Effects of nandrolone decanoate on bone mass in established osteoporosis.

A double-blind, randomized, placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of nandrolone decanoate on the bone mineral density (BMD) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover. The patients received intramuscular injections of placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months. Overall, vertebral BMD increased by 2.9% in the nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD showed a slight but transient improvement, with a subsequent return to basal levels in the nandrolone decanoate group, whereas there was a progressive decrease in the placebo group. Patients treated with nandrolone decanoate also complained less of bone pain. Urinary hydroxyproline decreased significantly in treated patients, whereas osteocalcin tended to increase, but the change was not significant. HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the nandrolone decanoate group. Two patients treated with nandrolone decanoate withdrew from the study because of hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis.

[Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography]. / Lipidi ed apoproteine sieriche in soggetti con aterosclerosi coronarica di grado lieve o moderata valutata angiograficamente.

In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease.

Habitual leisure-time physical activity is associated with differences in various risk factors for coronary artery disease.

Various risk factors for coronary artery disease (CAD) were compared in 100 healthy, male factory workers, divided into two groups of 50 each on the basis of their leisure-time activity. The two groups, designated as sedentary and physically active, were similar in terms of age and body mass index, but the physically active group had a significantly slower pulse rate. In addition, the plasma glucose and insulin responses to an oral glucose load were significantly lower in physically active individuals. Furthermore, fasting plasma triglyceride concentration was significantly lower and the high-density lipoprotein-cholesterol concentration was higher in the physically active individuals. Thus, substantial benefits in terms of CAD risk were associated with increased leisure-time physical activity.

[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.

The effects of methotrexate (MTX) on bone. A densitometric study conducted on 59 patients with MTX administered at different doses.

The bone density of two groups of patients with osteosarcoma treated with high and low doses of MTX is compared with that of a group of healthy subjects of the same age. Bone density was measured in the radius at the mid point and at the trabecular distal point. In the patients treated with low doses there were differences in bone density as compared with the controls. In those treated with high doses the bone mineral content values were significantly lower than those for the controls (p greater than 0.01) at the trabecular distal point but not at the mid point. The significant reduction in BMC in patients treated with high doses indicated that the osteopaenic effect is dose-dependent. The decrease in density only at the site at which trabecular bone is prevalent shows that MTX acts mainly at the level of this type of bone in accordance with the proven greater sensitivity of trabecular bone to the action of other osteopaenic agents.

Hepatic alterations in indomethacin-treated rabbits.

Indomethacin was parenterally administered (6 mg/Kg/day) for 30 days to rabbits, to evaluate changes in serum biochemical parameters and any ultrastructural alterations induced by the drug at the hepatic level. An analysis of the results demonstrated that when the group of rabbits, a statistically significant increase in the serum ALT was found in the treated rabbits. Ultrastructural observations showed the following hepatocyte alterations: 1) minimum mitochondrial alterations 2) mild signs of cholestasis (pericanalicular osmophilic bodies) 3) Smooth endoplasmic reticulum hyperplasia. These findings suggest that indomethacin has the capacity to induce hepatic lesions in the rabbit and this is probably due to the surfactant mechanism.

Amikacin-induced liver toxicity: correlations between biochemical indexes and ultrastructural features in an experimental model.

In previous studies, aminoglycosides (AG) as gentamicin (G), dibekacin (D), tobramycin (T), netilmicin (N) and Sysomicin (S) were proved to induce ultrastructural alterations in the liver of experimental animals. The aim of this studies is to investigate the effect of amikacin (AK) on rabbit liver which is commonly used in infections resistant to other AG; this was done studying both the common blood parameters and ultrastructural changes. The study was accomplished in 24 New-Zealand rabbits, twelve received 20 mg/kg AK every 12 hours for 2 weeks. Thereafter the animals were anesthesized and liver slices were obtained for transmission electron microscopy. As results obvious signs of primary and secondary microcholestasis associated to mitochondrial cristae detachment and phospholipid aggregations were noted; this last finding was less marked when compared to previous studies employing other AG. In the AK treated group, blood tests showed a significant increased in only Blood Urea Nitrogen (BUN) and an insignificant rise in AST levels. Our findings are consistent with an AK induced liver toxicity albeit less evident with respect to the other AG.

Whole blood filterability in elderly obese women.

In order to establish whether obesity alters whole blood filterability, the corrected whole blood filtration (VRBC) was measured in 54 elderly obese women (mean age +/- SE = 67 +/- 2 years) without (n = 15) or with associated cardiovascular risk factors such as impaired glucose tolerance (IGT) (n = 11), non-insulin dependent diabetes mellitus (NIDDM) (n = 14) or hypertension (n = 14). Twenty-two age matched women with normal body weight participated as controls. VRBC values were similar in normal controls and obese women with normal glucose tolerance (NGT), whereas they were significantly lower in obese subjects with hypertension, NIDDM or IGT. When subjects with normal and impaired glucose tolerance were combined, a significant negative correlation was found between glucose incretory areas during OGTT and VRBC values. These data demonstrate that obesity per se does not alter whole blood filterability; furthermore, our results indicate that this modification is a precocious and sensitive index of altered glucose metabolism.

[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.

Impaired calcitonin secretion following stimulation in spasmophilic women.

Calcitonin (CT) secretion following stimulation was studied in 9 young women suffering from spasmophilia, this having been diagnosed by clinical and electromyographic criteria. The controls were 9 women, matched by age, who responded negatively to the diagnostic tests. After rapid intravenous infusion (60 sec) of 4 mg/kg/lean body mass of calcium (as gluconate), CT concentration increased measurably (p less than 0.0001) in the controls, while remaining unchanged in the spasmophilic. The average increase per cent vs. the baseline values was 225% in the controls and 34% in those with spasmophilia (p less than 0.005). 5 out of 9 of the patients showed a completely flat curve. This finding, due to a diminished CT reserve in spasmophilia, may be considered a possible diagnostic feature as well as a fundamental pathological element in the reduction of the intracellular calcium pool responsible for the neuromuscular hyperexcitability. Moreover, the therapeutic use of the hormone in this condition is to be encouraged.

[Ultrastructural study of the liver in rabbits treated with diclofenac]. / Studio ultrastrutturale epatico in conigli trattati con diclofenac.

The existence of alterations of common indexes of hepatic function, and the case-reports of acute hepatitis after the use of diclofenac sodium are the rationale for this experimental study, in which 8 rabbits were given 15 mg/kg day of diclofenac, to check ultrastructural modifications with respect to a control group. The analysis showed the typical signs of primary and secondary microcholestasis, indicating the existence of liver distress. This finding, from a clinical standpoint, suggests caution in the administration of this drug, chiefly in the hepatopathic patients.