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Biological adaptive control model: a mechanical analogue of multi-factorial bone density adaptation.

The mechanism of how bone adapts to every day demands needs to be better understood to gain insight into situations in which the musculoskeletal system is perturbed. This paper offers a novel multi-factorial mathematical model of bone density adaptation which combines previous single-factor models in a single adaptation system as a means of gaining this insight. Unique aspects of the model include provision for interaction between factors and an estimation of the relative contribution of each factor. This interacting system is considered analogous to a Newtonian mechanical system and the governing response equation is derived as a linear version of the adaptation process. The transient solution to sudden environmental change is found to be exponential or oscillatory depending on the balance between cellular activation and deactivation frequencies.

Adaptation, Physiological↗

Value of bone scintigraphy for detection and ageing of vertebral fractures in patients with severe osteoporosis and correlation between bone scintigraphy and mineral bone density.

Osteoporosis is the most common of the metabolic bone diseases, and is an important cause of morbidity in the elderly. Bone scintigraphy is used to detect skeletal lesions at the earliest possible time, to monitor the course of the skeletal discase and to evaluate the metabolic activity of skeletal lesions. The aim of this study was to determine, by using the bone scan age of vertebral fractures in patients with severe osteoporosis, and make correlation between bone scintigraphy and mineral bone density. Material and methods 30 female patients were studied with bone scintigraphy after BMD.BMD was measurred with DEXA Hologic QDR 4500 Elite System. Correlation between T-score and uptake of radiofarmaceutical (Tc-99mMDP) was 0.849, and it was high. Intensity of uptake of Tc-99m MDP scintigraphy is an accurate method for the detection and ageing of fractures in osteoporotic patients.

Absorptiometry, Photon↗

Effect of increasing dietary vitamin A on bone density in adult dogs.

There has been an increase in vitamin A fortification of livestock feeds resulting in increased residual vitamin A in organ meats, which are often used in canned dog foods. The effect on bone density of feeding various concentrations of vitamin A in a canned dog food product was investigated. Thirty-two random-source dogs were assigned to four treatments in a randomized complete block design. The diets contained 15,000, 50,000, 116,000, or 225,000 IU vitamin A/1,000 kcal ME. Diets were fed up to 1 yr. Computed tomography was used to determine bone density of the right tibia at 0, 3, 6, 9, and 12 mo. Computed tomography is a more sensitive technique for determining bone density in vivo than conventional x-rays. There were no differences (P > .10) in tibia bone or marrow density in any of the dogs fed the various concentrations of vitamin A. There was no interaction of time x diet on bone density (P > .05) or bone marrow density (P > .05). In addition, there were no changes in serum alkaline phosphatase, calcium, or phosphorus. These results indicate that concentrations of vitamin A three times the recommended maximum safe amount (71,429 IU/1,000 kcal ME) are not detrimental to normal bone health in dogs. Therefore, these data support the hypothesis that canines are less sensitive to excess vitamin A in the diet than some other mammals.

Alkaline Phosphatase↗

Axial bone density in rheumatoid arthritis: comparison of dual-energy projection radiography and dual-photon absorptiometry.

The usefulness of dual-energy projection radiography (DEPR) in the evaluation of rheumatoid arthritis was compared with that of dual-photon absorptiometry (DPA). Bone density measurements of the lumbar spine and the proximal femur were obtained with DPA in 75 patients (45 women and 30 men). For comparison, the bone density of the lumbar spine was measured with DEPR in a subset of 52 patients (33 women and 19 men). High correlation was documented between DEPR and DPA measurements of the lumbar spine. No significant relationship between bone density and age was observed, in contrast to the known relationship in healthy subjects regardless of sex, site of measurement, or measurement technique. Bone density values in the spine and the proximal femur were significantly reduced for both sexes as compared with matched normative data. Interlevel variation in lumbar vertebral density as measured with DEPR was not significantly different in patients with rheumatoid arthritis as compared with control subjects. Significant correlation between bone density determination and body weight, as well as duration of menopause, was noted, whereas duration of disease, functional status, and cumulative corticosteroid dose were not predictive. Rheumatoid arthritis did not appear to influence the relationship between DEPR and DPA measurements of the spine, and neither method nor site of measurement exhibited a consistent advantage in discriminating patients with rheumatoid arthritis from healthy control subjects.

