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Investigations with bone-seeking radionuclides (47Ca, 99mTc-PP, 113Sn) in rats of different age demonstrated a true accumulation in teeth as compared to bone. Blood flow was evaluated by 99mTcO4 and 51Cr-Albumin. Differences of accumulation depended on the isotopes used and on the age of the animals.
1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards. 2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced. 3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D3 nor alkaline phosphatase provided satisfactory discrimination between the groups. 4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.
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During experimental research work carried out on animals with a view to clearing up the caries-forming processes, metabolic disturbances could be detected in the hard tissues of teeth after administering a cariogenic diet. The aim of the present work was to investigate the effects of tooth-pastes with calcium, phosphate and fluoride content upon changes in metabolic processes, and thus to clarify the mechanism of the anti-cariogenic effect exerted by fluoride tooth-pastes.
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Dependence of large intestinal calcium transport on vitamin D has been examined in vitro in colon only. The authors studied calcium fluxes in cecum and colon in vivo by perfusion with 1.6 mM calcium chloride in saline. Tracer 45Ca either was injected parenterally 24 hr before study or was added to the perfusates. For 8--10 wk after weaning, rats had been fed a rachitogenic diet; 48 and 24 hr before study, 50% of the animals were treated with 20,000 IU vitamin E2. In a separate set of animals, mucosal calcium binding protein was analyzed by the Chelex assay method. In comparison with vitamin D-deficient rats, the colon of vitamin D-treated rats showed higher lumen-to-plasma flux and lower plasma-to-lumen flux and net absorption instead of net secretion. In cecum, calcium transport was not significantly altered by vitamin D treatment. Mucosal calcium binding protein was higher in cecum than in colon in both groups and was higher in vitamin-D-treated than in vitamin D-deficient animals in both segments. The current study shows that in the rat colon calcium fluxes both into and out of the lumen as well as net transport are significantly by vitamin D treatment, but that cecal transport rates are not affected. In both cecum and colon, mucosal calcium binding protein increases with vitamin D treatment.
This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99 m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99 m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99 m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.
Many hundreds of clearance curves for plasma and urine after a single injection of tracer are well fitted by y = sigmari = Ai exp(-Bit), r = 2 or 3, based on models with homogeneous compartments. Reanalyzing such sums as in a plot of log y versus log t shows that many of the original curves would fit y = At-alpha or At-alpha exp(-betat) over wide ranges of time and specific acitivity. Results of such reanalyses for a complete published series for serum albumin 131I are given, and an outline of those for various compounds in the human body labeled by 3H. For radiocalcium two such power laws can be fitted in one curve, with a transition between about 1 and 3 days, so that much of the log y versus log t plot consists of two straight lines. These lines are used for starting a numerical analysis that splits the curve into 2 non-linear components, plus a third one that is neglibible after 5 min from injection. An outline of the iteration method is given. The components are interpreted physiologically and used to predict total bone activities by (de)convolution, and these are compared with observed ankle activities and with excretion rates. The bone accretion rate is obtained mainly from the middle component and comes to 2 to 3 g Ca/day, while return of 47Ca from bone to plasma begins at about 1/2 day. These results seem imcompatible with any based on compartments. The concept of biological half-life then needs to be reconsidered.
Studies of calcium metabolism in 38 patients with cancer indicated that: 1) intestinal absorption of calcium was reduced in patients with skeletal metastases and in those with hypercalcemia; 2) calcium-47 space (a measurement of bone turnover rate) was high in the patients with skeletal metastases; 3) hypercalcemic patients had higher urinary and endogenous fecal excretion of calcium than those who were normocalcemic; 4) levels of plasma immunoreactive parathyroid hormone were similar in normo- and hypercalcemic patients, but the levels for a given serum calcium in malignant disease were lower than those in primary hyperparathyroidism; and 5) some patients had elevated calcitonin levels. Hypercalcemia complicating malignant disease is therefore not due to hyperabsorption or diminished excretion of calcium, and a low calcium diet is unlikely to benefit these patients. Measurement of 47Ca space could be of use in monitoring therapy of patients with skeletal metastases, and measurement of plasma parathyroid hormone could be useful in the differential diagnosis of hypercalcemia.
