Diabetes and CoViD-19: Experience from the frontline of Internal Medicine wards in Italy.

Available data suggest that the issue of CoViD-19 is particularly critical in patients with diabetes. In Italy, Internal Medicine (IM) wards have played a pivotal role in contrasting the spread of SARS-Cov2. During this pandemic, FADOI submitted a brief questionnaire to a group of its members acting as Head of IM units. Considering 38 units, 58% of beds dedicated to CoViD patients in CoViD Hospitals were in charge of IM, and globally cared for 6650 patients during a six-week period. Of these patients, 1264 (19%) had diabetes. Mortality rate in CoViD patients with or without diabetes were 20.5% and 14%, respectively (p < 0.001). Our survey seems to confirm that diabetes is a major comorbidity of CoViD-19, but it does not support an increased incidence of CoViD-19 infection in people with diabetes, if compared with the figures of patients with diabetes and hospitalized before the outbreak. On the other side, patients with diabetes appeared at a significantly increased risk of worse outcome. This finding underlines the importance of paying special attention to this patient population and its management.

Hospitalization and mortality for acute exacerbation of chronic obstructive pulmonary disease (COPD): an Italian population-based study.

OBJECTIVE: Patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) have a significant mortality and morbidity. Previous studies have identified a number of independent prognostic factors. However, information on hospital admission databases is limited and data regarding short-term prognosis of these patients in Italian hospitals are lacking. Thus, we performed an epidemiological study on hospital admission for COPD acute exacerbation in Italy. PATIENTS AND METHODS: Patients were identified using clinical Modification (ICD-9-CM) codes. Information was collected on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses. Comorbidity was evaluated using the Charlson comorbidity index (CCI). RESULTS: During the observation period (2013-2014), 170,684 patients with COPD acute exacerbation were hospitalized. Mean length of hospitalization (LOH) was 9.95±8.69 days and mean in-hospital mortality was 5.30%. These data correspond to the 4.1% of all hospitalizations and to the 2.8% of all the days of hospitalization in Italy during the study period. In-hospital mortality and LOH varied among different regions (from 3.13 to 7.59% and from 8.22 to 11.28 days respectively). Old age, male gender, low discharge volume, previous hospitalization for COPD exacerbation and CCI resulted as significantly associated with higher in-hospital mortality. CONCLUSIONS: Hospitalization for COPD exacerbation is extremely frequent even in contemporary Italian population. COPD exacerbation is clinically demanding with a not negligible short-term mortality rate and a mean LOH approaching 10 days. These latter findings were quite variable in different regions but should be further analyzed to set up appropriate health-care policies on COPD patients.

Antidiabetic therapy effects on bone metabolism and fracture risk.

Patients with diabetes are at greater risk of fractures mostly due to not only to extraskeletal factors, such as propensity to fall, but also to bone quality alteration, which reduces bone strength. In people with diabetes, insulin deficiency and hyperglycaemia seem to play a role in determining bone formation alteration by advanced glycation end product (AGE) accumulation or AGE/RAGE (receptors for AGE) axis imbalance, which directly influence osteoblast activity. Moreover, hyperglycaemia and oxidative stress are able to negatively influence osteocalcin production and the Wnt signalling pathways with an imbalance of osteoblast/osteoclast activity leading to bone quality reduction as global effect. In addition, other factors such as insulin growth factors and peroxisome proliferator-activated receptor-γ pathways seem to have an important role in the pathophysiology of osteoporosis in diabetes. Although there are conflicting data in literature, adequate glycaemic control with hypoglycaemic treatment may be an important element in preventing bone tissue alterations in both type 1 and type 2 diabetes. Attention should be paid to the use of thiazolidinediones, especially in older women, because the direct negative effect on bone could exceed the positive effect of glycaemic control. Finally, preliminary data on animals and in humans suggest the hypothesis that incretins and dipeptidyl peptidase-4 inhibitors could have a positive effect on bone metabolism by a direct effect on bone cells; however, such issue needs further investigations.

The effects on lipid serum levels of a 2-year adjuvant treatment with exemestane after tamoxifen in postmenopausal women with early breast cancer.

