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PubMed1985

Postmenopausal bone density and milk consumption in childhood and adolescence.

Skeletal mass is a major determinant of susceptibility to osteoporotic fracture in menopause. At menopause, the skeletal mass is the resultant of the Peak Skeletal Mass (PSM) reached early adulthood minus the bone mass lost through the process of Adult Bone Loss (ABL). Current interventions for the maintenance of skeletal resilience in advanced age address the ABL peri- or postmenopausally. This study indicates that the effects of milk consumption in childhood and adolescence on bone density may manifest as higher bone density decades later in menopause. The assumed mechanism of the reported effect is through augmentation of the PSM, and acquisition of favorable nutritional habits which may influence the extent of ABL.

Adolescent↗
PubMed1987

The correlation of serum estrogens and androgens with bone density in the late postmenopause.

A pilot group of 16 women in the late postmenopause were evaluated for bone density by computerized axial tomography (CT) scanning and for hormonal milieu. A highly statistically significant positive correlation between lumbar-3 spongiosum density and both dehydroepiandrosterone-sulfate (DHEA-S), r = 0.67; P less than 0.005 and androstenedione (A), r = 0.56; P less than 0.03 was found. No such correlations were observed with estradiol (E2), estrone (E1) or an array of other hormones. The results of this preliminary report indicate a clear association of weak androgens with bone density in the late postmenopause.

Aged↗
PubMed1977

Evaluation of a computerised image analyser for studying alterations in radiographic bone density in the rat.

A computerised image analyser has been used experimentally to determine its possible usefulness in quantifying bone density. Rats were prepared for this purpose and ash weight/volume readings were obtained on femora which had been radiographed and studied to estimate radiographic density by means of the image analyser. The findings indicated that rats can be prepared by administering oestradiol or by allowing an additional week's growth, both of which give a statistically significant increase of bone density. The computerised image analyser was able to detect these differences but the correlations, although real and linear, between ash weight/volume and radiographic density were not large. Further refinements in techniques will be needed before the system is applied clinically.

Aminopropionitrile↗
PubMed2006

Bone density, geometry, and fracture in elderly men.

Bone geometry is a major determinant of the mechanical resistance of bone. Mechanical strength of the vertebrae depends on the cross-sectional area of the vertebral body and on the size of the posterior arch. Smaller bone width is associated with higher risk of stress fracture. A longer femoral neck axis and a more open neck-shaft angle are associated with higher risk of cervical hip fracture. No consistent association between the femoral neck width and the cervical fracture risk was found. Areal bone mineral density (aBMD) is not a good tool for the identification of elderly men with high fracture risk. Fracture risk increases with decreasing aBMD, but only a minority of men who will sustain an osteoporotic fracture are identified by a given threshold of baseline aBMD. Bone width seems to be an independent predictor of the fracture risk in elderly men, and its assessment can improve the prediction of fractures in this population.

Aged↗
PubMed2003

Further validation of a questionnaire to identify women likely to have low bone density.

UNLABELLED: A questionnaire instrument called the Simple Calculated Osteoporosis Risk Estimation (SCORE*) stratifies risk for osteoporosis, potentially reducing population-screening costs. SCORE is calculated using race, weight, age, history of estrogen use, fracture history, and presence/absence of rheumatoid arthritis. We tested SCORE in 912 postmenopausal women aged 45 yr or more using a Hologic QDR4500C densitometer for the total hip, femoral neck, and lumbar spine. National Health and Nutrition Examination Survey (NHANES III) norms were used to calculate hip T-scores. Low bone density (T-score < -2.0) was found in 29.6% of patients at the femoral neck, 17.7% at the total hip, 36.1% at the lumbar spine, and 46.1% at one or more sites. The sensitivity/specificity of the SCORE model (using a threshold of 6 points) was 0.97/0.36 for the femoral neck, 0.95/0.30 for the total hip, 0.86/0.35 for the spine, and 0.88/0.41 for any site (total hip, femoral neck, or spine). When used to detect low bone density at any site, SCORE would have deferred 27.6% of women referred for DXA scans, but 20.7% of these (5.7% of the entire population) would have been false-negatives, and thus inappropriately deferred. At a cutpoint of 3 instead of 6, sensitivity/specificity was 0.96/0.16. In those aged 50-60, the group with the greatest need for risk stratification, sensitivity/specificity for low density at any site was 0.72/0.54, and 46.1% would have been deferred, but 18.5% of this group would have been false-negatives. A cutpoint of 1 in this age group yielded sensitivity/specificity of 0.94/0.16. After age 65, few women would be deferred. CONCLUSION: When used to detect low bone density at any site with sufficient sensitivity for clinical practice, SCORE did not have sufficient discriminatory power to be broadly applicable.

