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Biomedical subjects

R R Recker

Publications and source records attributed to R R Recker.

At least 127 records · Page 7Linked to original sources

Normal vertebral dimensions and normal variation in serial measurements of vertebrae.

A total of 568 lateral spine radiographs of 191 generally healthy white perimenopausal women were used to determine the limits of normal for shape and dimensions of the vertebral bodies most often involved in osteoporotic fracture. Anterior and posterior vertebral heights for T7-L4 were used to compute wedge shape, relative posterior height, and relative serial change. Wedge shape was defined as anterior height minus posterior height divided by posterior height. Relative posterior height was defined as the posterior height of a vertebra minus the posterior height of the vertebra superior divided by the posterior height of the vertebra superior. The degree of normal wedging depended on position: wedge values progressed down the spine, from a mean of -0.106 at T7 to 0.048 at L4. The minimum normal wedge value ranged from -0.209 at T7 to -0.083 at L4. Radiographs on a cohort of 28 osteoporotic women were evaluated both by ordinary clinical reading of the radiographs and by using the standards developed from the normal subjects. Initial agreement between the two modes of assessment was 85.4%, and in resolving the remaining disagreements the clinician agreed that he had initially misread the films in all but 3.2%. On the basis of this limited experience, we conclude that the use of such objective standards, in a computer-operated algorithm, is more accurate than routine radiographic assessment. Serial x-rays spanning a 15-20 year period in these women permitted determination of both reproducibility and longitudinal change in vertebral dimensions in the perimenopause. The mean relative serial change was not significantly different from zero for all vertebrae.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗

Calcium absorption in women: relationships to calcium intake, estrogen status, and age.

A total of 526 absorption studies, using both the double-isotope and balance-based methods, were performed in 189 middle-aged women in good general health. The study extended over 17 years of observation, with most subjects studied from two to four times at 5 year intervals. Each study was done on the woman's own self-selected calcium intake and was carried out under inpatient, metabolic balance controls. There was a highly significant inverse correlation between calcium intake and absorption fraction, with the best fit provided by an hyperbola in which absorption fraction is approximately inversely proportional to the square root of intake. The range of absorptive performance was very broad at all intake levels. Mean absorption fraction declined from a value of 0.45 at very low intakes (approximately 200 mg Ca per day) to approximately 0.15 at intakes above 2000 mg/day. There was a highly significant fall in absorption efficiency with age, amounting to approximately 0.0021 per year and a one-time decrease, amounting to approximately 0.022 at the time of menopausal estrogen loss.

Absorption↗

Time course of calcium absorption in humans: evidence for a colonic component.

We examined the time course of calcium absorption (CaAbs) in 155 studies, using a double isotope technique. The subjects were 118 healthy peri-menopausal women (mean age 53.3 years), studied as inpatients under metabolic balance conditions. We measured the ratio of radiolabeled calcium (oral:IV) in serum and urine for 144 hours after the oral dose, and generated a composite CaAbs curve for all 155 studies using normalized data. Although CaAbs was 80.9% complete at 3 hours, it was still only 95.8% complete at 7 hours; the remaining 4.2% was absorbed in a slower late component, and did not reach completion until about 26 hours. The rapid initial component probably represents mainly small intestinal absorption and the late component, colonic. At the dietary intakes of our subjects, we estimate the size of the late component at about 6.8 mg/day. For fully accurate measurements of CaAbs, it is necessary to allow for this small late component.

Calcium Radioisotopes↗

Meal effects on calcium absorption.

The effect of coingestion of a meal on calcium absorption efficiency was investigated using Ca carbonate, milk, and a new Ca delivery system, CCM. Six experiments with 168 rats and two experiments with 46 normal young women showed that coingestion of a light meal of varied composition enhanced absorption efficiency from all three sources by 10-30% above levels achieved when the test load was ingested without other foods. The differences taken as a whole were highly statistically significant.

Adult↗

Low bone mass may not be the only cause of skeletal fragility in osteoporosis.

Skeletal fragility in postmenopausal osteoporosis is not due solely to reduction in bone mass. This fact explains some of the overlap in bone mineral measurements observed between patients who are fracturing and age- and sex-matched normals who are not. Changes in skeletal architecture and bone remodeling occur with age which can account for some of the fragility. These changes are exaggerated in patients with postmenopausal osteoporosis who are suffering spine fractures. Three abnormalities have been described by histomorphometric methods which can account for skeletal fragility out of proportion to the degree of bone loss. They are: (i) loss of trabecular connectivity such that vertical weight-bearing bars lose their cross-attachments with each other, thus becoming susceptible to buckling; (ii) inefficient and prolonged microdamage repair due to periods of pause in the formation phase of remodeling; and (iii) accumulation of unrepaired microdamage in unremodeled bone tissue in the central part of trabeculae due to reduced osteon wall thickness coupled with maintenance of trabecular thickness. Recognition of these abnormalities should broaden our approach to the study of skeletal fragility in the syndrome of postmenopausal osteoporosis.

