Serum isoforms of bone alkaline phosphatase increase during physical exercise in women.

Physical activity is an important factor for maintaining and probably increasing bone mass in humans. However, the mechanism by which this takes place is not completely understood. The purpose of this study was to examine the influence of physical exercise on serum alkaline phosphatase (ALP) and in particular, the bone isoforms of ALP. Six ALP isoforms were quantified by high-performance liquid chromatography: three bone (B/I, B1, and B2), and three liver ALP isoforms. In addition, serum calcium, parathyroid hormone (PTH), and other markers of bone formation and degradation, as measured by osteocalcin and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), were analyzed. The study groups comprised 15 women, 8 postmenopausal (range 51-62 years) and 7 near age of peak bone mass (range 21-27 years). When the postmenopausal women exercised on an ergometer cycle until exhaustion we found significant increases in serum of bone ALP isoforms B1 and B2, and phosphate, even considering the hemoconcentration that occurred during the exercise. When the young women jogged in a moderate tempo for 40-40 minutes the levels of serum B2 and PTH increased. All changes turned towards baseline within 20 minutes after exercise. In conclusion, exercise increased serum ALP bone isoforms B1 and B2, and their responses were differentiated. As B1 and B2 are known to represent specific bone compartments, cortical and trabecular bone, the present findings may indicate different effects on bone of weight- and nonweight-bearing exercise.

Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells.

Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10(-6) mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.

Platelet and plasma catecholamines in relation to plasma minerals and parathyroid hormone following acute myocardial infarction.

Epinephrine has been shown to lower the plasma concentrations of several minerals and elevate those of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of such experimental observations, 34 patients with acute myocardial infarction (AMI) were studied with daily determinations of plasma catecholamines, minerals, and PTH during the first week after AMI and at follow-up one month later. In addition, platelet catecholamines were determined as they fluctuate more slowly than plasma catecholamines. After infarction initial platelet epinephrine and norepinephrine levels were higher (p less than 0.05 for both) in nonsurvivors than survivors during a one year follow-up. Results suggested that activation of the sympathoadrenal system influences calcium homeostasis following AMI, but that the impact of sympathoadrenal activation on mineral metabolism is of minor clinical significance in the average AMI patient. High platelet catecholamine levels may predict a poor outcome after AMI.

Effects of prolonged adrenaline infusion and of mental stress on plasma minerals and parathyroid hormone.

The role of the sympatho-adrenal system for the secretion of PTH in humans is not established. Previous studies on the effects of adrenaline on plasma mineral homeostasis have focused on injections or short-term infusions of adrenaline, and conflicting results concerning calcium and parathyroid hormone (PTH) responses have been reported. We therefore infused adrenaline or placebo continuously for 3 h to 10 healthy volunteers and studied several plasma minerals, as well as PTH levels. Venous plasma adrenaline concentrations increased to the upper physiological range (5 nmol l-1) during adrenaline infusion. Another nine volunteers were exposed for 25 min to mental stress (a colour word conflict test; CWT), which causes marked circulatory changes and raises plasma catecholamine concentrations. Plasma ionized and total calcium, and magnesium concentrations were slowly and gradually reduced during infusion of adrenaline, but there was only a small increase in PTH. Plasma potassium was decreased by adrenaline within 30 min and thereafter did not change further during infusion. There was a marked but transient increase in the plasma free fatty acids concentration, which were not related to the reduction of the calcium or magnesium levels. The adrenaline-induced decrements in calcium, magnesium and potassium, and increases in heart rates persisted 30 min after the infusion, despite a rapid decrease in plasma adrenaline concentrations within 5 min of termination of the infusion. Plasma phosphate concentrations were lowered during the first 90 min of adrenaline infusion, but after 3 h they had returned to baseline despite continued infusion. CWT induced small increments of the plasma ionized calcium and PTH concentrations. Plasma potassium levels were raised despite increases in plasma adrenaline at the beginning of the stress test, while phosphate values were reduced at the end of the test. Thus, long-lasting elevations of circulating adrenaline lower plasma ionized and total calcium, phosphate, magnesium and potassium, but the time courses for these changes differed markedly. Despite the reduction of plasma ionized calcium there was only little increase in PTH and thus no indication that sustained elevations of circulating adrenaline stimulates the secretion of PTH in vivo in humans. Responses to acute mental stress and adrenaline infusion differed qualitatively, indicating that adrenaline responses to stress are of minor importance in this respect.

