Arne Leth

Iliac crest biopsy in longitudinal therapeutic trials of osteoporosis.

Changes in tetracycline-labelled iliac crest biopsies taken before and after 1 year of treatment with nandrolone decanoate + calcium, 17 beta-estradiol + norethisterone acetate + calcium or placebo were compared with changes in plasma bone Gla protein (pBGP), serum alkaline phosphatase (sAP), whole body retention (WBR) of Technetium-99m-diphosphonate [( 99mTc]DP) and bone mineral content (BMC) of the forearm. Based on a comparison between biopsy and noninvasive results, as well as on evaluation of the variation in the groups, certain guidelines for the use of bone histomorphometry in longitudinal therapeutic trials are suggested. It is proposed that bone biopsy is not used to monitor changes in amount of bone and that evaluation of changes in biopsy evaluated bone turnover is only attempted when the groups are large.

Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients.

Total body potassium content, plasma potassium concentration, blood pressure, and plasma concentrations of renin, angiotensin II, and aldosterone were measured in patients with essential hypertension after a run‐in period of 8 wk on a regimen of hydrochlorothiazide (median dosage 75 mg/day). Patients were then randomly assigned to continued hydrochlorothiazide therapy (group I) or to receive adjunctive treatment with amiloride (group II, median dosage 15 mg/day or 5 mg per 25 mg hydrochlorothiazide) for the following 3 mo. There were no changes in group I patients during 3 mo on hydrochlorothiazide in plasma potassium, total body potassium content, or the renin‐angiotensin‐aldosterone system. Blood pressure was also unchanged. In group II patients addition of amiloride to hydrochlorothiazide induced a rise in plasma and total body potassium of approximately 15% and 4%. The potassium‐retaining effect was maintained throughout the 12‐wk period, although the maximal changes were observed after 8 wk of treatment. Supine blood pressure did not change, but there was a significant decrease in standing systolic blood pressure. There was a marked rise in plasma concentrations of renin, angiotensin II, and aldosterone.

Effects of combined therapy with amiloride and hydrochlorothiazide on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in hypertensive patients

SummaryAfter a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.