BACKGROUND: The third-generation aromatase inhibitor exemestane represents a new development in the treatment of estrogen-positive breast cancer. The aim of this study was to evaluate the effects on lipid profile and body composition of the shift from tamoxifen to exemestane. METHODS: After 2-3 years of tamoxifen adjuvant treatment, 68 postmenopausal women were randomly assigned to either continue tamoxifen 20 mg/day (n = 35) or to switch to exemestane 25 mg/day (n = 33). RESULTS: No significant changes in lipid profile were found in patients continuing on tamoxifen. In the exemestane group, serum HDL-cholesterol (HDL-C) and triglycerides (TG) decreased significantly (p < 0.01) and serum LDL-cholesterol (LDL-C) increased significantly (p < 0.05) with respect to baseline. The difference between the two groups was significant. Moreover, in the exemestane group, fat mass (FM) and fat-free mass (FFM) showed an opposite trend, which determined a progressive and significant increase in the FFM/FM ratio. CONCLUSION: This study shows that the choice of first-line treatment or adjuvant therapy for breast cancer should also take the individual lipid and body composition profile into account.

Bone ultrasonography at phalanxes in patients with Rett syndrome: a 3-year longitudinal study.

Osteopenia is a frequent and early complication of Rett syndrome. This study aimed to evaluate the usefulness of Quantitative Ultrasonography (QUS) at phalanxes in the assessment and monitoring of bone status in Rett patients. We studied 109 girls (10.1+/-6.1 years; range 3-25 years) and 101 age-matched controls. Serum calcium (Ca), bone alkaline phosphatase (B-ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD) and QUS parameters at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT) were measured. At baseline both QUS parameters and 25OHD levels were significantly lower in Rett patients than in controls. Serum 25OHD was inversely correlated with serum PTH and BTT Z-score and BTT Z-score was significantly lower (p<0.05) in the girls with a 25OHD serum levels

Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane.

Recently the third generation aromatase inhibitors have proved their efficacy and tolerability compared with tamoxifen in the adjuvant treatment of women with hormone responsive early breast cancer. However, there is some concern about the possible negative impact of these drugs on bone. The aim of the study was to evaluate the effects of the steroidal aromatase inactivator exemestane on bone turnover markers and on bone mineral density (BMD). Seventy postmenopausal women (62.0+/-8.9 years) with completely resected breast cancer and who were disease-free following 2-3 years on tamoxifen were randomly assigned to continue tamoxifen (n=36) or switch to exemestane (n=34). Sixty-one patients completed the 2-year study period. Bone alkaline phosphatase (B-ALP) and the carboxy-terminal telopeptide of type I collagen (CTX) were measured at baseline and after 3, 6, 9, 12, 18 and 24 months. BMD at lumbar spine (BMD-LS), at femoral neck (BMD-FN), at total hip (BMD-T) and at whole body (BMD-WB) were measured at 6-monthly intervals. Exemestane-treated women showed significant (p<0.01) increases with respect to baseline in both B-ALP and CTX. The difference between the 2 groups reached the statistical significance at month 6 for CTX (p<0.05) and at month 9 for B-ALP (p<0.01). Moreover, the exemestane-treated women showed an early decrease in PTH serum levels (-20.4%, p<0.01 at month 6). In the E group, the percentage changes were -2.37 (p<0.05) BMD-LS, -1.24 (p<0.05) BMD-FN, -1.1 (n.s.) BMD-T, -1.03 (n.s.) BMD-WB at month 12 and -2.99 (p<0.01) BMD-LS, -1.92 (p<0.01) BMD-FN, -2.01 (p<0.05) BMD-T, -1.3 (n.s.) BMD-WB at month 24. The tamoxifen group did not show significant changes in BMD. The differences between the two groups were significant at all skeletal sites except BMD-WB. Our data suggest that switching postmenopausal women from tamoxifen to exemestane causes a marked increase in bone turnover markers with a consequent reduction in BMD. These findings could be due to both the direct effect of exemestane and to the loss of the protective effect of tamoxifen. Therefore, the postmenopausal women switched from tamoxifen to exemestane should be monitored for bone loss especially if other risk factors for osteoporosis are present.

