[Guidelines for the diagnosis, prevention and treatment of osteoporosis]. / Linee guida per la diagnosi, prevenzione e terapia dell'osteoporosi Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro - SIOMMMS.

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.

[Italian guidelines for the diagnosis and treatment of Paget's disease of bone]. / Linee guida per la diagnosi e la terapia del morbo di Paget.

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.

Quantitative heel ultrasound in a population-based study in Italy and its relationship with fracture history: the ESOPO study.

We assessed the clinical usefulness of quantitative ultrasound (QUS) in defining the prevalence rates of osteoporosis and osteopenia and their association with fractures of the forearm, vertebrae, and hip. The ESOPO study was conducted in 2001 and assessed a random sample of 11,011 women and 4,981 men, in 83 centers spread all over Italy. A large array of risk factors was investigated, and self-reported history of fractures was collected in a questionnaire. After the patient had undergone interview and a brief physical examination, QUS of the heel was performed, using the Achilles apparatus (GE-Lunar, Madison, USA). The prevalence rate of osteoporosis in women 40-79 years old was approximately 18.5%, while the rate of osteopenia was about 44.7%; in men 60-79 years of age the rates were 10% and 36%, respectively. A strong association with fractures was found for osteoporosis and osteopenia in both men and women, independently of all traditional risk factors, including age. These results confirm the suitability of US measurements as a tool for detecting individuals at risk of fractures.

Association of quantitative heel ultrasound with history of osteoporotic fractures in elderly men: the ESOPO study.

In order to evaluate the usefulness of calcaneal quantitative ultrasound (QUS) in the assessment of male osteoporosis, a cross-sectional, population-based study was performed. A cohort of 4,832 men, randomly selected, community-dwelling, aged 60-80 years and representative of the general older male Italian population was recruited. QUS measurements were assessed in 83 centers distributed all over Italy and equipped with an Achilles device (GE-Lunar, Madison, Wisconsin, USA). All participants were administered a questionnaire covering lifestyle variables and medical history. Low-energy fractures that had occurred since age 50 were recorded. Overall, 43 subjects reported a previous hip fracture and 455 subjects reported other non-spinal fractures. Univariate analysis showed that fractured subjects were older, with a lower level of outdoor physical activity and a more frequent history of prolonged bedridden periods in comparison with unfractured subjects. Men reporting non-spinal fractures showed a higher prevalence of smoking, while no difference was found among groups in anthropometric measures and calcium intake. QUS measurements showed that all QUS parameters were significantly lower in both fracture groups (p<0.001). Multiple logistic regression analysis demonstrated that each SD reduction in QUS measures was associated with an approximate doubling of the risk for hip fracture, independent of age and other clinical variables (broadband ultrasound attenuation [BUA]: odds ratio [OR]=2.24; 95% confidence interval [CI] 1.61-3.08; stiffness index: OR=2.19; CI 1.56-3.11; speed of sound [SOS]: OR=1.71; CI 1.18-3.24) and with an increase of the risk of other non-spinal fractures (BUA: 1.38; CI 1.22-1.59; stiffness index: OR=1.27; CI 1.17-1.38; SOS: OR=1.14; CI 0.96-1.40). It can be concluded that calcaneal QUS measurement is associated with the risk for hip fracture and any non-spinal fractures among a community-dwelling cohort of elderly men. The strength of the association between QUS measurement and fracture is similar to that observed in elderly women.

Effect of age, weight and lifestyle factors on calcaneal quantitative ultrasound in premenopausal women: the ESOPO study.

The objective of this study was to identify the determinants of bone mass as measured by quantitative ultrasound (QUS) in premenopausal women. The study population is part of the "Epidemiological Study On the Prevalence of Osteoporosis" (ESOPO) on risk of the general population of Italy. We report the data on 2727 premenopausal women aged 40-50 years who are still regularly menstruating. Bone stiffness (called simplicity stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sound (SoS), was measured by a heel QUS device (Achilles Apparatus, Lunar, Co. USA). The most commonly recognized determinants of bone mass were modelled with stiffness by multiple regression analysis or analysis of variance (ANOVA). Bone stiffness was negatively related to age and number of cigarettes and positively to body weight, body weight at 25 years, height and estimated daily calcium intake. By multiple regression analysis, independent, positive, predictors of bone stiffness were age, weight at 25 years and daily calcium intake. Bone stiffness adjusted for age and body weight at 25 years was positively associated with outdoor activity score and negatively with number of pregnancies, chronic use of any drug, smoking and subjective health status. Bone stiffness was also somewhat (p < 0.015) negatively related to history of prolonged bedrest and thyroxin use. In conclusion, our results indicate that risk factors usually associated in other studies with DXA-BMD in elderly women are also associated with calcaneal bone stiffness, as measured by QUS in premenopausal women. These findings should help to identify premenopausal women at risk and to design an early strategy for osteoporosis prevention based on eliminating modifiable risks.

