Harlan J. Evans

Clomiphene protects against osteoporosis in the mature ovariectomized rat

SummaryClomiphene citrate, a mixed estrogen agonist-antagonist, protects mature ovariectomized breeder rats from changes in total body calcium and from deterioration of femur structure. Over 6 months, mature ovariectomized rats took up calcium at the rate of 0.7 ± 0.5 mg/day, while normal controls gained 2.5±0.7 mg/day (mean±SE) as measured by whole body neutron activation analysis. Injections of clomiphene (20 mg/kg/week) kept ovariectomized rats in positive calcium balance at 2.0±0.5 mg/day. Reductions in total femur calcium content, cortical thickness, and visible trabeculae of femurs in ovariectomized animals were prevented by chronic clomiphene administration. These results in animals suggest a possible new line of investigation of the use of antiestrogenic drugs as therapeutic agents for hormone-dependent osteoporosis in animals and humans.

Relaxation times of normal and atrophied muscle

Magnetic resonance imaging is being used to investigate physiological changes induced by microgravity. Using human (bed rest) and animal (tail suspension) models simulating zero gravity, muscle atrophy was studied. Despite significant physiological changes in muscle mass, distribution of blood flow, and muscle water, no changes in muscle proton relaxation times were found at several different resonant frequencies (6, 10, 20, and 200 MHz). These results suggest that observed changes in relaxation times as reported in pathologic studies are likely due to the pathological changes and not the accompanying muscle atrophy.

Bone mineral content reflects total body calcium in neonatal miniature piglets.

ABSTRACT: We measured bone mineral content (BMC) in 18 neonatal miniature piglets by single photon absorptiometry, total body calcium (TBC) by total body neutron activation analysis, growth, and serum indices of mineral status (calcium, phosphorus, alkaline phosphatase activity). Measurements were begun on day 6, when the piglets were weaned, and were continued to day 19. After weaning, the piglets were assigned randomly to receive one of three diets which differed only in their concentrations of calcium and phosphorus: 100% of the recommended level (diet A), 60% (diet B), and 20% (diet C). No differences were observed among groups during the 19-day study, either in weight gain (48 ± 2 g/day) or increment in crown-rump length (2.4 ± 0.2 cm/wk). BMC correlated significantly (p < 0.001) with TBC at 6 (r = 0.83), 13 (r = 0.77), and 19 (r = 0.93) days. BMC correlated significantly (p < 0.001) with the ash weight (r = 0.87) and calcium content (r = 0.90) of the corresponding tibial bone segment. Anthropometric parameters and serum indices of mineral status did not predict TBC as accurately as did BMC measurements. We observed a range in BMC measurements in this study that was similar to the range reported for infants in the 1st yr of life. The high correlation between BMC and TBC suggested that BMC is useful in the assessment of mineral status in infants.

T2 vertebral bone marrow changes after space flight.

Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume‐localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight. Magn Reson Med 41:495–498, 1999.

Facility for regional in vivo neutron activation analysis of skeletal calcium

Describes the authors facility which was designed and built to measure regional changes in skeletal calcium of human subjects or animals, and to measure whole body calcium in small animals. This facility employs a collimated beam of neutrons obtained from a 3 mg252Cf source. The neutrons have a fission spectrum of mean energy 2.3 MeV.

High resolution bone mineral densitometry with a gamma camera

A technique is described by which the regional distribution of bone mineral can be determined in bone samples from small animals. The technique employs an Anger camera interfaced to a medical computer. High resolution (less than 1 mm) imaging is possible by producing magnified images of the bone samples. Regional densitometry of femurs from oophorectomised and bone grafted rats demonstrated significant heterogenity of bone mineral loss.

Feasibility study: In vivo neutron activation for regional measurement of calcium using Californium 252

The feasibility of using a collimated 252Cf neutron source to measure regional changes in skeletal calcium was tested because in vivo regional activation of diseased bone should offer advantages over the more widely reported total-body calcium measuring techniques. Regional activation allows examination of discrete regions where the greatest changes in calcium content occur. Additionally, a simpler radiation facility is required for regional studies. Using a 5.5-mug 252Cf source, thermal neutron flux and absorbed dose were measured in a tissue-equivalent phantom. Detection efficiency of 49Ca gamma rays for conditions simulating regional activation were measured using a 29-cm-diameter X 10-cm-thickness sodium iodide detector. These in vitro measurements indicate that a collimated 252Cf source can be used for regional neutron activation of the lower spine and legs. Preliminary calculations indicate that a 1-3-mg source provides adequate count rates for statistical accuracy with a bone marrow dosage acceptable for human patients and normal subjects.