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids.

Recent studies have shown that administering the aromatase inhibitor exemestane after 2-3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with standard 5-year tamoxifen treatment. Although many of the adverse effects associated with exemestane and tamoxifen have been analysed, there are no comparative data concerning body weight and body composition. The aim of this randomised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane. In total, 60 overweight or obese postmenopausal patients were enrolled. Their anthropometric data, body composition, including fat mass (FM) and fat-free mass (FFM), and lipid profiles, caloric intake and physical activity were assessed 1 week before randomisation, and 6 and 12 months later. In all, 55 patients (27 on tamoxifen and 28 on exemestane) completed the 1-year study period. Fat mass had significantly decreased by month 12 in the exemestane, but not in the tamoxifen group; the between-group difference was statistically significant (P<0.01). The FFM/FM ratio had significantly increased in the exemestane group, but not the tamoxifen group; the between-group difference was statistically significant (P<0.05). Triglycerides and high-density lipoprotein cholesterol significantly decreased (P<0.01; P<0.05), and low-density lipoprotein cholesterol significantly increased (P<0.01) in the exemestane group at the end of the 1-year study period. Our findings suggest that switching patients to adjuvant exemestane treatment after at least 2 years of tamoxifen therapy may be associated with an advantage over continuing adjuvant tamoxifen treatment in terms of body composition.

Teriparatide's effects on quantitative ultrasound parameters and bone density in women with established osteoporosis.

This study aimed to evaluate the effects of teriparatide [hPTH (1-34)] on quantitative ultrasound (QUS) parameters and bone mineral density (BMD) at the axial and appendicular (hand) skeleton in women with established osteoporosis who had been previously treated with antiresorptive drugs. Sixty postmenopausal women (age 71.1+/-6.8 years) were randomly assigned to either receive once-daily 20-mug subcutaneous teriparatide (n=30) or continue the antiresorptive treatment (n=30). At baseline and at 2-month intervals we measured QUS parameters at the calcaneus using the Achilles Plus (GE, Lunar), measuring speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index; QUS parameters at the phalanxes using the Bone Profiler (IGEA), measuring amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and fast wave amplitude (FWA); and BMD values at the right hand using dual x-ray absorptiometry. BMD at the lumbar spine, femur, and whole body were measured on a 6-monthly basis. After 1 year of teriparatide treatment, the changes in BMD were 7.1% at the lumbar spine, 2.6% at the femoral neck, -0.8% at the total hip, and -0.6% for the whole body. Teriparatide induced a significant and persistent decrease in BMD at the hand (-3.6% at month 6 and -2.7% at month 12). In the teriparatide group at month 12, AD-SoS was slightly increased (0.7%; not significant), whereas BTT significantly decreased (-16.4%, p<0.001) and FWA significantly increased (17.5%, p<0.001). The FWA/BTT ratio increased by 26.6% and 32.9% at months 6 and 12, respectively, in the teriparatide group and remained unchanged in the antiresorptive group. In women with established osteoporosis who had previously been treated with various antiresorptive drugs, 1 year of teriparatide treatment determined the expected increase in BMD at the axial skeleton and a significant and prolonged decrease in BMD at the hand. Moreover, teriparatide determined important changes in BTT and FWA, two parameters obtained from the analysis of ultrasonographic trace at the phalanxes, which could be considered in monitoring for the early effect of teriparatide on bone.

Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis.

The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.

Bone ultrasonography in glucocorticoid-induced osteoporosis.

Osteoporosis is one of the major complications of glucocorticoid (GC) therapy. Few data are available on the usefulness of quantitative ultrasound (QUS), a technique that could also theoretically provide information on bone structure, in the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1) to evaluate the ability of QUS in detecting bone impairment and in being associated with the prevalence of fragility fracture in GC patients; and (2) to assess whether QUS parameters, and particularly the graphic trace analysis of QUS signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at least 6 months, and 192 sex- and age-matched controls. In all subjects, we measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were significantly lower in GC patients than in controls and in fracture than in nonfracture GC patients. BMD at lumbar spine showed the best ability in discriminating GC patients with or without fractures. Among QUS parameters, stiffness showed a discriminatory ability significantly better than AD-SoS. BMD at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the odds of fragility fracture event. QUS parameters of the postmenopausal GC patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also compared with those obtained in a separate sample of 90 postmenopausal osteoporotic women (PMO). All parameters were significantly lower in GC patients and in PMO than in controls, without any significant difference between GC and PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid-induced bone impairment. In addition, in this study we found no alteration in QUS parameters or in the graphic trace analysis which could differentiate between GIO and PMO. Further longitudinal studies are needed to define the role of QUS in the prediction of fracture risk and in the clinical management of GIO.

