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Biomedical subjects

R R Recker

Publications and source records attributed to R R Recker.

At least 109 records · Page 6Linked to original sources

Long-standing remission after 25-OH D3 treatment in a case of chronic myelomonocytic leukaemia.

This report describes a case of chronic myelomonocytic leukaemia (CMML) in whom a complete remission was achieved and sustained 15 months after treatment with 25-OH vitamin D3. No side-effects were observed. Although vitamin D1 has been used in the treatment of myelodysplastic syndromes, to our knowledge this is the first case of long-standing remission in a patient with CMML. This 'differentiation therapy' might be considered as a possible alternative in the management of this disease.

Aged↗

The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats.

The purpose of this study was to evaluate the dose-effect relationship of recombinant human PTH [hPTH-(1-84)] and synthetic human PTH [sPTH-(1-34)] for the skeleton of estrogen-deplete osteopenic rats. Ex vivo densitometry of regionalized whole femurs and histomorphometry of proximal tibial cancellous bone were the end points. Retired breeder female rats, aged 6-7 months, were used. Ten were killed at baseline, and the rest were ovariectomized (OVX). On day 42, a pre-PTH treatment OVX group was killed. The rest were then treated by daily sc injection with hPTH (0, 1.55, 15.5, or 155 micrograms/kg BW.day) or sPTH (0.55, 5.5, or 55 micrograms/kg BW.day) and killed on day 70. The level of cancellous bone mineral was lower in pretreatment OVX rats than at baseline. It was higher in rats treated with 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH than in pretreatment and vehicle-treated OVX rats. Cancellous bone volume was also lower both 42 and 70 days after OVX. Although hPTH did not affect cancellous bone volume, treatment with 5.5-55 micrograms/kg.day sPTH caused higher bone volume than in either pretreatment or vehicle-treated OVX rats. Trabecular number declined after OVX and did not change with PTH treatment. In contrast, trabecular thickness declined after OVX, but was higher after 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH treatment. In OVX rats, the amount of mineralizing surface was greater by day 42 and fell toward control levels by day 70. It was greater in rats treated with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH than in vehicle-treated OVX rats. On a molar basis, sPTH was modestly more potent than hPTH. Osteoclast surface was not affected by PTH treatment. Treating estrogen-deplete osteopenic adult rats for 28 days with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH increases trabecular thickness, but not trabecular number, to cause a rise in bone mass. The extent of mineralizing surface rises without a change in resorption surface. The marked rise in mineralizing surfaces suggests that extended in vivo treatment with PTH activates osteogenic precursor cells near once quiescent surfaces to become osteoblasts.

Animals↗

Bone gain in young adult women.

OBJECTIVE: To test whether bone mass increases in healthy nonpregnant white women during early adult life after cessation of linear growth; and to test whether various self-chosen levels of physical activity and nutrient intake or use of oral contraceptives influences this increase in bone mass. DESIGN: Longitudinal prospective study of up to 5 years of 156 healthy college-aged women full-time students attending professional schools in universities in the Omaha, Neb, area. SETTING: University medical center. PARTICIPANTS: A convenience sample of healthy women students from Omaha-area professional schools. Any candidate with an illness, condition, or medication (except oral contraceptives) thought to affect general health or bone mass was excluded. INTERVENTIONS: None. OUTCOME MEASURES: Clinical and family histories of disease, particularly osteoporosis; oral contraceptive use; bone mineral densities of the spine, forearm, and total body by dual- and single-photon absorptiometry; estimates of nutrient intake by repeated 7-day diet diaries; and measures of physical activity using a physical activity monitor. RESULTS: The median gain in bone mass for the third decade of life, expressed as a percentage per decade, was 4.8% for the forearm, 5.9% for lumbar bone mineral content, 6.8% for lumbar bone mineral density, and 12.5% for total body bone mass (P < .0001 in all cases). By both bivariate and multiple regression analysis the rate of gain in bone density of the spine was negatively correlated with age and positively correlated with calcium/protein intake ratio and physical activity (multiple r = .31; P = .004). Bivariate analysis showed that use of oral contraceptives was associated with greater gain in total body bone mass (r = .31, P = .01). The estimated age when mineral acquisition ceased ranged from 28.3 years to 29.5 years at the several study sites. CONCLUSIONS: Gain in bone mass occurs in healthy young women during the third decade of life. Physical activity and dietary calcium intake both exert a positive effect on this bone gain. Use of oral contraceptives exerts a further independent positive effect. Changes in life-style among college-aged women, involving relatively modest increases in physical activity and calcium intake, may significantly reduce the risk of osteoporosis late in life.