Biomechanical Phenomena↗

Static and tetracycline-based bone histomorphometric data from 34 normal postmenopausal females.

Transilial bone biopsies were obtained from 34 healthy postmenopausal women following in vivo fluorochrome labeling. Stained and unstained undecalcified sections were evaluated using a Merz grid. Standard histomorphometric data from cancellous bone tissue were collected and the results were evaluated and presented as variables commonly used in bone histomorphometry. The normal ranges, medians, means, and standard deviations for the group of 34 are presented in tabular form for structural, surface, basic dynamic, and derived dynamic data. Similar data for individuals grouped by ages 45-54, 55-64, and 65-74 are also presented. Secular trends for the whole group are evaluated. The structural and surface data are not much different from previous reports of sudden-death accident victims, when methodologic differences are considered. The mineral apposition rate (MAR) was 0.53 +/- 0.08 micron/day, similar to previous reports in cancellous bone, but one-third less than in cortical bone. MAR showed a marked decline with age. In contrast, the extent of tetracycline-labeled surfaces varied widely without a secular trend. Double-label surface (dLS/BS) ranged from 0.5 to 8.0% and single-label surface (sLS/BS), from 0.5 to 10.5%. Mineralizing osteoid surface (MS/OS) varied from 2 to 64%. Using only double-label surface to represent mineralizing surface, volume-based bone formation rate (BFR/BV) ranged from 0.7 to 28%/yr, and the remodeling period (Rm.P) varied from 0.28 to 4.5 years. Calculations using other representations of mineralizing surface [double plus one-half single label (MS/BS"); all label (MS/BS')] are also presented. These bone histomorphometric data are important because: (1) they come from a cohort of living subjects that was recruited solely for the purpose of establishing normal bone histomorphometry; (2) they represent the age range of patients with postmenopausal osteoporosis; and (3) they markedly expand the bone histomorphometric database of healthy persons given in vivo fluorochrome labeling prior to transilial biopsy.

Aged↗

Calcium absorbability from milk products, an imitation milk, and calcium carbonate.

Whole milk, chocolate milk, yogurt, imitation milk (prepared from dairy and nondairy products), cheese, and calcium carbonate were labeled with 45Ca and administered as a series of test meals to 10 healthy postmenopausal women. Carrier Ca content of the test meals was held constant at 250 mg and subjects fasted before each meal. The absorbability of Ca from the six sources was compared by measuring fractional absorption by the double isotope method. The mean absorption values for all six sources were tightly clustered between 21 and 26% and none was significantly different from the others using one-way analysis of variance. We conclude that none of the sources was significantly superior or inferior to the others.

Absorption↗

Variability of calcium absorption.

Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption.

Absorption↗

Calcium absorbability from spinach.

The absorbability of calcium from spinach was compared with the absorbability of Ca from milk in 13 healthy adults in a randomized cross-over design in which the test meal of either milk or spinach had 200 mg of Ca labeled with 45Ca. Absorption was measured by the standard double-isotope method in which both the test food and the miscible Ca pool are labeled with different Ca tracers. Measurement of both Ca and oxalate in our test spinach revealed a very slight stoichiometric excess of oxalate; hence it is likely that all of the spinach Ca was effectively bound. Absorption was higher from milk in every case, with the mean absorption from milk averaging 27.6% and from spinach, 5.1%. The mean within-subject difference between Ca absorption from milk and from spinach was 22.5 +/- 9.5% (P less than 0.0001). These results conclusively establish that spinach Ca is much less readily available than milk Ca.

Adult↗

The proportion of trabecular bone in human vertebrae.

The proportion of trabecular bone in human cadaver vertebrae was assessed by anatomic dissection. Thirty-two whole thoracic and lumbar vertebrae were obtained from 10 normal human postmenopausal female cadavers, 14 from 4 normal adult human male cadavers of similar age, and 8 from one female osteoporotic cadaver. Each vertebra was opened by saw cuts and separated into four tissue types: (1) body trabecular bone and marrow; (2) body cortical bone; (3) vertebral arch trabecular bone and marrow; and (4) vertebral arch cortical bone. Calcium was determined in each tissue type for each vertebra by ashing and atomic absorption spectrophotometry. Trabeculae accounted for 24.4 +/- 4.5% of the total calcium in whole female vertebrae, and 18.8 +/- 4.4% in whole male vertebrae (p less than 0.001). The body averaged 41.8% trabecular bone in females and 33.5% in males. The arch averaged 9.7% trabecular bone in females and 4.9% in males. The proportion of trabecular bone in the whole vertebrae in the single osteoporotic spine was 28.5 +/- 3.2%, a value not significantly different from the trabecular fraction in normal females. These data indicate that whole human thoraco-lumbar vertebrae are composed of a substantially lower proportion of trabecular bone than is usually assumed, and they suggest that cortical and trabecular bone are eventually lost in equal proportion from the vertebrae during the development of spinal osteoporosis. These results are important for the interpretation of data from noninvasive bone measurement techniques that evaluate the spine, and they suggest that studies of this type are important for any site where noninvasive bone mass measurement is done.