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study.

Bisphosphonates have been widely used in the treatment of osteoporosis in women, whereas until now there have been few data on their use in men. The aim of this study was to evaluate the effect of a 3-year alendronate treatment on bone mineral density (BMD) and quantitative ultrasound (QUS) in men with primary osteoporosis. We studied 77 osteoporotic men (aged 57.1 +/- 10.8 yrs) who completed a 3-year treatment with alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 39), or calcium alone (n = 38). At baseline and at a 12-month interval, we measured BMD at the lumbar spine and femur (femoral neck and total hip) by DXA (Hologic) and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness (S) at the os calcis by Achilles plus (Lunar). Alendronate treatment had significantly increased lumbar spine BMD by 4.2% at year 1, by 6.3% at year 2, and 8.8% at year 3. BMD at the femoral neck and total hip had increased by 2.1% and 1.6% at year 1, by 3.2% and 2.9% at year 2, and by 4.2% and 3.9% at year 3, respectively. BUA and Stiffness showed a significant increase in the alendronate-treated group at year 2 (3.2% and 4.9%, respectively) and at year 3 (3.8% and 6%, respectively). BMD at the lumbar spine showed the best longitudinal sensitivity whereas longitudinal sensitivity of both QUS at the heel and femur BMD were similar. In conclusion, this study confirms that alendronate represents an important therapeutic advance in the management of male osteoporosis. BMD at the lumbar spine appears to be the best method for monitoring the effect of alendronate on bone mass in osteoporotic men.

A new serum assay to measure N-terminal fragment of telopeptide of type I collagen in patients with renal osteodystrophy.

BACKGROUND: Up until now, there was little known about the use of bone resorption markers in the assessment of bone status in patients with chronic renal failure (CRF). The present study evaluated the ability of a new immunoassay for N-terminal telopeptide of type I collagen to assess bone turnover in a group of hemodialyzed patients. METHODS: The following parameters were measured in a fasting blood sample from 111 patients on maintenance hemodialysis for at least 2 years and in 120 healthy subjects: calcium, phosphorus, magnesium, BALP, PTH, and N-terminal telopeptide of type I collagen (NTx-ELISA, OSTEOMARK NTx Siero-Ostex International). RESULTS: Serum PTH, BALP, and NTx were significantly higher (P<0.001) in hemodialyzed (HD) patients than in healthy subjects. In HD patients, PTH was correlated to BALP and NTx (r=0.40 and 0.55, respectively). When combining PTH and BALP serum levels, 17 patients showed high turnover (HT) and 65 were found to have a normal to low turnover (N-LT). In HT patients, serum NTx and dialytic age were significantly (P<0.01) higher than in N-LT patients. Moreover, even after adjusting for age, body mass index, dialytic age, and calcium-vitamin D treatment, serum NTx discriminated between HT and N-LT with a sensitivity of 97.6% and a specificity of 90.9%. CONCLUSION: Although bone biopsy remains the reference method for the diagnosis of renal osteodystrophy, the combined use of markers of bone resorption and bone formation could improve the clinical management of renal bone diseases.

Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study.

