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R Nuti

Publications and source records attributed to R Nuti.

At least 19 recordsLinked to original sources

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.

Aged↗

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.

Alkaline Phosphatase↗

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Age Factors↗

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.

Aged↗

A case of acute heart failure associated with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a disease of the peripheral nervous system, which is caused by aberrant immune responses directed against some components of peripheral nerves. GBS is rarely accompanied by cardiovascular involvement. We describe a case of acute neuropathy complicated by sudden heart failure and left ventricular dysfunction which had a presumably neurogenic origin. Pathogenesis of acute heart failure is probably due to transitorial stunned myocardium and neurogenic cardiac injury. We show a rare case of transitorial and acute cardiac dysfunction by echocardiography and laboratory markers of heart failure.

Aged↗

Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis.

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.

Aged↗

Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review.

Osteoporosis (OMIM166710) is a common skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with increased susceptibility to fracture. Osteoporosis has a complex etiology and is considered a multifactorial polygenic disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. Estrogens are known to play an important role in regulating bone homeostasis and preventing postmenopausal bone loss. They act through binding to two different estrogen receptors (ERs), ER alpha (OMIM133430) and ER beta (OMIM601663), which are members of the nuclear receptor superfamily of ligand-activated transcription factors. Different polymorphisms have been described in both the ER alpha and ER beta genes. Although a large number of association studies have been performed, the individual contribution of these polymorphisms to the pathogenesis of osteoporosis remains to be universally confirmed. Moreover, an important aim in future work will be to define their functional molecular consequences and their interaction with the environment in the causation of the osteoporotic phenotype. A further promising application of these polymorphisms comes from their pharmacogenomic implications, with the possibility of providing better guidance for therapeutic regimens, such as estrogen replacement therapy and selective ER modulators. At the moment, no recommendations for population-based screening can be made.

Bone Density↗

Increased phospholipase activity in Helicobacter pylori strains isolated from patients with gastric carcinoma.

PURPOSE: Phospholipase activity, one of Helicobacter pylori pathogenicity factors, has not been investigated enough, so far, although it may induce a remarkable damage to the gastric mucosa. In the present work, we have compared the whole phospholipase activity of H. pylori strains isolated from patients with gastric carcinoma with that of strains isolated from dyspeptic patients without gastric carcinoma. METHODS: We measured the phospholipase activity of one distinct H. pylori colony isolated from each of 10 patients with gastric carcinoma and 10 controls, dyspeptic patients without endoscopic and histological signs of gastric carcinoma. We also determined the phospholipase activity of 20 additional strains isolated from different areas of neoplastic and non-neoplastic tissue of two patients with gastric carcinoma, the cagA and vacA positive G27 and 328 wild strains and their respective vacA and cagA negative isogenic mutants. The whole phospholipase activity of strains was determined by measuring the release of (14)C-labeled palmitic acid from the radioactive l-3-phosphatidylcholine, 1,2-di[1-(14)C]palmiloyl substrate; results were expressed in pmol of palmitic acid per mg of protein. RESULTS: H. pylori strains isolated from patients with gastric carcinoma had levels of phospholipase activity significantly higher than those of strains isolated from controls (99.37 [S.D. 40.45] versus 34.46 [S.D. 16.46], P<0.001). In patients with gastric carcinoma, the mean phospholipase activity of strains isolated from neoplastic tissue was similar to that of strains isolated from non-neoplastic tissues (123.02 [S.D. 44.36] and 115.77 [S.D. 81.48], respectively. Interruption of cagA gene caused a ca. 20% reduction of phospholipase activity (36.38 versus 45.22 of the wild strain); that of vacA caused no reduction of phospholipase activity (26.53 and 25.37 of the wild strain). CONCLUSIONS: The infection by H. pylori strains that produce high levels of phospholipase may increase the risk of developing gastric carcinoma. We hypothesise that indirect products of phospholipase activity, such as prostaglandins, leukotrienes and lysophospholipids, may mediate carcinogenesis.

Antigens, Bacterial↗

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.

Aged↗

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Accidental Falls↗

Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure.

