Marco Galli

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis

SummarySerum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 μg/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3).Basal serum BGP was significantly lower in osteoporotic women (3.8±1.4 ng/ml) than in agematched controls (6.8±2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8±1.5) was significantly higher than the mean basal value.It is known that BGP synthesis is stimulated by 1,25 (OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation.

Effects of parathroid hormone and calcitonin on plasma and nephrogenous cclic adenosine‐3.,5 ‐monophosphate in normal subjects and in pathological conditions

Abstract. To evaluate the response of bone cells and kidne to parathroid hormone (PTH) and calcitonin (CT), the acute effects of these hormones given intravenousl on plasma cclic adenosine 3′,5′‐monophos‐phate (cAMP), nephrogenous cAMP and clearance ratio (cAMPxreatinine), have been studied in normal subjects and in patients with Pagets disease, hpoparathroidism and osteopetrosis.

Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

The 24-h urinary cyclic adenosine 3′, 5′-monophosphate/creatinine ratio: an useful approach to the diagnosis of parathyroid disorders and function

Abstract24-h urinary cyclic adenosine 3′,5′-monophosphate/creatinine (cAMP/Cr) ratio was assessed in 10 patients with hypoparathyroidism, 6 with primary hyperparathyroidism, 7 with normocalcemic hypercalciuria and recurrent nephrolithiasis, 14 with osteomalacia, 25 with Paget’s disease and 53 with symptomatic postmenopausal osteoporosis. In hypoparathyroid subjects the mean values of 24 h cAMP/Cr ratio were significantly lower than the control values, whereas in patients with parathyroid adenoma the mean values were higher and fell after parathyroid surgery. Patients with nephrolithiasis due to absorptive hypercalciuria showed low or normal cAMP/Cr ratio, whereas in those with osteomalacia the mean values of cAMP/Cr ratio were significantly higher than the control values and decreased after vitamin D treatment. The mean value of the 24 h urine cAMP/Cr ratio was normal in patients with Paget’s disease or postmenopausal osteoporosis and increased significantly after long term treatment with calcitonin or diphosphonate. This increase paralleled a significant decrease of calcium plasma level. A significant improvement of fractional calcium absorption was observed in women with postmenopausal osteoporosis at the end of treatment with calcitonin or diphosphonate.

Serum osteocalcin radioimmunoassay in bone diseases

SummaryOsteocalcin (or bone Gla protein, BGP) is a non-collagenous vitamin K-dependent protein accounting for 1–2% of the total bone proteins. It represents a specific index of osteoblastic activity and directly reflects the bone turnover. Serum levels of osteocalcin were measured by a radioimmunoassay method. In 40 postmenopausal women with osteoporosis, mean serum BGP levels were lower than the normal range (3.69 ± 1.35 ng/ml), whereas they significantly increased in 7 patients with osteomalacia (10.48 ± 3.05 ng/ml), in 12 patients with secondary hyperparathyroidism (11.1 ±0 4.9 ng/ml) and in 41 patients with Paget’s disease (12.09 ± 6.5 ng/ml). Four patients with primary hyperparathyroidism showed very high BGP levels (64.0 ± 32.3 ng/ml), which strikingly fell after the surgical removal of a parathyroid adenoma. These results confirm that the quantitation of serum osteocalcin is a specific and sensitive method in the diagnosis of bone disease, represents a useful index of bone turnover and is particularly helpful in the follow-up of patients with treated bone disease.

A new radioimmunological method for determining free thyroxine.

SummaryA new method for determining free thyroxine in human serum was evaluated. It is a radioimmunological direct assay method using an anti-thyroxine antiserum which is very specific and bound to a solid-phase. To determine the accuracy of the method, we measured ‘with-in-assay’ reproducibility to have a CV% maximum of 2.9, and ‘between-assay’ reproducibility (for three sera with three different FT4 levels) to have a mean CV% of 8.2; the reproducibility of the standard curves in 12 different assays showed a maximum CV% of 9.2. FT4 levels were also evaluated in 167 subjects: in 55 normal subjects a mean FT4 value equal to 13.99 ng/l (range 8.8–19.1) was obtained; in 25 euthyroid subjects with high TBG and in 5 with low TBG normal values were obtained in 97% of the cases, whilst FTI values were within normal limits in only 77%; in 25 euthyroid patients with goitre, FT4 values were always within normal limits, in contrast with TT4 and FTI values (92%); in 25 patients with hyperactive ‘hot’ thyroid nodules, values which were on average higher (15.2 ng/l) than the range were obtained in 24% of the cases, whilst TT4 and FTI were higher than the range in 12% of the cases; in hyperthyroid (no.=24) and hypothyroid patients (no.=16), FT4 values were not within the normal range. The assay method was compared with another commercial method (radioimmunological, after separation of bound and free fractions by chromatography on Sephadex). There was a highly satisfactory correlation between the two methods (y=4.12+0.96x, r=0.982) in 123 samples, although a tendency was observed for the new method to show higher values than the older. We conclude by stating that the method studies is convenient and has acceptable accuracy and clinico-diagnostic reliability.

Seasonal variation in urinary excretion of cyclic AMP in healthy people

In a group of healthy young men and women the daily urinary excretion of cyclic adenosine 3′, 5′-monophosphate (cAMP), calcium, hydroxyproline and the renal threshold phosphate concentration were evaluated at monthly intervals during 1 yr. A significant seasonal variation in cAMP urinary excretion was demonstrated, with a maximum occurring in spring and a minimum in winter. A clear annual rhythm was also observed when the other above parameters were considered. These findings are of importance in the interpretation of urinary cAMP values in clinical situations, and in the study of bone metabolism.