Absorptiometry, Photon↗

Change in bone mass immediately before menopause.

A group of 75 healthy women nearing menopause were entered into a longitudinal study of bone mass and bone cell function. All were at least 46 years, were still menstruating, and had premenopausal levels of follicle stimulating hormone (FSH) and estradiol (E2). Bone density measurements of the spine (dual-photon absorptiometry, DPA) and total-body (DPA) and forearm (single-photon absorptiometry, SPA) were made at 6 month intervals along with measurements of FSH and E2 over an average of 2.04 +/- 0.45 years. The annual rate of change in bone mass was determined for each individual by regressing the bone mass measurement at each site at the time of observation. The slopes were pooled, and the percentage annual change was calculated as the mean slope divided by the initial mean bone mass value. The mean rates of change in bone mass were calculated with and without weighting by length of observation. No meaningful differences in the results were seen in the weighted values compared to the unweighted values, and none of the sites showed a slope significantly different from zero. Demonstrated reproducibility and sample size provided sufficient power to detect annual weighted rates of change of 0.81% for spine BMC, 0.69% for spine BMD, 1.31% for forearm BMC, 1.55% for forearm BMC/BW, and 1.09% for total body bone mineral. We conclude that if changes in bone mineral are occurring in women at this age, they are substantially less than 1%/year for spine and not much more for the forearm or total skeleton.

Absorptiometry, Photon↗

Fracture risk as determined by prospective and retrospective study designs.

Both retrospectively and prospectively designed studies consistently show low bone mass and/or bone mineral content (BMC) to be risk factor for low-trauma fractures in postmenopausal women. Along with the reports of such studies there has been concern expressed that BMC measurements overlap between fracture groups, i.e., some women with high BMC develop fractures and some women with low BMC do not. In these commonly used epidemiologic study designs, BMC does not discriminate between those who have and have not experienced the untoward event at some level of the exposure factor. The ability to discriminate is more properly determined by the sensitivity and specificity of the measured value. To contrast the concepts of risk and sensitivity, a nested case-control study was conducted within a 24-year cohort study of women at risk for osteoporosis. We found that for each 1.0 decrement of BMC z-scores, the adjusted relative risk for the prospective study design was 1.67, while the odds ratio obtained from the most recent BMC z-score measurements was 1.87. A receiver operating characteristic (ROC) curve, calculated from the nested case-control study data, showed that BMC z-scores, measured after low-trauma fracture, have both low sensitivity and low specificity to detect existing fracture status.

Adult↗

Characterization of in vivo strain in the rat tibia during external application of a four-point bending load.

This paper describes a technique for characterizing strains and stresses induced in vivo in the rat tibia during application of an external four-point bending load. An external load was applied through the muscle and soft tissue with a four-point bending device, to induce strain in a 11 mm section of the right tibiae of ten adult female Sprague-Dawley rats. Induced strains were measured in vivo on the lateral surface of the tibia. Inter-rat difference, leg positioning and strain gage placement were evaluated as sources of variability of applied strains. Beam bending theory was used to predict externally induced in vivo strains. Finite element analysis was used to quantify the magnitude of shear stresses induced by this type of loading. There was a linear relationship between applied load and induced in vivo strains. In vivo strains induced by external loading were linearly correlated (R2 = 0.87) with the strains calculated using beam bending theory. The finite element analysis predicted shear stresses at less than 10% of the longitudinal stresses resulting from four-point bending. Strains predicted along the tibia by finite element analysis and beam bending theory were well-correlated. Inter-rat variability due to tibia size and shape difference was the most important source of variation in induced strain (CV = 21.6%). Leg positioning was less important (CV = 9.5%).

