Osteoporosis management in long-term care. Survey of Ontario physicians.

OBJECTIVE: To survey physicians in Ontario regarding their approach to diagnosis and treatment of osteoporosis among residents of long-term care facilities. DESIGN: Mailed questionnaire covering physician demographics; current clinical practice relating to osteoporosis; and perceived barriers to prevention, diagnosis, and treatment of the disease. SETTING: Long-term care facilities in Ontario. PARTICIPANTS: Medical directors of long-term care facilities. MAIN OUTCOME MEASURES: Demographic variables; physician attitudes; and practices concerning awareness, diagnosis, and treatment of osteoporosis. RESULTS: Respondents returned 275 of 490 questionnaires, for a response rate of 56.1%. Most respondents (92.4%) were family physicians; 28.7% were caring for more than 100 patients in long-term care. Most (85.8%) saw from one to 10 hip fractures yearly in their practices. Although 49.6% of respondents estimated the prevalence of osteoporosis to be 40% to 80% among their long-term care patients, 45.5% said that they did not routinely assess their patients for the disease, and 26.8% do not routinely treat it. Half (50.9%) of physicians would treat patients at high risk based on clinical history; 47.9% if patients had a vertebral compression fracture on plain x-ray examination; 43.8% if patients were highly functional; 42.0% if osteoporosis were confirmed with bone mineral densitometry; and 30.0% if patients had a recent fracture. Perceived barriers to initiating treatment included cost of therapy, patient or family reluctance to accept therapy, and time or cost of diagnosis. CONCLUSION: Although physicians are aware that patients in long-term care facilities are at high risk for osteoporosis and hip fractures, the disease remains underdiagnosed and undertreated.

Digoxin concentrations in postmortem human tissues.

An extraction procedure is described that allows the application of a commercially available enzyme-multiplied immunoassay technique to the measurement of digoxin in whole blood, liver, and kidney. The concentrations of digoxin were measured in tissues obtained at autopsy from five patients who had been taking therapeutic doses of digoxin prior to death. Blood concentrations at autopsy were found to be higher than the therapeutic range, perhaps due to postmortem redistribution. Liver concentrations of digoxin showed a positive correlation with blood concentrations; this was not found for kidney concentrations of the drug.

Ionized calcium measurement in vitro: is it necessary?

Experimental data obtained from a study on the inhibition of placental Ca-ATPase by ethacrynic acid were graphically analyzed using either total calcium or ionized calcium as the independent variable. Correct interpretation of the results required actual measurement of ionized calcium in the incubation medium. The assumption that ionized calcium is equal to the total calcium resulted in artifacts and led to erroneous conclusions. These observations emphasize the necessity for accurate measurement of ionized calcium in test systems where calcium effects are being examined.

Effects of pharmacological and physiological modulators on Ca-ATPase and alkaline phosphatase activities from guinea-pig placenta in vitro.

In a search for modulators of Ca-ATPase and AP activities, we examined three pharmacological agents and the cations Ca2+ and Zn2+. Placental Ca-ATPase specific activity was uncompetitively inhibited in vitro by millimolar concentrations of the diuretics ethacrynic acid and furosemide. Cysteine, a sulphydryl donor, partially reversed the ethacrynic acid inhibition but enhanced the furosemide inhibition, indicating that sulphydryl-binding may be part of the mechanism of the inhibition of Ca-ATPase by ethacrynic acid but not by furosemide. In contrast to Ca-ATPase, AP activity was enhanced by both ethacrynic acid and furosemide. Zinc inhibited Ca-ATPase activity at all concentrations tested, but enhanced and, at higher concentrations, inhibited AP activity. The inhibition of AP activity by D-penicillamine was reversed by Zn, supporting the view that this drug acts by chelating Zn which is essential for AP activity. D-penicillamine had no significant effect on Ca-ATPase activity. Calcium activated both enzyme activities but inhibited only AP activity at higher concentrations. These results indicate that placental Ca-ATPase and AP activities may be distinct and dissociable based on responses to various pharmacological and physiological modulators.

