.767 + 0.03 g/cm2; p < 0.005, Total Body BMD 1.013 +/- 0.02 g/cm2 vs 0.933 +/- 0.01 g/cm2; p < 0.05) respectively. No significant differences were found in plasma Ca, P, AP, BAP between both groups. A statistically significant positive correlation (p < 0.001) was found between duration of GFD and AP-spine BMD and total body BMD, respectively. A statistically significant positive correlation (p < 0.05) was also found between duration of GFD and BMI. CONCLUSION: Long-term GFD significantly improves BMD and BMI in children with CD.

Absorptiometry, Photon↗
PubMed2002

[Precision of rat BMD measurements by dual-energy X-ray absorptiometry in vitro].

OBJECTIVE: To evaluate the precision of rat bone mineral density (BMD) measurements by Norland Excellplus dual-energy X-ray absorptiometry (DXA) and to investigate the BMD changes in ovariectomized (Ovx) rats in vitro. METHODS: (1) The coefficients of variation (CV) for BMD measurements at various skeletal regions were repeatedly determined by DXA in 10 Wistar rats in vitro. (2) BMD in lumbar vertebra (L5) and both sides of femurs was measured in total 90 rats. And (3) changes in BMD between Ovx and sham rats were compared. RESULTS: (1) The short-term CVs of BMD measurements in different regions by DXA were as follows, 1.58% for lumbar vertebra (L5), 0.90% for left femur, and 0.86% for right femur, respectively. The long-term CVs were 2.22% for lumbar vertebra (L5), 1.09% for left femur, and 1.20% for right femur. (2) The BMD values in 90 Wistar rats were (127.5 +/- 12.3) in lumbar vertebra (L5), (82.6 +/- 11.3) in corpus vertebra (L5'), (150.7 +/- 10.6) in left femur and (149.9 +/- 10.6) mg/cm2 in right femur, respectively. The correlation coefficient of BMD measurements between left and right femurs was 0.792 (P < 0.001). (3) In Ovx group, the BMD values of corpus vertebra (L5') and distal femurs were significantly decreased, that was 10.0%-17.5% lower in comparison with sham group (P < 0.001). CONCLUSIONS: Measurement of rat BMD in vitro by Norland Excellplus DXA is a useful method, and it can reflect the changes in rat bone masses with good precision.

Absorptiometry, Photon↗
PubMed1994

Forearm BMD as measured by peripheral quantitative computed tomography (pQCT) in a German reference population.

Low bone mass as estimated by decreased bone mineral density (BMD) is an established predictor of osteoporotic fractures. One of the latest developments in bone densitometry is peripheral quantitative computed tomography (pQCT) of the forearm. In Germany, the CT bone scanner XCT 900 has already been widely used; however, interpretation of measurements with respect to osteoporosis risk assessment can be improved by better defined and validated reference data. In the present study, this device was used to measure BMD at the distal radius in a well-defined healthy population of 179 German adults (91 men, 88 women) aged 20-79 years. In vivo precision was 1.67% for trabecular and 0.81% for total BMD measurements. Peak values of trabecular and total BMD were observed at the ages 40-50 years in women and 30-40 years in men. Beyond these ages, both trabecular and total BMD showed a linear decline with age, decreasing by 0.85% and 1.08% per year in women and by 0.59% and 0.54% in men, respectively. Measures of BMD were not influenced by weight, height or body mass index (BMI). In both sexes, trabecular and total radial BMD showed a positive and significant correlation with femoral BMD measures obtained by dual X-ray absorptiometry (DXA). Weaker correlations were observed with DXA measures of the lumbar spine. Compared with the 95% reference range provided by the manufacturer, the distribution of age- and sex-specific values of trabecular BMD of the distal radius was shifted to lower values by up to 1 standard deviation.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed2002

Relationships of urinary phyto-oestrogen excretion to BMD in postmenopausal women.

