Lawrence Flora

Calcium absorption from a new calcium delivery system (CCM)

Absorption of calcium from a highly soluble form of calcium, a mixed calcium citrate-malate* salt (CCM), was tested against calcium carbonate and milk in both rats and humans. The rat method estimated absorption from the 6-day retention of an oral tracer, and the human method employed the standard double-isotope procedure. CCM was given both as a dry powder and in an organe juice beverage. In two experiments in rats calcium from CCM was absorbed at least as well as, if not better than from calcium carbonate or milk. In two separate experiments in humans, calcium from CCM was absorbed significantly better than from calcium carbonate or milk. We conclude that CCM exhibits excellent bioavailability and that this formulation is a useful addition to the forms of calcium now available either for direct supplementation or for food fortification.

The effects of dichloromethylene diphosphonate on hypercalcemia and other parameters of the humoral hypercalcemia of malignancy in the rat leydig cell tumor

SummaryThere is a high frequency of Leydig cell tumors associated with hypercalcemia in the aged Fischer 344 rat. We studied a transplantable tumor cell line (Rice D-6) which is associated with hypercalcemia, hypercalciuria, hypophosphatemia, renal phosphate wasting, increased urinary cyclic adenosine monophosphate (AMP) excretion, absence of bone metastases, increased osteoclastic bone resorption, and suppressed immunoreactive parathyroid hormone (iPTH) concentrations. We examined the ability of dichloromethylene diphosphonate (Cl2MDP) to lower serum calcium and decrease the parameters of increased bone resorption. We used this drug also as a pharmacologic tool to determine the relationship of hypercalcemia and increased bone resorption to the abnormalities in renal tubular function associated with the humoral hypercalcemia of malignancy.Daily administration of Cl2MDP before development of hypercalcemia, in doses from 2.5–40 mg/kg body weight subcutaneously, delayed and suppressed both the hypercalcemia and hypercalciuria. There was an increase in bone mass and decrease in both osteoclast number and activity compared with bones from untreated tumor-bearing animals. The urinary hydroxyproline excretion in treated animals declined towards the normal range. There were no significant effects on serum phosphorus, urine phosphorus, or urine cyclic AMP excretion.These data suggest that Cl2MDP reverses the increased bone resorption that occurs in the humoral hypercalcemia of malignancy, and confirms that diphosphonates are effective agents in the prevention and treatment of increased bone resorption associated with malignant disease. They also suggest that renal phosphate wasting and increased urinary cyclic AMP excretion are not directly related to the hypercalcemia.

Calcium absorption in children estimated from single and double stable calcium isotope techniques.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.

The effects of EHDP on regenerating trabecular bone usingin vivo microscopic, light and electron microscopic, and electron microprobe techniques

Metallic chambers were implanted into the proximal tibiae of rabbits to permit microscopic examination of living bonein situ. The bone repair process secondary to the injury produced during installation of the chamber, was visualized. Six to 8 weeks after implantation, osteoid and/or bone could be seen.The effects of various doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the repair and regeneration processes following chamber implantation were studied. Data from various techniques indicated that: (1) following low dose EHDP (0.25 mg/kg/day) chambers contained bone tissue morphologically and ultrastructurally indistinguishable from controls; and (2) with higher doses of EHDP (2.5 or 10 mg/kg/day) chamber contained spicules of normal osteoid, osteoblasts and osteocytes, but were devoid of osteoclasts.The effects of the various regimes of EHDP also were assessed on regenerated, trabecular bone contained within the tibia chambers three months after implantation of the chambers.Data from various methods of analysis supported the following conclusions: (1) the low dose of EHDP (0.25 mg/kg/day) had no toxic effects on the trabecular bone within the chambers but there appeared to be an increase in bone formation as compared to saline control; (2) higher doses of EHDP (2.5 or 10 mg/kg/day) were not toxic to bone cells but thick osteoid seams formed on the trabecular bone within the chambers. No osteoclasts were found associated with the bone apparently due to the coverage of bone surfaces by osteoid seams; and (3) osteoid which accumulated after EHDP treatment of 2.5 mg/kg/day for 2 months remained uncalcified for as long as 2 months following withdrawal of EHDP administration.The results showed the value of tibial chamber for examining microscopically living bonein situ and demonstrated the inhibitory effect of EHDP on mineralization of newly formed osteoid and a lack of effect on bone cells.