Relationship between quantitative ultrasound parameters at the calcaneus and health-related quality of life in postmenopausal Italian women: the FEDRO study.

Reduced bone mineral density has been reported to adversely affect health-related quality of life (HRQoL) in postmenopausal women without vertebral fracture. To date, no data exist in the literature about any possible influences of quantitative ultrasonographic (QUS) parameters on HRQoL. This study aimed to assess whether QUS parameters at the calcaneus may be associated with HRQoL. In 1,812 ambulatory postmenopausal women aged 60 years or over, we measured HRQoL by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) and stiffness index using QUS at the calcaneus. By grouping the 1,812 women on the basis of stiffness index, a highly significant (p < 0.001) difference was found for both total QUALEFFO and five domains of the QUALEFFO, whereas for the Pain and Mental Function domains the significance was modest. Stiffness was inversely associated (p < 0.01) with total QUALEFFO and with all QUALEFFO domains. In stepwise multiple logistic regression analysis stiffness values were negatively associated with both QUALEFFO total score and all domains of the QUALEFFO-41. The presence of concomitant diseases was associated with a worsening of HRQoL in all domains of the QUALEFFO, whereas age was associated with the three domains of physical function but not with the Pain and Mental Function domains. Our study suggests that in postmenopausal women there is a close relationship between bone status measured by QUS at the calcaneus and quality of life assessed by the QUALEFFO. Therefore, QUS at the calcaneus may have a role in early strategies to prevent HRQoL impairment and osteoporosis exacerbation.

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.

The relationship of ghrelin and adiponectin with bone mineral density and bone turnover markers in elderly men.

Body weight is commonly considered a significant predictor of bone mineral density (BMD). Adiponectin, an adipocyte-derived hormone, could modulate BMD. Moreover, recent studies have reported that ghrelin is able to stimulate bone formation. In this study, we investigated any associations of adiponectin and ghrelin serum levels with bone turnover markers and BMD in elderly men. In 137 men aged 55 years and older (mean age 67.4 +/- 5.4 years, mean body mass index [BMI] 26.6 +/- 3.4 kg/m2), we evaluated serum adiponectin, serum ghrelin, body composition (fat mass and lean mass), BMD, bone alkaline phosphatase (ALP), and the carboxy-terminal telopeptide of type I collagen (betaCTX). Ghrelin showed significant correlations with BMD at the femoral neck (r = 0.25, P < 0.01), total femur (r = 0.22, P < 0.05), and whole body (r = 0.18, P < 0.05). However, after adjusting for age, BMI, and calcium intake, the correlation remained significant only for femoral neck BMD. Ghrelin showed a significant correlation with lean mass but not with fat mass and bone turnover markers. Adiponectin showed a positive association with both bone ALP and betaCTX; the correlation between adiponectin and bone ALP (r = 0.25, P < 0.01) remained significant after adjusting for confounding variables. No significant correlations between adiponectin and BMD at all skeletal sites were observed. In conclusion, our study suggests that in elderly Italian men serum ghrelin was significantly associated with femoral neck BMD and that adiponectin was positively associated with bone ALP. Further studies are needed to elucidate the role of adipocytokines in bone metabolism.

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.