[Measurement of bone density and early diagnosis of bone loss by Compton spectroscopy].
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Bone Diseases↗
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Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group.
Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.
Aged↗
[Effectiveness of screening for osteoporosis by bone density measurement for the prevention of fractures: a review of the evidence].
To review evidence on the benefits of screening women and men for osteoporosis, a Pub Med search was performed in English papers published between 1990 and 2002. We used data from a cohort study to estimate risk of fracture from bone mineral density. Bone mineral density measured by dual X-ray absorptiometry (DXA) can predict bone fracture among elderly women, peri- and early post-menopausal women, and elderly men. It is recommended that all white women older than 65 years be screened routinely for osteoporosis. We suggest that Japanese elderly women should receive BMD measurements as a screening, but we have still issues to be solved including age from when the screening should be started, methods, and how to treat the women found to have osteoporosis at the screening. For peri- and postmenopausal women and elderly men, it might be beneficial to measure BMD as a screening and start treatment for those patients found to have osteoporosis. However, incidence of fractures for these people is lower than that for elderly women. One bone mass measurement can predict bone fracture risk for as long as over 10 years or more, but predictive ability of BMD decreases with time. Therefore, cost effectiveness needs to be reviewed to determine the benefits of screening among peri-menopausal women and men. Although bone assessment by quantitative ultra sound (QUS) method by ultrasound can also predict future fractures, only a relatively small number of longitudinal studies have been conducted in the Western countries, and there is no established evidence by means of longitudinal studies among Japanese. It is necessary in Japan to seek such evidence, however, since this method is widely used for an osteoporosis examinations.
Aged↗
[A clinical analysis on the variance of bone density in patients with cirrhosis].
In 46 patients with decompensated posthepatitis cirrhosis, various clinical manifestations resulted from changes of bone density were noted. The relation between the changes of bone density and the level of blood calcium, blood phosphorus and alkaline phosphatase (AKP) as well as the metabolism of vitamin D was studied. It is shown that: (1) Bone mineral content (BMC) in the cirrhosis group decreased as compared with that in a control group (P < 0.05). (2) Blood calcium and phosphorus level decreased, whereas AKP level increased significantly (P < 0.01) in the cirrhosis group. (3) When BMC decreased, blood calcium and phosphorus level also decreased significantly (P < 0.01). When the condition of cirrhosis deteriorated, these changes became more obvious. The reasons may be: (1) Disorder of vitamin D metabolism in cirrhosis. (2) Decrease of calcium absorption by intestine. (3) Nutritional disturbance. It is suggested that the occurrence of bone rarefaction in cirrhosis was due to multiple factors.
Adult↗
Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.
To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.
Bone Density↗
Effects of inhaled glucocorticoids on bone density in premenopausal women.
BACKGROUND: Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma. METHODS: We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 microg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device. RESULTS: Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss. CONCLUSIONS: Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.
Administration, Inhalation↗
Klotho gene polymorphisms associated with bone density of aged postmenopausal women.
Because mice deficient in klotho gene expression exhibit multiple aging phenotypes including osteopenia, we explored the possibility that the klotho gene may contribute to age-related bone loss in humans by examining the association between klotho gene polymorphisms and bone density in two genetically distinct racial populations: the white and the Japanese. Screening of single-nucleotide polymorphisms (SNPs) in the human klotho gene identified 11 polymorphisms, and three of them were common in both populations. Associations of the common SNPs with bone density were investigated in populations of 1187 white women and of 215 Japanese postmenopausal women. In the white population, one in the promoter region (G-395A, p = 0.001) and one in exon 4 (C1818T, p = 0.010) and their haplotypes (p < 0.0001) were significantly associated with bone density in aged postmenopausal women (> or = 65 years), but not in premenopausal or younger postmenopausal women. These associations were also seen in Japanese postmenopausal women. An electrophoretic mobility shift analysis revealed that the G-A substitution in the promoter region affected DNA-protein interaction in cultured human kidney 293 cells. These results indicate that the klotho gene may be involved in the pathophysiology of bone loss with aging in humans.
Aged↗
Estrogen action on the bone mass of postmenopausal women is dependent on body mass and initial bone density.