Analysis of Variance↗

Calcium supplements: anion effects.

The effects on bone remodeling of two anions commonly associated with calcium in the food and supplement chain (carbonate and phosphate) were evaluated in a pilot study in eight normal premenopausal women. Each woman was studied twice under full metabolic balance controls, once before starting treatment and then a second time after 4 months of treatment with either sodium bicarbonate in a dose providing 3240 mg carbonate daily or a mixture of sodium and potassium phosphates, providing 1144 mg additional phosphorus daily. Intakes of calcium and protein remained approximately constant between studies. Remodeling was measured by paired studies of both whole body calcium kinetics and trans-ilial bone biopsies. The extra phosphate was almost completely absorbed and produced the expected decline in urine calcium. Both anions were associated with slight decreases in intestinal calcium absorption efficiency; however neither anion altered bone remodeling as measured either by radiocalcium kinetics or by histomorphometry. Since the anion doses we used were larger than the average woman is likely to receive from either food or supplement sources, we conclude that neither anion alters bone remodeling in humans to a clinically significant degree. Additionally these findings underscore the essential safety of increased phosphorus intakes and have relevance to the use of phosphate as a remodeling activator in the ADFR (coherence therapy) approach to treatment of osteoporosis.

Adult↗

The label escape error: comparison of measured and theoretical fraction of total bone-trabecular surface covered by single label in normals and patients with osteoporosis.

Thirty-four normal Caucasian women and 69 patients with osteoporosis were given two bone-labeling agents. Transilial biopsies were obtained and embedded undecalcified. Fractional surfaces covered by double label and single label were determined, along with total surface and double label width by fluorescent microscopy. Mean wall thickness was measured on toluidine blue-stained sections. The mathematical model for predicting the amount of single-labeled surface was compared to the actual amount of surface covered by single label. We found an excess of single labels compared to the model in both groups, more so in the normals, and suggest the explanation is that bone-formation pauses at formation sites in both groups but tends not to resume in the patients. This results in a shortened functional life span of the osteoblast and bone loss. Further, the data suggest that for accurate expression of bone formation rates in trabecular bone using a volume referent, one should use the whole bone tissue including bone and marrow and should express the bone-forming surface as the double-labeled surface plus one-half the measured single-labeled surface.

Aged↗

Distribution of calcium absorption in middle-aged women.

Distribution of true fractional absorption of calcium in estrogen-deprived, nonosteoporotic, middle-aged women was examined in 273 person-studies, using a double-tracer method. Fractional absorption averaged 0.266 (+/- 0.096). Calcium intake averaged 0.802 g/day (+/- 0.419) and urine calcium, 0.144 g/day (+/- 0.062). Fractional absorption was inversely correlated with intake. Using parameters of the regression equation for the two variables, each absorption value was adjusted to the mean intake of the group so that absorption could be evaluated apart from the effect of intake. The distribution of such diet-adjusted values revealed that 55% of these estrogen-deprived women had insufficient absorption to maintain calcium balance at an intake equal to the 1980 RDA. Nearly one-fourth would still be in negative balance at an intake of 1.5 g/day. Since urine calcium was positively correlated with absorbed calcium (r = 0.521), we conclude that defective absorption and not bone breakdown is the basis for low absorptive performance in these women.

Absorption↗

Calcium absorption and achlorhydria.

Defective absorption of calcium has been thought to exist in patients with achlorhydria. I compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.

Achlorhydria↗

Placebo therapy for postmenopausal osteoporosis.

Eighteen postmenopausal osteoporotic (PMO) women on placebo therapy were followed for 1 year. Serial measurements of calcium balance and kinetics, bone histomorphometry, photon absorptiometry, and radiogrammetry were obtained. Few significant changes in balance and kinetics or bone histology were seen in these women over time. Photon absorptiometry and radiogrammetry of the femoral cortex showed a significant annual bone loss however. When compared with premenopausal and healthy postmenopausal women, the annual bone loss in those with PMO was significantly greater. The ability of balance studies, photon absorptiometry, and radiogrammetry to predict the magnitude of this bone loss was similar. Finally, there was an illustration of the use of the estimated variance provided by this study for estimating sample size for future studies.

Aged↗