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Increase in femoral bone density in young women following high-impact exercise.

Healthy premenopausal women were randomized into control and test groups; both exercised weekly in class and daily at home for a year. The test class did intermittent high-impact exercise; the control class did low-impact exercise. Bone density was assessed blind using dual energy X-ray absorptiometry at the femur (neck, Ward's triangle and trochanter) and at the lumbar spine (antero-posterior L1-4) on entry into the study, and again after 6 months (n = 27) and 12 months (n = 19). At 6 months the test group (n = 14) showed a significant increase of 3.4% in trochanteric bone density (p = 0.01) and this was significantly different from control (p = 0.05). In the second 6 months the control group was crossed over to high-impact exercise and showed a significant increase of 4.1% in trochanteric density (n = 7) while the original group maintained their improvement relative to baseline.

Adult↗

Bone density in medieval skeletons.

We studied the most complete skeletons found in an excavation from the 14th and 15th century in central Stockholm. One hundred eighty-seven were from men and 156 from women: 241 individuals were estimated to be between 20 and 39 and 102 between 40 and 59 years old at death. We examined the bones radiographically and by dual photon absorptiometry. The bone mineral density (BMD) was similar to the finding in North America and Northern Europe today as was the relationship between men and women. However, there appeared to be a higher diaphyseal bone density in the lower extremities, especially in men. The femur score was higher and the BMD of the femoral and tibial shafts was higher than today. In the upper extremities the diaphyseal bone density was lower. Meema's index, as well as the metacarpal score, was smaller than in individuals in this century and the BMD of the humeral shaft was also lower than seen today. Overall, the metaphyseal bone density was similar to what we now consider normal; i.e., the mean BMD of the femoral neck was 0.96 g/cm2 in men and 0.90 g/cm2 in women and of the distal radius 0.43 and 0.32 g/cm2, respectively. The low diaphyseal density and in the upper extremities may be related to the nutritional status, whereas the greater need for walking and standing in the 14th and 15th century might have led to the high diaphyseal density in the lower extremities. There was no evidence of bone loss after 40 years of age in either sex in our study. The average expected lifespan for an adult individual was less than 50 years and we suggest that the relatively high bone density in the older age group may be due to selection of the most physically fit. The activity pattern, therefore, may be considered the most important determinant for the differences.

Adult↗

Mutation analysis of coding sequences for type I procollagen in individuals with low bone density.

Mutations in one of the two genes encoding type I procollagen (COL1A1 and COL1A2) are frequently the cause of osteogenesis imperfecta (OI), a disorder characterized by brittle bones. Here we tested whether patients with low bone density also have mutations in these genes. The 26 patients studied had no apparent metabolic bone disease, but most had a positive family history of osteopenia or osteoporosis. Although a diagnosis of OI was considered by the clinician in some cases, the clinical criteria for OI were not satisfied. Our strategy for mutation analysis consisted of PCR amplification of cDNA made to fibroblast mRNA using primers specific for the coding regions of COL1A1 and COL1A2. The PCR products were then sequenced directly with primers located within each PCR product. We found that 3 of 26 patients had mutations that altered the encoded amino acid. One mutation, at position alpha 2(I)-661 has been reported (Spotila et al. 1991 Proc Natl Acad Sci USA PNAS 88:5423). The other 2 patients, who were not related to each other, had a mutation that altered the proline codon at alpha 1(I)-27 to alanine. This mutation was not found in 81 normal individuals or in 37 additional osteopenic individuals. However, its effect on the biologic function of type I collagen, as well as its role in osteopenia, is uncertain. In addition to the two mutations, we found a polymorphism in codon alpha 2(I)-459. Although this polymorphism involved an amino acid substitution, it was present with equal frequency in the patient and the normal population. By analyzing this and previously reported neutral sequence variants in the COL1A2 gene, we determined that all patients expressed both alleles of the COL1A2 gene. The 12 patients who were heterozygous for a COL1A1 neutral sequence variant also expressed both alleles. Here we present all PCR primer and sequencing primer information. The results suggest that surveying a larger group of similarly selected individuals may reveal additional mutations in the COL1A1 or COL1A2 genes.

