Bone turnover in spinal osteoporosis.

We have investigated biochemical indices of bone formation and bone resorption: serum alkaline phosphatase (sAP) plasma bone Gla protein (pBGP), fasting urinary hydroxyproline corrected for creatinine (FuHP/Cr), and fasting urinary calcium corrected for creatinine (FuCa/Cr) in 43 postmenopausal women with spinal fractures. Furthermore, histomorphometric indices of bone resorption and bone formation, as well as whole body retention (WBR) of 99m-technetium-diphosphonate (99mTc-DP), were determined. The results are compared to pre- and postmenopausal normal subjects. The results showed that indices of bone formation were mutually correlated except for sAP vs. WBR. sAP, WBR, and pBGP increased with age. sAP and WBR were not different between osteoporotics and age-matched controls, while pBGP and probably histological indices of bone formation were lower in osteoporotics than in age-matched controls. pBGP--and to a lesser extent sAP--were significantly correlated with all histological parameters reflecting bone formation. Finally, biochemical indices of bone resorption were high in osteoporotic patients and poorly correlated with histological bone resorption. The discrepancy between biochemical markers of bone formation may be related to the low sensitivity of sAP and WBR. Conversely, pBGP, sAP, and WBR may reflect different aspects of osteoblastic activity and bone mineralization. Finally, our data suggest that bone turnover increases with aging and that osteoporotic patients have higher bone resorption and probably lower bone formation than age-matched controls.

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.

Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors.

Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol, has been suggested as an important anti-risk factor for the development of atherosclerosis as explained by the oxidative theory. Forty-five hypercholesterolemic patients were randomized in a double-blind trial in order to be treated with increasing dosages of either lovastatin (20-80 mg/day) or pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme Q10 were measured parallel to the levels of cholesterol at baseline on placebo and diet and during active treatment. A dose-related significant decline of the total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/- 0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/- S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001. Although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term therapy.

Diurnal monitoring of blood pressure and the renin-angiotensin system in hypertensive patients on long-term angiotensin converting enzyme inhibition.

The temporal blood pressure course and the diurnal profile of the renin-angiotensin system were examined in 13 patients with essential hypertension receiving hydrochlorothiazide and enalapril once daily. Blood samples were taken and blood pressure was measured before the habitual morning dose of hydrochlorothiazide and enalapril (at 8.00 a.m.) and at seven time points over the next 24 h. During the period of maximal effect of enalapril (from 11.00 a.m. to 2.00 p.m.), the increase in plasma renin concentration ranged from no change to an 800% increase. A negative correlation was observed between an increase in plasma renin and a decrease in immunoreactive plasma angiotensin II concentration (Spearman rank-order correlation coefficient = 0.83). Notably, the greatest changes in plasma renin and angiotensin II concentrations after enalapril were seen in those patients whose blood pressure fell most during the day. We conclude that hypertensive patients on long-term therapy with enalapril once daily vary widely in their between-dose biochemical response to the drug, and that there is a significant association between the responsiveness of the plasma renin-angiotensin system and the effect on 24 h blood pressure.

Changed cyclic guanosine monophosphate atrial natriuretic factor relationship in hypertensive man.

Plasma concentrations of atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (cGMP) were measured in 10 patients with essential hypertension and 10 normotensive controls on the fifth day of a low (50 mmol/day), a medium (180 mmol/day) and a high (380 mmol/day) dietary sodium intake. Plasma ANF and cGMP concentrations were less on the low than on the high sodium intake. Values for ANF on the medium sodium intake were intermediate. In normotensive subjects cGMP concentrations did not differ significantly on the low and the medium sodium intake. As compared with the controls plasma concentrations of cGMP were significantly increased in hypertensive patients on all three levels of sodium intake, while ANF concentrations were identical in the two groups. Since cGMP is a second messenger to ANF the data suggest an increased cellular response to ANF in patients with essential hypertension.

Normal renal tubular response to changes of sodium intake in hypertensive man.

In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intensive dietary advice for patients with severe hypercholesterolemia]. / Intensiv diaetetisk vejledning af patienter med svaer hyperkolesterolaemi.

