Biomedical subjects
V Matkovic
Publications and source records attributed to V Matkovic.
Comparison of absorptiometric evaluations from total-body and local-regional skeletal scans.
The most common measurement sites for dual-energy absorptiometry (DXA) in clinical practice are posteroanterior (PA) spine and femur. However, other skeletal regions may provide different bone density information. The purpose of this study was to establish the least number of DXA measurements needed to obtain complete information about bone. A total of 262 normal female subjects, 8-50, were measured on a Lunar DPX-L scanner under total body, PA spine, lateral spine, and femur protocol. Forearm measurements were performed with a Lunar SP2 single-photon absorptiometry scanner. The various measurements were compared based on a linear regression model. The correlation coefficients for bone mineral density (BMD) between adjacent vertebrae were 0.92-0.95, and the associated standard errors of the estimate (SEE) were 4.5-5.5%. Total-body BMD can best predict BMD of the trunk, arms, and legs (SEE<4.3%), but least that of the lateral view of the spine (SEE>13.9%). BMD values of the leg from total-body scans predict those from the femoral neck with an error of 9.0%, and those of the trochanteric region with 11.1%. The error between adjacent vertebrae (6%) is considered acceptable, then a total-body measurement combined with a lateral view of the spine and a femur scan are adequate.
Relation of nutrition, body composition and physical activity to skeletal development: a cross-sectional study in preadolescent females.
OBJECTIVE: To examine the relation of anthropometric and growth parameters (weight, stature, body composition, age, and skeletal age), nutritional factors, and physical activity to the total body and radius bone mineral density and content and radiogrammetry parameters of the second metacarpal. STUDY DESIGN: The study was a cross-sectional evaluation of 456 healthy, Caucasian girls, ages 8 to 13 years. Multiple regression models were created based on Cp statistics to determine the association between bone parameters and various independent variables. RESULTS: Mean calcium intake was 956+/-381 mg/day, about 20% below the RDA of 1200 mg/day and about 36% below the threshold intake of approximately 1500 mg/day. The most significant predictors for total body and radius bone mineral density were corresponding bone areas, lean body mass, body fat, skeletal age, dietary calcium, and stature (only for total body) with corresponding R2(adjusted) of 48% and 36%. The total body and radius bone mineral content was positively associated with corresponding bone areas, lean body mass, body fat, calcium intake, and skeletal age with corresponding R2(adjusted) of 86% and 72%. Energy expenditure (corrected for BMI) was stratified into quartiles and bone mass parameters were distributed accordingly. A statistically significant difference in total body and radius bone mineral density and content was noted between the fourth and lower quartiles (ANOVA, p<0.05 to p<0.0001). CONCLUSION: The most significant predictors of bone mass in preadolescent females evaluated in this study are bone area, lean body mass, body fat, skeletal age and dietary calcium.
Iron status, menarche, and calcium supplementation in adolescent girls.
The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.
Calcitriol and bone mass accumulation in females during puberty.
Adolescence is characterized by rapid skeletal development and high demands for bone minerals. Though the stimulative effect of calcitriol on intestinal calcium and phosphorus absorption is well understood, its effect on bone development is not completely clear. It may be directly involved in the facilitation of calcium economy during this critical phase of skeletal development. Therefore, we evaluated the serum concentrations of calcitriol in relation to skeletal development in a cross-sectional study of 178 healthy Caucasian females during different pubertal stages, extending from childhood to young adulthood. In addition, a subsample of 57 younger girls was followed for a 1-year period to evaluate the association among serum calcitriol, nutrition parameters (dietary calcium, phosphorus, and vitamin D), bone mass accumulation, and biochemical markers of bone turnover. The serum calcitriol concentration in a cross-sectional sample was the highest during pubertal growth spurt (sexual maturity index 3-4, age 11-13 years) (ANOVA; F = 2.4945; P = 0.0329). This correlated to the peak skeletal calcium accretion (g/year) and bone mass accumulation in total body and forearm. In a longitudinal sample, there was a positive association between annual change in TBBMC (P = 0.0255); TBBMD (P = 0.0168); proximal radius (1/3 distance from styloid process) BMC (P = 0.0096); BMD (P = 0.0541), and baseline calcitriol level in forward stepwise regression analyses. The results of the forward stepwise regression analyses with serum calcitriol as a dependent variable and different serum, urinary, and dietary parameters measured at baseline (age 11 years, n = 114) and after 1 year (age 12 years, n = 57) showed that osteocalcin was positively associated with calcitriol in both years; more so in a second year (P = 0.0514, P < 0.001, respectively). Dietary vitamin D and phosphorus showed negative association with serum calcitriol at age 11, and dietary Ca and P were selected at age 12. The results of this study show that calcitriol is a significant correlate of bone mass accumulation during pubertal growth, presumably in response to the high requirements for calcium during this critical phase of skeletal development.
Zinc balance in adolescent females consuming a low- or high-calcium diet.
There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.
Leptin is inversely related to age at menarche in human females.