Although several studies have reported a lower risk of osteoporotic fracture in hypercholesterolemic patients treated with statins, so far longitudinal studies on the effects of statins on bone are lacking. The aim of the present study was to evaluate bone mineral density (BMD) and bone turnover changes induced by 1-year simvastatin treatment on postmenopausal women. Thirty consecutive postmenopausal hypercholesterolemic women (61.2 +/- 4.9 years) were treated for 12 months with 40 mg/day simvastatin and 30 normocholesterolemic age-matched postmenopausal women provided control data. In all subjects, at baseline and at 3-month intervals, serum lipids, calcium, phosphate, total and bone alkaline phosphatase (Bone-ALP), and carboxy-terminal fragment of type I collagen (CTx) were measured in a fasting blood sample. At baseline and after 6 and 12 months BMD was measured at lumbar spine (BMD-LS) and at femur (BMD-Ftot) and at femoral neck (BMD-Fn) by DXA. In the simvastatin-treated group Bone-ALP showed a significant increase (P < 0.05) with respect to baseline from the sixth month, whereas serum CTx showed a weak and nonsignificant increase over the study period. In treated women BMD-LS, BMD-Fn, and BMD-Ftot increased respectively by 1.1, 0.9, and 0.4% at Month 6; and by 2.8, 1.0, and 0.8% at Month 12. In controls BMD-LS, BMD-Fn, and BMD-Ftot at the end of the study period decreased by 1.6, 1.4, and 1.2%, respectively. The difference between controls and simvastatin-treated patients was significant (P < 0.05) for both BMD-LS and BMD-Fn only at Month 12. In conclusion our results, although obtained from a small sample of postmenopausal hypercholesterolemic women, suggest a probable positive effect of simvastatin on bone formation and BMD.

Changes in serum HDL and LDL cholesterol in patients with Paget's bone disease treated with pamidronate.

Amino bisphosphonates represent one of the most important advances in the management of Paget's and other metabolic bone diseases. Although their mechanism of action has not yet been completely clarified, they seem to inhibit the mevalonate pathway and so they could interfere with cholesterol synthesis. The present study aimed to evaluate cholesterol and lipoprotein serum levels in patients with Paget's bone disease treated with intravenous pamidronate. The study included 20 consecutive patients (mean age, 67.6 +/- 11.0 years) with Paget's bone disease for at least 1 year, who needed intravenous amino bisphosphonate treatment; 12 patients with inactive Paget's bone disease served as controls. The patients with active Paget's bone disease underwent three cycles (every 3 months) of treatment with 60 mg of intravenous pamidronate. Controls were given a saline infusion following the same administration schedule. In all subjects total alkaline phosphatase (total ALP), bone alkaline phosphatase (bone ALP), total cholesterol (TC), tryglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively) were measured before infusions (pamidronate or saline) at baseline and at 3-month intervals up to 9 months. In the control group no significant changes were observed through the study period for any of the biochemical parameters. In the pamidronate-treated patients, both bone ALP and total ALP significantly fell at the end of the study. In patients with active treatment, at the end of the study period HDL-C significantly (P < 0.05) increased by 10.3%, whereas LDL-C significantly (P < 0.05) decreased by 5.5%. In these patients TC showed a negative trend without reaching statistical significance, whereas the HDL-C/LDL-C ratio rose 16.2% above the basal value and TC/HDL-C decreased by 12.5%. In conclusion, pamidronate given intravenously seems to be able to induce a prolonged shifting in circulating cholesterol from the LDL-C to the HDL-C from associated with a weak decrease in total cholesterol, thus producing a possible improvement in the atherosclerotic risk index.

Heel ultrasonography in monitoring alendronate therapy: a four-year longitudinal study.