The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.
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The relationship between local blood flow and bone clearance of 18 F, 32 P-P (orthophosphate), 32 P-PPi (pyrophosphate), 45 Ca, 85 Sr, 99mTc- and 113 Sn-EHDP was evaluated in the non-adult rat. During one single blood passage nearly 100% of 18 F was extracted in the femoral diaphysis, the extraction efficiency for the other radiopharmaceuticals was about 40%. Blood flow and bone clearance was higher and the extraction efficiency lower in the distal femoral epiphysis including the growth plate. The short-term bone uptake of 32 P-P was lowered considerably by the simultaneous application of inactive orthophosphate, whereas the bone uptake of 32 P-PPi was not suppressed. It is suggested that the rapid deposition of radiopharmaceuticals in bone is not caused by an ionic exchange process on crystal surfaces of already existing mineral but is due to an ionic exchange during the precipitation of calcium phosphate in the calcifying bone matrix. Only 18 F is exchanged with hydroxyl groups of already precipitated hydroxyapatite, whereas the calcium and phosphate ions in the precipitated hydroxyapatite are not further accessible to an exchange process.
Female Wistar rats were used to determine the effects of the chelating agents, EDTA and EGTA, on the in vitro 45Ca2+ accumulation by mitochondria isolated from the skeletal muscle of fatigued animals. The rats were divided into three groups: sedentary-rested (SR), trained-rested (TR), trained-exhausted (TE). The trained groups were exercised on a treadmill for 1 h daily, five times a week, for 22 weeks. At the conclusion of the training program, the TE group was rapidly exercised to exhaustion immediately following their daily 1-h run. In the TR group EDTA reduced 45Ca2+ binding while both EDTA and EGTA appeared to increase mitochondrial Ca2+ and Mg2+ content. In the TE group, EDTA reduced endogenous mitochondrial Ca2+ and Mg2+ content, while both EDTA and EGTA increased 45Ca2+ binding. Since chelating Ca2+ and Mg2+ from the membrane may affect the structure and function of the mitochondria, it is suggested that the use of chelating agents during the isolation of mitochondria from the skeletal muscle of trained rats be viewed with caution.
In order to ascertain the effects of long-term exercise training and long-term exhaustive exercise on mitochondrial 45Ca2+ uptake and related variables in rat skeletal muscle, female rats were randomly divided into three groups: sedentary-rested (SR), trained-rested (TR), and trained-exhausted (TE). The trained groups were exercised five times per week on a treadmill for 22 weeks. At the conclusion of the training period, the TE group was exercised to exhaustion following their daily 1 h run. The 45Ca2+ uptake and endogenous mitochodrial Ca2+ content of skeletal muscle followed stepwise increases of approximately 25% and 50%, respectively, across the groups, suggesting that long-term exercise induces the mitochondria to play an important role as a Ca2+ uptake buffer. A 75--83% reduction in 45Ca2+ binding in the TE group suggests a selective loss and partial saturation of membrane phospholipids with exhaustive exercise. The TE group had a two-fold greater content of mitochondrial Mg2+ than did the rested groups. It is speculated that the mitochondria accumulate Mg2+ during acute exercise to maintain the functional integrity of the membrane, thus offsetting the deleterious effects of excessive Ca2+ uptake
Calcium metabolism was studied in a 12-year-old girl preseting with idiopathic juvenile osteoporosis. Absorption of orally administered 47-Ca was high. Serum calcium and phosphorus, serum immunoreactive PTH and CT and tubular phosphate reabsorption were found to be within normal limits. The data suggest that calcium malabsorption, nutritional calcium deficiency, hyperparathyroidism, a dysfunction related to sex hormones, and Cushing's syndrome cannot be implicated in the aetiology of the osteoporosis in this case who recovered spontaneously with sexual maturation.