Absorptiometry, Photon↗

Urinary hormonal concentrations and spinal bone densities of premenopausal vegetarian and nonvegetarian women.

We evaluated the relationships among nutrition, hormone concentrations, and bone density of the spine in 27 vegetarian and 37 nonvegetarian premenopausal women. The two groups were indistinguishable with respect to age, height, weight, menarche, years of formal education, and medical histories. The frequency of menstrual irregularity was significantly higher in the vegetarian group. The bone densities of the vegetarians and the nonvegetarians were not significantly different. Caffeine intake in both groups had a positive effect on urinary calcium excretion, but no association was observed between bone density and caffeine intake. Total fat, monosaturated fat, and oleic acid intake were positively associated with luteinizing hormone concentrations of the vegetarians only. Overall, the differences in dietary practices of these premenopausal vegetarian and nonvegetarian women did not appear to have major effects on bone biology or reproductive history.

Adult↗

Three-dimensional quantitative CT of the proximal femur: relationship to vertebral trabecular bone density in postmenopausal women.

Dual-photon absorptiometry (DPA) of the proximal femur cannot independently measure cortical and high-turnover cancellous bone. In this investigation, integrated cancellous, cortical, and total bone densities in the femoral neck and intertrochanteric region were measured bilaterally in 22 women aged 42-75 years. Contiguous section data were analyzed with two different protocols by means of three-dimensional histogram software. Single-section quantitative computed tomography (CT) was used to determine mean mineral equivalent values for vertebral cancellous bone from T-11 to L-3 in each woman. Significant correlation was found between cancellous bone density at the two sites, as well as between total femoral and vertebral measurements. Femoral cortical bone density was predicted less well by means of the vertebral cancellous data. Cortical, cancellous, and total proximal femoral density values tended to exhibit bilateral symmetry. Quantitative three-dimensional volumetric CT affords comprehensive evaluation of proximal femoral mineral status because of its capability for selective measurement of cortical, cancellous, and total bone density.

Absorptiometry, Photon↗

The effects of bone density and disc degeneration on the structural property distributions in the lower lumbar vertebral endplates.

In this study, we hypothesized that vertebral bone density and disc degeneration would affect the structural property distributions of the lower lumbar vertebral endplates (L3-L5). The results may have implications for improving interbody implant designs to better resist subsidence. A 3 mm diameter hemispherical indenter was used to perform indentation tests at 0.2 mm/s to a depth of 3 mm at 27 standardized locations in 55 bony endplates of intact human lumbar vertebrae (L3-L5). The resulting load-displacement curves were used to extract the failure load and stiffness of each test site. Bone density was measured using lateral DEXA scans. Disc condition was determined using a four-point grading scale. Three-way analyses of variance were used to analyze the relationships between the data. The overall failure load decreased with bone mineral density (BMD) in the superior (p < 0.0001) and inferior (p = 0.011) lumbar endplates. In both endplates, the posterolateral regions were significantly stronger than more central regions. With increasing BMD, this difference became more pronounced in the superior endplates only (p = 0.005). Increased disc degeneration was associated with an overall failure load decrease in the inferior lumbar endplates (p = 0.002). The strength in the central regions of the superior endplates was reduced with increasing degeneration, but this was not observed peripherally (p = 0.001). Stiffness magnitude or distribution was not significantly affected by BMD or disc degeneration. The locations of the strongest regions of the endplate did not change with either bone density or disc degeneration. This implies that implant shapes designed using the basic structural property maps for the L3-L5 endplates are appropriate for use in patients with a wide range of pathologies, even though overall failure loads are generally lower in patients with reduced bone density and greater degrees of disc degeneration.

Absorptiometry, Photon↗

Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density.

OBJECTIVE: To determine if plasma levels of Interleukin-6 (IL-6) across the lifespan correlate with bone density or plasma osteocalcin. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-five healthy community-dwelling volunteers aged 25-74 years. Exclusion criteria were smoking use of medications known to affect bone metabolism (corticosteroids, heparin, thyroxine, thiazides, and anticonvulsants), and presence of chronic inflammatory disease. MEASUREMENTS: Bone density was measured by dual-energy X-ray absorptiometry at the femoral neck and lumbar spine. Plasma levels of IL-6 and osteocalcin were determined by ELISA and RIA, respectively. RESULTS: Plasma levels of IL-6 increased with advancing age (P < .0001) and correlated with postmenopausal status (P < .0001). No correlation was observed between plasma IL-6 level and bone mineral density at either the lumbar spine or femoral neck, and none was observed with plasma osteocalcin. CONCLUSIONS: The elevation of plasma IL-6 observed following menopause is consistent with the proposed importance of estrogen in the regulation of IL-6. These findings do not provide support for a role of IL-6 in determination of peak bone density or subsequent development of osteoporosis. However, it is possible that plasma levels of IL-6 differ from those in the bone microenvironment.