Clinical determinants of bone mass and bone ultrasonometry in patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc). METHODS: Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment. RESULTS: BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p < 0.01; femoral neck: 0.832 vs 0.955, p < 0.05; total body 1.050 vs 1.168, p < 0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p < 0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved. CONCLUSION: SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.

Physical and mechanical properties of cement-based products containing incineration bottom ash.

This paper presents the results of a wider experimental programme conducted in the framework of the NNAPICS ("Neural Network Analysis for Prediction of Interactions in Cement/Waste Systems") project funded by the European Commission and a number of industrial partners under Brite-EuRamIII. Based on the fact that bottom ashes from waste incineration are classified as non-hazardous wastes according to the European Waste Catalogue, the aim of the present work was to investigate the feasibility of addressing the potential use of such residues in cement-based mixtures. This issue was suggested by the analysis of the properties of different bottom ashes coming from Italian municipal and hospital solid waste incinerators, which showed a chemical composition potentially suitable for such applications. Different mixes were prepared by blending bottom ash with ordinary Portland cement in different proportions and at different water dosages. The solidified products were tested for setting time and bulk density, unconfined compressive strength and evaporable water content at different curing times. The results of the experimental campaign were analysed through a statistical procedure (analysis of variance), in order to investigate the effect of mixture composition (waste replacement level and water dosage) on the product properties.

Short-term intravenous therapy with Neridronate in Paget's disease.

AIMS: To describe the effects of two consecutive intravenous infusions of aminohexane bisphosphonate (Neridronate) in patients with active Paget's disease of bone. METHODS: The study population included 83 patients, aged 41 to 85 years, randomized to 4 cumulative doses of Neridronate (25, 50, 100, 200 mg) given over 2 days, with a follow up of 180 days. The baseline serum alkaline phosphatase activity was at least 10% above the upper limit of the laboratory range. The response to treatment was assessed by changes in the serum total alkaline phosphatase (primary end point of the study), bone alkaline phosphatase and N-telopeptide urinary excretion. RESULTS: All Neridronate doses significantly suppressed the biochemical indices of disease activity. The nadir of total alkaline phosphatase levels ranged from -16 % to -57.5% of pretreatment values in the four groups, with a dose-response relationship that was apparent even between the two highest doses. The proportion of patients still maintaining a partial response (decreases in serum total alkaline phosphatase >25%) at the 6 month follow-up was also related to the dose: 98%, 67%, 57%, 21% in the patients given 200, 100, 50, 25 mg respectively. The proportion of responders in terms of bone alkaline phosphatase and N-telopeptide excretion changes was similar. Bone pain attributed to Paget's disease was significantly reduced. A typical acute phase reaction (fever and/or arthromyalgia) occurred in 16 out of 83 patients. CONCLUSIONS: We conclude that all of the Neridronate doses tested here were well tolerated and effective in decreasing, in a dose-related manner the bone turnover parameters of Paget's disease. The highest dose (200 mg) resulted in the normalization of the markers of disease activity in more than 60% of the patients.

Bone mineral density in patients with psoriatic arthritis.

