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The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has elaborated the following guidelines about the definition, prevention and treatment of inadequate vitamin D status. The highlights are presented here. Daily vitamin D allowance ranges from 1,500 IU (healthy adults) to 2,300 IU (elderly with low calcium intake). Since the average Italian diet includes around 300 IU/day, subjects with no effective sun exposure should be supplemented with 1,200-2,000 IU vitamin D per day. The serum 25-hydroxy-vitamin D [25(OH)D] levels represents the most accurate way to assess vitamin D repletion, even though there are still no standardized assay methods. Conditions of “deficiency” and “insufficiency” are defined by the following ranges of 25(OH)D levels: less than 20 ng/ml and 20-30 ng/ml, respectively. In Italy, approximately 50% of young healthy subjects have vitamin D insufficiency during the winter months. The prevalence of deficiency increases with ageing, affecting almost all elderly subjects not on vitamin D supplements. When a condition of deficiency has been identified, a cumulative dose of 300,000-1,000,000 IU, over 1-4 weeks is recommended. In subjects recently treated for deficiency-insufficiency, a maintenance dose of 800-2,000 IU/day (or weekly equivalent) is recommended. In patients on daily doses over 1,000 IU, 25(OH)D levels should be checked regularly (e.g. once every two years). The highest tolerated daily dose has been identified as 4,000 IU/day. Vitamin D supplementation should be carefully monitored in patients at higher risk of vitamin D intoxication (granulomatosis) or with primary hyperparathyroidism. In pregnant women, vitamin D supplements should be given as in non-pregnant women, but bolus administration (i.e.: single dose >25,000 IU) should be avoided.

Unlabelled: The guidelines for the osteoporosis management were first drafted by a working group and then critically evaluated by the board of SIOMMMS. The most relevant points are:, Definition: Osteoporosis is defined as a quantitative and qualitative deterioration of bone tissue leading to increased risk of fracture. Postmenopausal and senile osteoporosis are defined as primitive., Diagnosis: The cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T-score values <-2.5, following the WHO definition. Other DXA sites or technologies for measuring bone mass are also acceptable when the former is not accessible. A BMD evaluation is recommended to all women above 65 years of age. At younger age or in man the bone assessment is recommended only in subjects with specific risk factors. A control of bone mass measurement is seldom required before 2 years., Differential Diagnosis: A few biochemical tests such as serum and urinary calcium, protein electrophoresis, serum creatinine and ESR are usually sufficient to exclude most secondary types of osteoporosis. The value of the so called bone turnover markers for the diagnosis and follow-up of osteoporosis remains uncertain. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management., Prevention: The osteoporosis prevention should be based on the elimination of specific risk factors such as inadequate calcium and vitamin D intake, smoking and sedentary life. The use of pharmacological agents in subjects with BMD values >-2.5 is usually not justified. Pharmacological intervention: The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk. This is the case only when the risk of fracture is rather high. FRAX is recognized as a useful tool for easily estimate the long-term fracture risk. SIOMMMS with these guidelines is committed to validate and further develop this diagnostic tool.

Several studies have demonstrated the usefulness of B-type natriuretic peptide (BNP) dosage in patients referring for acute dyspnea in the emergency department. BNP is strongly associated not only with the evidence but even with the degree of heart failure, and BNP values are particularly increased in the advanced NYHA classes and in patients with poor prognosis. High BNP levels correlate with echocardiographic indexes of left ventricular and right ventricular systolic dysfunction but even better with diastolic dysfunction and degree of left ventricular filling pressure. However, in presence of some clinical confounders, such as obesity, renal insufficiency and anemia, BNP dosage itself cannot be interpretable. Under these circumstances, Doppler echocardiography is able to identify with better accuracy patients affected by heart failure. Algorithms built taking into account clinical and echocardiographic parameters as well as BNP measurements are already available in the guidelines of the European Society of Cardiology on heart failure with normal ejection fraction. They will lead to a better and earlier identification, better risk stratification and management of patients referring for heart failure.

