The relationship between serum ghrelin and body composition with bone mineral density and QUS parameters in subjects with Rett syndrome.

Several studies have reported that females with Rett's syndrome frequently have marked decreases in bone mineral density (BMD). However, the pathogenesis of impaired bone status in RTT girls remains controversial. This study aimed to investigate whether ghrelin, an orexigenic peptide secreted by the stomach, was associated with body composition parameters, bone mineral density and quantitative ultrasound (QUS) in girls with Rett's syndrome. In 123 Rett girls (13.6±8.2 years) and in 55 similar age range controls we evaluated ghrelin serum levels, 25OHD, quantitative ultrasound parameters at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT), total body bone mineral density (BMD-WB) by Hologic QDR 4500. Whole body mineral content (BMC-WB), BMC-WB/height, fat mass (FM), fat percentage and lean mass (LM) were determined by using the same DXA device. We found that serum ghrelin levels were significantly higher in the Rett patients with respect to the control group (p<0.05). In Rett girls ghrelin serum levels were inversely correlated with both age (R(2)=0.17, p<0.001) and BMI (R(2)=0.14, p<0.001). Moreover, in Rett subjects the values of BMD-WB, BMC-WB, BMC-WB/height and QUS parameters were significantly lower than in control subjects. Fat mass and lean mass were lower in Rett subjects than in controls, but the difference reached the statistical significance only for lean mass. In Rett girls ghrelin serum levels were not predictors of bone status. Instead, we found that in Rett subjects, lean mass, age and 25OHD were significant independent predictors of BMC-WB/h, whereas both age and height were independent predictors of BMD-WB. Moreover, AD-SoS was predicted by age, fat percentage and height; while BTT was predicted only by height. In conclusion, our findings indicate that ghrelin levels were higher in Rett girls with respect to healthy controls, and negatively associated with both DXA and QUS parameters. However, in our study ghrelin was not found to be an independent predictor of bone mass, so supporting the hypothesis that ghrelin is elevated in Rett subjects in a compensatory manner.

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.

Serum OPG and RANKL levels before and after intravenous bisphosphonate treatment in Paget's disease of bone.

Paget's disease of bone (PDB) is a focal disorder of bone remodeling characterized by increased osteoclast-mediated bone resorption. Even though increasing evidence indicates enhanced nuclear factor-kB (NF-kB) signaling as a common mechanism involved in PDB and other related disorders, few studies investigated circulating osteoprotegerin (OPG) and receptor of activator of NF-kB-ligand (RANKL) levels in PDB patients. In this study we explored the relationships between OPG or RANKL levels and bone turnover markers in a group of patients with PDB, before and after intravenous bisphosphonate treatment (pamidronate 60 mg). Both OPG and RANKL were markedly elevated in PDB patients with respect to control groups (healthy or osteoporotic postmenopausal women and elderly men) and were positively associated with bone turnover markers. Higher levels of these cytokines were observed in polyostotic than monostotic PDB cases. The ratio between RANKL and OPG was more than 3-fold higher in PDB patients than in controls. Interestingly, in the group of patients treated with pamidronate, we found an increase in OPG levels that become statistically significant after 3 and 6 months from treatment. A trend toward a decrease in RANKL levels after treatment was also observed. The RANKL/OPG ratio was significantly reduced after 3 and 6 months of therapy. In contrast, in patients classified as non-responders, OPG and RANKL levels after pamidronate infusion did not significantly differ with respect to pre-treatment values. Thus, the positive effect of amino bisphosphonates in the treatment of PDB may be due to either direct or indirect suppression of RANKL-induced bone resorption through decreased RANKL and increased OPG production.

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.

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.

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.

Risk factors for acquiring Helicobacter pylori infection in a group of Tuscan teenagers.

Risk factors for acquiring Helicobacter pylori infection include hygienic, social, and environmental conditions. Some of these conditions usually change over time. We therefore investigated the existence of risk factors in a group of teenagers living in a place with the same environmental characteristics, in which hygienic and crowding conditions have not changed significantly in the last 20 years. A group of 164 students, mostly borne in 1977, attending four different schools, were examined serologically for H. pylori infection and CagA status. The importance of the risk factors for the transmission of the infection were evaluated by the chi2 test. P values <0.05 were considered significant. Twenty-two students (13.4%) were H. pylori seropositive. Students attending teachers' college and high school of arts were infected significantly more often than those attending high school (P = 0.011 and P = 0.012, respectively). Students who smoked and students whose parents had a manual job had an increased risk of acquiring the infection (P = 0.002, and P = 0.036, respectively). Crowding conditions and the presence of domestic animals were close to being statistically significant. Other factors, such as gender, number of bathrooms and bedrooms, sharing the bed with adults as a child, presence of a sexual partner, and a family history of peptic ulcer and gastric cancer, did not increase the risk of infection. The prevalence of seropositivity for CagA was similar in the various risk groups. Manual job of parents and smoking were the most important factors for acquiring H. pylori infection.

Dual X-ray absorptiometry and bone ultrasonography in patients with Rett syndrome.

This study evaluated bone status and bone turnover in 82 females (ages 2-21 years) with the Rett Syndrome (RS) and 82 age-matched controls. Bone mineral density (BMD) by dual X-ray absorptiometry (DXA) at the ultradistal and proximal radius and ultrasonographic (QUS) parameters at the calcaneus [speed of sound(SOS), broadband ultrasound attenuation(BUA), and stiffness] and at the phalanxes (amplitude dependent speed of sound: AD-SOS) were measured. We also measured serum calcium, phosphate, 25-hydroxyvitamin D, and biochemical markers of bone turnover. DXA and QUS parameters were significantly lower in patients with RS compared with controls and, among RS alone, in those treated with anticonvulsants and in those who are nonambulatory. Ambulatory RS patients showed QUS and DXA parameters significantly greater than nonambulatory patients but significantly lower than controls. Patients with RS treated with anticonvulsants presented QUS and DXA parameters lower than those of other RS. In RS patients, walking significantly influences BMD-UD, BMD-P, SOS. BUA. and Stiffness. Serum 25-hydroxyvitamin D was significantly lower in RS than in controls. These results suggest that ambulatory status, to a major extent, and anticonvulsant therapy certainly play an important role in the reduction of bone mass and bone quality, but they cannot completely explain the altered bone status. Whatever the cause, girls with RS present abnormal bone status with an increase in the risk of fracture.

Bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases.

We have investigated the clinical utility of a new quantitative two-site radioimmunometric assay specific for bone alkaline phosphatase (B-ALP) in 219 healthy control subjects and in 264 patients with various metabolic bone diseases. B-ALP was compared with total alkaline phosphatase (T-ALP) and with osteocalcin (BGP). B-ALP increased linearly with age in both sexes. In postmenopausal normal women B-ALP increased by 82% compared with premenopausal normal women, whereas the differences between pre- and postmenopausal women for T-ALP and BGP were 18% and 30% respectively. As assessed by Z-score, the highest values of B-ALP were found in patients with Paget's disease of bone, bone metastases or hyperparathyroidism and in patients on maintenance haemodialysis. In osteoporotic patients, B-ALP< but not T-ALP, showed a slight but significant (P < 0.05) difference compared with normal women. On the basis of bone turnover, osteoporotic patients were divided into two groups: high turnover and low turnover; B-ALP, like BGP, was significantly (P < 0.01) higher in patients with high turnover. In conclusion, B-ALP, measured by this new method, can be considered a sensitive marker of bone turnover and could be especially useful in identifying women at risk of developing osteoporosis.