Absorptiometry, Photon↗

The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women.

SUMMARY: We performed a 2-year extension of our previous 2-year randomized controlled trial of the effects of hydrochlorothiazide on bone mineral density. The improvements in bone density seen in the first 2 years were sustained throughout the extension study. Thiazides provide a further option in the prevention of postmenopausal bone loss. INTRODUCTION: Thiazide diuretics reduce urinary calcium excretion and therefore might prevent osteoporosis. Previously we reported a 2-year randomized controlled trial of hydrochlorothiazide treatment in 185 postmenopausal women that showed positive benefits of hydrochlorothiazide on bone density. Here, we report the results of a 2-year extension to that study. METHODS: Of 185 healthy postmenopausal women, 122 agreed to continue in a double-blinded 2-year extension taking 50 mg hydrochlorothiazide or placebo daily. Measurements of bone density occurred every 6 months and of calcium metabolism at 2 and 4 years. RESULTS: The improvements in bone density seen in the first 2 years of the trial were sustained throughout the extension. There were significant between-groups differences in the change in bone density over 4 years at the total body (0.9%, P<0.001), legs (1.0%, P=0.002), mid-forearm (1.1%, P=0.03), and ultradistal forearm (1.4%, P=0.04). At the lumbar spine (0.9%, P=0.76) and femoral neck (0.4%, P=0.53) the between-groups differences did not reach statistical significance. CONCLUSIONS: Hydrochlorothiazide produces small positive benefits on cortical bone density that are sustained for at least the first 4 years of treatment. They provide a further option in the prevention of postmenopausal bone loss, especially for women with hypertension or a history of kidney stones.

Blood Chemical Analysis↗

Measurement of bone density by gas displacement.

Small bone volumes, porous and irregular structured objects with volumes 0.05-2 cm3, were measured by differential pressure of displaced air. The differential air pressure was measured by a piezoelectric resistor pressure gauge. The gas-displacement system was used to measure the volumes of 234 bone specimens for calculation of bone density. The operation of the system, calibration, sensitivity, and errors of measurement are described.

Animals↗

A Romanian instrument to facilitate bone density measurement indication in postmenopausal women.

UNLABELLED: The aim of the study is to find and valid a clinical instrument which identifies the women that need a bone density measurement because of their high risk for osteoporosis. MATERIAL AND METHOD: A number of 356 women were enrolled in this study. They filled in a study formular and their bone density was measured by DEXA exam (dual energy X-ray absorbtiometry) in the lumbar spine and proximal femur. Statistical correlations between the dependent variable minimal T-score and the other variables (clinical risk factors) were established. The most significant osteoporosis risk factor were included in a classification tree for the dependent variable minimal T-score with 5 splits, 5 independent splitting variables and 6 terminal knots. RESULTS: The most significant osteoporosis predictors included in our classification tree are: current weight, decreasing of height, sedentary life, alcohol consumption, number of deliveries. In predicting osteoporosis, the classification tree has high values both for sensitivity and for specificity (88.2%, respectively 74.11%).The osteoporosis prevalence is very high (74.34%) within the group predicted as having osteoporosis (53.7% of all women). The osteoporosis prevalence was 11% within the group predicted as having osteopenia. CONCLUSIONS: The classification tree facilitates a bone density measurement strategy and establishes the criteria for initiation of the treatment in high risk osteoporosis cases. It allows postponing the DEXA-exam for low risk women and selective measurement of the bone density for intermediar osteoporosis risk women.

Absorptiometry, Photon↗

Exercise patterns and trabecular bone density in college women.