Paget's disease of bone is a chronic focal abnormality of bone turnover that remains totally asymptomatic over a very long period of time but that eventually ensue in bone pain and skeletal deformities. Although, in the last decade new insights have been obtained on its etiology, this remains largely obscure. Effective medical treatment (based on the use of bisphosphonates) has become available and the diagnostic procedures are now well defined. However, there remains considerable controversy regarding the hierarchy of diagnostic procedures and the medical treatment threshold. In the last few years different institution have published national guidelines, reflecting local national health systems and the available medical treatment. In this review, a working group derived from members of the SIOMMMS has examined the information available regarding the diagnosis and treatment of Paget's disease in order to develop guidelines to assist in the management of this condition. The first draft was then extensively reviewed by experts derived from the most representative scientific societies of rheumatology, internal medicine, and orthopaedic surgery. The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments.

Background: Mitral and tricuspid valve asymmetric annular dilation represents the most important mechanism which produces insufficiency. Recent computerized in vitro and in vivo three-dimensional models have been developed in order to better understand the competing factors (annular dilation, displacement of papillary muscles, left and right ventricular geometry). The leading cause of mitral and tricuspid competence is a sphincteric action of both annuli, during systole and diastole, the loss of which produces asymmetric dilation and therefore the absence of cusp coaptation. The Cosgrove-Edwards dynamic ring corrects, alone or in combination with other procedures on the valves, this patho-anatomic feature in a physiological way by restoring the normal annular dimensions and the sphincteric movements during the cardiac cycle., Methods: Between June 1998 and May 1999, 30 adult patients underwent mitral (n = 20, Group I) or tricuspid valve repair (n = 10, Group II). Regurgitation was due to a degenerative disease in 13 Group I patients and to ischemic (n = 3), congenital (n = 2) or dilated cardiomyopathy (n = 2) in the others. In Group II the leading cause of insufficiency was functional regurgitation in 7 patients and organic in 3. Associated procedures were carried out in 4 Group I patients and in all Group II patients. Regurgitation was evaluated by transesophageal echocardiography before, during and 3 months after operation. The maximal regurgitant area (MRA) and the grade of insufficiency were evaluated using the equation: MRA < 2 cm2 = grade 0, MRA > 2 < 4 cm2 = 1+, MRA > 4 < 7 cm2 = grade 2+, MRA > 7 < 10 cm2 = 3+, MRA > 10 cm2 = 4+., Results: The operative mortality was 0%. One Group I patient died 3 months after operation due to bronchopneumonia. No patient was reoperated on for plasty failure in both groups during the follow-up. Mitral insufficiency was absent (grade 0) in 17 Group I patients and mild (grade 1+) in 3 at the end of operation. At 3-month postoperative transesophageal echocardiographic control mitral insufficiency was absent in 14 patients, mild (1+) in 4 and moderate (2+) in 2. MRA was 3 cm2 in the 2 patients operated on for dilated cardiomyopathy and < 3 cm2 in the others. Preoperative tricuspid insufficiency of grade 4+ in all Group II patients became absent in 9 of them either at the end of operation or at 3-month postoperative control., Conclusions: The Cosgrove-Edwards dynamic ring as isolated device or in combination with other plasty mitral or tricuspid procedures is a safe, simple, and reproducible method to restore the distorted motion of valvular annuli. It preserves the sphincteric mechanism of the valve and allows for the coaptation of cusps. Although in a small number of patients and for a short period of follow-up our experience corroborates what other more consistent series of patients operated on have shown.

"Pseudomembranous colitis" is a disease which has gained importance in the last decades. It is caused by intestinal colonization by "Clostridium Difficilis" which in normal situations, especially in the evolutive age, is a component of the normal saprophytic flora. Antibiotic therapy, or reduction of the immunological defenses by surgical procedures, infections, weakening diseases or malnutrition states may produce an alteration of the intestinal flora with a prevalence of Clostridium Difficilis which causes, with its intestinal toxin, organic and functional damages. The diagnosis is based on clinical symptoms and on endoscopic picture. The isolation of Clostridium Difficilis and its toxin in the patient's faeces is possible only in well-trained laboratories. The disease subsides with antibiotic interruption and with Vancomycin oral therapy. The Authors describe a paradigmatic case characterized by the simultaneous presence of antibiotic therapy, surgical procedure, characteristic endoscopic picture and by the prompt clinical and endoscopic recovery with Vancomycin.

