Determine Bone Density Research Articles

Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women

The association between follicle-stimulating hormone (FSH) and bone density was tested in 111 postmenopausal women aged 50-64years. In the multivariable analysis, weight and race were important determinants of bone mineral density. FSH, bioavailable estradiol, and other hormonal variables did not show statistically significant associations with bone density at any site. FSH has been associated with bone density loss in animal models and longitudinal studies of women. Most of these analyses have not considered the effect of weight or race. We tested the association between FSH and bone density in younger postmenopausal women, adjusting for patient-related factors. In 111 postmenopausal women aged 50-64years, areal bone mineral density (BMD) was measured at the lumbar spine, femoral neck, total hip, and distal radius using dual-energy X-ray absorptiometry, and volumetric BMD was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Height, weight, osteoporosis risk factors, and serum hormonal factors were assessed. FSH inversely correlated with weight, bioavailable estradiol, areal BMD at the lumbar spine and hip, and volumetric BMD at the ultradistal radius. In the multivariable analysis, no hormonal variable showed a statistically significant association with areal BMD at any site. Weight was independently associated with BMD at all central sites (p < 0.001), but not with BMD or pQCT measures at the distal radius. Race was independently associated with areal BMD at all sites (p ≤ 0.008) and with cortical area at the 33% distal radius (p = 0.004). Correlations between FSH and bioavailable estradiol and BMD did not persist after adjustment for weight and race in younger postmenopausal women. Weight and race were more important determinants of bone density and should be included in analyses of hormonal influences on bone.

High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women.

Association with replication between estrogen-related receptor γ (ESRRγ) Polymorphisms and bone phenotypes in women of European ancestry

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women.

Augmentation Improves Human Cadaveric Vertebral Body Compression Mechanics for Lumbar Total Disc Replacement

Cadaveric biomechanical study. To quantify the effects of vertebral body augmentation on biomechanics under axial compression by a total disc replacement (TDR) implant. TDR is a surgical alternative to lumbar spinal fusion to treat degenerative disc disease. Osteoporosis in the adjacent vertebrae to the interposed TDR may lead to implant subsidence or vertebral body fracture. Vertebral augmentation is used to treat osteoporotic compression fracture. This study sought to evaluate whether vertebral augmentation improves biomechanics under TDR axial loading. Forty-five L1-L5 lumbar vertebral body segments with intact posterior elements were used. Peripheral quantitative computed tomography scans were performed to determine bone density, and specimens were block-randomized by bone density into augmentation and control groups. A semiconstrained keeled lumbar disc replacement device was implanted, providing 50% endplate coverage. Vertebral augmentation of 17.6% +/- 0.9% vertebral volume fill with Cortoss was performed on the augmentation group. All segments underwent axial compression at a rate of 0.2 mm/s to 6 mm. The load-displacement response for all specimens was nonlinear. Subfailure mechanical properties with augmentation were significantly different from control; in all cases, the augmented group was 2 times higher than control. At failure, the maximum load and stiffness with augmentation was not significantly different from control. The maximum apparent stress and modulus with augmentation were 2 times and 1.3 times greater than control, respectively. The subfailure stress and apparent modulus with augmentation were moderately correlated with bone density whereas the control subfailure properties were not. The augmented maximum stress was not correlated with bone density, whereas the control was weakly correlated. The maximum apparent modulus was moderately correlated with bone density for both the augmented and the control groups. Augmentation improved the mechanical properties of the lumbar vertebral body for compression by a TDR implant.

Bone density measurement in interdental areas with simulated placement of orthodontic miniscrew implants

The purposes of this study were to determine bone density at various orthodontic implant sites and compare them according to depth and area (anterior and posterior, buccal and lingual, and maxilla and mandible). Maxillofacial computed tomography scan data were obtained from 30 adults with normal occlusion. Bone density was recorded in Hounsfield units with simulated placement of miniscrews with the V-Implant program (CyberMed, Seoul, Korea). Bone density was measured to a depth of 6 mm at 1-mm intervals in 60 interdental areas (30 in the maxilla, 30 in the mandible), and mean bone density was calculated at each site. Bone density tended to decrease with increasing depth, particularly in the posterior area. Mean bone density showed a progressive increase from posterior to anterior except for the mandibular buccal side, which had no significant differences. A comparison of the mean bone densities between the buccal and lingual sides in the mandible showed that the lingual side had higher values in the anterior area and vice versa in the posterior area. On the other hand, there were no distinct differences between the buccal and lingual sides in the maxilla. A comparison of the mean bone densities between the maxilla and the mandible showed higher values in the mandible, and these differences were more significant on the buccal side of the posterior. The differences in bone densities according to depth and area should be considered when selecting and placing miniscrew implants for orthodontic anchorage.