Area Under Curve↗
PubMed2004

Bone density in myasthenia gravis patients receiving long-term prednisolone therapy.

Osteoporosis is an adverse effect of prednisolone therapy, although no study has been conducted on myasthenia gravis patients receiving high-dose prednisolone. We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases). This frequency is lower than the presumptive rate of the general population in Japan (22.6%). No osteoporosis was detected in male patients. In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered.

Absorptiometry, Photon↗
PubMed1998

Review of 3,530 referrals for bone density measurements of spine and femur: evidence that radiographic osteopenia predicts low bone mass.

PURPOSE: To determine the relationship between bone mineral density (BMD) measurements and the initial reason for referral to a BMD screening service. MATERIALS AND METHODS: Referral letters for 3,479 of the 3,530 women referred for BMD screening were classified according to the indication for screening. Mean age-matched standard deviation scores (Z scores) were derived for each of the 10 most common indications. Mean BMD between each group was compared with the age-matched value from the local normal range by means of a one-sample Student t test. Mean young normal standard deviation scores (T scores) were derived, and the percentages of women with osteopenia or osteoporosis from each referral group were calculated on the basis of the World Health Organization criteria. RESULTS: The most common reason for referral was to aid in a decision regarding hormone replacement therapy (n = 700). The highest proportion of women with osteoporosis in any group was in the radiographic osteopenia group (n = 269). CONCLUSION: Radiographic evidence of osteopenia is a strong predictor of osteoporosis. Screening for osteopenia appears justified in this and other high-risk groups and those seeking a rationale for preventive therapy.

Adolescent↗
PubMed1997

Moderate alcohol consumption does not augment bone density in ovariectomized rats.

Moderate levels of alcohol consumption have been reported to have a beneficial effect on bone mineral density in postmenopausal women. The objective of this study was to examine the effect of a moderate level of alcohol consumption on bone density in a rigorously controlled animal model of osteoporosis. Ovariectomized and nonovariectomized rats were placed on standard lab pellets with free access to deionized water ad libitum. Alcohol-treated animals were given 0.38 g/kg of alcohol daily by intubation in the mid-afternoon and free access to standard lab pellets for 6 weeks. The amount of the alcohol solution was calculated daily to give the human equivalent of 2 glasses of wine/day. Pair-fed control animals were given, on the following day, an equal volume of the diet consumed by individual ethanol-fed rats. They received daily intubation solutions, with the ethanol replaced by isocaloric and isovolumetric amounts of maltose-dextrin. Chow-fed control animals received no intubations and were given access to standard lab pellets ad libitum. Ovariectomized animals had increased weight and decreased femur density and bone volume per total volume. They also had decreased total trabecular area, trabecular area, and number, as well as increased trabecular separation. Significant differences were found between the ovariectomized and nonovariectomized animals in the parameters under discussion, but there were no differences between diet groups. No beneficial effects were found after daily alcohol treatments.

Aged↗
PubMed2005

Effect of alendronate administration on bone mineral density and bone strength in castrated rats.

