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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.

Chronic renal insufficiency (CRI) causes important modifications in the metabolism of phosphorus and calcium, to which frequently resulting in serious disorders of the skeleton, including demineralization, reduction of the bone resistance and a higher risk of fractures. Renal osteodystrophy is the term used to describe these disorders; they are generally heterogeneous and are classified according to the state of bone turnover into secondary hyperparathyroidism, adynamic bone, and osteomalacia. The incidence of hip fractures in the patients with CRI is higher than in the general population. Hip fractures are an important cause of morbidity and mortality. The evaluation of the fracture risk in the patients with different degrees of CRI is problematic, in particular because of the difficulty in identifying fractures, especially vertebral ones. The instrumental index that best expresses the fracture risk in the general population is bone mineral density (BMD); however, the relationship between low BMD and CRI is disputed. Bone disorders in patients with CRI have in fact a multifactorial pathogenesis and low BMD is not the only risk factor for fractures. Besides densitometric evaluation, also that vertebral morphometric evaluation would be desirable in patients with CRI. The fracture risk increases progressively with the severity of chronic renal disease and it is especially high in patients with renal insufficiency in more advanced-stages CRI (creatinine clearance<15-20 mL/min). However, not only in patients with severe CRI undergoing dialysis, but also in those with milder renal disease is the risk of bone fractures high.

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.

Many study in literature have suggested a possible role of T cells and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of bone loss that occurs in pathological conditions, such as systemic inflammatory diseases; the molecular bases through which this phenomenon occurs and the relevance of this mechanism also in estrogen deficiency induced bone loss remain unclear. In our study we observed that TNF-alpha knock-out mice (TNF-/-), as well as transgenic mice without thymus (and therefore without mature T cell), do not lose bone after ovariectomy like observed for mice of normal genetic background (wild type, WT). Moreover, after transfer into athymic mice of T cell isolated from WT ovariectomized animals (and so stimulated by estrogen deficiency to proliferate and to produce TNF-alpha), ovariectomy recovers its ability to induce bone loss; whereas there is no change in bone density after injection into athymic mice of T-cell purified from TNF-/- animals which, even if mature, are unable to produce TNF-alpha. Therefore the presence of TNF-alpha producing T-cell is essential for estrogen deficiency to influence bone metabolism. In the following study of the research group of Prof. Pacifici it has been shown that the increased activation of TNF-alpha producing T-cell in the ovariectomized mice is due to increased INF-gamma levels, resulting from ovariectomy-induced enhanced secretion of IL-12 and IL-18 by macrophages. INF-gamma promotes expression in immunocompetent cells of class II transactivator (CIITA), that, up-regulating expression of the major system of histocompatibility of class II, makes the macrophages more active in antigen presentation to T-cells, which in turn start producing TNF. For the first time an immune mechanism is involved in the pathogenesis of post-menopausal osteoporosis; nevertheless the applicability of these conclusions also in humans remains still to be proved.

Intramuscular and intranasal synthetic salmon calcitonin (sCT) has long been used in the treatment of involutional osteoporosis. A new suppository formulation was developed and many studies demonstrated that rectally administered sCT is efficacious and well tolerated. Thirty postmenopausal women, who had a bone mineral density at the lumbar spine below the mean of age-matched women, were enrolled in this study. Using an open balanced, randomized design, the patients were allocated to two groups of treatment: sCT suppositories at the dose of 100 UI/day or 200 UI every other day for six months. Treatment with sCT suppositories caused a statistically significant decrease of pain in both study groups. Bone mineral density at lumbar spine showed an increase in both study groups with significant difference respect the basal value for the patients treated with sCT on alternate day. Based on the results of this study, we can thus conclude that sCT in suppository formulation is effective in reducing pain sintomatology, bone loss and turnover in involutional osteoporosis.