Recent evidence suggests that estrogen replacement therapy (ERT) may be effective in preventing bone loss even in late postmenopausal women. We analyzed the role of age and other factors as determinants of ERT action on vertebral bone density (VBD) in 73 consecutive Caucasian postmenopausal women treated for 1 yr or longer. A group of 44 women who received calcium supplements only were analyzed as controls. VBD was measured every 6 months by dual energy x-ray absorptiometry, and yearly rates of change were calculated by linear regression for each subject. VBD increased in the estrogen-treated group (+17.32 +/- 2.84 mg/cm2.yr; 2.42 +/- 0.37%/yr) and did not significantly change in untreated subjects (-4.08 +/- 3.68 mg/cm2/yr; -0.60 +/- 0.58%/yr). Women older than 60 yr experienced greater, although not significant, increments compared to younger subjects (+3.23 +/- 4.03% vs. +1.42 +/- 3.00%/yr), as did women more than 10 yr postmenopausal compared to patients within 10 yr after the menopause (+3.38 +/- 4.11% vs. +1.19 +/- 2.70%/yr). Rates of VBD change were positively correlated with age (r = 0.29; P = 0.014), years since menopause (r = 0.33; P = 0.005), and body mass index (BMI; r = 0.35; P = 0.003) and negatively with estimated initial VBD (r = -0.23; P = 0.05). However, only the relationships between bone density changes and BMI (r = 0.33; P < 0.01) and estimated initial VBD (r = -0.26; P < 0.05) held in a partial correlation analysis. BMI and estimated initial VBD were the only significant predictive factors for response to ERT (r2 = 21%) in a multivariate regression model. Therefore, the response to ERT depends mostly on BMI and initial VBD. Women with large body frames and those with lower initial VBD respond better to estrogen than slender women with higher bone mass.
Age Factors↗
Pubertal bone growth in the femoral neck is predominantly characterized by increased bone size and not by increased bone density--a 4-year longitudinal study.
Fragility fractures are correlated to reduced bone size and/or reduced volumetric bone density (vBMD). These region-specific deficits may originate from reduced mineral accrual and/or reduced skeletal growth during the first 2 decades of life. Before pathological development can be defined, normal skeletal growth must be described. To evaluate growth of bone size, accrual of bone mineral content (BMC), areal bone mineral density (aBMD) and vBMD in a population-based cohort, 44 boys and 42 girls were followed by annual measurements from the age of 12 to 16 (attendance rates 90-100%). Segmental bone length, bone width, BMC, aBMD and vBMD were measured by dual-energy X-ray absorptiometry (DXA). Data were compared with predicted adult peak, as determined in 36 men aged 27.7+/-4.6 years and 44 women aged 26.8+/-4.9 years. Growth in width of the femoral neck precedes accrual of BMC in the femoral neck in both genders up to age 15. The girls were at all ages closer to their predicted adult peak in both bone width and BMC compared with the boys except in the femoral neck. As femoral neck vBMD had reached its predicted adult peak already at 12 years in both genders, the increase in femoral neck BMC and femoral neck aBMD from age 12 to 16 was most likely to be explained by the increase in bone size. In boys the peak velocity growth was recorded at ~14 years for BMC, height, width and lean mass. Growth from the age of 12 to 16 seems to build a bigger but not a denser skeleton in the femoral neck.
Adolescent↗
Interrelationships of diet, athletic activity, menstrual status, and bone density in collegiate women.
We undertook a case-control study to examine the effect of nutritional factors on menstrual function and bone density in collegiate athletes. Three groups, matched with respect to age, height, and weight, were studied: eumenorrheic collegiate athletes, oligomenorrheic collegiate athletes, and eumenorrheic sedentary collegiate control subjects. Menarche was delayed in the eumenorrheic (13.1 y) and oligomenorrheic (14.3 y) athletic groups compared with the sedentary control subjects (12.2 y) (p less than 0.05). Average bone density tended (p = 0.10) to be lower in the oligomenorrheic athletes (158 mg/mL) compared with the eumenorrheic athletes (184 mg/mL) or sedentary control subjects (173 mg/mL). Dietary fiber intake was significantly elevated (p less than 0.05) in the oligomenorrheic athletes (5.74 g/d) compared with the eumenorrheic athletes (3.62 g/d) or sedentary control subjects (2.97 g/d). We conclude that increased dietary fiber intake is associated with menstrual dysfunction of these collegiate athletes. These factors may contribute to decreased bone density.
Adult↗
Non-invasive assessment of bone density in primary biliary cirrhosis.
BACKGROUND/AIMS: Low bone mass is an important complication of primary biliary cirrhosis (PBC), resulting in an increased risk of fractures and reduced mobility. In the present study, we sought to determine the frequency of low bone mass in PBC, and its relationship to disease severity and non-invasive markers of bone turnover. METHODS: In 36 women with PBC, bone mineral density of the lumbar spine and hip was assessed by dual emission X-ray absorptiometry. Serum and urinary markers of bone turnover were compared with those from age- and sex-matched controls. RESULTS: Spinal osteopenia (T score, -1.5 to -2.5) was present in 15 of the 36 patients (42%), while six others (16%) had established osteoporosis (T < -2.5). Osteopenia of the femoral neck was found in 17 patients (47%), and osteoporosis in five (14%). The severity of liver disease, as determined by Mayo Clinic R score and histological stage, correlated negatively with both regional bone mineral density and total bone mineral content expressed as a ratio to lean body mass. There was a strong positive correlation between serum levels of the procollagen degradation peptides, PICP and PIIINP (r = 0.65, P < 0.001), and both peptides correlated significantly (P < 0.001) with histological stage and Mayo Clinic R score. Fasting urinary pyridinoline and deoxypyridinoline to creatinine ratios were also significantly raised. CONCLUSIONS: Low bone mass in PBC correlates positively with disease severity, and is associated with a net increase in bone resorption, as assessed by urinary collagen cross-link excretion. These markers of bone turnover may be of value in controlled clinical trials aimed at improving bone mass in PBC.
