Clinical observations with a new specific assay for bone alkaline phosphatase: a cross-sectional study in osteoporotic and pagetic subjects and a longitudinal evaluation of the response to ovariectomy, estrogens, and bisphosphonates.

The purpose of this study was to examine the serum levels of bone alkaline phosphatase (BALP) measured with a new assay in normal and in osteoporotic women, and to evaluate prospectively its responsiveness to changes of bone metabolism. The following groups of subjects were studied: (1) 95 healthy women (44-75 years) (22 pre- and 73 postmenopausal) and 35 osteoporotic women [vertebral bone mineral density (BMD) more than 2.5 SD below the normal adult mean]; (2) 10 women (44-50 years) ovariectomized (OVX) for benign uterine diseases, examined before and 12 months after surgery; (3) 16 OVX women (36-54 years), examined before and after 12 months of transdermal estrogen replacement therapy (50 microg/day); (4) 12 previously untreated pagetic patients (4 women and 8 men, 50-80 years), examined before and 3 months after the I.V. administration of clodronate (600 mg) or alendronate (5 mg) for 2 consecutive days. The median BALP value was 11.6 U/liter (25-75th percentiles: 10.5-12. 7; range 7.7-19.3) in healthy premenopausal (PreMP) women and significantly higher (median: 16.8 U/liter; 25-75th percentile: 13. 8-21.8; P < 0.01) in postmenopausal (PostMP) women. There was a clear age-related increase in normal subjects (r = 0.43; P < 0.001). In the osteoporotic group, BALP levels, as well as other biochemical parameters of bone turnover, were not significantly different from those of normal women when adjusted for age. In OVX women, BALP levels showed a marked increase 12 months after surgery (median: 113%; 25-75th percentile: 87-139%), significantly higher than the increase of total ALP (median: 43%; 25-75th percentile: 25-66%; P < 0.001), and similar to the increases of serum osteocalcin and urinary hydroxyproline. Transdermal estrogen treatment prevented the BALP increase, even if no reduction was observed; total ALP showed a similar behavior. The basal levels of BALP were significantly elevated in pagetic patients (median: 91 U/liter; range 18-610 U/liter) and correlated to the scintigraphic extent of the disease (r = 0.76; P < 0.01). Three months after the I.V. administration of bisphosphonates, the decrease of BALP was more marked than that of total ALP (median: -54% versus -41%; P < 0.05). In conclusion, these results suggest that BALP measurement with this immunoassay may be clinically useful, and more sensitive than total ALP, in the assessment of bone turnover during changes of the estrogen status as well as in monitoring the effects of treatments that modify the metabolic activity of the skeleton.

Association between salt sensitivity and insulin concentrations in patients with hypertension.

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

Acute effects of bisphosphonates on new and traditional markers of bone resorption.

Bisphosphonates are known to be potent inhibitors of osteoclast activity and their only clinically relevant effect in the short-term is the selective inhibition of bone resorption. The purpose of this study was to compare the response to the intravenous administration of two bisphosphonates, clodronate and alendronate, of several biochemical markers of bone resorption, including tartrate-resistant acid phosphatase (TRAP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) in serum and hydroxyproline (OHP), free pyridinium cross-links (Pyr), and cross-linked N-telopeptides of collagen I (NTx) in urine. The study was carried out on 11 osteoporotic and 12 Pagetic subjects of both sexes, treated with clodronate (600 mg/day for 2 days) or alendronate (5 mg/day for 2 days), and monitored for 28 days after bisphosphonate administration. All the urinary markers of bone resorption showed a prompt decline after bisphosphonates, with maximum reductions after 7-14 days: Pyr decreased by 43% +/- 9% and 42% +/- 22% (mean +/- SD), respectively in osteoporotic and pagetic subjects, OHP by 51% +/- 14% and 51% +/- 20%, and NTx by 55% +/- 15% and 65% +/- 26%. In the osteoporotic group, the urinary markers began to increase again at 30 days, though still remaining well below the basal level, whereas in the pagetic group, the excretion of all markers remained depressed until the end of the observation period. The reduction of NTx was significantly greater than that of Pyr and OHP in pagetic patients (P < 0.05) and tended to be greater than that of Pyr in osteoporotic patients (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperinsulinaemia, obesity, and syndrome X.