The possibility of using quantitative ultrasound (QUS) in monitoring the response to antiresorptive drugs has yet to be defined. The aim of the present study was to evaluate whether heel ultrasonography, considering its characteristics of long-term precision, is able to monitor osteoporotic patients treated with alendronate. We studied 150 postmenopausal osteoporotic women (age 59.6 +/- 5.3 years) treated with alendronate and calcium (n = 74) or with calcium alone (n = 76) for 4 years. At baseline and after 12, 24, 36 and 48 months, we measured bone mineral density (BMD) at the lumbar spine by dual-energy X-ray absorptiometry (DXA, Hologic 4500), and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness at the calcaneus by Achilles plus. Moreover, the longitudinal precision of QUS parameters was assessed by measuring 10 subjects once a month for 1 year and, on the basis of the coefficients of variation we obtained, we calculated the Least Significant Change between two measurements. In the alendronate-treated patients, at year 1, BMD increased by 4.2%, SOS by 0.4%, BUA by 1.1% and Stiffness by 3.2%; at year 2, BMD increased by 5.0%, SOS by 0.7%, BUA by 1.4% and Stiffness by 5.7%. At year 3, BMD increased by 6.2%, SOS by 0.9%, BUA by 1.8% and Stiffness by 7.6%. At the end of the study period, BMD increased by 7.6%, SOS by 1.2%, BUA by 1.9% and Stiffness by 9.0%. The minimal significant difference between two measurements was 0.8% for SOS, 5.6% for BUA and 5.0% for Stiffness. Among the QUS parameters, Stiffness showed the greatest total treatment effect and a longitudinal sensitivity which was only slightly lower than BMD. The MTI, which represents the period between scans required to show that a 'true' change has occurred, was 1.8, 2.7, 11.9 and 2.2 years for BMD, SOS, BUA and Stiffness respectively. Therefore, although the spinal BMD remains the optimal method, QUS at the heel, and in particular Stiffness, seems to be a sensitive tool for monitoring the response to alendronate.

Graphic trace analysis of ultrasound at the phalanges may differentiate between subjects with primary hyperparathyroidism and with osteoporosis: a pilot study.

Bone loss characterizes both primary hyperparathyroidism (PHPT) and osteoporosis (OP) but with a different histologic pattern, and this could partially explain the different fracture incidence in these two populations. Quantitative ultrasound (QUS), influenced by bone structural parameters other than bone mineral density (BMD), could evidence these differences, opening new perspectives in the evaluation of patients with metabolic bone diseases. The aim of the present study was to investigate the usefulness of QUS graphic trace parameters, assessed at the phalanx, in discriminating between PHPT bone disease and osteoporosis. We studied 34 patients with PHPT (mean age 59.7 +/- 12.7 years), 35 patients with OP (mean age 60.6 +/- 7.1 years) and 34 healthy subjects as controls (mean age 59.1+/- 9.4 years). In all subjects QUS measurements were performed at the phalanx with a Bone Profiler (IGEA, Italy), obtaining the amplitude-dependent speed of sound (AD-SoS), fast wave amplitude (FWA), signal dynamic (SDy), bone transmission time (BTT) and ultrasound bone profile index (UBPI). Moreover, serum calcium, phosphorus, parathyroid hormone (PTH), bone isoenzyme of alkaline phosphatase (B-ALP) and ionized calcium were measured in all subjects in the morning under fasting conditions. In PHPT patients BTT was correlated with PTH, ionized calcium and B-ALP levels (r = -0.47, -0.57 and -0.44, respectively; p < 0.01), whereas FWA, SDy and UBPI correlated only with B-ALP (r = -0.43, -0.46 and -0.50, respectively; p <0.01). Moreover, FWA, SDY and UBPI were significantly (p<0.01) lower and BTT significantly (p<0.001) higher in OP than in PHPT patients. UBPI, BTT, FWA and the BTT/FWA ratio, but not SDy, were able to discriminate between the two groups (area under the curve =0.66, 0.69, 0.67 and 0.81, respectively). Our findings show that ultrasound signal parameters are differently influenced by bone changes characterizing primary hyperparathyroidism or osteoporosis. This suggests that the QUS signal could be a useful instrument in discriminating and studying some of the bone alterations typical of metabolic bone diseases.

Urinary calcium excretion in the monitoring of bone metastases from prostatic carcinoma.