Editor's Summary and Q&A: Bone density measurement in interdental areas with simulated placement of orthodontic miniscrew implants

<h3>Introduction</h3> The purposes of this study were to determine bone density at various orthodontic implant sites and compare them according to depth and area (anterior and posterior, buccal and lingual, and maxilla and mandible). <h3>Methods</h3> Maxillofacial computed tomography scan data were obtained from 30 adults with normal occlusion. Bone density was recorded in Hounsfield units with simulated placement of miniscrews with the V-Implant program (CyberMed, Seoul, Korea). Bone density was measured to a depth of 6 mm at 1-mm intervals in 60 interdental areas (30 in the maxilla, 30 in the mandible), and mean bone density was calculated at each site. <h3>Results</h3> Bone density tended to decrease with increasing depth, particularly in the posterior area. Mean bone density showed a progressive increase from posterior to anterior except for the mandibular buccal side, which had no significant differences. A comparison of the mean bone densities between the buccal and lingual sides in the mandible showed that the lingual side had higher values in the anterior area and vice versa in the posterior area. On the other hand, there were no distinct differences between the buccal and lingual sides in the maxilla. A comparison of the mean bone densities between the maxilla and the mandible showed higher values in the mandible, and these differences were more significant on the buccal side of the posterior. <h3>Conclusions</h3> The differences in bone densities according to depth and area should be considered when selecting and placing miniscrew implants for orthodontic anchorage.

Reference values for areal bone mineral density among a healthy Mexican population

Compare the influence of ethnicity in the prevalence of osteopenia and osteoporosis in various Mexican populations using two normal dual X-ray absorptiometry (DXA) reference databases: manufacturer's incorporating US Hispanic population and a normal mestizo Mexican population. MMP included 9 946 subjects participating in an ongoing long-term cohort study focusing on lifestyle and chronic diseases, of which 6 487 MMP males and females aged 7 to 80 years were the normal subjects used to determine bone density T- and Z-scores, following WHO criteria, and peak bone mass values. Abnormal bone mass density values estimated by the manufacturer's and peak bone mass reference values were compared. Our results show that by using the manufacturer's T-score values in the mestizo Mexican population we are underestimating the number of abnormal bone mass BMD populations.

Short‐term etidronate treatment prevents glucocorticoid‐induced bone debility of the mandible in growing rats

To analyse the effects of short-term treatment with etidronate on the glucocorticoid-induced retardation of bone growth and deterioration of bone structure in the prepubertal rat mandible. Fifty 5-week-old male rats were divided into five groups. Etidronate or vehicle treatment (5 mg/kg/day, daily, subcutaneous injection) was initiated after glucocorticoid administration (30 mg/kg/day, on alternate days, orally) for 6 weeks and was continued for 3 weeks. Then, bone growth was measured using lateral cephalometric analysis. Peripheral quantitative computed tomography was used to determine bone density, bone cross-sectional area and bone strength. Glucocorticoid-treated rats had significantly lower body weight, mandibular length, cortical bone density, bone strength and cross-sectional area in trabecular and cortical bone, but had significantly higher trabecular bone density than untreated rats. No significant difference in mandibular height was observed between the glucocorticoid-treated group and the untreated control group. Etidronate treatment improved the glucocorticoid-induced decrease in bone strength and increased density in trabecular and cortical bone above the untreated control level, but had no significant effects on the reduction in mandibular length. These findings suggest that etidronate can potentially reverse the glucocorticoid-induced deterioration of internal bone structure, but has no beneficial effects on the glucocorticoid-induced retardation of bone growth in the growing rat mandible.