After having briefly illustrated the main theories of photonic ray bone densitometry, the authors describe the various techniques used to evaluate bone mass and bone mineral density as accurately and precisely as possible both at an appendicular level and at lumbar and femoral sites. Since these data only provide a static measurement and are unable to provide information regarding bone mass evolution in time, a method is illustrated which is theoretically capable of identifying high risk subjects, namely those who, on the basis of simple blood and urine tests for some biochemical parameters, are likely to undergo a significant reduction in bone mass in the future. Lastly, the paper reports the preliminary results of a study carried out in immediately post-menopausal women in whom rapid loss of bone mass was followed by a greater reduction in bone mineral density measured at an appendicular level.

The increased average life expectancy of the inhabitants of industrialised countries has led to a marked increase in degenerative pathologies, including osteoporosis. This has made it necessary to elaborate instrumental tests capable of identifying risk subjects in order to intervene as quickly as possible using appropriate prophylactic and therapeutic measures. Single and dual photon ray densitometry represents the first correct approach to quantitatively assess bone mineral content. It not only allows an early diagnosis to be made but also enables a longitudinal study to be made of patients receiving treatment. The main studies on the accuracy and precision of dual photon ray densitometry are reported together with the authors' findings regarding the definition of the fracture threshold and osteoporosis caused by metabolic and endocrinological disorders.

Pharmacological treatments of osteoporosis can improve bone mineral content, but are not able to restore trabecular bone structure in presence of microfractures. It is therefore necessary to carry out at the right moment some preventive actions to increase peak bone mass in premenopausal age: adequate calcium intake, systematic physical activity and, if necessary, oestrogen administration before menopause are correct prophylactic measures against osteoporosis; moreover risk factors identification allows to perform a preliminary screening. Serial bone absorptiometry at lumbar level is able to identify fast losers women by means of integrating densitometric data and some metabolic results. Utilizing these methods it is possible to activate proper preventive or therapeutic measures and prevent osteoporotic complications.

Many authors have shown that osteoporosis is an important complication in male hypogonadism, due to the chronic lack of androgens; but in hypogonadal males the pathogenesis of osteopenia isn't completely explained. In this work we examined in 10 hypogonadal males (4 with Klinefelter's Syndrome and 6 with Hypogonadotropic Hypogonadism) lumbar bone mineral content (BMC) and the effects of testosterone (Sustanon) administration on BMC and other phosphocalcium parameters. We evidenced lower BMC levels in hypogonadal subjects if compared to those observed in the control age-matched group; moreover after 3 months of treatment a statistically significant increment of plasma bone gla protein, calcitonin and lumbar BMC was observed. On the contrary no significant variation was observed in osteoclastic indexes (PTH-MM, OHPU/CrU, CaU/CrU) after treatment. In addition both calcitonin basal levels and secretory reserve, measured with calcium infusion, were significantly increased after treatment. Our data confirm the hypothesis that androgen acts on bone principally directly at osteoblastic level, in a stimulatory manner, and indirectly, with calcitonin mediation, with inhibition of osteoclasts.

In 16 patients with high cortisol plasma levels MRI and CT investigation of adrenal gland region was performed; 13 also had the pituitary region examined. CT and MRI results in Cushing's Syndrome due to adrenal glands etiology (8 cases) are overlapping. The morphological criteria utilized consist in the radiological finding of bilateral adrenal hyperplasia or adrenal mass (adenoma, carcinoma). The great amount of retroperitoneal fat increases the normal contrast with both techniques. In the pituitary Cushing's Syndrome MRI was more sensible than CT as far as it concerns ACTH producing pituitary lesion assessment; this technique may show 5 mm diameter adenomas for their high signal intensity.

Main epidemiological studies about osteoporosis are described: the availability of sophisticated techniques as double photon absorptiometry permits to establish that in U.S.A. there is at least 1.2 million osteoporosis fractures each year, mainly at trabecular level and in postmenopausal women. Moreover the hip fractures induce a significant reduction in life expectancy (between 12% and 20%) with very important social costs. In Italy some recent data documented that the social costs in relation to osteoporosis fractures can be evaluated in 1983 between 80 and 153 milliard liras. Some data about annual bone density decrement in normal population are reported: 0.38%/year in females and 0.22%/year in males. Moreover the theoretical fracture threshold, defined as B.M.D. level 2.5 SD under the mean value founded in young age, was evaluated (0.67 gHA/cm2). Finally in 15% of our patients with more than 65 years almost one vertebral fracture was found.