Adolescent↗

Plasma leptin concentration and change in bone density among elderly men and women: the Hertfordshire Cohort Study.

Several studies have shown an association between circulating leptin concentration and bone mineral density. but most studies are cross-sectional in design and report findings in women only. We per-formed a population-based longitudinal study relating baseline plasma leptin concentration to bone mass at the lumbar spine and femoral neck and to change in bone density at these sites over four years in a cohort of 302 men and women aged 60 75 years born and still resident in Hertfordshire, UK. Baseline plasma leptin concentration was strongly positively correlated with body mass index (men: r = 0.71, P 0.0001; women: r = 0.79, P < 0.0001) and with bone mineral content,bone mineral density, and volumetric bone mineral density at all sites (r = 0.24-0.36, P < 0.001) in both sexes: associations with change in bone density were markedly weaker and inconsistent. Adjustment for adult lifestyle determinants of osteoporosis made little difference to our results, but the associations of leptin with bone mass were no longer significant after adjustment for body mass index. These results suggest that the relationship between plasma leptin and bone mass is similar in men and women and that it is mediated through the strong association of both variables with adiposity, rather than through a direct association of leptin on bone cell function.

Aged↗

Subregion analysis of the rat femur: a sensitive indicator of changes in bone density following treatment with thyroid hormone or bisphosphonates.

Measurement of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) is a precise and accurate way to assess changes in BMD due to a variety of causes. However, the degree of bone loss may vary depending on the skeletal site examined. We postulated that interventions that change bone density would have a different effect on an area rich in trabecular bone, such as the distal femur, than on other subregions of the femur. Male Sprague-Dawley rats (325-350 g) were treated with triiodothyronine (T3), a bisphosphonate (pamidronate), or placebo for 21 days and then sacrificed. Ex vivo BMD of the proximal, distal, mid and total femur were measured by DXA. We found that mean BMD of hyperthyroid rats was significantly lower than controls at all femoral subregions. However, the difference in mean BMD between hyperthyroid and control rats was greatest at the distal femur (8.6%). In rats treated with bisphosphonate, mean BMD was significantly higher than controls at the proximal, distal, and total femur. The difference in mean BMD between controls and rats treated with bisphosphonate was greatest at the distal femur (31.8%). Furthermore, pamidronate (APD)-treated rats had lower mean mid-femur BMD than controls. We conclude that changes in BMD after treatment with bisphosphonate or T3 are greatest at the distal femur subregion, and that treatment with bisphosphonate may cause a slight reduction in mid-femur BMD. Future studies examining changes in BMD in the rat femur after interventions that alter mineral metabolism should include subregion analysis.

Absorptiometry, Photon↗

[Effect of soybean intake on bone mineral density and bone turnover markers in postmenopausal women].

OBJECTIVE: The purpose of this study was to evaluate the effects of soybean intake on bone mineral density and bone turnover markers in postmenopausal rural Korean women. METHOD: This study was carried out during nine months from Oct. 25 2004 to Aug. 31 2005. The subjects of this study were female patients over 50 living in rural areas diagnosed with osteoporosis. There were 18 women in the experimental group and 20 in the control group. In this study, the experimental group received 100 mg of isoflavone (soybean) and calcium 1,500 mg for nine months while the control group received 1,500 mg of calcium only. RESULTS: After the soybean intake, the change of bone mineral density between the experimental group and control group was statistically significant. However, the bone turnover markers of osteocalcin and deoxypyridinoline between the experimental group and control group were not significantly different statistically. In the Pearson Correlation between bone mineral density and bone turnover markers, the osteocalcin and deoxypyridinoline of the experimental group had a positive correlation, and osteocalcin and DPD/osteocalcin ratio had a negative correlation. In the control group, osteocalcin and DPD/osteocalcin ratio had a negative correlation. CONCLUSIONS: This result showed that soybean intake changed bone mineral density in postmenopausal woman.