Placental calcium and phosphorus transfer in the guinea pig: lack of effect of modulators of Ca-ATPase and alkaline phosphatase activity.

The effects of modulators of Ca-ATPase and alkaline phosphatase (AP) activity on placental calcium and phosphorus transfer were studied using the in situ perfused guinea pig placenta. The diuretics ethacrynic acid and furosemide had no significant effect on placental calcium and phosphorus transfer when injected into the mother (1.0 or 10.0 mg X kg-1) or added to the solution perfusing the fetal side of the placenta (0.25 or 2.0 mM). These two drugs have previously been shown to inhibit placental Ca-ATPase and enhance AP activity in vitro. D-Penicillamine, which inhibits placental AP but not Ca-ATPase activity in vitro, also had no significant effect on net calcium and phosphorus transfer from mother to fetus either when given to the mother (50 mg X kg-1) or added to the placental perfusion solution (0.25 or 2.0 mM). These results suggest that placental transfer of calcium and phosphorus in the guinea pig may not be directly related to placental Ca-ATPase and AP activities.

Placental transfer of calcium (Ca) and phosphorus (Pi) in the guinea pig: lack of correlation with placental Ca-ATPase and alkaline phosphatase (AP) activities.

In summary, it has been observed that in vitro inhibitors of placental Ca-ATPase and AP activities (EA, F, D-pen) and activators of placental AP (EA,F) are not associated with changes in Ca and Pi transfer across the in situ perfused guinea pig placenta. Assuming that the two enzyme activities were altered in vivo by these drugs, it may be that they are not directly related to active transport of Ca and Pi across the placenta.

Calcium and phosphate fluxes across the fetal membranes of the guinea pig: in vitro measurement.

Bidirectional calcium (45Ca) and phosphate (32P) fluxes across the amnion and visceral yolk sac of the guinea pig were measured in vitro in modified Ussing chambers. The net flux of these ions across both fetal membranes was in the maternal-to-fetal direction. The net flux of 45Ca and 32P across the yolk sac was significantly greater than that across the amnion. This difference was due to a greater maternal-to-fetal flux across the yolk sac. In addition, net 32P flux was greater than net 45Ca flux across the yolk sac, while in the amnion, there was no significant difference in the net flux of the two ions. It is suggested that the fetal membranes, especially the visceral yolk sac, contribute significantly to fetal acquisition of calcium and phosphate in mammals possessing a functional yolk sac placenta.

Effect of salmon calcitonin on plasma calcium and phosphorus in pregnant and non-pregnant guinea pigs.

The effect of salmon calcitonin (SCT) on plasma calcium ion activity (ICa) and inorganic phosphorus (Pi) was investigated in pregnant and non-pregnant guinea pigs. Basal plasma ICa and Pi were lower in pregnant compared to non-pregnant animals. Intravenous administration of SCT in doses ranging from 120 to 520 MRC mU . kg-1 resulted in hypocalcemia in both groups. Pregnant guinea pigs responded with a more pronounced and sustained hypocalcemia compared to non-pregnant animals. The observed effects on plasma Pi were less consistent, with hypophosphatemia evident only in the non-pregnant guinea pigs. It is suggested that the sensitivity of pregnant guinea pigs to the hypocalcemic effect of SCT may be a result of a higher rate of bone turnover.

The effect of porcine calcitonin on intestinal calcium and phosphate fluxes in the young piglet.

The effects of a physiological (3.8 ng.mL-1) and a pharmacological (120 ng.mL-1) concentration of porcine calcitonin (CT) on transmucosal calcium and phosphate flux rates were determined in intestinal mucosa from young piglets (4--40 days) mounted in Ussing flux chambers. The physiological concentration of the hormone inhibited net absorptive calcium flux rates in the proximal jejunum and distal ileum but not in the duodenum. No effect of either concentration of CT on phosphate flux rates was observed. The inhibitory effect of the physiological concentration may indicate a role for CT in the maintenance of calcium homeostasis in the young suckling mammal.