OBJECTIVE: Phyto-oestrogens are plant compounds with both oestrogenic and anti-oestrogenic properties. However, it is not known whether natural phyto-oestrogens are beneficial or harmful in human osteoporosis. This study was performed to investigate the relationships between urinary phyto-oestrogens and bone mineral density (BMD) in Korean postmenopausal women. DESIGN: The subjects were classified into osteoporotic, osteopenic and normal groups according to their BMD as defined by WHO criteria. We compared the urinary phyto-oestrogens of each group and studied whether urinary phyto-oestrogens correlate with BMD. PATIENTS: The subjects were 75 Korean postmenopausal women with ages ranging from 52 to 65 years (mean 58 +/- 1.1 years). Mean number of years after menopause was 7.3 +/- 1.3. MEASUREMENTS: Twenty-four-hour urinary phyto-oestrogens were measured by gas chromatography-mass spectrometry (GCMS) and BMD by dual-energy X-ray absorptiometry (DXA, Lunar Expert-XL, Lunar Co., WI, USA). RESULTS: In Korean postmenopausal women, urinary enterolactone (1.46 +/- 1.11 micromol/day) was lower and daidzein (2.59 +/- 3.25 micromol/day) was higher than in western women, and both levels were comparable to those in Japanese women. Daily urinary excretion of genistein and apigenin were 1.09 +/- 0.912 and 0.48 +/- 0.40 micromol/day, respectively. In subjects with osteoporosis, urinary enterolactone was lower (P < 0.05) but apigenin was significantly higher (P < 0.05) than in the controls. BMD of L2-L4 correlated positively with urinary enterolactone (r = 0.388, P < 0.01), and BMD of the femoral neck and Ward's triangle correlated positively with urinary enterolactone (r = 0.271, P < 0.05 and r = 0.322, P < 0.05) but negatively with apigenin (r = -0.412, P < 0.01 and r = -0.395, P < 0.01). By multiple stepwise regression, the variables associated with spinal BMD were age, the amount of urinary apigenin and body mass index (BMI). The variables associated with femoral neck BMD were age and urinary apigenin. CONCLUSIONS: From these results, we conclude that urinary phyto-oestrogens, especially enterolactone and apigenin, are related to BMD in Korean postmenopausal women. Our results also suggest the possibility that phyto-oestrogens have differential effects on bone density. Further studies are needed to clarify the exact biological roles of phyto-oestrogenic components on bone metabolism.

4-Butyrolactone↗
PubMed2000

Comparison of bone mineral density and quantitative ultrasound of the calcaneus: site-matched correlation and discrimination of axial BMD status.

The performance of quantitative ultrasound (QUS) and dual energy X-ray absorptiometry (DXA) bone densitometry of the calcaneus have been compared, both in terms of site-matched correlation and their discriminatory ability to identify osteoporotic and osteoporotic or osteopenic subjects. 91 female subjects (aged 56.9 +/- 9.6 years, 31-84 years) who were routinely referred for axial BMD assessment of the lumbar spine and femoral neck by DXA (Lunar DPX-L), consented to have additional measurements of QUS (McCue CubaClinical Mk II) and DXA (Lunar PIXI) of their left calcaneus. The site-matched correlation between calcaneal BMD with QUS parameters were: (a) broadband ultrasound attenuation (BUA) alone, adj-R2 = 62.7%, p < 0.0001; (b) velocity (VOS) alone, adj-R2 = 48.4%, p < 0.0001; and (c) BUA and VOS combined, adj-R2 = 65.2%, p < 0.0001. The site-matched correlations are towards the higher end of data reported by other researchers, indicative of the exacting measurement protocol implemented here. 30 subjects were categorized as normal, 38 being osteopenic and 23 being osteoporotic. Optimum accuracies and odds ratios were obtained using logistic regression. The differences in accuracy between calcaneal BMD and calcaneal QUS parameters were statistically insignificant, with zero included within the confidence intervals, for the identification of both (a) osteoporotic and (b) osteoporotic or osteopenic subjects. The odds ratios for the discrimination of subject status achieved with calcaneal BMD were higher, although statistically insignificant, than achieved with the QUS parameters. Receiver operator characteristic (ROC) analysis for the identification of subjects into the categories (a) and (b) above was performed. Areas under the ROC curve (AUC) (95% confidence intervals) for the logit of the probability that a subject would be osteoporotic were: 0.814 (0.700, 0.928) for calcaneal BMD; 0.791 (0.673, 0.909) for BUA; 0.717 (0.588, 0.846) for VOS; and 0.793 (0.675, 0.911) for BUA and VOS combined. For the identification of osteoporotic or osteopenic subjects, the ROC areas were: 0.851 (0.774, 0.928) for calcaneal BMD; 0.773 (0.678, 0.868) for BUA; 0.783 (0.690, 0.877) for VOS; and 0.778 (0.685, 0.871) for BUA and VOS combined. Again, calcaneal BMD provided a higher, yet statistically insignificant, AUC than any QUS parameter. In conclusion, for the identification of subjects defined by World Health Organization criteria for axial BMD, the performance of BMD and QUS calcaneal parameters were statistically comparable. The choice of peripheral bone densitometry modality should therefore be made upon factors external to their discriminatory performance.