Aged↗

Lateral bone density measurements in osteoarthritis of the lumbar spine.

OBJECTIVE: To investigate whether spinal osteoarthritis (OA) is responsible for the common finding that lumbar spine bone mineral density (BMD) is greater when measured in the anteroposterior plane than when measured in the lateral plane. METHODS: We studied lateral spine radiographs from 63 women who attended a hospital outpatient department for bone density measurement and who also underwent lumbar spine radiography. Osteoarthritis was assessed using both the Kellgren and Lawrence scale and a scoring system for osteophytosis. Bone density was measured in the anteroposterior and lateral planes using a Hologic QDR-2000 instrument. RESULTS: The mean anteroposterior BMD (0.92 g/cm2) was significantly greater than the lateral BMD (0.59 g/cm2) (p < 0.01), and the difference between antero-posterior and lateral measurements was significantly associated with both increasing Kellgren and Lawrence score and osteophyte score, even after adjustment for age. CONCLUSION: These data suggest that spinal OA is a major cause of the difference between anteroposterior and lateral BMD and that lateral BMD may provide a more accurate representation of true vertebral body bone density in patients with OA of the lumbar spine.

Absorptiometry, Photon↗

[Measurement of vertebral bone density. Quantitative tomodensitometry or dual-photon absorptiometry?].

We have compared vertebral bone density measurements (QCT and DXA) in women in the postmenopausal period who underwent both examinations. Our aim was to study the results and to define the respective indications of QCT and DXA in various clinical pictures of osteoporosis. The subjects of the study were distributed into various groups according to the presence or absence of vertebral collapse and/or peripheral fractures. The results of the measurements were expressed as Z-scores (deviation from age-normal average) to suppress the age effect and to make comparison between both methods possible. The values of both measurements are significantly lower in case of vertebral involvement. QCT is more sensitive than DXA to discriminate vertebral collapse. A vertebral fragility threshold was defined at a Z-score of -1 with DXA and -1.25 with QCT, corresponding to the best sensitivity for an acceptable specificity. The results of densitometry suggest that there is a peripheral osteoporosis, different from vertebral osteoporosis, as early as the postmenopausal period. Since DXA is easy to implement, it can be used to screen osteoporosis. When the vertebral measurement with DXA is normal although osteoporosis is obvious (previous collapse or fracture), QCT must be used as it is more sensitive.

Absorptiometry, Photon↗

Functional significance of bone density measurements in children with osteogenesis imperfecta.

BACKGROUND: The treatment of osteogenesis imperfecta has been directed at improvement of bone mineral density, yet the importance of bone mineral density in predicting functional and clinical outcome in this patient population has not been demonstrated. We used a validated functional outcome measure to identify the relationship between bone mineral density and physical function in children with osteogenesis imperfecta, and we also evaluated the relationship of bone mineral density to the rate of surgery and fracture in patients with osteogenesis imperfecta. METHODS: Twenty patients (age range, four to seventeen years) with osteogenesis imperfecta who had undergone bone mineral densitometry as measured by dual x-ray absorptiometry of the lumbar spine, wrist, and proximal aspect of the femur between November 1999 and April 2001 were retrospectively analyzed. Functional outcome was measured with use of the Pediatric Outcomes Data Collection Instrument. These questionnaires were completed by the parents of all twenty patients and, in addition, by fifteen patients in the study who were between the ages of eleven and eighteen years. Fracture and surgery rates were calculated on the basis of the number of documented fractures and surgical procedures that the patient had had from the time of the initial presentation until the time of the latest follow-up visit. RESULTS: There were significant relationships between the bone mineral density of the lumbar spine and the scores obtained on the parent-completed questionnaires with regard to upper-extremity functioning (r = 0.57, p < 0.01), transfers and basic mobility (r = 0.55, p = 0.01), sports and physical functioning (r = 0.55, p = 0.01), and global functioning (r = 0.60, p < 0.004). There were also significant relationships between the bone mineral density of the wrist and the scores obtained on the child-completed questionnaires with regard to upper-extremity functioning (r = 0.82, p < 0.01), sports and physical functioning (r = 0.76, p < 0.01), and global functioning (r = 0.83, p = 0.001). There were significant negative relationships between the bone mineral density of the lumbar spine and the rate of fractures (r = -0.69, p < 0.001) and the bone mineral density of the lumbar spine and the rate of surgery (r = -0.60, p < 0.01). CONCLUSIONS: There is a relationship between bone mineral density and the functional outcome, rate of fracture, and rate of surgery in patients with osteogenesis imperfecta. Bone mineral density appears to be an indicator of disease severity and may be predictive of long-term functional outcome. To establish specific guidelines for treatment, more data on normative bone-mineral density in children with osteogenesis imperfecta will be needed.