Castration of male rats leads to increased bone turnover and osteopenia. This study was conducted to examine the effects of the aminobisphosphonate alendronate on castration-induced bone changes. Bisphosphonates are drugs that inhibit bone turnover by decreasing the resorption. Since they suppress bone remodeling, they may also prevent the repair of microdamage and decrease bone strength. Although the mechanical properties of bones are directly related to the determination of fracture risk, bisphosphonate effects on the related variables have scarcely been investigated. Twenty-four male Wistar rats at two months of age were castrated or sham-operated to evaluate the effects of long-term administration (six months) of sodium alendronate at a dose of 1 mg/kg/day. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. High bone remodeling seen in castrated rats expressed by increased TrACP and B-ALP was suppressed by alendronate administration. Bone from castrated rats was characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone and femoral cortical thickness. When castrated rats were treated with high dose of alendronate, the changes in bone density resulting from castration were entirely prevented, and mechanical analysis revealed preserved mechanical strength of femur and cortical thickness. We conclude that castration induces cortical bone loss associated with high bone turnover in the male rat, and this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity, while preserving the mechanical properties of bone. These results document the efficacy of alendronate, even at high doses, in preventing bone loss, loss of bone mechanical strength, and the rise in biochemical bone turnover indicators due to castration in rats, and raises the possibility that a alendronate could be equally effective in humans.

Acid Phosphatase↗
PubMed2003

Milk intake during childhood and adolescence, adult bone density, and osteoporotic fractures in US women.

BACKGROUND: Calcium supplements increase bone mass in children, but the effect does not persist once supplementation is discontinued. OBJECTIVE: The objective of this study was to determine whether milk intake during childhood and adolescence, when controlled for current calcium intake, is associated with adult bone mass (ie, bone mineral content), bone mineral density, and the incidence of osteoporotic fracture. DESIGN: We used data from the third National Health and Nutrition Examination Survey of 3251 non-Hispanic, white women age >or=20 y. Bone density was measured at the hip. History of fracture of the hip, spine, or forearm was classified as a lifetime fracture (occurring after age 13 y) or an osteoporotic fracture (occurring after age 50 y). Subjects reported frequency of milk consumption during childhood (aged 5-12 y) and during adolescence (aged 13-17 y). Regression models controlled for weight, height, age, menopause and use of estrogen, physical activity, smoking, and current calcium intake. RESULTS: Among women aged 20-49 y, bone mineral content was 5.6% lower in those who consumed <1 serving of milk/wk (low intake) than in those who consumed >1 serving/d (high intake) during childhood (P < 0.01). Low milk intake during adolescence was associated with a 3% reduction in hip bone mineral content and bone mineral density (P < 0.02). Among women aged >or=50 y, there was a nonlinear association between milk intake during childhood and adolescence and hip bone mineral content and bone mineral density (P < 0.04). Low milk intake during childhood was associated with a 2-fold greater risk of fracture (P < 0.05). CONCLUSION: Women with low milk intake during childhood and adolescence have less bone mass in adulthood and greater risk of fracture.

Absorptiometry, Photon↗
PubMed1997

Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral density and bone turnover.