Screening in general practice revealed a total of 124 patients (71 men and 53 women) with severe hypercholesterolaemia, defined as serum cholesterol levels over the 95th percentile for sex and age. The average serum cholesterol was 9.3 mmol/l with a maximal value of 15.5 mmol/l. On the basis of a dietary history for 48 hours and a dietetic interview, a dietician undertook a dietary analysis with the help of a computer programme (DANKOST) before and after dietary alterations for one and three months. The aims were normal body weight, cholesterol intake of under 200 mg/day, ratio between saturated and unsaturated fat between 1.0 and 1.8 and a roughage content of 26-30 g/day. A total of 61 patients completed the recommended dietary alterations. Alcohol intake was significantly higher in men and constituted more than 8% of the energy intake in 43 patients. Serum cholesterol was reduced by a total of 15.3%, triglyceride by nearly 20% while high density lipoprotein remained unchanged. The maximal decrease in serum cholesterol was 43%. In patients who adhered to the dietary changes, the average decrease was over 20%. Patients with hypertension and patients with serum cholesterol levels greater than or equal to 9 mmol/l showed greater decreases than the group as a whole. On the basis of the dietary interview, it did not prove possible to predict which patients would stick to the dietary restrictions.

[Treatment of severe primary hypercholesterolemia with lovastatin (Mevacor). A new therapeutic principle]. / Behandling af svaer primaer hyperkolesterolaemi med lovastatin (Mevacor). Et nyt behandlingsprincip.

An open clinical trial comprising 59 outpatients with severe hypercholesterolemia (including 35 patients with familial hypercholesterolaemia) and considerable predisposition to ischaemic cardiac disease revealed a dosage-related pronounced effect of lovastatin on serum cholesterol and subfractions of this. After dietary regulation for a period of four months, a decrease in serum cholesterol of 11.7% was observed and after further treatment for six months with lovastatin with an average dose of 59 mg per 24 hours, the serum cholesterol decreased with a total of 45% of original value. Low density lipoprotein (LDL)-cholesterol decreased 44% and high density lipoprotein (HDL)-cholesterol increased by over 21%. Serum triglyceride fell by 20%. The serum-cholesterol/HDL-cholesterol ratio was reduced from 8.8 to 4.9. Only slight and transient subjective side-effects were observed and none of the patients dropped out of the trial for this reason. One patient with recognized ischaemic heart disease died from myocardial infarction. A tendency towards increasing liver parameters and creatin kinase was observed in the group as a whole but was not significant.

[Recommendations for clinical-chemical departments: lipid-lipoprotein analysis]. / Rekommandationer for klinisk-kemiske afdelinger: lipid- og lipoproteinanalyser.

The section for preventive cardiology within the Danish Society for Cardiology has established a lipid group with representatives from The Danish Society for Clinical Chemistry, The Danish Society for Internal Medicine, The Danish Society for Cardiology, The Danish Society of Hypertension, The Danish College of General Practitioners, and The Danish Paediatric Society. The lipid group has elaborated recommendations for clinical chemical departments regarding lipid and lipoprotein analyses. The group suggests that doctors ordering lipid and lipoprotein analyses are offered the following: S-Cholesterol (total), substance conc., (fPt)S-Triglycerides, substance conc., S-HDL-cholesterol, substance conc., and (fPt)S-LDL-cholesterol, substance conc. (calculated). It is recommended that the biological variation be minimized by sampling in a sitting position after a 15 minutes' rest and by basing the clinical decision on a minimum of 2-3 determinations with an interval of about one month. The analytical variations should be reduced to below 3% (calculated as the variation coefficient), and it is recommended that laboratories participate in external quality control systems at least four times annually by reporting at least two human reference materials with different concentrations. As the use of reference intervals dependent on age and sex, based on random samplings of the background population, are less informative, it is recommended to refer to cutoff values for the clinical decision. The following cutoff values are recommended: S-Cholesterol (total), substance conc.: 6 mmol/l, (fPt)S-Triglycerides, substance conc.; 2.5 mmol/l, S-HDL-cholesterol, substance conc.: 0.9 mmol/l (fPt)-LDL-cholesterol, substance conc. (calculated): 4.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)