To assess the effects of physical activity patterns on trabecular bone density in college women, we studied three groups of nonsmoking eumenorrheic women with different (but chronic) exercise regimens. There were nine sedentary (SED) women exercising less than 1 h/week, nine women who performed aerobic (AER) exercise greater than 2.5 h/week, and nine women who supplemented aerobics with muscle-building activities (MB) for more than 1 h/week. Resting energy expenditure, calorie, protein, and calcium intake, total body weight, and body mass index were not statistically different among the three groups. AER and SED women had similar lumbar bone mineral density (BMD). MB women had significantly greater spinal bone density (p less than 0.007 versus SED, AER). IGF-1 (insulin-like growth factor) concentrations were greatest in MB (p less than 0.01), and hours muscle building per week correlated with IGF-1 (r = 0.86, p less than 0.03). For all 27 women (mean age 24.5 years), body mass index was the single best predictor of lumbar BMD (r = 0.42, p less than 0.03); hours in muscle-building exercise per week conferred an additive effect on lumbar BMD. This cross-sectional study of young women suggests chronic muscle-building exercises may augment lumbar bone mass. The additive effect of anaerobic exercise on bone density may be mediated by both local weight-bearing changes and possible systemic factors.

Adult↗

Age and loss of bone density in pre-menopausal women.

Some studies have suggested that premenopausal women show a decline in bone mass in function of age while other studies have not. Bone density in the spinal column and proximal femur (neck, Ward's triangle and trochanter) in 75 healthy white women between the ages of 30 and 49 without a history of irregular menstrual periods was correlated with age, weight, height and body mass. No statistically significant decline in bone density with age was seen during the premenopausal period. There was a positive correlation between bone density in the spine and proximal femur and weight and body mass indices. Our results suggest that healthy women do not show loss before menopause and it also seems that obesity has a favorable effect on these women's bone mass.

Absorptiometry, Photon↗

Effects of long-term use of high-dose inhaled steroids on bone density and calcium metabolism.

BACKGROUND: Inhaled steroids are the mainstay in the antiinflammatory treatment of asthma. In the last few years, these agents have been used in increasing doses. Because high doses of inhaled steroids can reduce serum osteocalcin levels, there are concerns regarding their long-term effects on bone metabolism. METHODS: We examined the effects of doses of 800 micrograms/day or greater of beclomethasone or budesonide for more than 18 months in 37 asthmatic subjects (group A), matched to a control group of 37 asthmatic subjects using little or no inhaled steroids (< 500 micrograms, group B). All had a clinical evaluation, measurements of expiratory flows, and determination of serum creatinine, calcium, phosphate, gamma-glutamyl transpeptidase, alkaline phosphatase, cortisol, and osteocalcin levels. A 2-hour urinary sample was obtained for creatinine, calcium, phosphate, hydroxyproline, and cortisol measurements. Bone density was assessed at the lumbar spine level and at the hip with a Hologic-QDR-2000 osteodensitometer (Hologic, Boston, Mass.). RESULTS: The mean (+/- SD) daily dose of inhaled steroids over the last 2 years was 1140 +/- 353 micrograms in group A (mean duration of use of > 800 micrograms/day, 34.2 +/- 13.0 months) and 89 +/- 98 micrograms for group B (mean duration of use of < 500 micrograms/day, 15.7 +/- 18.8 months). The number of oral steroid treatments (< 15 days) during the last 2 years was small in the two groups, 0.92 +/- 1.27 in group A and 0.05 +/- 0.23 in group B (p > 0.05). The only differences between our two groups in terms of serum or urinary parameters were for mean osteocalcin level, which was lower in group A (2.16 +/- 1.09 ng/ml) than in group B (2.70 +/- 0.98 ng/ml) (p = 0.029), and in mean urinary phosphorous level, which was higher in group A (1.44 +/- 0.76 mmol/2 hr) than in group B (1.26 +/- 0.89 mmol/2 hr (p = 0.034). Mean urinary hydroxyproline levels were 15.51 +/- 6.98 mumol/2 hr in group A and 13.53 +/- 7.13 mumol/2 hr in group B (p > 0.05). Mean mineral bone densities of the lumbar spine and hip were similar in the two groups with values of 0.923 +/- 0.136 gm/cm2 and 0.719 +/- 0.147 gm/cm2 in group A and 0.933 +/- 0.154 gm/cm2 and 0.694 +/- 0.095 gm/cm2 in group B (p > 0.05). The T and Z scores for lumbar spine were -1.32 +/- 1.22 and -0.85 +/- 1.02 in group A and -1.19 +/- 1.33 and -0.72 +/- 1.08 in group B (p > 0.05). There was no correlation between the duration or dose of steroid use and bone density or osteocalcin. Although the serum osteocalcin level was lower in the group of subjects using high-dose inhaled steroids, suggesting an osteoblastic depression, bone density was not significantly different compared with the control group. CONCLUSIONS: This study shows that although the serum osteocalcin level was lower and the urinary phosphorus level was higher in subjects using high-dose inhaled steroids for a mean of 34 months, compared with a control group, no significant difference in bone density or other markers of bone metabolism was found between the two groups.