Determination of cancellous bone density using low frequency acoustic measurements

In this article we offer a novel method for interrogating cancellous bone using ultra sound measurements. The problem is first modelled in terms of the acoustic pressure in the water bath surrounding the bone sample, the pore pressure and the displacement of the elastic matrix describing the cancellous bone specimen. The fluid pressure in the water tank is represented in terms of a boundary integral equation. Source points are placed on a parallel line on one side of the bone; whereas, receivers are placed on the other side of the bone. Sensitivity tests are run for two frequencies which show that the corresponding inverse problem leads to reasonable good results.

Identification of a Role for the ARHGEF3 Gene in Postmenopausal Osteoporosis

Osteoporosis is a common and debilitating bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Genome-wide linkage studies have identified 3p14-p21 as a quantitative trait locus for BMD. The ARHGEF3 gene is situated within this region and was identified as a strong positional candidate. The aim of this study was to evaluate the role of variation in ARHGEF3 on bone density in women. Sequence variation within ARHGEF3 was analyzed with 17 single-nucleotide polymorphisms (SNPs) in a discovery cohort of 769 female sibs. Significant associations were found with family-based association tests between five SNPs and various measures of age-adjusted BMD (p = 0.0007-0.041) with rs7646054 showing maximal association. Analysis of the data with QPDTPHASE suggested that the more common G allele at rs7646054 is associated with decreased age-adjusted BMD. Significant associations were also demonstrated between 3-SNP haplotypes and age-adjusted spine and femoral-neck BMD (p = 0.002 and 0.003, respectively). rs7646054 was then genotyped in a replication cohort, and significant associations with hip and spine BMD were confirmed (p = 0.003-0.038), as well as an association with fracture rate (p = 0.02). Again, the G allele was associated with a decrease in age-adjusted BMD at each site studied. In conclusion, genetic variation in ARHGEF3 plays a role in the determination of bone density in Caucasian women. This data implicates the RhoGTPase-RhoGEF pathway in osteoporosis.

Validity and reproducibility of osteodensitometric DEXA-measurements following total hip endoprosthesis

For the determination of reproducibility of bone densitometric measurements we performed a measurement according to the DEXA- method. 35 patients after implantation of total hip replacement were examined with a Lunar DPX-L. We received a maximum reproduction error of 1.2% according to the GRUEN-analysis. The operated hip of 17 patients showed an increase in bone density between 5 and 18% by the implantation of an arthroplasty compared to the preoperative values. The non-operated prosthesis-corrected hip showed a reproduction error of 3.8% in ROI 1 in 17 patients, otherwise a maximum of 1.3%. Considering an interfemoral difference in bone density of up to 20%, differences in periprosthetic bone density of up to 40% compared to the contralateral side can be within the normal range in a retrospective measurement. Therefore retrospective determination of bone density after cementless hip arthroplasty only is of limited value. Only prospective analysis can provide reliable information about the actual loss of bone density.

Limitations of Peripheral Quantitative Computed Tomography Metaphyseal Bone Density Measurements

Peripheral quantitative computed tomography (pQCT) measurements are frequently obtained to assess cancellous bone density in the appendicular skeleton. Large variations in bone morphology associated with skeletal development may limit the interpretation of pediatric pQCT studies based on a single slice. The objective of the study was to characterize the variability in trabecular bone density values along the length of the metaphysis. The design was an analysis of pQCT bone density data. The study was conducted at a hospital radiology department. The study included 35 children with cerebral palsy aged 6-12 yr. Variations in cancellous bone density along the length of the proximal tibial metaphysis were measured. The patterns of decay in metaphyseal trabecular bone density were different in all subjects, and the density changed from the physis to the shaft at a rate of 16.8 +/- 8.2% per 1 mm (range 8.6-37.9% per 1 mm). The slopes of the density curve drastically changed in some children over a short period of 6 months. Even with a high correlation (r(2) = 0.88) between the density of a slice located a fixed distance from the growth plate and the overall mean metaphysis density, the respective changes in density over 6 months were only moderately correlated (r(2) = 0.58). These results underscore the difficulty in interpreting metaphyseal pQCT bone density measurements from a single slice and highlight the need for developing pQCT acquisition techniques that provide more representative bone density determinations in the appendicular skeleton of children.