Isolated hypogonadotropic hypogonadism (IHH) presents with delayed puberty in the late teens or early twenties, with a period of testosterone deficiency during active growth. The aims of the study were to determine 1) whether long term treatment of IHH results in normalization of bone density (BMD) and bone turnover, and 2) whether BMD and bone turnover respond to increasing doses of hCG. We studied 10 men, aged 26-46 yr, with IHH who were treated with hCG or testosterone esters (Sustanon) for 2-22 yr, with age at the start of treatment between 17-29 yr, and 10 age- and body weight-matched normal men as a control group. At baseline, lumbar spine, femoral neck, trochanter, and Ward's triangle BMD values were decreased, and serum bone Gla-protein, bone alkaline phosphatase, and urinary pyridinoline, deoxypyridinoline, and N-terminal telopeptide of type I collagen were increased compared with control values (by paired t test, P = 0.02, 0.03, 0.01, 0.05, 0.002, 0.02, 0.02, 0.007, and 0.006, respectively). The age at initial therapy was significantly correlated with total body BMD (r = -0.73; P = 0.017) and lumbar spine BMD (r = -0.756; P = 0.0097). Serum free testosterone was correlated with total body and trochanter BMD (r = 0.635; P = 0.048 and r = 0.629; P = 0.05), and serum free estradiol was correlated with total body and trochanter BMD (r = 0.641; P = 0.045 and r = 0.634; P = 0.048). Six of the 10 patients were recruited for a longitudinal study in which the dose of hCG was increased monthly from 2000 i.u. twice per week to 6000 i.u. twice per week. After increasing doses of hCG, levels of serum testosterone and estradiol and total body BMD increased significantly (by paired t test P = 0.001, 0.003, and 0.01, respectively). Serum bone Gla-protein levels increased by the first month and then decreased (paired t test, corrected by Bonferroni's method). Serum bone alkaline phosphatase and urinary N-terminal telopeptide of type I collagen/creatinine levels decreased significantly after increasing the dose of hCG. We conclude that patients with IHH who have serum testosterone within the laboratory reference range may require a higher dose of hCG to normalize BMD and bone turnover.

Adult↗
PubMed1999

Changes in bone density after exposure to oral anticoagulants: a meta-analysis.

Oral anticoagulants are putative risk factors for osteoporosis, but observational cross-sectional studies describing their effects on bone mineral density have reported conflicting results, prospective studies are not available, and randomized trials are not feasible. To determine the association between exposure to oral anticoagulants and changes in bone density, we systematically reviewed nine original cross-sectional studies on the effect of long-term exposure to any oral anticoagulant on bone density in adults. The effect size was assessed by standardized mean difference (SMD, exposed minus unexposed) and pooled by skeletal site; results are reported in standard deviation units. Bone density was significantly decreased among exposed subjects in the ultradistal radius (SMD, -0.39; 95% CI, -0.67 to -0.10) but not in the distal radius (SMD, -0.47; 95% CI, -0.97 to 0.04), lumbar spine (SMD, -0.27; 95% CI, -0.59 to 0.05), femoral neck (SMD, 0.03; 95% CI, -0.22 to 0.29) or femoral trochanter (SMD, -0.18; 95% CI, -0.48 to 0.11). The evidence should be considered with caution, but it is consistent with a negative association of oral anticoagulants with bone density in the ultradistal radius, although not in the spine or hip. This suggests that long-term oral anticoagulation might be associated with no more than a modest increase in osteoporotic fracture risk, but this should be verified in future longitudinal studies.

Administration, Oral↗
PubMed2002

Clinical risk factors but not bone density are associated with prevalent fractures in prepubertal children.

OBJECTIVE: The aim of this study was to investigate the association of clinical risk factors and bone density with prevalent fractures in prepubertal children. METHODS: Bone mineral density (BMD) in lumbar spine, femoral neck and total body bone was assessed by dual-energy X-ray absorptiometry. Clinical data on risk factors were collected by measurement and questionnaires. RESULTS: Of 324 children, 32 (10%) had a prevalent fracture (upper limb 69%). Most fractures were due to low-energy falls at home (69%). Children with fractures were older (P = 0.04), had higher levels of sports participation (P = 0.03), lower levels of breastfeeding (P = 0.05) and tended towards higher usage of inhaled corticosteroids in the previous year (P = 0.05). However, both BMD and apparent BMD did not differ between those with and without prevalent fracture. No differences were observed in the proportion of maternal fractures, maternal smoking during pregnancy, asthma history and oral prednisolone in last year (all P > 0.05). A final model incorporating age, weight, height, breastfeeding history, sports participation and inhaled corticosteroid usage accounted for 10% of the variability in the odds of fracture (P = 0.03). CONCLUSION: These results suggest that BMD may be less important than clinical risk factors for total fracture risk in prepubertal children. However, sample size limitations mean that further investigation in larger populations with less heterogeneity in fracture types is warranted.