BACKGROUND: One of the greatest problems in treating advanced prostate carcinoma is monitoring the therapeutic response of bone metastases. As these metastases are mainly osteosclerotic and lead to a markedly increased bone calcium requirement that may give rise to an imbalance in calcium homeostasis, the authors investigated whether changes in calcium balance may be useful for evaluating the response of bone metastases to treatment. METHODS: The study involved 268 prostate carcinoma patients: 142 in Stage A-C2 (International Union Against Cancer [UICC] staging system, 1998) and 126 with bone metastases who had failed to respond to hormone therapy and were receiving chemotherapy. Prostate-specific antigen (PSA), calcium and phosphate metabolism, and the main bone formation and resorption markers were all assayed before and after chemotherapy. RESULTS: Of the 126 patients on chemotherapy, 109 were evaluable for response: according to standard criteria, 25 (23%) had improved, 43 (39.5%) were unchanged, and 41 (37.5%) had worsened. All of the improved and 16 unchanged patients had decreased PSA and bone marker levels and an increased urinary calcium/creatinine ratio (UCa/Cr); the worsened patients had increased PSA and bone marker levels, and their UCa/Cr decreased after only six treatment cycles. PSA and UCa/Cr were the biochemical markers whose changes showed the best agreement with treatment response. CONCLUSION: The UCa/Cr ratio was the most useful marker of clinical response, mainly because it allowed an early decision to continue or to stop chemotherapy. Furthermore, UCa/Cr and PSA together identified a percentage of patients classified as unchanged on the basis of standard criteria but whose condition had actually improved.

Usefulness of bone quantitative ultrasound in management of osteoporosis in men.

In order to evaluate the usefulness of QUS at the phalanx in the diagnosis of osteoporosis and in the prediction of fracture risk in males. The study consisted of 182 subjects (age 61.2 +/- 9.4 yr), of which 22 had had a previous nontraumatic bone fracture. In all subjects, bone mineral density (BMD) at the lumbar spine and femur was measured by DXA. Moreover, in the same subjects, QUS parameters, the amplitude-dependent speed of sound (AD-SOS), and the parameters characterizing the graphic trace (fast-wave amplitude, signal dynamic, and bone transmission time [BTT]) were assessed at the phalanxes using the DBM Sonic 1200 (IGEA). According to World Health Organization (WHO) criteria, all the patients were divided into two groups: 62 osteoporotic subjects and 120 nonosteoporotic subjects. All QUS parameters were significantly lower in osteoporotic than in nonosteoporotic patients. Receiver operating characteristic (ROC) analysis showed a moderate ability of AD-SOS, BTT, and ultrasound bone profile index (UBPI) in distinguishing between healthy and osteoporotic men. Among osteoporotic patients, BMD values were lower in patients with fracture than in those without fracture. AD-SOS and BTT were significantly reduced in men with fracture. Furthermore, in a regression analysis, only BTT and DXA parameters were predictive of fracture. Moreover, performing a multivariate regression analysis BTT entered before BMD at the lumbar spine and at Ward's triangle. In conclusion, our data show that QUS parameters are reduced in osteoporotic males; however, only BTT was comparable to DXA parameters in the prediction of fracture risk in men.

Quantitative ultrasound at the phalanges in healthy Italian men.

In the last decade there has been a growing interest in quantitative ultrasound (QUS) techniques as a new method in the assessment of bone status in metabolic bone diseases. Many studies have shown that QUS parameters can predict vertebral and femoral fracture risk in patients with osteoporosis. However, most of the studies were performed in women, whereas few data are available for men. The aim of this study was to build up a normative database on a healthy Italian male population for QUS parameters at the phalanges. Amplitude-dependent speed of sound (AD-SoS) and three parameters (first wave amplitude, FWA; signal dynamic, SDy; time frame, TF) characterizing the graphic trace of the ultrasound signal were measured at the phalanges in 286 healthy subjects (age range 20-87 years). First, the QUS device was adapted to compensate for the difference in finger thickness between men and women. Preliminary data on 150 healthy subjects showed a significant difference between the traditional and adapted device, and the latter was independent of finger thickness variations. AD-SoS showed a significant (p<0.001) decrease with aging, expressed by a second-order polynomial equation. The peak value (2122 m/s) was observed in the fourth decade; thereafter it decreased to 1980 m/s at the ninth decade. Likewise, FWA and SDy were significantly (p<0.001) reduced after the fourth decade, whereas TF remained stable over time until the last decade. In conclusion, in men AD-SoS showed a negative trend with aging. The pattern with aging of parameters characterizing the graphic trace was different from the pattern for AD-SoS, suggesting the possibility of obtaining further information on phalanx bone physical properties which could be useful in the differential diagnosis of metabolic bone diseases and in the assessment of fracture risk.