Over the last century there has been a trend toward an earlier onset of menarche attributed to better nutrition and body fatness. With the discovery of the obesity gene and its product, leptin, we reexamined this hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the relation between leptin and bone mass. Body composition and serum leptin levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-ray absorptiometry, and leptin by a new RIA. All participants were premenarcheal at baseline (aged 8.3-13.1 yr). Leptin was strongly associated with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0.58; P < 0.0001). The rise in serum leptin concentration up to the level of 12.2 ng/mL (95% confidence interval, 7.2-16.7) was associated with the decline in age at menarche. An increase of 1 ng/mL in serum leptin lowered the age at menarche by 1 month. A serum leptin level of 12.2 ng/mL corresponded to a relative percent body fat of 29.7%, a body mass index of 22.3, and-body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively related to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001). A critical blood leptin level is necessary to trigger reproductive ability in women, suggesting a threshold effect. Leptin is a mediator between adipose tissue and the gonads. Leptin may also mediate the effect of obesity on bone mass by influencing the periosteal envelope. This may have implications for the development of osteoporosis and osteoarthritis.
Gain in body fat is inversely related to the nocturnal rise in serum leptin level in young females.
Both genetic and environmental factors contribute to adolescent obesity. Evidence of a genetic basis for obesity development is substantial, although the exact mechanism of action has yet to be identified. The purpose of this study was to document the circadian rhythmicity of the serum leptin level in young females and to assess the impact of the change in body fat stores during growth on the nocturnal rise in the serum leptin level with implications for obesity traits. There was a significant rise in serum leptin at midnight and 0400 h, suggesting a diurnal variation in serum leptin concentrations (ANOVA F ratio = 6.2; P < 0.0001). There was also a strong association between relative total body fat and the average daytime serum leptin level (r = 0.78; P < 0.0001). The percent increase in the nocturnal leptin concentration was inversely related to the percent gain in total body fat (r = 0.45; P < 0.024). Forward stepwise regression analysis selected the change in total body fat over a 6-month interval as the most powerful determinant of the percent increase in the nocturnal leptin concentration (partial R2 = 0.203; beta = -0.450; SE of beta = 0.186; t = -2.418; P < 0.024). If the lack of a nocturnal rise in serum leptin persists over a longer period of time, it may have implications for the development of obesity, presumably by inadequate suppression of nighttime appetite.
Skeletal age as a determinant of bone mass in preadolescent females.
OBJECTIVE: To evaluate the association between chronological age, skeletal age, pubertal stage, and basic anthropometry with bone mass of the total body, forearm, and second metacarpal bone in 456 healthy Caucasian females, aged 8-13 years. DESIGN: Total body and forearm bone measurements were performed by dual X-ray absorptiometry, while bone mass of the second metacarpal was assessed by radiogrammetry. Skeletal age (SA) was assessed by the FELS method and pubertal stage was self-determined by selecting corresponding illustrations of breast and public hair development. The Cp criterion was used to select the best multiple regression model containing the subset of independent variables with the least bias and best predictive ability for each of the measured bone mass variables. RESULTS: Of all the independent variables, weight, stature, and SA emerged as the most significant predictors for almost all the bone mass variables. Multiple regression models were created based on the Cp criterion with the resulting R2 (adjusted) for bone mineral content of total body, proximal forearm, ultradistal forearm, length of second metacarpal, as well as of total, medullary, and cortical areas: 0.793, 0.523, 0.390, 0.602, 0.232, 0.073, and 0.264, respectively. The measured bone variables were also regressed on SA using either quadratic or linear equations, depending on the shape of the cubic splines used for the best curve fitting. Significant positive association (p < 0.0001) of SA and each of the bone variables was noted, the highest being with bone mineral density and content of total body (R2 = 0.176, 0.338) and proximal and ultradistal forearm (R2 = 0.216, 0.203, 0.106, 0.201), respectively, as well as with the length of the second metacarpal bone (R2 = 0.339). Chronological age and pubertal stage did not have statistically significant predictive abilities for bone mass variables in the multiple regression models. CONCLUSIONS: We conclude that skeletal age is a powerful determinant of bone mass in children. It can be used as the criterion for the selection of a biologically homogeneous population with regard to bone mass. This may be important for the design of intervention studies targeting bone mass of children and adolescents.
Nutrition, genetics and skeletal development.
From infancy through young adulthood the activity of bone formation predominates, resulting in a steady accumulation of bone mass. As the rate of growth changes with age, so skeletal modeling progresses through phases of different intensity with time. This is paralleled by concomitant changes in bone and calcium metabolism. Bone modeling and skeletal consolidation probably result from a complex sequence of hormonal changes in interaction with nutritional factors. However, current knowledge of the role, sequence, and genetic regulation of hormonal events during puberty, and of the response of bone tissue in interaction with nutrition is limited. This interaction is now beginning to be elucidated. The importance of this interaction with regard to fracture epidemiology in children and peak bone mass acquisition has been discussed.