Serum electrolytes and parathyroid hormone in patients in a coronary care unit.

A prospective study was carried out in 499 patients admitted to a coronary care unit (CCU) in order to evaluate the incidence of clinically significant electrolyte disturbances. Low serum potassium values (less than 3.6 mmol l) occurred in 7% of the CCU patients and low serum magnesium values (less than 0.70 mmol l-1) in 6%. Few patients had low values of both these ions (1.9%). In 49 patients the contents of these electrolytes in muscle biopsies were similar to the values of control subjects and were unrelated to treatment with diuretics. Serum calcium was determined in 444 of the patients and was above the reference range in 11 (2.5%). If we consider their concomitant parathyroid hormone (PTH) values, primary hyperparathyroidism was likely to occur in at least seven patients (1.5%). Patients with acute myocardial infarction (AMI) had mean PTH and electrolyte values similar to those of individuals without this disease. In conclusion, the present study indicates that clinically important disturbances of magnesium, potassium or calcium homeostasis are rare among unselected patients admitted to a CCU.

Increase in serum parathyroid hormone levels after prolonged physical exercise.

Serum concentrations of parathyroid hormone (PTH), calcium, magnesium, phosphate and myoglobin were measured regularly during a 5-d recovery period in 17 men who had participated in a 7-d field exercise maneuver with intense physical activity. Immediately after the exercise, there was an increase in serum PTH levels of the same magnitude as the maximal rise during a hypocalcemic test. The rise in PTH was not related to changes in serum electrolytes, but was significantly correlated to an increase in serum myoglobin, indicating that those who performed the largest amount of work also experienced the greatest stimulus for secretion of PTH. There were no significant changes of the serum total calcium and only a small initial rise of the magnesium concentrations. Serum phosphate levels were greatly reduced and gradually returned during recovery. This study extends previous observations, from short-term investigations, that physical activity stimulates secretion of PTH.

Effects of propranolol and verapamil on plasma ionized calcium and parathyroid hormone in short-term intense isokinetic leg exercise.

Physical exercise, beta-adrenergic stimulation and calcium channel blockade can affect calcium homeostasis. The present study investigated, in eight healthy males, the effects of orally administered propranolol or verapamil during a 2-min maximal, isokinetic, leg exercise. Immediately after exercise the plasma ionized calcium concentrations were increased, in control and drug tests, by 5-6%, and within 5 min of recovery they were almost returned to baseline. Serum parathyroid hormone (PTH) concentrations were unchanged at termination of exercise, but they increased during the first 5 min of recovery, coincident with the decline in calcium concentrations, which, however, were still elevated. Neither verapamil nor propranolol selectively changed basal or exercise plasma ionized calcium or serum PTH concentrations. Muscle strength, blood pH, lactate concentrations and plasma volume changes were not affected by any drug. Verapamil did not have any specific effect on the concentrations of plasma magnesium, phosphate, potassium or sodium while propranolol increased the concentrations of plasma potassium and decreased those of phosphate during exercise as well as recovery.

Maximal isokinetic muscle strength in patients with primary hyperparathyroidism before and after parathyroid surgery.

Primary hyperparathyroidism (HPT) is associated with symptoms of generalized fatigue and muscle weakness. The purpose of this study was to investigate muscular function in HPT quantitatively and to evaluate the effect of parathyroid surgery in this respect. The maximal isokinetic muscle strength (peak torque) of knee extension and flexion was measured with a Cybex-II dynamometer in 16 patients with primary HPT (mean serum calcium 2.81 +/- 0.14 mmol/l), four of whom had subjective impairment of strength, and in nine control patients submitted to hemithyroidectomy due to atoxic thyroid adenoma. Before surgery there was no significant difference in muscle strength between the two groups, neither was there any consistent relationship between the subjective feeling of muscular weakness and the measured peak torque. Seven months after surgery the HPT patients had increased their muscle strength by 8 per cent (P less than 0.05). The improvement was correlated with the pre-operative serum calcium levels (r = 0.56, P = 0.02) and was particularly seen in patients with pre-operative subjective muscular weakness. Patients with only slightly raised calcium values and without subjective muscular symptoms did not benefit clearly from surgery, compared with the controls. The study demonstrates that HPT patients, especially those with neuromuscular symptoms, can improve their muscle strength after parathyroid surgery.