With the advent of dual-energy x-ray absorptiometry (DXA) total body scans can be done in only 10-20 minutes rather than the 60-80 minutes required by dual-photon absorptiometry (DPA). The DXA approach replace the Gd153 radionuclide source of DPA and provides substantially greater output intensity. The higher radiation flux achievable provides several advantages over conventional DPA: this makes total body scans routinely accessible. The measures of the entire skeleton and its major subregions cut down the problems of representativeness and relocation. The short term precision (coefficient of variation) was 0.5% for total body-bone mineral density (BMD) and about 1% for regional-BMD. We studied 885 women; study cohort consisted of 161 healthy postmenopausal women, 357 healthy postmenopausal women and 367 osteoporotic women with one or more vertebral crushes. The results indicate that bone mass begin decreasing during the last period of the premenopausal phase; the advent of menopause brings about a dramatic reduction of both total body and single area BMD: this phenomenon is particularly marked in subjects with osteoporosis. The single most important factor in determining BMD changes, is years since menopause. In order to assess the ability of DXA total body to distinguish women with postmenopausal osteoporosis of variable radiological degress from healthy postmenopausal women, we studied 330 postmenopausal females aged 42-85 years. There were 63 healthy women who were considered controls (Group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Drug costs of various general anaesthesia techniques have been assessed. These costs are used as a basis to point out the economies that could be made in the conduct of general anaesthesia.

In the past twenty years autopsies are performed much less frequently in the elderly than in younger patients. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 214 patients who died from 1 January 1986 to 31 December 1989 at our Institute to determine the accuracy of clinical cause of death with respect to the pathologic cause of death. The most common cause of death were bronchopneumonia (25.2%) followed by gastroenteric and lung cancer (20%), cerebrovascular accident (15.8%), myocardial infarction (8%) and pulmonary embolism (7.4%). Pulmonary embolism was correctly classified only in 25% of patients. The most accurately diagnosed condition were neoplastic diseases (88%) and cerebrovascular accident (84.8%) while bronchopneumonia were correctly diagnosed antemortem in 72.2% of the patients studied. Our data suggest that advances in diagnostic technology have not reduced the value of the autopsy and that a goal-directed autopsy remains a vital component in the assurance of good medical care.

"Total body" densitometry, which was first used to determine total-body mineral content, allows, above all in the most recent X-ray (DXA) version, an accurate study to be made of soft tissues in relation to both their adipose and nonadipose components. In addition to being used for overall evaluations, it is possible to use DXA for regional studies of body tissue distribution, thus allowing obesity to be analysed not only in quantitative but also qualitative or more specifically endocrine-metabolic terms. In comparison to other methods DXA is noninvasive, quick to use, low cost and risk free. Given its high accuracy rate it can also be used to monitor patients with demineralizing pathologies, obesity, thinness due to global and/or district edema receiving dietary and/or pharmacological treatment.

Post-menopausal osteoporosis is a metabolic bone disease which is histologically characterised by a reduction of bone mass with normal mineral content of the remaining bone tissue. In clinical term, the symptoms of disease include pain in the bones, pathological fractures (of the vertebra, femur, wrist) and consequent deformations of the skeletons. X-ray is still the most efficient diagnostic tool, although it is only capable of revealing osteopenia when bone has lost more than 40% of its mineral content. Bone densitometry is an important stage in the diagnosis and study of osteoporosis. It is first performed at the distal extremity of the forearm, then at the lumbar vertebra and head of the femur. Bone mineralometry is also currently used to study the skeleton as a whole (total body absorptiometry). This method, which has a high level of precision and no positioning problems, is able to provide extremely reliable measurements of bone mineral content, in particular during monitoring. It is worth underlining, however, that other bone metabolic diseases, namely osteomalacia, are also characterised by reduced bone density: the level of bone density should therefore not be considered as an expression of bone mass. In biochemical terms, post-menopausal osteoporosis leads to minimum modifications of the phospho-calcium metabolism: only during stages of accelerated bone turnover is it possible to observe a small increase in calciuria, hydroxyprolinuria and serum osteocalcin levels. A prime factor for the diagnosis of post-menopausal osteoporosis is the intestinal calcium absorption test: post-menopausal osteoporosis is characterized by insufficient intestinal calcium transport.(ABSTRACT TRUNCATED AT 250 WORDS)