Absorptiometry, Photon↗
[Review of cranio-maxillo-facial malformations characterized by abnormal bone density].
This paper is a review of cranio-maxillo-facial bone malformations, characterized by an abnormal cortical bone density. For each lesion, clinical and radiological cranio-maxillo-facial features are described. Whenever possible, recent etiopathogenic and differential diagnostic elements are included, on the basis of a review of the literature.
Adult↗
In vivo relationship between marrow T2* and trabecular bone density determined with a chemical shift-selective asymmetric spin-echo sequence.
Magnetic field inhomogeneities due to differences in susceptibility between trabecular bone and bone marrow result in a reduction in T2*. The authors previously quantified the relationship between the relaxation rate enhancement per unit change in bone density, delta R2*, using dried, excised vertebral bodies immersed in saline. In the present study, they investigated the precision and reproducibility of such measurements in vitro and found that the short-term precision ranges from 2% to 11%, while the long-term precision error, which may be governed by the placement of the region of interest, can vary up to 50%. A chemical shift-selective asymmetric spin-echo sequence was used to assess T2* changes in the saturated fat component of bone marrow in vivo. It was shown that the marrow fat relaxation rate increases as the surrounding trabecular bone density increases and that the delta R2* of the marrow fat component was 0.20 sec-1/mg/cm3. The results also indicate that the distribution of T2* varies with image resolution. Both in vitro and in vivo, characteristics of the relaxation time distribution such as the mean, standard deviation, and skewness decrease as image resolution decreases, the degree of variation depending on the density of the surrounding trabecular network.
Bone Density↗
Plain radiographs can be useful in estimating lumbar bone density.
On standard lateral roentgenograms of the lumbar spine, a decrease in bone density is said to be detectable only after a bone loss of about 40%. To evaluate this view, we compared findings on plain films with bone mineral content of L1 determined by quantitative computed tomography in 80 healthy subjects with a mean age of 60 years. The highest correlations with bone mineral content were found for the criteria "vertebral density versus soft tissue" (r = 0.5, p less than 0.0001), the "amount of trabeculations" (r = 0.49, p less than 0.0001), and for the "overall" estimate of osteopenia in the vertebra (r = 0.55, p less than 0.0001). Surprisingly, these three radiographic criteria proved to be most helpful in subjects with bone mineral content above 110 mg/cm3 (nonosteoporotic range). We conclude that lateral radiographs of the lumbar spine can provide a rough estimate of bone density in nonosteoporotic subjects which may be helpful in determining when further analysis with more precise methods is appropriate.
Bone Density↗
Growth hormone predicts bone density in elderly women.
Evidence is accumulating that the risk of osteoporosis may be influenced by environmental factors during intrauterine and early postnatal life; such programming might be mediated through modification of the GH/IGF-1 axis during critical periods in its development. To address this issue, we explored the relationships among birth weight, circulating GH profile, bone density, and bone loss rate in a group of British women. The study population consisted of 38 women 60-75 years old resident in Hertfordshire for whom detailed birth records were available. Twenty-four-hour circulating GH profiles were obtained during an inpatient stay on a metabolic ward, after an overnight rest. The circulating profile of GH was characterised by estimating the peak, median, trough, and total concentrations from 72 samples measured sequentially over 24 h in each subject. Bone mineral density was assessed at the lumbar spine and femoral neck at baseline and at follow-up 4 years later. Lumbar spine bone mineral content (BMC) and density (BMD) were positively associated with all measures of GH concentration, although relationships were strongest for BMC with trough GH (r = 0.47, P < 0.01). Associations persisted after adjustment for age, body mass index, smoking, alcohol consumption, physical activity, and osteoarthritis score in multiple regression models. However, associations of GH concentration with femoral neck BMC were weak, and there was no association between any measure of GH concentration and bone loss at either site. Total (integrated) daily GH concentration tended to increase (P = 0.08) with rising birth weight, while IGF-1 concentration fell (P = 0.05) with rising birth weight, suggesting a role for the GH/IGF-1 axis in the programming of adult bone mass among women.
Aged↗
Bone density changes in Paget's disease 2 years after iv pamidronate: profound, sustained increases in pagetic bone with severity-related loss in forearm nonpagetic cortical bone.