OBJECTIVE: Little information is available concerning bone mass in patients with psoriatic arthritis (PsA): the existence of less severe periarticular osteoporosis is considered possible, but there are no data concerning the existence of systemic osteoporosis. We investigated bone mineral density (BMD) in patients with PsA. METHODS: We studied 186 patients with non-axial PsA and 100 healthy subjects, equally divided into 3 groups: women of child-bearing age, women in menopause, and men. No patient had previously received steroid treatment. In all patients, evaluation was made of disease duration, inflammation indices (erythrocyte sedimentation rate, C-reactive protein), functional indices (Steinbrocker scale), and the Health Assessment Questionnaire (HAQ). BMD was measured by fan-beam x-ray densitometry of the lumbar spine, femur, and total body (evaluating the whole skeleton, as well as the spine, trunk, and upper and lower limbs). Ultrasound densitometry of the heel was also performed. RESULTS: BMD was significantly lower in the arthritic than in the healthy subjects regardless of sex, menopausal status, or age, as expressed in g/cm2 (lumbar spine 1.112 vs 1.326; femoral neck 0.870 vs 1.006; total body 1.125 vs 1.203) or by T and Z scores (lumbar T = -1.36, Z = -0.98; femoral neck T = -1.12, Z = -0.83; total body T = -1.09, Z = -0.65). Ultrasound densitometry of the heel was similarly altered (stiffness 96 vs 77; T -1.78; Z -1.29). Among the PsA patients, demineralization in at least one skeletal region was observed in 67% of premenopausal women (marked in 11%), 100% of postmenopausal women (marked in 47%), and 80% of the men (marked in 29%). In premenopausal women, demineralization did not correlate with the disease variables; in postmenopausal women and the men, it correlated with a decline in the functional indices and the HAQ score. This was confirmed by analysis of the relative risk of osteoporosis expressed in odds ratios (HAQ: 1.6; age: 1.4; years since menopause: 1.7). CONCLUSION: Demineralization was observed in more than 2/3 of our PsA patients without axial involvement. This demineralization was not related to the indices of inflammation or disease duration, but there is a delayed correlation with HAQ score, as well as age and the number of years since menopause.

Intermittent versus continuous clodronate administration in postmenopausal women with low bone mass.

The aim of the study was to compare the effects on bone mass and turnover of continuous vs. intermittent clodronate administration on 120 postmenopausal women (average age 61 years) with low bone mass (femoral neck bone mineral density [BMD] of at least -1 SD or more, T-score), with another 30 women as a control group. Participants were given 1800 mg of clodronate every 6 months over 2 years using different treatment patterns: a) two continuous regimens, consisting of a daily oral dose of 400 mg or 100 mg every 10 days by intramuscular injection, the latter being considered continuous because the interval between injections is shorter than the time employed by each bone remodelling unit to complete the resorption phase of a remodelling cycle; and b) two intermittent regimens, consisting of 1800 mg every 6 months administered either as a single 18-h intravenous infusion or by separate infusions of 300 mg over 6 consecutive days. All women, including those in the control group, received calcium and vitamin D supplementation. After 2 years, continuous clodronate regimens caused an increase in BMD both at lumbar spine and proximal femur (L(1-4) BMD = 3.07% and 2.69%; femoral neck = 2.12% and 2.09%, respectively, with intramuscular and oral regimens). Intermittent clodronate administration was associated with a small increase or a stabilization in bone mass (L(1-4) BMD = 0.53% and 1.22%; femoral neck = 0.30% and 0.77%, respectively, with 1- and 6-day intravenous infusion regimens). From the 12th month, changes in spine and femoral neck BMD after continuous regimens were statistically different compared with that obtained with intermittent ones. Twenty-five of the 150 women (16.7%) discontinued the study before the end of the 2-year follow-up, but of these, only 7 dropped out because of adverse events related to the treatment itself. To summarize, intermittent clodronate administration could be a suitable option for the prevention of osteoporosis.

Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin.

AIMS: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients. METHODS: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. RESULTS: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group. CONCLUSIONS: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.

Paget's disease of bone: benefits of neridonate as a first treatment and in cases of relapse after clodronate.

This study assessed the efficacy of 200 mg of aminohexane bisphosphonate (neridronate) administered by intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active Paget's disease of bone. Fifteen patients had never been treated with any antiresorptive agent and 17 had had unsatisfactory results from a prior clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after clodronate infusion. In the present study bone-specific alkaline phosphatase (bAp), deoxypyridinoline (dPyr), and N- and C-terminal polypeptide of collagen type 1 (Ntx, Ctx) were determined before neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 +/- 2.3 microg/L, range 31.7-92.5 (normal range 6.2-23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 +/- 4.1) and those suffering a relapse after clodronate (bAp = 48.8 +/- 2.6). Neridronate induced an average percent change from baseline in excess bAp of 68.0 +/- 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 +/- 11, 60.6 +/- 8.5, and 86.7 +/- 7.8, respectively. Markers of bone resorption declined more slowly in patients treated previously with clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after clodronate. In 15 of 21 patients requiring analgesics to alleviate bone pain, pain was reduced or completely alleviated in 8. A slight, short-lived acute phase reaction (fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that neridronate can be used safely in the treatment of patients with Paget's disease of bone either as a first bisphosphonate treatment or as retreatment for patients relapsing after clodronate.