Adolescent↗

Filling a cervical spine cage with local autograft: change of bone density and assessment of bony fusion.

To date, it remains debatable whether cervical spine fusion cages should be filled with any kind of bone or bone substitute. Using a bone substitute would produce additional costs, using an autologous bone graft from the iliac crest would make the use of the cage at least questionable. As an alternative, cortical and subcortical bone from the anterior osteophytes of the segment in which the disc has been removed could be used to fill the cage: higher costs and complications at the iliac crest could both be avoided and the cage could be filled. However, the fate of these bone chips made from the anterior osteophytes is unclear as well as whether fusion will occur using this technique. The objective of the current study was to investigate possible changes in the bone density of this local autograft in the cage within the first 12 months after surgery by means of computed tomography. A second objective was to assess segmental bony fusion using this technique. 21 patients, suffering from degenerative disc disease of the cervical spine, were included into this prospective study. They all underwent anterior decompression, cage insertion and plate stabilisation. The cage (Rabea, Signus Medizintechnik, Alzenau, Germany), was filled with bone chips made from the anterior osteophytes of the segment that underwent discectomy. On the third day after surgery as well as three, six and 12 months after surgery, an axial computed tomography scan through the cage was taken and density within the apertures of the cage was measured in a standardised manner. Flexion-extension lateral radiographs were taken to investigate segmental fusion. Statistical significance was assumed to be at a 95 % level of significance. 23 cages were implanted. The mean value of the bone density obtained by computed tomography was 505 (+/- 119) HU on day three, 635 (+/- 156) HU after three months, 769 (+/- 162) HU after six months, and 814 (+/- 198) after 12 months. There was a significant difference when the values after 12 months were compared to those obtained after three days (p < 0.001) and after three months (p = 0.004). Bony fusion was seen in 21 out of 23 segments (91.3 %) after 12 months. It may be concluded that this technique could be an alternative to the current treatment options.

Bone Density↗

High bone density due to a mutation in LDL-receptor-related protein 5.

BACKGROUND: Osteoporosis is a major public health problem of largely unknown cause. Loss-of-function mutations in the gene for low-density lipoprotein receptor-related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis-pseudoglioma. METHODS: We performed genetic and biochemical analyses of a kindred with an autosomal dominant syndrome characterized by high bone density, a wide and deep mandible, and torus palatinus. RESULTS: Genetic analysis revealed linkage of the syndrome to chromosome 11q12-13 (odds of linkage, >1 million to 1), an interval that contains LRP5. Affected members of the kindred had a mutation in this gene, with valine substituted for glycine at codon 171 (LRP5V171). This mutation segregated with the trait in the family and was absent in control subjects. The normal glycine lies in a so-called propeller motif that is highly conserved from fruit flies to humans. Markers of bone resorption were normal in the affected subjects, whereas markers of bone formation such as osteocalcin were markedly elevated. Levels of fibronectin, a known target of signaling by Wnt, a developmental protein, were also elevated. In vitro studies showed that the normal inhibition of Wnt signaling by another protein, Dickkopf-1 (Dkk-1), was defective in the presence of LRP5V171 and that this resulted in increased signaling due to unopposed Wnt activity. CONCLUSIONS: The LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass and point to Dkk as a potential target for the prevention or treatment of osteoporosis.