Bone mineral density (BMD) was measured at three sites (forearm, spine, and hip) using dual X-ray and single-photon absorptiometry in 68 patients with Paget's disease before and after treatment with iv pamidronate. Patients were treated according to the severity of their disease; the mild category (Group I, hydroxyproline excretion (Hyp(E)) <5.0 micromol/L GF) received 120 mg, the moderate category (Group II, Hyp(E) 5.0-9.99 micromol/GF) 180 mg, and the severe category (Group III, > or = 10.0 micromol/GF) 240 mg. Group I was followed for 1 year, and both Groups II and III for 2 years. At the lumbar spine in pagetic bone there were no differences between groups in early responses, with a profound increase 6 months after treatment 20.5 +/- 2.0% above baseline values to 1.403 +/- 0.063 g/cm(2) (mean +/- SEM)(P < 0.001). This increase in BMD was sustained to 2 years (1.355 +/- 0.078 g/cm(2), P < 0.001) and was 15.0 +/- 2.2% above baseline values. The pagetic total hip BMD increased after treatment in all groups, with a mean rise of 10.4 +/- 1.4% at 1 year to 1.505 +/- 0.083 g/cm(2) (P < 0.01). At the pagetic femoral neck the response was similar, with a peak significant rise at 1 year of 10.7 +/- 1.7% to 1.403 +/- 0.097 g/cm(2) (P < 0.01). In nonpagetic spinal bone there were no differences between the group responses, with a combined mean increase of 4.3 +/- 0.7% at 1 year to 0.999 +/- 0.027 g/cm(2) (P < 0.01). In both Groups II and III the increase in BMD was significantly higher than baseline values at 1 and 2 years (P < 0.01). In the nonpagetic total hip BMD remained unchanged over the 2-year period and likewise, there were no significant changes from baseline at the nonpagetic femoral neck site. In the nonpagetic forearm we found a significant loss in BMD at the ultradistal (mainly trabecular), midregion (80% cortical), and proximal shaft (95% cortical) sites in Group III, persisting to 2 years at the latter two sites. The increase in bone density in pagetic bone, persisting at least 2 years, provides a new modality of assessment of the response of pagetic bone to treatment and suggests a mechanism for the reduction in fracture risk in such bone after effective bisphosphonate treatment. Severity-dependent nonpagetic forearm bone loss, persisting to 2 years at cortical sites, suggests a potential drug-induced fracture risk at the forearm and possibly elsewhere in the absence of appropriate preventive cotreatment.
Aged↗
The effects of depth of penetration, screw orientation, and bone density on sacral screw fixation.
Obtaining adequate sacral fixation is an important and challenging clinical problem. Bicortical screw fixation has been used to provide improved mechanical strength. The goal of this study was to evaluate the effects of depth of penetration (unicortical versus bicortical), orientation (medial versus lateral), and bone density on the strength of the bone-screw interface. Seven-millimeter Steffee screws (Acromed, Cleveland, Ohio) were placed in human cadaveric sacra. The screws were placed either medially into the centrum of the S1 body or laterally into the sacral ala. The fixation systems used, either bicortical or unicortical, were tested on a Universal testing machine. The specimens were loaded to failure and biomechanical parameters were measured. Medially oriented screws sustained the highest load to failure. In an older population, unicortical fixation sustained load to failure and initial compliance findings were similar to those for bicortical fixation. The regional bone density in the centrum of the first sacral body was denser than that in the lateral alar region, and also provided more rigid bone screw fixation.
Aged↗
Serum leptin values in relation to bone density and growth hormone-insulin like growth factors axis in healthy men.
A novel action of leptin on bone formation has recently been described in animals. However, in humans, studies provide data, that, are less conclusive. So far, few studies investigated the leptin-bone density association in males. Moreover, it has been suggested that GH, IGF-1 and IGFBP-3 may be major players in the hormonal or paracrine pathways that regulate bone cell metabolism. Also, leptin has been shown to modulate the GH/IGF pathway. The aim of this study was to clarify further this issue by investigating (a) the influence of serum levels of leptin, GH, IGF-1 and IGFBP-3 on bone mass in various skeletal sites and, (b), the relationship between leptin and the GH/IGF axis. 363 healthy individuals were investigated. BMD and serum leptin, GH, IGF-1 and IGFBP-3 serum levels were assessed. Our results indicate that 11% of healthy males had bone density with T scores </=2.5 SD. No significant differences were found between men with normal and those with reduced BMD with regards to serum leptin, GH, IGF-1 and IGFBP-3 levels. A positive correlation was found between BMD and leptin levels in FN and T, and a negative one between leptin and IGF-1 levels. Further studies are needed before we reach final conclusions.
Adult↗