Meformin, plasma glucose and free fatty acids in type II diabetic out-patients: results of a clinical study.

Abnormalities in free fatty acid (FFA) metabolism are an intrinsic feature of type II diabetes mellitus and may even play a role in the development of glycaemic imbalance. This study investigated whether the anti-diabetic drug metformin can reduce FFA levels in clinical practice and whether this correlates with its anti-diabetic effect. For 6 months metformin was added to sulfonylurea therapy in 68 type II diabetic outpatients with poor glycaemic control, being administered before meals and at bed-time. Basal and daily area-under-the-curve (AUC) glucose levels dropped (both P < 0.0005) like basal and daily AUC FFA levels (P < 0.004 and P < 0.001 respectively) reductions were all correlated (P < 0.001 and P < 0.003 respectively). Reductions in fasting and daily AUC glucose correlated more closely with body fat distribution, expressed by waist-hip ratio (WHR) (P < 0.006 and P < 0.004 respectively), than with the body mass index (BMI) (P < 0.02 and P < 0.04 respectively). Similarly fasting and daily AUC FFA correlated with WHR (P < 0.007 and P < 0.01 respectively) but not with BMI (both P = ns). Subdividing male and female diabetic patients into groups with low and high WHRs, fasting and daily AUC glucose were reduced in men (P < 0.01 and P < 0.02) and in women (P < 0.02 and P < 0.04 respectively) with low WHRs less than in men and in women with higher WHRs (for each gender P < 0.0001 and P < 0.0002, respectively). Decreases in fasting and daily AUC FFA, which did not reach significance in either men or women with low WHRs, were statistically significant in men (P < 0.03 and P < 0.01 respectively) and in women (P < 0.02 and P < 0.005 respectively) with high WHRs. These findings suggest that an improvement in FFA plasma levels might contribute to metformin's anti-diabetic activity which appears to be more marked in patients with high WHRs. Moreover adding a bed-time dosage to the standard administration at meal times seems to be an effective therapeutical strategy.

Effects of glimepiride on insulin and glucagon release from isolated rat pancreas at different glucose concentrations.

The effects of glimepiride, the newest sulphonylureic compound, on pancreatic insulin and glucagon secretion were studied using the classical, isolated, perfused rat pancrease model. The influence of four different environmental glucose conditions (during a glycaemic stimulus with glucose increasing from 5 to 8.33 mM and at stable 0, 5 and 2.22 mM glucose levels) on the effects of glimepiride was also assessed. At a pharmacological concentration glimepiride strongly stimulated beta-cell activity, producing a characteristic biphasic insulin release with a sharp first-phase secretory peak, followed by a prolonged and sustained second phase. Environmental glucose concentrations markedly influenced the extent, but not the pattern of glimepiride-induced insulin secretion, as hormone release dropped significantly when the glucose level was reduced. Glimepiride failed to influence alpha-cell activity at any of the environmental glycaemic levels.

Cyclical intravenous clodronate in postmenopausal osteoporosis: results of a long-term clinical trial.

We report the results of long-term cyclical clodronate therapy (200 mg IV infusion every 3 weeks) on 235 women with postmenopausal osteoporosis recruited over 6 years. A retrospective analysis of clinical and instrumental findings in 183 postmenopausal osteoporotic patients was used as control data. Clodronate was well-tolerated and compliance was good. Bone mineral density (BMD) increased significantly and the upward trend persisted for all 6 years of therapy (5.69 +/- 0.184%) vs. controls: -1.47% +/- 0.813%, p <0.0001). The increase in BMD was greater in the 145 patients without vertebral fractures before starting clodronate. From year 3 onward clodronate reduced the incidence of new vertebral fractures. In closed subsets of patients and controls monitored for 3 and 4 years, respectively, the number of patients developing new vertebral fractures fell significantly in the clodronate group (two-sided p value = 0.0671 and p <0.0026, respectively). This trend was more marked in patients who were fracture-free at the beginning of each year. Cyclical clodronate is a safe and effective therapy for established osteoporosis, but clinical trials are necessary to compare its efficacy versus continuous therapy and, as in the case of the other bisphosphonates, to investigate its mechanisms of action in depth.

Is metformin safe enough for ageing type 2 diabetic patients?