Reduction of serum parathyroid hormone levels during sympathetic stimulation in man.

The parathyroid glands contain sympathetic nerve endings and the parathyroid cells are endowed with beta-adrenergic receptors. The physiological role of the sympathoadrenal system for the secretion of parathyroid hormone (PTH) has, however, not been clarified. Using the technique of lower body negative pressure (LBNP), which is an established method to achieve sympathetic nerve activation, it was found in 17 healthy subjects that the venous serum levels of PTH were reduced by 7% within 20 min [from 0.79 +/- 0.12 (SD) to 0.74 +/- 0.11 arbU/l, p less than 0.01, paired t test]. The reduction corresponds to 30% of the maximal suppressibility of PTH by induced hypercalcemia or following parathyroidectomy when studied with the same PTH assay and with the short time period involved. After cessation of LBNP the PTH levels returned to baseline within 20 min. There were no concomitant changes of the plasma ionized calcium concentrations. The findings are compatible with a role for the sympathetic nervous system in the physiologic regulation of the secretion of PTH.

Plasma potassium and phosphate concentrations--influence by adrenaline infusion, beta-blockade and physical exercise.

Infusion of adrenaline into healthy male subjects reduced the plasma concentrations of both potassium and phosphate to a similar extent, in a dose-dependent manner, an effect which was prevented by the administration of propranolol. Ergometer bicycling until exhaustion, which caused marked accumulation of lactic acid in the blood and reduction of pH, induced great elevations of both plasma potassium and phosphate with close relationships between the raised plasma concentrations and the reduction in pH, also during beta-blockade. However, longer-term aerobic exercise, without acidosis, also caused some rise of the potassium and phosphate concentrations. During recovery from anaerobic, but not from aerobic, exercise there was a rapid decrease of the plasma potassium levels while the phosphate values normalized gradually together with pH. From measurements of the ion concentrations both in the femoral effluent of one leg, which carried out maximal isokinetic work, and in the opposite antecubital vein it could be calculated that there was for potassium, but not for phosphate, a post-exercise uptake both in the exercised muscle and in the entire organism, indicating the participation of systemic factors.

Prolonged low-intensity exercise raises the serum parathyroid hormone levels.

Twelve healthy males performed 5 h exercise on a bicycle ergometer at a constant work load of approximately 50% of their maximum capacity. The serum concentrations of parathyroid hormone (PTH) increased after the first hour and were continuously elevated throughout the exercise period. The rise in PTH was 5-7% above pre-exercise levels, corresponding to 20-30% of the maximal increase obtained by the same assay during prolonged hypocalcaemia. The probable cause for the rise in PTH was that the plasma ionized calcium tended to be lowered during exercise. Since the total serum calcium concentrations were raised (by 3-5%) during exercise the reduction of the free, ionized, fraction was presumably largely due to increased complex-binding although an outward transport from plasma was not excluded. The serum concentrations of magnesium were gradually reduced during exercise while those of phosphate and potassium were raised throughout, probably as a result of leakage from the working muscle.

Serum electrolytes and parathyroid hormone concentrations in acute myocardial infarction.

Serum concentrations of calcium, magnesium, potassium and phosphate can be lowered experimentally by adrenaline, which also can stimulate the secretion of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of these mechanisms serial blood samples were drawn during the first three hospital days in 26 patients with acute myocardial infarction (AMI), a condition known to increase plasma catecholamine levels. During the study period there were no consistent significant changes of the serum electrolytes. The serum PTH levels, however, were significantly raised in the AMI patients already on admission and did not normalize during the observation time. The PTH concentrations were unexplained by infarct size, concomitant diseases or medication. These findings suggest that PTH could be an independent risk factor for AMI.

