R. Castrignano

Effects of one-year cyclical treatment with clodronate on postmenopausal bone loss.

We studied 60 women with postmenopausal bone loss randomly allocated to the following treatments: Group 1 (20 patients), no treatment; Group 2 (20 patients), clodronate 400 mg daily by mouth for 30 consecutive days, followed by 60 days of no treatment; Group 3 (20 patients) oral calcitriol 2 mcg by mouth for 5 days and oral clodronate 400 mg daily for additional 25 days, followed by 60 days of no treatment. The therapeutic cycles were repeated four times in the 12-month study period. In the 36 treated patients of Groups 2 and 3 who completed the study period we observed a progressive and significant increase in lumbar bone density both at 6 and 12 months of therapy, without significant differences between the two treatment protocols (+3.88 +/- 0.65%, P < 0.001 and +3.21 +/- 0.89%, P < 0.005 in Groups 2 and 3, respectively, at the end of the study). In contrast, there was a progressive and significant decline of bone mineral density in untreated patients (-2.34 +/- 0.49%, P < 0.001). After 12 months serum calcium values in treated subjects were higher than in untreated patients (P < 0.05). Serum phosphate was raised only in Group 2, mean values being higher after 12 months than before treatment (P < 0.05); parathyroid hormone (PTH) declined in all treated patients, the fall being significant in Group 2 (P < 0.02). No important side effects were observed with treatment and no patient withdrew because of these. We conclude that cyclical low dose clodronate therapy induced a gain in lumbar spine bone mass in patients with postmenopausal osteoporosis.

Longitudinal study on osteodystrophy in primary biliary cirrhosis (PBC) and a pilot study on calcitonin treatment

The aims of this study were to evaluate bone metabolism in primary biliary cirrhosis (PBC) and the effect of ADFR (activate, depress, free, repeat) therapy with vitamin D, calcium and calcitonin in preventing bone resorption. Sixty-nine female subjects entered the study: 38 PBC (AMA + ve) patients, 11 AMA-negative chronic liver disease patients and 20 age-matched healthy controls. Bone metabolism was evaluated by biochemical parameters and dual-photon absorptiometry of the lumbar spine at time 0, 6 and 18 months. Both PBC and chronic liver disease (CLD) patients showed low levels of serum 25-hydroxyvitamin D, osteocalcin and bone mineral content expressed as AAD (average area density) compared to healthy controls. Serum parathyroid hormone in PBC patients was at the lower limit of the normal range and was significantly lower than patients with chronic liver disease. At a 6-month interval, AAD significantly decreased in PBC patients (p less than 0.005). At the 6-month period PBC patients were allocated into two groups according to a cut-off AAD of 0.800 g/cm2: group A (no treatment, AAD greater than 0.800, n = 11), group B (treatment, AAD less than 0.800, n = 13). The latter group received a 4-week course with oral calcium carbonate (1500 mg daily) + oral 1,25-dihydroxyvitamin D (0.5 micrograms twice a day for 5 days) + carbocalcitonin (40 U MRC) i.m. thrice a week. The treatment was repeated with the same protocol at 2-month intervals for 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of captopril in hypertensive diabetic patients

Twenty hypertensive diabetic patients (10 with type I and 10 with type II) were treated with captopril, 50 mg twice a day, for three months. The drug was effective as monotherapy in 16 patients. An additional nine months of follow-up was obtained in 12 of these patients (four with type I and eight with type II) who did not need the addition of diuretics to achieve normal blood pressure. For these patients with long-term treatment, since there was no substantial difference between those with type I and those with type II, the data were pooled. Mean arterial pressure significantly decreased shortly after treatment was begun and the reduction was maintained. No significant change was induced by captopril in urine volume, osmolar clearance, and serum and urinary values of sodium, chloride, calcium, and magnesium, whereas significant reduction was found in fractional excretion of potassium and phosphate. The baseline levels of proteinuria were only slightly elevated, yet they fell in all patients during treatment. All patients maintained satisfactory control of carbohydrate metabolism, and none of them required substantial changes in hypoglycemic treatment. The administration of captopril as monotherapy appears to be an effective and safe way of lowering blood pressure in diabetic hypertensive patients, even in the long term, without effects on renal function and in carbohydrate metabolism.