OBJECTIVE: The major aim of this study was to compare various aspects of carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration, and blood pressure in normal subjects stratified on the basis of both plasma insulin concentration and degree of obesity. The hypothesis to be tested was that hyperinsulinaemia, per se, was associated with relative glucose intolerance, higher triglyceride and uric acid concentrations, lower high-density lipoprotein cholesterol concentration and higher blood pressure, irrespective of degree of obesity. DESIGN: This represents a case-control study, in which normal volunteers were subdivided into four equal groups based upon degree of obesity and plasma insulin response to a 74 g oral glucose challenge. SETTING: The study was performed in the out-patient clinic of a university hospital. SUBJECTS: Sixty-four individuals were recruited for this study, subdivided into four groups based upon their plasma insulin concentration and body mass index. Subjects were classified as hyperinsulinaemic if their plasma insulin concentrations in response to an oral glucose challenge were more than two standard deviations above the mean of 732 volunteers previously studied [1]. Obesity was defined as a body mass index of > 30 kg m-2, and individuals were classified as non-obese if their body mass index was < 27.0 kg m-2. Based upon these criteria, four experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper); (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normoinsulinaemic (NOB normo); and (iv) obese normoinsulinaemic (OB normo). MAIN OUTCOME MEASURES: Subject groups were compared on the basis of the integrated plasma glucose response to a 75 g oral glucose challenge, fasting plasma triglyceride, cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations, and blood pressure. RESULTS: Mean (+/- standard error of the mean) integrated plasma glucose response area for 2 h following a 75 g oral glucose load was significantly higher (13.4 +/- 0.4 vs. 11.0 +/- 0.4 mmol l-1, P < 0.001) in the hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 +/- 0.2 vs. 1.4 +/- 0.1 mmol l-1, P < 0.001) and uric acid (5.3 +/- 0.2 vs. 4.4 +/- 0.2 mmol l-1, P < 0.05) concentrations. In contrast, high-density lipoprotein concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 +/- 0.05 mmol l-1, P < 0.001). In addition, blood pressure was higher in the hyperinsulinaemic group (136 +/- 5/87 +/- 2 vs. 123 +/- 2/82 +/- 1 mmHg, P < 0.05). Furthermore, when each of the two groups were divided into obese (n = 16) and non-obese (n = 16) groups, all of the differences outlined above persisted. These changes were independent of age, gender distribution, generalized and abdominal obesity, cigarette smoking, and estimated physical activity. CONCLUSIONS: The cluster of changes subsumed under the heading of syndrome X are closely associated with hyperinsulinaemia (and presumably insulin resistance), and can be discerned irrespective of degree of obesity.

Changes in insulin and lipid metabolism in males with asymptomatic hyperuricaemia.

OBJECTIVES: To define the effect of asymptomatic hyperuricaemia on various facets of glucose, insulin, and lipoprotein metabolism. DESIGN: Case control study in health volunteers. SETTING: The volunteers for this study were selected on the basis of their laboratory results from a larger population participating in a general survey in one large factory. SUBJECTS: The study population consisted of 40 healthy males: 20 with asymptomatic hyperuricaemia (serum uric acid concentration equal to or greater than 420 mmol l-1) and 20 with normal serum uric acid concentrations (180-320 mmol l-1). The two groups were similar in terms of age, general obesity (estimated by body mass index), smoking and alcohol intake, and estimate of work and leisure time activity. INTERVENTIONS: All subjects received a 75 g oral glucose challenge, with blood taken before and at frequent intervals thereafter. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, and lipid concentrations and plasma glucose and insulin responses to the oral glucose challenge. RESULTS: By selection, mean (+/- SEM) serum uric acid concentration was higher in the hyperuricaemic individuals (454 +/- 7 vs. 274 +/- 12 mmol l-1). In addition, the plasma insulin response to oral glucose was increased in individuals with asymptomatic hyperuricaemia (P < 0.005) as were both systolic (136 +/- 3 vs. 126 +/- 3 mmHg, P < 0.05) and diastolic (91 +/- 1 vs. 82 +/- 1, P < 0.01) blood pressure. Furthermore, subjects with asymptomatic hyperuricaemia were dyslipidaemic (higher plasma TG and cholesterol and lower HDL-cholesterol concentrations) as compared to the normouricaemic control group (P < 0.07-0.005). CONCLUSIONS: These results provide a possible explanation for the well-known association of hyperuricaemia with coronary heart disease, as well as suggesting that hyperuricaemia be added to the cluster of metabolic and haemodynamic abnormalities associated with insulin resistance and/or hyperinsulinaemia and designated as Syndrome X.

Quantitative characterization of the growth of the fetal kidney.

The time-dependent changes in the antero-posterior (A-P) diamter and length (L) of fetal kidneys has been evaluated by means of statistical analysis of measurements made during the third trimester in a normal population. Two hundred eighty pregnant women were examined between 22 and 40 weeks of gestation. Differences between operator-scanner combinations were evaluated. The relationships of the A-P diameter and length to menstrual age were determined in cross-sectional and longitudinal studies of kidney growth. The results obtained confirmed that measurements of fetal kidney can be used as an additional parameter in the routine assessment of fetal well being and to rule out kidney malformations characterized by changes in kidney size.