Velimir Matkovic

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.

Calcium metabolism and calcium requirements during skeletal modeling and consolidation of bone mass.

The degree of positive calcium balance in young individuals necessary to achieve peak bone mass and density is unknown. To assess calcium requirements and metabolism during acquisition of peak bone mass, 487 calcium balance studies from published reports were analyzed. The results suggest that 1) calcium intake and skeletal modeling and turnover determine calcium balance during growth, 2) the highest requirements for calcium are during infancy and adolescence and then during childhood and young adulthood, 3) to meet high calcium requirements, infants and adolescents have higher calcium absorption, 4) calcium absorption during rapid bone modeling and turnover is mediated by the Nicolaysens endogenous factor, 5) urinary calcium reaches its maximum by the end of puberty, 6) calcium intake has little influence on urinary calcium excretion during the period of rapid growth, 7) the recommended dietary allowance for calcium should be higher than the amount currently established for children, adolescents, and young adults to ensure a level of skeletal retention of calcium for maximal peak bone mass, and 8) clinical trials with increased calcium intakes in each age segment of young populations are needed to clarify the above trends.

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.

Calcium and Dairy Product Modulation of Lipid Utilization and Energy Expenditure

Objective: The purpose of this study was to investigate the impact of dietary calcium or dairy product intake on total energy expenditure (TEE), fat oxidation, and thermic effect of a meal (TEM) during a weight loss trial.

Femurs from rats fed diets deficient in copper or iron have decreased mechanical strength and altered mineral composition

A study was conducted to evaluate the influence of copper and iron deficiencies upon femur mineral content and biomechanical properties. Radiogrametry and single photon absorptiometry were used to evaluate femur bone mass. Long-Evans male rats were fed purified diets either adequate or deficient in the selected element from weanling until 9 weeks of age. Results demonstrate that in rats fed both the copper and iron restricted diets, the breaking strength was significantly decreased in both femurs. Lower levels of iron and copper were observed in the livers of the respected trace element restricted groups, and femur iron and copper were depressed in both of these groups as well. Femur Cu:Zn was decreased in the copper deficient group and femur zinc levels were elevated in the iron deficient group. Copper and iron restricted rats had smaller cortical and, larger medullary area in a portion of the femur, 1/4 from the distal end, as determined by radiogrametry, but there were no differences at the mid point or proximal portions of the femurs. The influence of iron restriction upon the decreased bone biomechanical strength is a novel finding and deserves further attention, in that iron deficiency anemia is a prevalent public health problem. J. Trace Elem. Exp. Med. 10:197–203, 1997.

Use of gallium to treat Paget's disease of bone: a pilot study

The effects of gallium nitrate on bone turnover were evaluated in four patients with active Pagets disease. Treatment with gallium nitrate (100 mg/m2 daily for 5 days, intravenously in 5% glucose) significantly reduced serum calcium, serum phosphate, urinary calcium, and the ratio of maximum tubular reabsorption of phosphate to glomerular filtration rate in each patient. Serum parathyroid hormone levels rose. The findings suggest that the fall in serum calcium caused secondary hyperparathyroidism, resulting in a fall in serum phosphate. Serum alkaline phosphatase and urinary hydroxyproline levels fell substantially, showing that gallium effectively suppressed bone turnover. The fall in hydroxyproline excretion preceded that in serum alkaline phosphatase, suggesting that suppression of bone resorption by osteoclasts preceded that of bone formation by osteoblasts. Alkaline phosphatase levels remained low throughout follow-up (85-141 days), so the effect of gallium seems to be long-lasting.

Bone Mineral and Predictors of Bone Mass in White, Hispanic, and Asian Early Pubertal Girls

Differences in bone among racial/ethnic groups may be explained by differences in body size and shape. Previous studies have not completely explained differences among white, Asian, and Hispanic groups during growth. To determine racial/ethnic differences and predictors of bone mass in early pubertal girls, we measured bone mineral content (BMC) in white, Hispanic, and Asian sixth-grade girls across six states in the United States. We developed models for predicting BMC for the total-body, distal radius, total-hip, and lumbar spine for 748 subjects. For each of the bone sites, the corresponding area from dual-energy X-ray absorptiometry (DXA) was a strong predictor of BMC, with correlations ranging 0.78–0.98, confirming that larger subjects have more BMC. Anthropometric measures of bone area were nearly as effective as bone area from DXA at predicting BMC. For total-body, distal radius, lumbar spine, and total-hip BMC, racial/ethnic differences were explained by differences in bone area, sexual maturity, physical activity, and dairy calcium intake. Bone size explained most of the racial/ethnic differences in BMC, although behavioral indicators were also significant predictors of BMC.

Skeletal age as a determinant of bone mass in preadolescent females

Abstract 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 pubic hair development. The Cpcriterion 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 Cpcriterion 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.

A comparison of fatigue failure responses of old versus middle-aged lumbar motion segments in simulated flexed lifting

Study Design. Survival analysis techniques were used to compare the fatigue failure responses of elderly motion segments to a middle-aged sample. Objectives. To compare fatigue life of a middle-aged sample of lumbosacral motion segments to a previously tested elderly cohort. An additional objective was to evaluate the influence of bone mineral content on cycles to failure. Summary of Background Data. A previous investigation evaluated fatigue failure responses of 36 elderly lumbosacral motion segments (average age, 81 ± 8 years) subjected to spinal loads estimated when lifting a 9-kg load in 3 torso flexion angles (0°, 22.5°, and 45°). Results demonstrated rapid fatigue failure with increased torso flexion; however, a key limitation of this study was the old age of the specimens. Methods. Each lumbosacral spine was dissected into 3 motion segments (L1–L2, L3–L4, and L5–S1). Motion segments within each spine were randomly assigned to a spinal loading condition corresponding to lifting 9 kg in 3 torso flexion angles (0°, 22.5°, or 45°). Motion segments were statically loaded and allowed to creep for 15 minutes, then cyclically loaded at 0.33 Hz. Fatigue life was taken as the number of cycles to failure (10 mm displacement after creep loading). Results. Compared with the older sample of spines, the middle-aged sample exhibited increased fatigue life (cycles to failure) in all the torso flexion conditions. Increased fatigue life of the middle-aged specimens was associated with the increased bone mineral content (BMC) in younger motion segments (mean ± SD, 30.7 ± 11.1 g per motion segment vs. 27.8 ± 9.4 g). Increasing bone mineral content had a protective influence with each additional gram increasing survival times by approximately 12%. Conclusion. Younger motion segments survive considerably longer when exposed to similar spine loading conditions that simulate repetitive lifting in neutral and flexed torso postures, primarily associated with the increased bone mineral content possessed by younger motion segments. Cycles to failure of young specimens at 22.5° flexion were similar to that of older specimens at 0° flexion, and survivorship of young specimens at 45° flexion was similar to the older cohort at 22.5°.

Suppression of experimental autoimmune encephalomyelitis by gallium nitrate

We examined the effect of gallium (Ga) nitrate on the development of the development of experimental autoimmune encephalomyelitis (EAE). Weekly subcutaneous injections of 10-30 mg/kg prevented clinical signs as well as histopathological changes of EAE. The optimal timing of a single injection of Ga was 6 days after induction of EAE, with amelioration also apparent following a single injection on day 3 or 9 but not day 12. Ga administered in vivo suppressed myelin basic protein (MBP) and purified protein derivative-specific lymphocyte proliferative responses in vitro. Addition of Ga to MBP-specific T lymphocyte line cultures at various times after initiation of culture revealed that Ga exerts an effect at an early stage of cellular activation.