Biomarkers↗

Decreased bone density in carriers and patients of an Israeli family with the osteoporosis-pseudoglioma syndrome.

BACKGROUND: The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12. OBJECTIVE: To measure bone density in two siblings with the OPPG syndrome as well as in their family members (parents and siblings). METHODS: Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (> 95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry. RESULTS: The studies revealed osteoporotic changes both in the patients and the carriers. CONCLUSION: The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

Abnormalities, Multiple↗

Computer-assisted densitometric image analysis (CADIA) for the assessment of alveolar bone density changes in furcations.

The purpose of this study was to test the applicability of computer-assisted densitometric image analysis (CADIA) for the quantitative assessment of alveolar bone density changes in furcations of multirooted teeth. In 21 patients, standardized radiographs were obtained immediately after and at 1, 6 and 12 months after periodontal flap procedures. Digitized images were obtained by means of a video-camera combined with an image processor that was linked to a computer. Quantitative information regarding density changes within windows covering furcation areas was obtained after superimposition and grey-level correction of images to be compared. 1 month after flap reflection, significantly more density loss was obtained in test furcations exposed to periodontal surgery, compared to the density changes in control furcation exposed to scaling and root planing. At 12 months, however, significantly greater increase in density was measured in test furcations compared to the 1-month results. The radiographic data were compared to the clinical parameters. In test furcations, there was a negative correlation of r = -0.52 between the GI and the loss in density at 1 month, and a negative correlation of r = -0.61 between the loss in density at 6 months and the probing attachment level at 12 months. These results indicate that CADIA may give valuable additional diagnostic information regarding alveolar bone density changes in furcations in studies on periodontal therapy.

Alveolar Process↗

Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women.

66 early postmenopausal women were randomised to 28-day cycles of either transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl-norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of 30 women were studied concurrently. Bone density was measured in the lumbar spine and proximal femur by dual photon absorptiometry at 6-month intervals for 18 months. Skeletal turnover was assessed by serum measurements of calcium, phosphate, and alkaline phosphatase, and by urine estimations of hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment groups by comparison with the untreated groups by comparison with the untreated group, bone density increased in the vertebrae and proximal femur and biochemical measurements indicated a significant reduction in bone turnover.

Absorptiometry, Photon↗

Effect of recombinant human bone morphogenetic protein 7 on bone density during distraction osteogenesis of the rabbit mandible.

OBJECTIVES: To examine whether the quality of bone generation in distraction osteogenesis of the rabbit mandible is enhanced by administering recombinant human bone morphogenetic protein 7 (rhBMP-7) to the lengthened site at the end of the distraction phase. STUDY DESIGN: Prospective randomized study of 24 rabbits undergoing distraction osteogenesis of the mandible, followed by injection of rhBMP-7 or a lactate buffer. SETTINGS: McGill University animal care facility. METHODS: Twenty-four white New Zealand rabbits underwent unilateral mandibular osteotomy and application of an Orthofix uniplanar M-100 fixator (Orthofix Inc., Verona, Italy) to the mandible. Mandibular distraction was carried out for 3 weeks. The animals were divided into three groups: group 1 (eight rabbits), control group: distraction, no injection; group 2 (eight rabbits), study group: distaction + injection of 200 microg of rhBMP7-lactate buffer; group 2 (eight rabbits), comparison group: distraction + injection of lactate buffer. All rabbits were sacrificed 7 weeks after surgery. The mandibles underwent radiology and bone densitometry analysis. MAIN OUTCOME MEASURES: Radiology assessment of bone generation within distracted segments and objective analysis of bone mineral density. RESULTS: Radiology confirmed the presence of bone generate within distraction sites. Densitometry showed a difference in bone mineral density among the three groups (p < .05). CONCLUSION: Local injection of a single dose of 200 microg of rhBMP-7 did enhance bone density when compared with the control group, although not in a statistically significant way when analyzed by an x-ray bone densitometer. This study serves as a starting point for future studies in bone tissue engineering by guiding the strategic administration of rhBMPs and the use of new state-of-the-art technologies, such as micro CT scanning, to analyze in a more detailed way, the effects of rhBMP administration.