Regional and systemic effects of short-term intense muscular work on plasma concentration and content of total and ionized calcium.

Isokinetic work with one leg was carried out with maximal force for 2 min by five healthy subjects. The concentrations of plasma total calcium and of ionized calcium in the effluent from the leg increased by a mean of 13.6 +/- 1.8% (SD) and 16.2 +/- 2.0%, respectively. The corresponding rises in the resting arm were 7.7 +/- 4.3% and 8.1 +/- 3.0%. There was a close correlation (r = 0.86; P less than 0.001) between the degree of exercise-induced acidosis and the rise in plasma ionized calcium. However, the calcium values normalized both in the leg and in the arm within 5 min after the exercise and were similar at the two measuring sites despite a lower pH in the leg sample. During work there was a reduction of the plasma volume of 11.2 +/- 6.0% in the regional (femoral) and 12.4 +/- 4.2% in the systemic (antecubital) sample (P less than 0.001 compared to baseline values for both measurements). When adjustments were made for the reduction in plasma volume as well as for acidosis it was evident that, despite the apparent increases in the calcium concentrations, there was a net reduction of the plasma ionized calcium content (the total amount of plasma ionized calcium). This decrease was significantly (P less than 0.05) more pronounced in the exercising leg than in the systemic circulation but the difference could largely be explained by higher calcium-lactate complex formation in the leg.

Effects of exogenous catecholamines and exercise on plasma magnesium concentrations.

Catecholamines and physical exercise are known to influence the metabolism of several minerals in man, but the effects on magnesium (Mg) have been scarcely investigated. In the present study, infusion of adrenaline (5 micrograms/min for 30 min followed by 10 micrograms/min for 30 minutes) significantly reduced the plasma Mg levels in healthy males. This effect was abolished by simultaneous infusion of propranolol. Noradrenaline had no such effect. In order to stimulate endogenous catecholamine release healthy males carried out physical exercise in four different ways: ergometer bicycling at maximum load until exhaustion with and without oral beta-blockade, ergometer bicycling with stepwise increasing load until exhaustion, isokinetic maximal exercise with one leg, with blood sampling both from the venous effluent of the exercising leg and the opposite resting arm and long-term (60 min) steady state ergometer bicycling at approximately 65% of estimated maximum capacity. During short-term (less than 20 min) intense exercise (i.e. experiments 1-3) the plasma Mg concentrations were increased. This was probably due to a reduction of plasma volume and to an influx of Mg to the vascular pool. During long-term steady state exercise (experiment 4) the Mg levels were not significantly affected but decreased during the first hour of recovery. These results suggest that both the beta-adrenergic system and muscular activity by itself affect Mg homeostasis.

Effects of physical exercise on serum calcium and parathyroid hormone.

The effects of physical exercise on plasma ionized calcium, total serum calcium and parathyroid hormone (PTH) concentrations were evaluated in healthy subjects submitted to work on an ergometer bicycle. When the workload was increased stepwise there was a significant increase (P less than 0.001) in the calcium concentrations (ionized calcium from 1.13 +/- 0.03 (SD) to 1.24 +/- 0.03 mmol 1(-1) and total calcium from 2.35 +/- 0.07 to 2.48 +/- 0.07 mmol 1(-1] when the workload exceeded approximately 65% of the estimated maximum--i.e. a load that caused accumulation in blood of lactic acid. The rise in plasma ionized calcium was, therefore, presumably largely attributed to the acidosis but reduction of plasma volume and influx from extracellular sources might also have contributed. Beta blockade (with oral intake of propranolol) reduced physical capacity, shortened the duration of work and caused less acidosis. These factors were probably responsible for a smaller rise in ionized calcium during beta blockade (7 +/- 4%) than in control studies (21 +/- 5%) without medication in subjects examined during short-term maximal exercise. Long-term (1 h) steady-state work which caused fatigue without producing lactic acidosis did not affect the calcium concentrations. Despite the effects of work on calcium levels there was no discernible suppression of the PTH concentrations. This might have been due to a concomitant stimulation of PTH secretion by work.