10 patients suffering from post-menopausal osteoporosis were subjected to venous infusion of salmon calcitonine at a dose of 100 U.M.R.C. Essential inital biochemical data were hypocalcaemia associated with plasma increase in AMPc and, in the late phase, an increase in urinary excretion of phosphate and AMPc. In addition to conserving its physiological properties in osteoporotic disease also, the hormone is thus able to provoke a secondary secretion of parathormone. The use of CT in the treatment of post-menopausal osteoporosis is therefore recommended not only because of its evident action on bone reabsorption processes, which usually predominate in this dysmetabolic disease of the skeleton, but also in the indirect secretion of parathyroid hormone which is capable of positively affecting synthesis of 1-25 (OH)2 D3 and intestinal calcic absorption.

Bone mineralometry offers exact, reliable information on the extent of the bony mass in many dysmetabolic diseases. Post-menopausal osteoporosis is certainly one of the diseases that has been most widely investigated densitometrically. In a study of 192 patients carried out with a gamma-emitting monochromatic source (241Am) mineralometer reduced bone content was found to be particularly severe in some cases. A statistically significant correlation between bone mass and patient age was also apparent. Thirty-two women received long-term treatment with 1 microgram/day 1.25 (OH)2D3. In these cases, the percentage decrease in bone mass related to the mean values for age group was found to be proportional to the number of years since the climacterium under basal conditions, similar to the picture in corticosteroid osteoporosis, for which a study of 42 patients undergoing chronic cortisone treatment showed a significant correlation between reduction of bone mineral content and the period of treatment. A marked increase in this content was obtained with 1.25 (OH)2D3.

Salmon calcitonin has been administered at a dose of 100 U.M.R.C. for 6 months in 10 patients suffering from post-menopausal osteoporosis. During treatment, calcium plasma levels fluctuated but tended to fall, while urinary excretion of cyclic AMP rose, this pointing to an enhancement of parathyroid function. After 6 months an increase in intestinal calcium absorption and a decrease in bone turnover were also observed, the bone mineral content evaluated by bone densitometry showed a slight quantitative increase but proved to be substantially unchanged. Salmon calcitonin thus proved capable of interfering with bone turnover by reducing the bone resorption. By fostering an increase in parathyroid hormone production, it also made it possible to exploit that anabolic effect which, in low doses, the parathormone exerts on the bone tissue.

A case of chronic primitive osteomyelitis (Brodie's abscess) in a little girl twelve years old, is reported. Clinical symptomatology, radiologic feature and pathological anatomy are typical of this disease. Peculiar is the uncommon localization at the distal metaphysis of radius, whose frequency is of 1.6% on 181 cases related by Rizzoli Institute of Bologna (Italy) which have largest casuistry on the subject, within fifty years.

To evaluate the effects of a long-term treatment with nandrolone decanoate on metabolism of the skeleton, a double-blind randomized study was carried out in women with joint diseases without metabolic bone derangement. Ten patients were treated with 50 mg of nandrolone decanoate every three weeks for two years; in six subjects a treatment with placebo was performed. As it concerns plasma calcium and phosphate, serum alkaline phosphatase, urinary excretion of calcium, phosphate, hydroxyproline and cAMP, as parathyroid index, it was not observed significant differences in the two examined groups. While in placebo group at the end of the study the intestinal radiocalcium remained unchanged and bone mineral content showed a slight decrease, on the contrary nandrolone decanoate treatment promoted a significant improvement in intestinal calcium absorption and an increase in bone mineral content.

(Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered intravenously; nevertheless the hypocalcemic effect proved to be more persistent in Paget's disease patients treated with (Asu)E-CT. After intravenous infusion of (Asu)E-CT the plasma level of cAMP rose more evidently in pagetic than in normal subjects but the rise was lower than in H-CT and S-CT treated subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.