[Effects of alpha-calcidiol (1 alpha-hydroxy-cholecalciferol) on the serum levels of osteocalcin in involutional osteoporosis]. / Effetti dell'alfa-calcidolo (1 alpha-idrossi-colecalciferolo) sui livelli sierici di osteocalcina nell'osteoporosi involutiva.

We have examined the effects of 1 alpha-hydroxycolecalciferol (1 alpha) (1.5 micrograms for 5 days) on serum osteocalcin (OC) and other parameters of bone and mineral metabolism in 20 osteoporotic women and 11 age-matched normal women. After 1 alpha administration, a statistically significant (p less than 0.01) increase of serum OC, calcium and phosphate and urinary calcium and hydroxyproline was observed. In contrast, alkaline phosphatase was unchanged. There was no significant difference between normal and osteoporotic women in the changes of any of the parameters we monitored. In particular, OC increased in a comparable way in both groups. Thus, by means of an index that reflects the global activity of the skeleton, we could not find any apparent defect of osteoblastic responsiveness to the drug in osteoporotic subjects.

[Sequential calcitriol-calcitonin in the therapy of osteoporosis]. / La sequenza calcitriolo-calcitonina nella terapia dell'osteoporosi.

Different therapeutic regimens have been proposed by Authors in the treatment of involutional (and particularly postmenopausal) osteoporosis. Following the up to date concepts on bone remodelling, an ADFR (Activate, Depress, Free, Repeat) trial was performed in 20 females affected by involutional osteoporosis. They were treated with Calcitriol 2 mcg/d for 7 days, followed by a 21 days period of 100 U/d Salmon Calcitonin + 1 g/d Calcitonin, followed by a 2-month period of Calcium alone. The cycles were repeated for 1 year and the results of densitometric examinations (radial mineral content evaluated by single photon absorptiometer, and vertebral mineral content evaluated by dual photon absorptiometer) and of biochemical markers (Ca++, P, osteocalcin, alkaline phosphatase, hydroxyproline) controlled every 3 months, were compared with those obtained in a group of patients treated only with Salmon Calcitonin and in a group treated with Calcium for 1 year. After two therapeutical cycles radial bone mineral density significantly increased; vertebral bone density also increased but not significantly. The effects were more evident in comparison to calcitonin alone treatment. A significant reduction in serum osteocalcin was documented. At the end of the therapy no further improvement was registered. This suggests that some variations and adaptation of therapeutic strategy are needed to achieve a more important and substantial improvement of bone conditions.

[Changes in bone mass with age. Transversal study on a female population using photon densitometry]. / Variazioni della massa ossea con l'età. Studio trasversale su una popolazione femminile mediante densitometria fotonica.

In order to evaluate the age-related changes of the bone mineral content (BMC), 281 clinically healthy women (20-80 year old) underwent single photon abosorptiometry (SPA) on the distal third of the radius (where there is a prevalence of cortical bone); 161 subjects of this group were examined also by dual photon absorptiometry (DPA) of the lumbar tract of the spine (L2-L4) (trabecular bone). The relationship of trabecular BMC with age is described by a cubic polynomial regression (r = 0.46; p less than 0.0001) that shows an increase in BMC until 31 years of age followed by a decrease with a minimum at the age of 78; afterwards trabecular BMC adds an apparent increase. No increase in the rate of trabecular BMC loss was seen after the menopause. A positive correlation was found between body weight and vertebral BMC. The behaviour of cortical BMC with age is described by a quadratic regression (r = 0.42; p less than 0.0001) that shows an increase until 32 years of age followed by a decrease. Cortical BMC shows a significant decrease after menopause. No correlation was found between body weight and cortical BMC. These findings underline the different behaviour of trabecular and cortical bone tissue with age; in addition, the relation between trabecular (but not cortical) BMC and body weight argues for an important role of biomechanical factors in the local modulation of bone mass.

Short-term effects on bone and mineral metabolism of 4-amino-1-hydroxybutylidene-1,1-diphosphonate (ABDP) in Paget's disease of bone.

