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

Introduction 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. Methods Sixty postmenopausal women (age 71.1± 6.8 years) were randomly assigned to either receive oncedaily 20-μg 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. Results 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. Conclusions 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

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

The influence of weight and length at birth on bone status during childhood as evaluated by QUS

An impaired bone mineral status in children and adolescent may represent an increased risk of osteoporosis in adulthood. It has been demonstrated that quantitative ultrasound (QUS) at phalanxes is a reliable method for the assessment of bone status in growing subjects. In 88 consecutive healthy full-term newborns (37 males and 51 females; gestational age: 39,0 1,4 weeks) QUS parameters were assessed within three days of birth at distal diaphysis of humerus using Bone Profiler (IGEA, Italy), after an appropriate modification of calliper and software. After 4 years of life the standard technique were used for children. In all subjects we evaluated: AD-SoS (m/s), the characterizing graphic trace parameters (SDy, FWA and BTT), SoS (m/s), which is the speed of sound calculated on the first peak and hBTT, which is the interval time between the first peak of the ultrasound and when this reaches the speed of 1570 m/s, which is the velocity of ultrasound in the soft tissue. Demographic and anthropometric parameters were collected at birth and at 4 years. All QUS parameters were significantly reduced in children with a birth weight 3 Kg (p 50 cm. BTT and AD-SoS measured at four years were significantly correlated with weight at birth (r = 0.31; p<0.01 and r = 0.23 p<0.05 respectively). BTT and AD-SoS showed a correlation with length at birth without reaching any statistical significance (p<0.95). At the fourth year of life a significant correlation was found between QUS parameters and shoes size (p<0.01). The present study demonstrates that weight at birth markedly influences bone status in children aged 4 years

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

9nonenoneS. GONNELLI; A. MONTAGNANI; C. CAFFARELLI; A. CADIRNI; M. CAMPAGNA; M. B. FRANCI; B. LUCANI; E. GAGGIOTTI; R. NUTIS., Gonnelli; A., Montagnani; C., Caffarelli; A., Cadirni; Campagna, MARIA STELLA; M. B., Franci; B., Lucani; E., Gaggiotti; Nuti, Ranucci

The effects of 1-year ezetimibe treatment on vitamin D levels and bone turnover markers in postmenopausal women

This study aimed to evaluate the effects of ezetimibe 0E) on 25-hydroxyvitamin D (25OHD) levels and bone turnover markers. Among the patients referring to the Centre for Lipidic and Dietary Disorders at the University of Siena we selected 15 hypercholesterolemic postmenopausal women (61.1 -4- 5.6 yrs), who had not reached an adequate control of LDL-cholesterol (LDL-C) after a treatment of at least 3-months with atorvastatin (A) 20 mg daily. In these patients E 10 mg was associated to A 20 mg daily. As controls, we selected 15 hypercholesterolemic age-matched women (61.5 -4- 6.3 yrs) on treatment with A 20 mg daily who had reached a good control of serum cholesterol (LDL-C< 130 mg/dl), who continued the treatment. In all patients at baseline and after 3, 6 and 12 months we measured serum calcium, serum phosphate, 25OHD, parathyroid hormone (PTH), bone alkaline phoshatase (BALP) and carboxy terminal fragment of type I collagen (CTx). Daily calcium intake was measured by a validated questionnaire. Eleven of 15 patients of the E/A group at the end of the 1-year study period reached the target level of serum cholesterol (LDL-C< 130 mg/dl). PTH, 25OHD and serum calcium did not show any significant variation in both the two groups. No differences between the two study groups were found. BALP and CTx showed a no significant increase after 3-months in E/A group. No correlation was found between the changes bone turnover markers and 25OHD serum levels in both the two groups. In conclusion, the present study suggests that 1-yeax treatment with E does not influence 25OHD serum levels and bone turnover markers in postmenopausal hypercholesterolemic women

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 exemestanetreated 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

Bone ultrasonography in the longitudinal monitoring of bone status in patient with Rett’s syndrome

Rett Syndrome (RS), an X-linked neurodevelopmental disorder primarily affecting girls, is frequently characterized by osteopenia with a consequent increased risk of fragility fractures. In recent years there has been a growing interest in using Quantitative Ultrasound (QUS) for the evaluation of bone status. This study aimed to evaluate the usefulness of QUS in the monitoring RS parameters. Among the patients with RS referred to the Department of Child Neurology and Psychiatry we selected a cohort of 46 females (age range 5–30 years) for whom a follow-up of at least 4 years was available. In all at baseline and every 12 months over the 4-year study period we measured serum calcium, serum phosphate, alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D. At the same times we assessed QUS parameters at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). In our institution the precision was 0.8% for AD-SoS and 0.6% for BTT. The patients were divided into three groups: non-ambulatory (group 1; n = 11), with severe (group 2; n = 10) or mild-moderate (group 3; n = 25) ambulatory impairment. At baseline no significant differences in QUS parameters were found between the ambulatory and non-ambulatory patients. However, from the first year and thereafter during the whole 4-year study period, the non-ambulatory patients presented a reduction in both AD-SoS and BTT significantly (p < 0.01) higher with respect to the other 2 groups. At the end of the study the change in AD-SoS Z-score was-0.60 for group 1,-0.40 for group 2 and 0.10 for group 3. At baseline and at all follow-up time points alkaline phosphatase was significantly higher in non-ambulatory group. The RS patients were divided in tertiles on the basis of the dose of anticonvulsants (carbamazepine) and we found that at baseline both AD-SoS and BTT were significantly lower in the group with the higher dose with respect to the group with the lower dose of anticonvulsants (1838 vs. 1879 and 0.50 vs. 0.74 respectively). During the study period in the higher tertile BTT showed a tendency to decrease without reaching statistical significance. In conclusion QUS parameters seem to be a valuable tool in the monitoring of the patients with RS. The ambulatory ability and the use of anticonvulsants seem to be the main determinants of bone status in patients with RS

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