Absorptiometry, Photon↗

Effects of weight gain and resumption of menses on reduced bone density in patients with anorexia nervosa.

The bone mineral density (BMD) of the lumbar vertebrae (L2-L4) and of the whole body were measured in cross-sectional and longitudinal studies in female patients with eating disorders, using dual photon absorptiometry before and after weight gain with or without resumption of menses. In the cross-sectional study, the low-body-weight anorectic patients, with or without bulimia nervosa, were found to have lower BMD of the lumbar vertebrae associated with severe weight loss, low physical activity, and earlier onset and longer duration of amenorrhea. In the longitudinal study, 11 patients attained subnormal body weight (70%SBW < or = approximately < 85% SBW), 10 patients attained normal body weight (> or = 85%SBW, 6 patients of them resumed regular menses) after treatment. The BMD of the lumbar vertebrae was found to increase with weight gain, but not to the control level. The BMD was further increased with the resumption of menses in patients with anorexia nervosa. These results suggest that resumption of menses, in addition to weight gain, is essential to normalize reduced bone mineral density.

Absorptiometry, Photon↗

A peak in gh-receptor expression is associated with growth activation in Atlantic salmon vertebrae, while upregulation of igf-I receptor expression is related to increased bone density.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play major roles in the endocrine regulation of fish growth, but their interdependency and mode of action has not been well elucidated. The GH-IGF-I system is essential for normal vertebral growth in mouse, but this has not been studied in fish. To study the interplay between GH, IGF-I, and their receptors, postsmolt Atlantic salmon were studied during spring growth (January-June 2003). From January to June, fish were sampled regularly for plasma and vertebral bone. The vertebra was collected from the same anterior-posterior position. The growth hormone receptor (ghr) (There is no determined nomenclature of salmon genes but we stick to the nomenclature which is consequent for zebrafish, where all gene names are named with small letters and in italic.) expression in the vertebrae peaked in the end of February coinciding with high levels of plasma GH and IGF-I, and an increase of vertebral growth rate. From April to June, plasma IGF-I levels decreased together with ghr expression in the vertebrae, while plasma GH did not decrease. In May and June, expression of the igf-I receptor (igf-Ir) increased 4- to 5-fold, which coincided with an increase in bone density. The changes seen in gene expression of the IGF-I and GH receptors suggest that these hormones are involved in vertebral growth and bone density.

Animals↗

Effect of cortical thickness and cancellous bone density on the holding strength of internal fixator screws.

Internal fixators are a new class of implants designed to preserve the periosteal blood supply of the bone. In contrast to conventional plate fixation in which the screws have spherical heads and are loaded mainly by axial pullout forces, screws in internal fixators are "locked" within the plate and therefore subjected to axial as well as bending loads. In this study the ultimate loads of screws of a commercially available internal fixator system were tested in a pullout (n = 72) and cantilever bending mode (n = 72) in metaphyseal and diaphyseal regions of four pairs of human tibiae with different bone qualities. Cortical thickness and cancellous bone density were determined at the screw insertion sites. Stepwise multiple linear regression revealed that cortical thickness and cancellous density can explain 93% and 98% of the variance of the ultimate load of the screws in an axial pullout and cantilever bending mode. Screws in internal fixators are better suited to transmit shear forces and thereby make better use of the strength potential of bone than screws used in conventional plate fixation: this is especially advantageous when bone strength is reduced, e.g. due to osteoporosis.

Aged↗