Animals↗

Tallness versus shrinkage: do women shrink with age or grow taller with recent birth date?

This paper presents evidence that much of the high rate of age-related height loss in women reported in cross-sectional studies is actually a cohort effect rather than an aging effect. Data from a large cross-sectional study of healthy, white American women indicate that there has been a gain in peak adult height of 1.0 cm per decade for several decades from 1900 through 1965. Data from the HES, HANES I, and HANES II studies concur on this point. By contrast, data from a longitudinal study of 191 healthy white U.S. women show only a trivial rate of decline from peak adult height in the fifth and sixth decades of life. In an unselected population, some apparent height loss with age is probably due to disease processes, such as vertebral collapse. Caution is needed in using aging to interpret differences in height and in height-dependent variables, such as bone density, in cross-sectional studies.

Adolescent↗

A noninvasive, in vivo model for studying strain adaptive bone modeling.

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.

Adaptation, Physiological↗

Treatment of hypercalcemia of malignancy with intravenous etidronate. A controlled, multicenter study. The Hypercalcemia Study Group.

In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy.

Double-Blind Method↗

Calcium absorptive consistency.

Calcium absorption efficiency was measured two or three times each in 74 premenopausal and 142 postmenopausal women under conditions predicted to alter absorptive performance. A woman's absorptive consistency was evaluated across differing loads, differing intervals, and substances of differing intrinsic absorbability. In all these circumstances there was a statistically significant correlation between a woman's absorption under differing test situations accounting for up to 60% of the variance typically found in cross-sectional studies. For example, when the same substance but at differing load levels was tested three times over an 8 week period, various coefficients of correlation ranged from +0.773 to +0.849 (P less than 0.001). Even over intervals as long as 5 years correlation of absorption fraction within individuals remained significant (r = +0.487, P less than 0.001).

Adult↗

Absorbability of calcium sources: the limited role of solubility.

Fractional absorption of seven chemically defined calcium sources was measured in normal adult women under standardized load conditions. Solubility of the sources in water at neutral pH ranged from a low of 0.04 mM to a high of 1500 mM. The relationship of solubility to absorbability was weak. In the range from 0.1 to 10 mM, within which most calcium supplement sources fall, there was no detectable effect of solubility on absorption. Data from four food sources are presented for comparison. Absorbability of food calcium was not clearly related to absorbability of the dominant chemical form in the food concerned. These findings suggests that (1) even under controlled, chemically defined conditions, solubility of a source has very little influence on its absorbability; and (2) absorbability of calcium from food sources is determined mainly by other food components.

Adult↗

A comparison of iliac bone histomorphometric data in post-menopausal osteoporotic and normal subjects.

Transilial bone biopsies following in vivo fluorochrome labeling were obtained from 90 women with postmenopausal osteoporosis and 34 healthy post-menopausal women. Standard histomorphometric data were collected from undecalcified sections. The distribution of values for both structural and remodelling indices was the same for each group. Bone volume was 35% lower (P less than 0.001), wall thickness was 12% lower (P less than 0.001), and trabecular thickness was 11% lower (P less than 0.02) in osteoporotics. Trabecular separation was 34% greater (P less than 0.001) and trabecular number was 36% lower (P less than 0.001) in osteoporotics. Biopsy core width was 11% less (P less than 0.02) and cortical width was 35-50% less (P less than 0.001) in osteoporotics. Static indices of remodelling, mineralizing surfaces, and mineral apposition rate were similar in the two groups. The absolute values for bone histomorphometric variables for both groups are similar to most published data. Osteoporotics had poorer bone structure, marked by decreased trabecular connectivity and thin cortices. There were no major differences in dynamic indices of remodelling. Since the histomorphometric data were distributed the same in both groups, special subsets of osteoporotic subjects not in the normal population did not exist.

Aged↗

Reduced bone mineral in patients with eating disorders.