The authors evaluated the diagnostic reliability of echotomography in detecting parathyroid masses: 37 patients were studied with primary hyperparathyroidism, in four cases recurrent. They all underwent surgical ablation of the mass, identification of all glands, and biopsy of an apparently normal parathyroid. Echotomography was accurate in 91.4% of cases: it identified 27 out of 39 pathological glands (sensibility 69.2%) and gave no false-positive results (specificity 100%). Since parathyroid is often ectopic, oblique scans are suggested, i.e. of jugulum while the patient is swallowing. Such scans were always used in our study, in order to identify lesions even in case of "difficult" locations, such as the superior mediastinum.

Primary hyperparathyroidism may at times be associated with carcinoma of the parathyroids. A personal case of primary hyperparathyroidism was operated on by total thyro-parathyroidectomy. The histological picture presented atypical cell patterns and infiltrations of the thyroid capsule, together with adenomatuous parathyroid formations suggesting the possibility of a malignant transformation of initially benign process. Given the benign clinical course, it is possible that when subjected to radical, timely measures, even atypical parathyroid processes may be cured completely.

The identification and synthesis of thyrotrophin-releasing hormone (TRH) and luteinising hormone releasing hormone (LHRH) has widened our knowledge of hypothalamo-hypophyseal-thyroid and hypothalamo-hypophyseal-gonad diseases. More precisely, administration of these two releasing factors, by permitting the evaluation of pituitary TSH, LH, and FSH reserves, reveals otherwise undefinable changes in hypophyseal function. An account of the manner of execution and measurement, the administration route, and side-effects related to TRH and LHRH tests is followed by a description of the main diseases in which they offer the greatest degree of diagnostic assistance.

A case of adenoma-based hyperparathyroidism operated at the 4th month of pregnancy (third reported case) is described. The clinical picture was extremely flimsy and diagnosis was formulated exclusively on the observation of the characteristic alterations in the calcium-phosphorus metabolism. The validity of examining renal phosphate excretion for the diagnosis of hyperparathyroidism is considered and proposed evaluation indices (P.E.I. of Nordin and Fraser; I.P.E. OF Nordin and Bulusu) are discussed. The gravity of foetal prognosis in hyperparathyroid women is sufficient justification for surgery during pregnancy.

The incidence of osteoporosis in the West is considerable and its complications are such as to make it a common and disabling problem. Recent developments in the classification, pathogenesis and diagnosis of the disease are reported. Certain laboratory techniques have recently been developed that can provide adequate information about the degree of demineralisation present. Furthermore the accurate in vivo assessment of bone density is made possible by the development of double beam photon osteodensitometry that measures bone mineral content (BMC) with sensitivity and accuracy. On the treatment side, the various drugs available are reviewed with particular reference to estrogen, vitamin D, anabolisers (recently reassessed in radiogrammometric and densitometric studies) fluorides and calcitonin. Finally certain treatment protocols for post-menopausal and senile osteoporosis are proposed that should produce good results in a reasonably short space of time.

In this paper we summarize the main problems connected with the diagnosis of primary osteoporosis, after evidencing the remarkable social importance of the disease, linked to the great increase of aged population; finally the pathogenetic hypotheses more documented are described. From a diagnostic point of view common laboratory investigations are not mostly able to provide sufficient significant informations; recently the dosage of osteocalcin as index of osteoblastic activity and as marker of bone turnover has been suggested. Mainly traditional radiology does not provide sufficient information about the real demineralization rate, while the radiogrammometry can offer sufficiently reliable indications about bone mineral content. Of a greater diagnostic meaning can be considered the bone mineral absorptiometry and in particular the double photonic ray absorptiometry, effected at the level of lumbar spine, that is to say a side earlier affected by the osteoporotic process. With this methodology we are able to obtain precise information about the quantity of the bone mineral content, identifying, at an earlier stage, the patients at risk of osteoporosis.