To study the short-term effects on mineral and bone metabolism of a recently introduced amino-diphosphonate (4-amino-1-hydroxybutylidene-1,1-diphosphonate or ABDP), 10 patients suffering from active Paget's disease were examined. Each subject received intravenously 5 mg/day of ABDP for 4 days and the effects of treatment were monitored for 12 days. ABDP administration was followed by an early and significant decrease of the urinary hydroxyproline and calcium excretion, of the theoretical renal threshold for phosphate of the serum calcium. Serum phosphate also decreased, while its urinary excretion increased. Intact parathyroid hormone levels at the end of treatment were four times higher than basal levels. Total and bone alkaline phosphatase tended to decrease only slightly at the end of the observation, whereas serum osteocalcin, tended to increase. These findings indicate that the earlier effect of ABDP is a profound inhibition of bone resorption, which brings about a compensatory parathyroid hormone response. The decrease of urinary hydroxyproline follows an exponential curve, with a calculated half-life of 2.2 days, suggesting an approximate equivalency of 5 mg/day ABDP to slightly more than 30 mg/day 3-amino-1-hydroxypropylidene-1,1-diphosphonate. Bone formation seems scarcely influenced in the short-term, but osteoblastic indices show a contrasting behaviour, which may reflect a different biological origin and/or significance.

[The hormonal response to hypercalcemic stimulation: the difference between male and female young people]. / La risposta ormonale allo stimolo ipercalcemico: differenze tra maschi e femmine giovani.

The aim of our study was to evaluate the pattern of response of thyroid Calcitonin (CT) secretory cells in young healthy people after specific stimulation. For this purpose, test of 60'' i.v. calcium infusion in a dose of 4 mg/Kg lean body mass was employed. Blood samples were taken at times-5', 0', 2', 5', 10', 15', and 30' after the infusion, to determine total Calcium (Ca), ionized calcium (Ca++) and CT concentrations. As a result, plasma CT increased significantly (f = 24.51, p less than 0.000001) in both sexes, while males showed stimulated CT values about double than the female ones: the difference was statistically significant throughout the test. In males too, we observed a strong and significant (r = 0.92, p less than 0.01) correlation between ionized calcium increases and CT responses. This correlation was found neither in males as regards total calcium, nor in females. In conclusion, our data confirm the higher CT secretion in males, indicating also a more constant pattern of response in this sex. Eventually, ionized calcium proves to be the real effective provocative stimulus for CT secretion.

Meal-stimulated gastrin release and calcitonin secretion.

In order to study the effects of a physiologic meal on calcitonin (CT) secretion we studied 6 normal male volunteers (aged 28-34 yr). Each subject was given, on two separate days, either a mixed meal or 200 ml of distilled water, in random order. Gastrin (G) was effectively stimulated by the meal (F = 8.82; p less than 0.001) and reached a peak (with an average 100% increase) 30 min after the end of the meal, slowly decreasing thereafter; no increase was seen after water ingestion. On the other hand, CT levels remained stable throughout the observation period on both occasions. Ionized and total calcium did not show significant variations either after the meal or after water ingestion. These findings suggest that G alone, at the concentrations usually reached after a physiologic meal, is unable to stimulate CT secretion, at least in the absence of calcium increases.

Osteocalcin levels in diabetic subjects.

Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.

Spontaneous release of interleukin-1 (IL-1) from medullary mononuclear cells of pagetic subjects.

The Authors examined interleukin 1 (IL-1) secretion from the peripheral and medullary mononuclear cells, obtained with sequential separation on Ficoll-Hypaque and 45% Percoll gradient, in 6 pagetic subjects and 6 normal controls. Both peripheral and medullary cells from pagetic subjects showed a significantly greater IL-1 production after stimulation with lipopolysaccharides (LPS); moreover, we observed a spontaneous IL-1 release from medullary cells in pagetic subjects but not in normal controls. These findings suggest a possible role of IL-1 in the elevated bone turnover of Paget's disease of bone.

Calcitonin secretion rate in elderly normal subjects.

The aim of the study was to investigate the metabolic clearance rate (MCR) and the secretion rate (SR) of calcitonin (CT) in elderly men and women (mean age +/- SE: 75 +/- 3 and 78 +/- 3 yr, respectively). The basal levels of CT were higher in men than in women (9.6 +/- 3.2 vs 6.0 +/- 1.5 pg/ml; p less than 0.05). The MCR was not significantly different between sexes (905 +/- 54.2 vs 810 +/- 165.1 l/day). In contrast, CT SR was significantly higher in male subjects compared to women (8.7 +/- 3.1 vs 4.8 +/- 1.5 micrograms/day; p less than 0.05). These findings suggest that only a few units of CT are secreted daily by elderly subjects and that the lower basal values of the hormone in women are probably the result of a lower production rate.