Bone mineral measurements of the forearm and spine were made in 63 patients under treatment in the Eating Disorders Program of the University of Nebraska Medical Center, 26 with anorexia nervosa (AN), 11 with bulimia nervosa (BU) and 26 with features of both AN and BU (AN/BU). Comparison was made with a group of 211 normal women of similar age. Spinal bone mineral content (BMC) of L2-4 was 45.1 +/- 5.7 g in the normals, 38.0 +/- 7.5 in the AN's, 40.3 +/- 6.6 g in the AN/BU's and 44.4 +/- 6.9 g in the BU's. The AN and AN/BU averages were both significantly different from normal (p less than 0.0005), but the BU average was not. BMC was correlated with body weight in each group and weakly correlated with age in the patients under age 30 in the AN and AN/BU groups combined. Forearm bone mineral measurements in the AN's and AN/BU's were also significantly lower than normal, but the differences were not as great as for the spine. We conclude that bone mineral is reduced in these patients, severely in some of them, and that reduced body weight plays a role. Menstrual disturbances, inhibition of growth and development, and malnutrition remain open as causal factors. Potential for recovery from reduced bone mineral was not demonstrated in this study.

Adult↗

Long-term consistency of nutrient intakes in humans.

Consistency of intake over time for calcium, phosphorus, protein and energy, as estimated from diet diaries, was studied prospectively in two groups of women. One group provided short-term data (n = 165), and the other, data spanning intervals of up to 20 y (n = 164). Although group average intakes changed little, there was a great deal of individual variation. Even at intervals as short as 6 m, current intake estimates accounted for only about 40% of the variance of intakes at an earlier time. Over longer intervals, the predictive value of one estimate in respect to a second deteriorated even further. Thus, across 5 y, less than 25% of the variance of all four nutrient intakes could be accounted for by current intake. The 95% confidence interval for an estimate of earlier intake based upon a later measurement was more than +/- 700 mg for calcium, the least consistent nutrient. The other three nutrients showed nearly identical interstudy consistency, with uncertainties relative to their respective means being about half as large as for calcium. These data show that accurate longitudinal estimates of intake require continuous, prospective monitoring and that current intake is not a good estimator of past intake for most nutrients, especially for calcium.

Adult↗

Osteoporotic bone fragility. Detection by ultrasound transmission velocity.

We evaluated ultrasound transmission velocity at the patella as an indicator of osteoporotic fragility in 293 nonobese women. Osteoporosis was defined by atraumatic vertebral compression deformity. Ultrasound velocity averaged 1954 +/- 71 (+/- SD) m/s in premenopausal normal women and declined significantly with age after menopause, largely independently of age-related loss of spine bone mass. Postmenopausal osteoporotic women had lower velocities than normal women (-76 m/s). After allowing for slight differences in age between the groups, the difference (-54 m/s) was still significant. Women with velocities below 1825 m/s were about six times more likely to have one or more fractures than women with velocities about that level. By sensitivity-specificity analysis, ultrasound velocity discriminated between normal and osteoporotic women as well as direct measurement of spine bone mass. Ultrasound velocity measures both bone mass and a component of bone fragility distinct from decreased mass; it is a potentially valuable new tool for evaluating women for osteoporotic fragility.

Adult↗

Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis.

To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis, we studied a group of 39 women aged 69 +/- 7 (standard deviation, SD) years with severe osteoporosis. The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis. No subject had risk factors for osteopenia other than their age and postmenopausal status, and no subject was receiving therapy for bone disease at the onset of the study. Subjects were followed for 2 years after randomization to receive either 1200 mg/day of calcium (as calcium carbonate) and 40 micrograms/day of 25-OHD (calcium-25-OHD group), or 1200 mg/day of calcium plus placebo (calcium-placebo group). Calcium-25-OHD resulted in a clear increase in 25-OHD levels (p less than 0.001) and an increase in calcium absorption as indicated by urinary calcium excretion. Nevertheless, there was no significant change in fasting serum calcium, phosphorus, alkaline phosphatase, PTH, or 1,25-(OH)2D in either group. Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period. Unexpectedly, repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups, presumably as a result of the calcium supplementation alone. In summary, calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia. The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