AIM: Carvedilol treatment in chronic heart failure (CHF) demonstrated to reduce mortality and rehospitalisation, and improvement of cardiac systolic function with reduction of left ventricular volumes and remodelling. The effects of the drug on left ventricular (LV) filling are less studied. Systolic dysfunction is often associated to diastolic alteration, pseudonormal and restrictive filling pattern are related with poor prognosis. In this study we evaluated diastolic cardiac modifications during carvedilol therapy at early and long term in patients with advanced CHF and pseudonormal or restrictive filling pattern by echo Doppler method. METHODS: We studied 59 patients with severe but stable CHF (40 in class NYHA III and 19 in class NYHA IV) with both systolic and diastolic dysfunction due to idiopathic or ischemic cardiomyopathy. Group I (n=32) received preceding treatment plus carvedilol and Group II (n=27) continued standard therapy with ACE-inhibitors, diuretics, digossin and vasodilators. In all subjects were evaluated LV volumes mass and ejection fraction (EF). Therefore, we studied transmitral filling parameters: Early filling wave (E), atrial filling wave (A), E/A ratio, deceleration time of E (DT) and isovolumetric releasing time (IVRT) by echo Doppler method. RESULTS: After 4 months of therapy carvedilol group showed a significant increase of A wave (p<0.001) DT (p<0.0001) and IVRT (p<0.0001), and significant reduction of E/A ratio (p<0.0005) respect to Group II. Any significant changes were observed for volumes mass and EF. Transmitral Doppler measurements remained unchanged or further ameliorated at 12 months (A p<0.0005; DT p<0.00002; IVRT p<0.000004; E/A p<0.0008), we also observed E wave reduction (p<0.001) in Group I respect to controls. Besides, after 1 year of follow-up we observed a reduction of systolic volume (p<0.001) pulmonary pressure (p<0.0001) and consequent increase of EF (p<0.001) in group treated with beta-blockers. Multivariate analysis demonstrated that Doppler modification were minimally related to heart rate and blood pressure reduction. CONCLUSIONS: Carvedilol treatment improve diastolic function in CHF with severe diastolic impairment driving restrictive or pseudonormal filling pattern towards altered pattern at early time. These changes remained also after 1 year of therapy and appeared to precede increase of systolic function and improvement of emodynamic status.

Adrenergic beta-Antagonists↗

Professional sport activity and micronutrients: effects on bone mass.

Osteoporosis is the most prevalent metabolic bone disease among developed countries. Although bone mass and density are certainly determined by various concurrent factors such as genetics, hormones, life-style and the environment, and although the genetic program has a critical role in growth and in bone peak development, for their realization an adequate nutritional intake of nutrients and regular exercise are always necessary and may represent a way to prevent osteoporosis and fractures. Exercise and especially high-impact sport activity during growth and adolescence increases bone mineral density (BMD) in weight-loaded skeletal regions. Aerobics, weight bearing and resistance exercises may also be effective in increasing BMD in post-menopausal women. Even though most of the research on nutritional components has focused almost exclusively on calcium and vitamin D, there is now considerable interest in the effects of a variety of other nutrients on bone status.

Biological Availability↗

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.

Absorptiometry, Photon↗

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.

Adult↗

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.

Absorptiometry, Photon↗

Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women.

This study examines the influence of circulating insulin-like growth factor-1 (IGF-1) and serum leptin on bone mass as well as modulation of bone mass during skeletal development. Moreover, an inverse relationship between IGF-1 and leptin is reported. To evaluate the effects of serum IGF-1 and serum leptin on bone mass in healthy postmenopausal women, and the possible role of IGF-1 in leptin production, we studied a population of 123 women, aged 39-82 years. Bone mineral density (BMD) was determined by whole-body dual-energy X ray absorptiometry, which also enables measurement of body composition. Bone metabolism was assessed by measuring serum total alkaline phosphatase (TAP) and urinary hydroxyproline/creatinine (HP/Cr) excretion. IGF-1 correlated significantly with age (r = -0.28, p < 0.01) and years since menopause (r = -0.24, p < 0.01). A negative correlation was also found with weight and body mass index (r = -0.15, p < 0.05 and r = -0.19, p < 0.05, respectively). Leptin values were strongly correlated with weight (r = 0.7, p < 0.01), BMI (r = 0.7, p < 0.01), fat mass (r = 0.77, p < 0.01), and lean mass (r = 0.39, p < 0.01); a significant correlation was found with total body BMD (r = 0.29, p < 0.01), TAP (r = 0.15, p < 0.05), and HP/Cr (r = 0.18, p < 0.05). After adjustment for BMI, the significance of these relationships disappeared, demonstrating the lack of effect of serum leptin on BMD and bone turnover independent of body weight. On the other hand, the relationship between BMD and fat mass remained statistically significant after adjusting for serum leptin (r = 0.15, p < 0.05). Controlling for BMI eliminated the significant inverse correlation between IGF-1 and leptin; significant differences in leptin levels were found among women in the lower and higher quartile of IGF-1, suggesting that leptin production may be inhibited only at high values of serum IGF-1. We conclude that serum IGF-1 and serum leptin have no direct effect on bone mass and bone turnover.

Adult↗