Absorptiometry, Photon↗
PubMedDate not supplied

Sex- and race-related differences in cross-sectional geometry and bone density of the femoral mid-shaft in older adults.

BACKGROUND: Femoral shaft fracture incidence increases in older adults and is associated with low-energy trauma. Apart from bone density, the distribution and size of bone contributes to its strength. AIM: To examine if bone geometry and density of the femoral mid-shaft in older adults differs by sex and race, we studied 197 White women, 225 Black women, 242 White men, and 148 Black men aged 70-79 years participating in the Health, Aging, and Body Composition study; a prospective cohort study in the USA. A secondary purpose of the study was to examine the association of site-specific muscle and fat to bone geometry and density. SUBJECTS AND METHODS: Subjects were community-dwelling and reported no difficulty walking one-quarter of a mile or climbing stairs. Mid-femoral volumetric bone mineral density (vBMD, mg cm(-3)), total area (TA), cortical area (CA), medullary area (MA), cross-sectional moments of inertia (CSMI: I(x), I(y), J), and muscle and fat areas (cm(2)) were determined by computed tomography (CT; GE CT-9800, 10 mm slice thickness). RESULTS: vBMD was greater in men than women with no difference by race (p < 0.001). Bone areas and area moments of inertia were also greater in men than women (p < 0.001), with Black women having higher values than White women for TA and CA. Standardizing geometric parameters for body size differences by dividing by powers of femur length did not negate the sex difference for TA and MA. Significant differences (p < 0.05) among the four groups also remained for I(x) and J. Mid-thigh muscle area was an independent contributor to TA in all groups (Std beta = 0.181-0.351, p < 0.05) as well as CA in women (Std beta = 0.246-0.254, p < 0.01) and CSMI in White women (Std beta = 0.175-0.185, p < 0.05). Further, muscle area was a significant contributor to vBMD in Black women. CONCLUSION: These results indicate that bone geometry and density of the femoral diaphysis differs primarily by sex, rather than race, in older well-functioning adults. In addition, site-specific muscle area appears to have a potential contributory role to bone geometry parameters, especially in women.

Aged↗
PubMed1999

Increased loss of trabecular but not cortical bone density, 1 year after discontinuation of 2 years hormone replacement therapy with Tibolone.

OBJECTIVE: Assessment of loss of bone density (BD) 1 year after a 2-year period of hormone replacement therapy (HRT) with two doses of Tibolone as compared to placebo in early post-menopausal women. METHODS: Sixty-four out of 84 women (1-3 years following spontaneous menopause) who completed a 2-year randomised, placebo controlled study to evaluate effects of Tibolone participated in this follow-up study. Quantitative computed tomography was used to exclusively measure trabecular BD, microdensitometry of the mid-phalangeal shaft was used for estimation of cortical BD and biochemical markers of bone metabolism were assessed, 1 year after discontinuation of Tibolone. The study group received either placebo (n = 16), 1.25 mg/day Tibolone (n = 25) or 2.5 mg/day Tibolone (n = 23). RESULTS: Observations revealed a significantly greater decrease in trabecular BD during the post-trial year in both treatment groups compared to the placebo group (for 1.25 mg/day Tibolone, -6.0%, 95% CI -8.4 to -3.5; for 2.5 mg/day Tibolone, -10.0%, 95% CI: -12.9 to -6.9). In contrast, there was no significant difference in loss of phalangeal BD in both treatment groups compared to placebo. Biochemical markers (serum alkaline phosphatase, urinary excretion of hydroxyproline and calcium) do not suggest an increased bone turnover comparing Tibolone groups to placebo, 1 year after cessation of Tibolone. CONCLUSION: The present study suggests an increased loss of trabecular but not cortical BD as compared to the placebo group in the first year after cessation of HRT with Tibolone in early post-menopausal women.