Role of insulin-like growth factor-I in primary osteoporosis: A correlative study

Osteoporosis is characterized by impairment of bone mass and deterioration of bone microscopic structure, resulting in increased bone fragility and susceptibility to fracture. Recent reports have indicated that reduced plasma levels of IGF-I are associated with osteoporosis in both males and females. Moreover, there is accumulating clinical evidence that treatment with GH or IGF-I has beneficial effects on bone mass and bone remodeling in men with idiopathic osteoporosis, in the elderly and in hypopituitary patients. As correlative studies on IGF-I, IGF-BP3 and bone mass in the elderly are lacking, we studied the relationships between serum IGF-I, IGF-BP3, bone mineral density (BMD), body mass index (BMI), calciotropic hormones and age in 102 premenopausal and postmenopausal women. Our study indicates that the reduction of the anabolic processes mediated by IGF-I may account for the slow and progressive loss of bone mass that take place after the age of 40-50 years. In addition, nutritional caloric or proteic deficit may add to the effects of GH, age and other factors in decreasing IGF-I synthesis and therefore further contribute to the development of primary osteoporosis.

Effect of doxazosin in mild to moderate hypertensive patients with insulin-dependent diabetes mellitus

Abstract Diabetic patients often develop hypertension, and the presence of both hypertension and diabetes doubles the risk of death from coronary heart disease (CHD). Moreover, the presence and importance of abnormalities such as high low-density lipoprotein (LDL) cholesterol and triglycerides levels as CHD risk factors in insulin-dependent diabetes mellitus type 1 have been downplayed, while increasing evidence suggests that the management of type 1 patients should include control of dyslipidemia and hyperglycemia and an effective antihypertensive treatment able also to reduce risk factors for coronary artery events. In this study we assessed the antihypertensive and metabolic effects of doxazosin in hypertensive patients with type 1 diabetes. We show that the drug normalizes blood pressure, and while no improvement in glucose control was observed, it reduced total cholesterol and increased HDL cholesterol as well as the HDL to total cholesterol ratio. The changes of the various parameters studied, including the calculated CHD risk score based on the Framingham equation, suggest that doxazosine can reduce the CHD risk for hypertensive type 1 patients.

Role of Diet in Calcium Nephrolithiasis

We evaluated the self-chosen customary diet of a group of 88 patients (50 males, age 42.9±11.8 (±SD) years; 38 females, age 44.0±14.7 years) affected by calcium nephrolithiasis (1) (Table 1). Sixty-four patients had recurrent, and 45 patients had bilateral nephrolithiasis. Mean body weights for the male (73.4±8.8 kg) and the female (65.0±12.2 kg) groups were 13% and 18%, respectively, above their ideal body weight.

Bone Mineral Content and Recurrent Calcium Nephrolithiasis with Idiopathic Hypercalciuria

Hypercalciuria has been associated with a decrease in bone mineral content (BMC) but this finding is still debated (1). In the present study, we followed 12 male patients age 44.4±13.2(±SD) years with recurrent Ca nephrolithiasis (RCN) and idiopathic hypercalciuria (IH) for a one-year period, comparing their data with those of 12 matched normal subjects. In the patients, mean urinary Ca excretion was 372±128 mg/day and their average stone occurrence was 10.2±1.2 calculi/patient. All individuals had previously undergone conservative treatment for their stone disease using low Ca and oxalate diets and had not received any specific pharmacological therapy.

Modification in Renal Handling of Phosphate Induced by Hydrochlorothiazide (HCTZ) and Amiloride (A)

Hydrochlorothiazide (HCTZ) has long been known as an effective hypocalciuric agent (1–3). When associated with amiloride, which has been shown to have hypocalciuric effect similar to that of thiazide (4), it may effectively reduce urine calcium excretion at dosages which are lower than those required by the single administration of each drug (5). For these reasons the combination of HCTZ and A has been widely used in patients with recurrent calcium nephrolithiasis (RCN). However, the mechanisms by which HCTZ and A act on the renal tubules are far from being clearly established and it is not known whether this drug combination may affect transport system other than those for sodium and calcium.