Non-invasive spatial tissue discrimination in ancient mummies and bones in situ by portable nuclear magnetic resonance

Historic mummies and skeletons have been investigated extensively by modern diagnostic imaging using computed tomography. But magnetic resonance imaging (MRI) has never been applied successfully to mummies in a non-invasive way without tissue rehydration. The aim of this study is to show the feasibility and diagnostic impact of mobile MR technology to historic human tissues. The natural glacier mummy Iceman, a mummified recent human cadaver, historic mummified body parts, historic bones, and living volunteers have been analysed by non-invasive, single sided NMR with the NMR-MOUSE®. We acquired high-resolution depth profiles and T2 relaxation curves of the head region of the Iceman mummy in situ in the storage room at the Museum and of the cadaver in the hospital. A spatial differentiation of surface ice layer, cutis, and skull bone up to a depth of 5 mm was possible. In ancient Egyptian mummified specimens, the thickness of a fingernail and a differentiation of a single bandage layer versus the skin underneath were possible. A comparison of depth profiles through different foreheads of mummies, skulls, and living people gives strong evidence, that single-sided NMR with the NMR-MOUSE is a non-invasive technique to determine bone density. Our results demonstrate for the first time the feasibility of non-clinical MRI to visualize historic human tissues in a non-invasive approach.

Technical White Paper: Bone Densitometry

The Conference of Radiation Control Program Directors (CRCPD) Task Force on Bone Densitometry (H-30) was assigned by the Healing Arts Council on Emerging Issues to address issues of bone densitometry. Issues for clarification included the practice of precision testing, in which multiple bone density determinations are performed on one patient; the use of quantitative computed tomographic (CT) densitometry; and radiation dose to patients and operators. This paper is a condensation of the white paper produced by the task force, which addresses the various methods of measuring bone density, the qualifications and responsibilities of personnel, the rationale for precision testing, and the doses patients and operators may receive. The white paper is available in its entirety on the CRCPD's Web site (http://crcpd.org).

The Genetics of Low-Density Lipoprotein Receptor-Related Protein 5 in Bone: A Story of Extremes

A few years ago, human genetic studies provided compelling evidence that the low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the regulation of bone homeostasis because pathogenic LRP5 mutations were found in monogenic conditions with abnormal bone density. On the one hand, the osteoporosis pseudoglioma syndrome results from loss of function of LRP5, whereas on the other hand, gain-of-function mutations in LRP5 cause conditions with an increased bone density. On the molecular level, these types of mutations result in disturbed (respectively, decreased and increased) canonical Wnt signaling, an important metabolic pathway in osteoblasts during embryonic and postnatal osteogenesis. This signaling cascade is activated by binding of Wnt ligand to the Frizzled/LRP5 receptor complex. In addition to the involvement of LRP5 in conditions with extreme bone phenotypes, the genetic profile of this gene has also been shown to contribute to the determination of bone density in the general population. Quite a number of studies already demonstrated that common polymorphic variants in LRP5 are associated with bone mineral density and consequently osteoporosis, a multifactorial trait with low bone mass and porous bone structure. These genetic studies together with results obtained from in vitro and in vivo studies emphasize the importance of LRP5 and canonical Wnt signaling in the regulation of bone homeostasis. Therefore, unraveling the exact mechanisms of this signaling cascade has become an important area in bone research. This review focuses on the genetics of LRP5 and summarizes the findings on monogenic bone conditions as well as the current knowledge of its involvement in the pathogenesis of osteoporosis.

Bone mineral density determinations by dual-energy x-ray absorptiometry in the management of patients with Marfan syndrome--some factors which affect the measurement.

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993-2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.

Preparation and characterization of calibration standards for bone density determination by micro-computed tomography

Phantoms for the calibration of local bone mineral densities by micro-computed tomography (microCT), consisting of lithium tetraborate (Li(2)B(4)O(7)) with increasing concentrations of hydroxyapatite [HAp, Ca(10)(PO(4))6(OH)2] have been prepared and characterized for homogeneity. Large-scale homogeneity and concentration of HAp in the phantom materials was determined using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), while homogeneity on the micrometer scale was assessed through microCT. A series of standards was prepared by fusion of pure HAp with Li(2)B(4)O(7) in a concentration range between 0.12 and 0.74 g cm(-3). Furthermore, pressed and sintered pellets of pure HAp were prepared to extend the calibration range towards densities of up to 3.05 g cm(-3). A linear calibration curve was constructed using all individual standard materials and the slope of the curve was in good agreement with calculated absorption coefficients at the effective energy of the microCT scanner.