We assessed the effect of adding low doses of metformin to sulfonylurea therapy in 76 elderly Type 2 diabetic patients by monitoring glycaemic control and blood lactate for one year. Metformin markedly improved glycaemic control. Fasting lactate concentrations were not affected and post-meal lactate peaks were minimally increased. Additional benefits included an improvement in some lipid parameters, a reduction in serum uric acid and a significant weight loss in overweight patients. Metformin was clinically well-tolerated. Instead of advanced age alone, renal function and/or any other age-related factor likely to contribute to lactate overproduction should be the basis for deciding on metformin therapy. No evidence indicated that metformin should be denied "a priori" to ageing Type 2 diabetic patients.

Metformin treatment in elderly type II diabetic patients.

Pharmacological treatment in elderly patients with type II, non-insulin dependent diabetes mellitus (NIDDM) is becoming a growing and complex problem in the clinical practice, since longevity in almost every population is increasing, and the prevalence of NIDDM also rises with age. It is generally indicated that age over 65-70 years represents a specific contraindication against the administration of the biguanides since the risk of the drug-associated lactic acidosis increases with age. However very few data exist in literature about the effect of biguanides, particularly metformin, in aging patients. Therefore, we aimed to evaluate the effects of adding metformin to poorly controlled sulfonylurea-treated elderly diabetic subjects for a one year period. Eighty-four type II diabetic patients aged more than 70 years and with a poor glycemic control were recruited after an informed consent. All diabetic patients were treated with various sulfonylureas at medium doses and presented renal and liver biochemical function tests within normal ranges and were free of severe macroangiopathy and respiratory or congestive heart failure. Metformin treatment was added to the previous sulfonylurea dosages in order to achieve a satisfactory glycemic control. All patients showed a marked improvement in the glycemic control with no significant modification in fasting blood lactate and a mild increase in the post-prandial lactate peak which, however, always felt largely within the normal ranges. Metformin also improved some metabolic vascular risk factors such as plasma cholesterol levels that were reduced, circulating HDL-cholesterol levels that mildly but significantly increased and uric acid that was lowered. In conclusion our data further support the opinion that metformin has not to be denied to diabetic patients on the sole basis of their age.

Cyclical clodronate is effective in preventing postmenopausal bone loss: a comparative study with transcutaneous hormone replacement therapy.

An investigative study was carried out for 2 years involving 124 randomly selected early postmenopausal women with spine bone mineral density (BMD) below the mean value of a normal premenopausal subject. After random division into three groups, the first 42 patients were treated with transcutaneous 17-beta-estradiol (50 micrograms daily), the second 42 were treated with cyclical intravenous clodronate (200 mg/month iv infusion), and the third group of 40 (controls) was left untreated. After 2 years, the total drop in BMD within the control group was more than 7% as opposed to the values of -0.14% +/- 0.93 in the estradiol group and 0.67% +/- 0.84 in the clodronate group. A change in BMD of < 1% was considered satisfactory, and this result was obtained in 32% of the controls, in 79% of the estradiol group where the percentage change in BMD moderately correlated with serum estradiol levels (r = 0.399), and in 90% of the clodronate-treated patients, in whom the percentage change in BMD inversely correlated with basal values of markers of bone turnover. Both estrogen and clodronate prevent postmenopausal bone loss. The response to transcutaneous hormone replacement therapy may be influenced by transcutaneous absorption and by a lower sensitivity to estrogen. Response to cyclical clodronate seems to be influenced by the rate of bone turnover. An interdosage interval ranging from 2-4 weeks appears suitable for most patients.

[Percutaneous alcohol injection in hyperparathyroidism. Experience in 11 cases with an 18-month follow-up]. / Alcolizzazione percutanea nell'iperparatiroidismo. Esperienza in 11 casi con follow-up a 18 mesi.

The authors report the results of US-guided percutaneous ethanol injection into parathyroid glands of 11 patients with primary (2) and secondary (9) hyperparathyroidism. Selection criteria for choosing ethanol treatment were the patient's refuse of surgery and high surgical risks for age or severe chronic intercurrent conditions. At 18 months' follow-up, PTH serum levels had normalized in 2 primary and 2 secondary hyperparathyroidism patients; in all the others but one, PTH levels markedly decreased--always > 50% relative to pretreatment values. Serum calcium and phosphorus levels also decreased, which was not always the case with alkaline phosphatase. After injection, the glands became progressively hyperechoic, gland volume decreased and calcifications appeared. Parenchymal flow disappeared on color-Doppler US images. This study confirms the capabilities of US-guided ethanol injection in hyperfunctioning parathyroids, even though complications may occur and the condition recur. This method is thus suggested as an effective alternative to surgery.