Administration, Inhalation↗

The influence of partial gastrectomy on biochemical parameters of bone metabolism and bone density.

Since it has been suggested that gastric resections are followed by changes in bone metabolism, the aim of our study was to determine the biochemical parameters of bone metabolism and radial and lumbar bone density in 15 male ulcus patients treated by partial gastrectomy (Billroth II). Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography was statistically significantly lower (P less than 0.04) in the patient group, whereas the peripheral bone mass of the distal part of the nondominant forearm measured by single-photon absorptiometry showed no statistically significant difference. In addition, a marked increase in alkaline phosphatase (P less than 0.002) and urinary excretion of hydroxyproline (P less than 0.003) was found in gastrectomy group, whereas the 25-hydroxy-vitamin D levels were found to be significantly decreased (P less than 0.04). Osteocalcin, a biochemical marker for osteoblast activity, and the carboxy-terminal propeptide of type I procollagen (PICP), a marker of collagen formation, were slightly but not significantly higher in gastrectomy-treated patients. The serum parathyroid hormone levels were similar in both groups. As none of the patients had any radiologic evidence of osteopenia, the changes in biochemical parameters of bone metabolism and bone mass in patients who had undergone partial gastrectomy could be a marker of latent bone loss.

Absorptiometry, Photon↗

The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. OBJECTIVE: The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. DESIGN: Women aged 49-65 y (n = 205) were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. RESULTS: Loss of lumbar spine bone mineral content and bone mineral density was significantly (P = 0.04 and P = 0.03, respectively) lower in the women taking the isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased (P = 0.04 and P = 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I, respectively) in the intervention group compared with placebo in postmenopausal women. Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant. CONCLUSION: These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women.

Aged↗

Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group.

To determine whether measurement of bone density predicts hip fracture in women, we prospectively studied 9703 nonblack women aged 65 years and older who had measurements of bone mineral density using single-photon absorptiometry in the calcaneus, distal radius, and proximal radius. During an average of 1.6 years of follow-up, 53 hip fractures occurred. The risk of hip fracture was inversely related to bone density at all three measurement sites. After adjusting for age, the relative risk of hip fracture was 1.66 for a decrease of 1 SD in the bone density at the calcaneus (95% confidence interval, 1.22 to 2.26), 1.55 (95% confidence interval, 1.13 to 2.11) at the distal radius, and 1.41 (95% confidence interval, 1.06 to 1.88) at the proximal radius. None of the three measurements was a significantly better predictor of hip fracture than the others. After adjusting for bone mineral density, the risk of hip fracture doubled for each 10-year increase in age (relative risk, 2.09; 95% confidence interval, 1.31 to 3.33). We conclude that decreased bone density in the appendicular skeleton is associated with an increased risk of hip fracture, but this accounts for only part of the age-related increase in risk of hip fracture among older women.

Age Factors↗

Mother-daughter pairs: spinal and femoral bone densities and dietary intakes.

Bone mineral density (BMD) of the lumbar spine (L1-L4) and femur (femoral neck, Ward's triangle, and trochanter) was measured in 37 healthy, white mother-daughter pairs by dual-photon absorptiometry. Mothers and daughters were aged 52 +/- 7 and 25 +/- 4 y (mean +/- SD), respectively. Three-day dietary intakes were evaluated. Significant correlations between mother-daughter pairs for BMD of all lumbar and femoral areas [except for L2 (r = 0.26, P = 0.054)] indicated familial resemblances in bone mineralization. Total calcium intake was significantly correlated with three BMD values for the daughters (L2, femoral neck, and trochanter) but not for the mothers. When mothers were classified as pre- (n = 20) or postmenopausal (n = 17), correlation coefficients for BMD were higher for premenopausal mothers and their daughters and lower for postmenopausal mothers and their daughters, except for the trochanter. The results suggest that the nature of inheritance of bone mass of women may have at least two components, one influencing the level of peak bone mass and one related to bone loss at menopause.

Absorptiometry, Photon↗