Magnesium balance in adolescent females consuming a low- or high-calcium diet.
Increasing emphasis is being placed on optimizing calcium intake during growth as a way to enhance peak bone mass. Although some studies in adults have shown that high calcium intake may negatively affect magnesium utilization, few data are available regarding the interaction of calcium and magnesium in healthy children. The purpose of our study was to measure the effect of calcium intake on magnesium balance in 26 adolescent girls (mean age 11.3 y) during a 14-d period. Subjects ate a controlled basal diet containing 667 mg Ca and 176 mg Mg. In addition to the basal diet, subjects were randomly assigned in a double-blind fashion to consume 1000 mg elemental Ca/d as calcium citrate malate or a placebo. Magnesium use did not differ between the low-calcium and high-calcium groups as measured by absorption (50% compared with 55%), urinary excretion (70 compared with 74 mg/d), and fecal excretion (88 compared with 79 mg/d). Accordingly, magnesium balance was not different in subjects consuming 667 or 1667 mg Ca/d and averaged 21 mg Mg/d for the whole study group. Magnesium balance was significantly correlated with magnesium intake (r = 0.511, P = 0.008) and magnesium absorption (r = 0.723, P < 0.001). Prediction intervals from the regression of magnesium balance on intake indicated that the current recommended dietary allowance of magnesium would result in magnesium balance > or = 8.5 mg/d in 95% of the girls. This value appears consistent with long-term accretion rates needed to account for the expansion of the total-body magnesium pool during growth. In summary, our observations support the adequacy of the current recommended dietary allowance for magnesium and indicate that alterations in magnesium utilization should not be anticipated in adolescent females consuming a high-calcium diet.
Skeletal development and bone turnover revisited.
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Urinary calcium, sodium, and bone mass of young females.
Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of gallium nitrate on osteopenia induced by ovariectomy and a low-calcium diet in rats.
The effects of gallium nitrate (GN) were evaluated on osteopenia induced by ovariectomy (OVX) and a low-calcium diet (LCD) in Sprague-Dawley rats. Twenty-five rats (300-400 g) were randomized into four groups of 5-7 animals: (I) OVX LCD treated with GN for 22 weeks; (II) OVX LCD treated with GN for 10 weeks; (III) OVX LCD treated with saline; and (IV) sham-operated (SO), normal diet, treated with saline. GN-treated rats received a 30-mg/kg subcutaneous single dose of elemental gallium, followed by 10 mg/kg per week, whereas control animals received an equal volume of saline. All animals were euthanized at 22 weeks. Measurements of bone density and histomorphometry, performed on the proximal portion of the tibia, indicated significant bone loss in all OVX LCD animals. GN-treated rats in group I gained significantly less weight than those in the other groups, and their blood urea nitrogen increased, suggesting a nephrotoxic effect. After discontinuation of GN, rats in group II gained weight at the same rate as those which had received only saline. Bone formation rates in the GN-treated rats were double those of the saline-treated OVX animals and more than 10 times those of SO controls. Although the bone formation rate in GN-treated rats increased, GN had no effect in preventing the loss of bone surface, density and volume induced by OVX LCD. These findings suggest that although GN may enhance osteoblastic activity, this agent alone does not appear effective in the prevention of bone loss induced by OVX LCD.
Supplementation trials with calcium citrate malate: evidence in favor of increasing the calcium RDA during childhood and adolescence.
The vast majority of peak adult bone mass is accumulated by the time longitudinal growth is complete. As peak bone mass is an important determinant of future fracture risk, the goal of the current calcium recommended dietary allowance during youth is to provide a calcium intake that allows individuals to reach their full genetic potential for acquiring skeletal mass. The advent of controlled trials of calcium supplementation and total body bone mass measurements in children and adolescents provide the first direct way of determining the amount of calcium necessary to achieve optimal skeletal accretion. These studies indicate that the current RDAs are insufficient to support optimal bone mass gain during growth and development. Based on the recent intervention trials, recommendations are made for an RDA of 1250 mg during childhood and 1450 mg during adolescence. These values are consistent with established calcium balance intake thresholds for growth during pre-adolescence and adolescence.
Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model.
To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result of continuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized.
Influence of age, sex and diet on bone mass and fracture rate.
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Calcium requirements for growth: are current recommendations adequate?
Peak adult bone mass is determined in each individual by a combination of endogenous and environmental factors. Insufficient accumulation of skeletal mass by the time young adulthood is reached appears to enhance the likelihood of fractures later in life. It is speculated that environment (nutrition and exercise) contributes to about 20% of the variance in bone mass. Although much is yet to be learned about how diet contributes to skeletal growth and development, it now appears that calcium intake may be an important factor in the attainment of peak bone mass. A review of the scientific literature suggests that the current recommended dietary allowance (RDA) for calcium may not be high enough to optimize the genetically programmed peak bone mass in a substantial number of growing individuals. New standards for dietary calcium intakes during growth may be indicated.