Absorptiometry, Photon↗
PubMed2002

Influence of region of interest and bone size on calcaneal BMD: implications for the accuracy of quantitative ultrasound assessments at the calcaneus.

There is considerable technological diversity among quantitative ultrasound (QUS) devices used to assess osteoporosis. Because the distance between the transducer and the footplate remains constant, the location of the calcaneus measured will vary with foot size. This study was designed to quantify the variation in bone mineral density (BMD) between a manufacturer's region of interest (ROI_M), which is fixed relative to the footplate, and an anatomical region of interest (ROI_A), which is defined as 20% of calcaneal length. The effect of foot length and width on QUS variables measured using two Food and Drug Administration cleared QUS devices, the Sahara (Hologic) and the Achilles+ (Lunar) was assessed. 26 healthy subjects (12 male and 14 female), aged 22-54 years (35.6+/-10 years) and with foot lengths of 21.5 cm to 29.7 cm (25.1+/-2.3 cm) were recruited. QUS assessments were performed at the right calcaneus. In addition, a Hologic 4500 densitometer was used to measure the BMD of the calcaneus in the ROI_M and ROI_A. The sizes of the ROIs were approximated to the sizes of the transducers of the Sahara and Achilles+ devices. The results showed a significant difference in BMD between the two ROI locations for the Sahara device (BMD 0.642+/-0.135 g cm(-2) vs 0.616+/-0.114 g cm(-2), p=0.014), but no significant difference was found in BMD between the two locations for the Achilles device (BMD 0.661+/-0.120 g cm(-2) vs 0.662+/-0.123 g cm(-2), p=0.818). At the ROI_A, there was a significant difference in BMD between the two QUS devices (p<0.001). The correlation between QUS variables and BMD was slightly higher for the ROI_M (r=0.68-0.79, since this is site-matched) than the ROI_A (r=0.59-0.70) for the Achilles device, while for the Sahara device the correlations were r=0.35-0.40 and r=0.51-0.54, respectively. The smaller ROI of the Sahara device resulted in more than 50% of the subjects having BMD differences of greater than 5% between the ROI_A and the ROI_M, compared with only 20% of the subjects on the Achilles device. ROIs containing cortical bone edge and other soft tissues were found in 58% of cases for the Achilles device and 46% of cases for the Sahara device. The greatest differences occurred in very small and very large feet. Calcaneal length correlated significantly with Sahara speed of sound (SOS), and heel width correlated significantly with Achilles SOS. Heel width also correlated significantly with Sahara broadband ultrasound attenuation (BUA) but not Achilles+ BUA. These results suggest that variation in ROI and bone size might affect the accuracy of QUS measurements, since the calcaneus is heterogeneous both in terms of its external geometry and its internal structure and density.

Adult↗
PubMed2005

A frequent regulatory variant of the estrogen-related receptor alpha gene associated with BMD in French-Canadian premenopausal women.

UNLABELLED: Genes are important BMD determinants. We studied the association of an ESRRA gene functional variant with BMD in 1335 premenopausal women. The ESRRA genotype was an independent predictor of L2-L4 BMD, with an effect similar to smoking and equivalent to a 10-kg difference in weight. INTRODUCTION: Several genetic polymorphisms have been associated with osteoporosis or osteoporosis fractures, but no functional effect has been shown for most of these gene variants. Because functional studies have implicated estrogen-related receptor alpha (ESRRA) in bone metabolism, we evaluated whether a recently described regulatory variant of the ESRRA gene is associated with lumbar and hip BMD as measured by DXA and with heel bone parameters as measured by quantitative ultrasound (QUS). MATERIALS AND METHODS: Heel bone parameters were measured by right calcaneal QUS in 1335 healthy French-Canadian premenopausal women, and one-half of these women also had their BMD evaluated at two sites: femoral neck and lumbar spine (L2-L4) by DXA. All bone measures were tested separately for association with the ESRRA genotype by analysis of covariance. The significance of the ESRRA contribution to the model was also assessed by two different permutation tests. RESULTS: A statistically significant association between ESRRA genotype and lumbar spine BMD was observed: women carrying the long ESRRA genotype had a 3.9% (0.045 g/cm2) higher lumbar spine BMD than those carrying the short ESRRA genotype (p = 0.004), independently of other risk factors measured. This effect of ESRRA genotype is similar to the effect of smoking and equivalent to a 10-kg difference in weight. This association was confirmed by permutation tests (p = 0.004). The same trend was observed for femoral neck BMD (2.6%, p = 0.07). However, no association was observed between ESRRA and QUS heel bone measures. CONCLUSION: These results support the genetic influence of this ESRRA regulatory variant on BMD.