Anabolic Agents↗
PubMed2006

Change in cortical bone density and its distribution differs between boys and girls during puberty.

CONCEPT: Postmenarchal girls and premenopausal women have 3-4% higher cortical bone density (CoD, milligrams per cubic centimeter), compared with postpubertal boys and men, respectively. Females' denser cortical bone is thought to serve as a calcium reservoir for reproductive needs. However, prospective data are lacking that describe CoD development and bone mineral density distribution during puberty in both sexes. OBJECTIVE: Thus, our objectives were to assess maturity and sex differences in the 20-month change of CoD and radial distribution of bone mineral density (RDBMD, milligrams per cubic centimeter) in early-, peri-, and postpubertal girls and boys. Maturity groups were based on change in menarcheal status (girls, n = 68) and pubic hair stage (Tanner) (boys, n = 59). Peripheral quantitative computed tomography was used to measure CoD and RDBMD at the tibial middiaphysis. RESULTS: The increase in average CoD was 1.9% [22.8 mg/cm(3); 95% confidence interval (CI), 10-36], 2.8% (33.8 mg/cm(3); 95% CI, 21-47), and 1.5% (55.0 mg/cm(3); 95% CI, 17-93) greater in early, peri-, and postpubertal girls, compared with boys, respectively. Analysis of RDBMD revealed that the change in density distribution varied across pubertal groups in girls. Across puberty, all girls showed an increase in the high density midcortical region, whereas only peripubertal girls showed an increase in the lower density subcortical region. A sex-difference in RDBMD change was noted within early and peripubertal groups. CONCLUSIONS: Our findings of sexual dimorphism in CoD development give support to the hypothesis that female bone deposits calcium for reproductive needs by consolidation of cortical bone during puberty.

Adolescent↗
PubMed2002

Ibandronate treatment decreases the effects of tumor-associated lesions on bone density and strength in the rat.

Bisphosphonate treatment is beneficial against symptoms of metastatic bone disease, although less is known about the effect of preventative treatment schedules. We investigated the effect of various treatment regimens of the bisphosphonate, ibandronate (IB), on the preservation of bone quality in a rat model of tumor-induced osteolysis. Osteolytic Walker 256 (W256) carcinosarcoma cells were implanted into the left femur of female Sprague-Dawley rats, resulting in a 10% reduction in bone mineral density (BMD), a 16% reduction in bone density (BD), and a 26% reduction in failure load compared with the right femur 28 days after implantation. IB was administered subcutaneously in five different treatment schedules: (1) IB PRE-POST received IB for 26 days, prior to implantation of W256 cells in the medullary canal of the femur, and for 28 additional days after surgery; (2) IB PRE-POST SHAM received the same IB administration, but with a sham operation; (3) IB PRE received IB injections before W256 cell insertion only; (4) IB PRE-0 received IB injections for 26 days and was then killed to serve as a time zero control; and (5) IB POST received sham injection with saline before W256 cell insertion, and then received IB injections for 28 days until killing. Controls (TUMOR ONLY) received sham injections with saline prior to W256 cell insertion, and then for 28 additional days until killing. We used dual-energy X-ray absorptiometry (DXA) to measure distal femur BMD and bone mineral content (BMC), peripheral quantitative computed tomography (pQCT) to measure distal femur BD, and torsion testing to obtain torsional failure load. Combined preventative and interventional IB treatment best preserved bone mass and strength, although all treatment schedules resulted in significant improvement compared with untreated controls (TUMOR ONLY). The possibility of reducing or even preventing skeletal morbidity in cancer patients with a high risk of developing metastatic spreading to bone is exciting, and warrants further exploration.

Animals↗