Bone density and primary stability in implant therapy

To improve patient comfort, deviations from the very successful standard osseointegration protocol are being developed. To keep implant failure rates as low as possible, the most perfect treatment planning and a good patient selection are extremely important. Because bone density plays an important role in implant outcome, known relations of bone density could improve treatment planning. A Pubmed search revealed 66 manuscripts investigating and discussing bone density of human jawbone whether or not related to implant stability or outcome. Forty-five of these will be discussed in this review. Many pre-operative methods of jawbone density assessment are available. Most of those techniques correlate well with one another. Some are more elaborate to use in clinical practice. Primary stability measurements show significant correlations with different bone densities and also with implant outcome; however, not many studies investigate both at the same time. To investigate the outcome of adaptation methods of the surgical protocol with regard to the jawbone density, an objective pre-surgical determination of bone density is necessary.

The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease—A cross sectional study

Chronic obstructive pulmonary disease (COPD) is a complex disease, where the initial symptoms are often cough as a result of excessive mucus production and dyspnea. With disease progression several other symptoms may develop, and patients with moderate to severe COPD have often multiorganic disease with severely impaired respiratory dysfunction, decreased physical activity, right ventricular failure of the heart, and a decreased quality of life. In addition osteoporosis might develop possibly due to a number of factors related to the disease. We wanted to investigate the prevalence of osteoporosis in a population of patients with severe COPD as well as to correlate the use of glucocorticoid treatment to the occurrence of osteoporosis in this population. Outpatients from the respiratory unit with COPD, a history of forced expiratory volume in 1s (FEV1) less than 1.3 L, with FEV1% pred. ranging from 17.3% to 45.3% (mean 31.4%, standard deviation (sd) 7.3%). Patients between 50 and 70 years were included. Other causes of osteoporosis were excluded before inclusion. At study entry spirometry, X-ray of the spine (to evaluate presence of vertebral fractures), and bone mineral density of lumbar spine and hip were performed. Of 181 patients invited by mail, 62 patients were included (46 females and 16 males). All had symptoms of COPD such as exertional dyspnea, productive cough, limitations in physical activity etc. The mean FEV1 was 0.90 L (sd: 0.43 L) and the mean FEV1% pred. of 32.6% (sd: 14.1%). All had sufficient daily intake of calcium and vitamin D. In 15 patients, X-ray revealed compression fractures previously not diagnosed. Bone density measurements showed osteoporosis in 22 patients and osteopenia in 16. In total, 26 of the COPD patients were osteoporotic as evaluated from both X-ray and bone density determinations. Thus 68% of the participants had osteoporosis or osteopenia, but glucocorticoid use alone could not explain the increased prevalence of osteoporosis. A large fraction of these needed treatment for severe osteoporosis in order to prevent further bone loss and to reduce future risk of osteoporotic fractures. Thus, there is a significant need to screen patients with COPD to select the individuals in risk of fracture and to initiate prophylaxis or treatment for the disease.

Bone health of children with cerebral palsy

There is widespread interest and concern about bone health in children with chronic disease. Unfortunately, much of this interest has centered on the use of methods for determining bone density which may be flawed. The Journal recently published a review of such methods (2005;146:726). In this issue, Binkley et al use state-of-the-art methodology, peripheral quantitative computed tomography (pQCT) to examine the bone health of children with cerebral palsy (CP). CP presents a real problem for measuring bone mineral density, since there are a number of reasons (eg, deformities, contractures) that make conventional techniques such as DXA invalid. Using pQCT, this group has shown that the major defect in children with CP is not so much a reduction in cortical bone density as it is bone geometry (smaller and thinner bones). The reader of this paper may wish to refer to the above-referenced Medical Progress article for a “refresher” on these measurements and their significance.