Absorptiometry, Photon↗
PubMed2005

Association of functionally different RUNX2 P2 promoter alleles with BMD.

UNLABELLED: RUNX2 gene SNPs were genotyped in subjects from the upper and lower deciles of age- and weight-adjusted femoral neck BMD. Of 16 SNPs in RUNX2 and its two promoters (P1 and P2), only SNPs in the P2 promoter were significantly associated with BMD. These P2 promoter SNPs were functionally different in gel-shift and promoter activity assays. INTRODUCTION: Specific osteoblast genes are induced by Runx2, a cell-specific transcription factor that is a candidate gene for controlling BMD. We tested the hypothesis that RUNX2 genetic variation is associated with BMD. MATERIALS AND METHODS: From a population repository of normal subjects, the age- and weight-adjusted femoral neck BMD was ranked, and the upper and lower deciles (n = 132 each) were taken to represent the adjusted extremes of the population distribution. In these 264 subjects, we identified 16 allelic variations within the RUNX2 gene and promoters (P1 and P2) through DNA sequencing and denaturing high-performance liquid chromatography. Characterization of these alleles was performed through allele-specific cloning, transfection into ROS 17/2.8 cells, luciferase reporter analysis, and electrophoretic mobility shift assays. RESULTS: Within the P2 promoter were three polymorphic nucleotides for which the minor alleles were over-represented in the upper decile of BMD (0.117 and 0.064 in the upper and lower deciles, respectively). These alleles are in near complete linkage disequilibrium with each other and represent a haplotype block that is significantly associated with increased BMD. The common and rare P2 promoter alleles were cloned upstream of luciferase, and when transfected into osteoblast-like cells, the construct representing the rare haplotype showed significantly greater P2 promoter activity than the common haplotype. CONCLUSIONS: Because the high BMD allele had higher P2 promoter activity, the data suggest that greater RUNX2 P2 promoter activity is associated with higher BMD.

Absorptiometry, Photon↗
PubMed2005

Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial.

UNLABELLED: A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta. INTRODUCTION: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta. MATERIALS AND METHODS: We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily. RESULTS: The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003). CONCLUSIONS: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.

Absorptiometry, Photon↗
PubMed2006

Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.

UNLABELLED: The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.

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PubMed2006

Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study.

UNLABELLED: We studied the relation of leptin to bone, bone loss, and bone turnover in community-dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4-year bone loss in either sex. INTRODUCTION: Leptin, the protein product of the obesity (OB) gene produced in fat tissue, was originally thought to be involved only in the regulation of food intake and energy balance. Recent evidence suggests that leptin may play a role in the pathophysiology of several chronic diseases. Studies of the association between leptin and bone have been numerous yet inconclusive. Only one previous longitudinal study has been reported, which showed no association of leptin with BMD after adjusting for body size. MATERIALS AND METHODS: We report the association of serum leptin with BMD at the hip, spine, and midshaft radius in community-dwelling men (n = 498) and nonestrogen-using postmenopausal women (n = 411) 45-92 years of age. Serum leptin was measured in blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA; at the same visit, height, weight, and body fat (by bioelectrical impedance analysis) were measured, and bone resorption was assessed in a subset of men (n = 286) and women (n = 241) using urine N-telopeptide (NTX). Four years later, axial BMD was remeasured in 536 participants. Sex-specific associations of leptin with BMD, NTX, and bone loss were tested using regression analysis. RESULTS: In unadjusted analyses, leptin was associated with BMD at the femoral neck, total hip, lumbar spine, and midshaft radius in both sexes (p < 0.01). In multiple regression analyses, adjusted for age, BMI, and other bone-related factors, only women showed a graded stepwise positive association between serum leptin and BMD at all sites and a negative stepwise association with NTX (all p for trend < 0.01). Baseline leptin levels did not predict 4-year bone loss in either sex. CONCLUSIONS: A favorable dose-dependent leptin-BMD association unexplained by obesity was observed only in women. The reason for the sex difference is unknown.

Absorptiometry, Photon↗