Abstract Evaluation of osteoporotic vertebral fracture risk is currently based on measurement of bone mineral density (BMD), but bone strength depends also on bone quality parameters. Aim of this ...study was to evaluate the validity of a new vertebral morphometric index, the Anterior Vertebral Heights sum (AHs) in discriminating women at high risk of vertebral fracture, comparing its diagnostic accuracy with that of BMD measured at lumbar spine (LS-BMD) and femoral neck (FN-BMD). Materials and methods A total of 163 Caucasian post-menopausal women (age range 46–74 years, mean age ± SD = 63.8 ± 7.1 years), who did not present prevalent fractures at baseline evaluation, were observed at longitudinal follow-up. X-ray of the thoracic and lumbar spine, LS-BMD and FN-BMD measurements were obtained in all patients at baseline and repeated at the second follow-up visit 18–24 months later (mean 21 ± 1.7 months). Radiographs of spine were analysed in order to identify vertebral fractures using a visual semiquantitative method (SQ) and vertebral morphometry as well as by calculating the AHs morphometric index. Results During follow-up, 21/163 patients (12.9%) sustained a new vertebral fracture; 95.2% (20/21) of fractured patients but only 4.9% (7/142) of non-fractured women had reduced AHs values. As regarding BMD, 66.6% (14/21) and 61.9% (13/21) of women with incident fracture were osteoporotic at lumbar spine and femoral neck baseline evaluation , whereas among non-fractured women, 38% (54/142) at LS-BMD and 33.1% (47/142) at FN-BMD were osteoporotic . Analyses of Receiver Operating Characteristic (ROC) curves showed that AHs discriminated vertebral fractures almost perfectly (AUC 0.97; 95% CI 0.95–0.99). On the other hand, the AUC for LS-BMD was only 0.73 (95% CI 0.64–0.81) and for FN-BMD was 0.72 (95%CI 0.63–0.80), showing that the diagnostic accuracy of AHs was significantly higher compared to that of LS-BMD ( p < 0.001) or FN-BMD ( p < 0.001). A modified Poisson regression model for binary data was used to assess the independent role of AHs in predicting vertebral fracture. The effect of AHs remained statistically significant ( p < 0.001) after adjusting by FN-BMD, age, weight and body height. Conclusions Results of this study indicate the validity of this new morphometric index in evaluating the risk of osteoporotic vertebral fractures thus suggesting that AHs should be considered a valid parameter in clinical practice to assess the need for primary prevention of vertebral fractures.
The purpose of our study was to evaluate the behaviour of blood pressure (BP) by ambulatory monitoring of blood pressure (AMBP) in 53 patients with primary hyperparathyroidism (PHPT) compared to 100 ...essential hypertensive (EH) and 31 healthy subjects (HS). The correlations between calcium-phosphorus metabolism and haemodynamic parameters in all groups are included in the study. AMBP was performed using the oscillometric technique (Space-Labs, 90207, Redmond, WA, USA) and the following AMBP parameters were evaluated: average day time systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) (when awake), average night time SBP, DBP and HR (when asleep) and average 24-h-SBP, DBP and HR. The definition of 'dipper' or 'non-dipper' subjects was established if night time SBP and DBP fall was >10% and <10%, respectively. In total, 25 PHPT patients (47.2%) were hypertensive (HT-PHPT) and 28 PHPT (52.8%) were normotensive (NT-PHPT). Mean 24-h-SBP and DBP obtained by AMBP was higher in HT-PHPT (P < 0.05) and EH (P < 0.05) than in NT-PHPT and HS. The multiple linear regression has shown that in PHPT-HT patients ionized calcium is an independent factor for the rise of 24-h-DBP values (r: 0.497; P < 0.05) and daytime DBP values (r: 0.497; P < 0.05). In 56% of HT-PHPT patients there is an absence of physiological BP nocturnal fall ('non-dipper'), which is statistically significant (P < 0.05) compared with 'non-dipper' EH patients (30%). In conclusion, in our study the prevalence of hypertension in PHPT was 47%. AMBP revealed that the 'non-dipping 'pattern was much higher in HT-PHPT patients in respect to EH patients.
Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast ...function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.
The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 ...normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 ± 7.9 pg/mL) than in HS (11.3 ± 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 ± 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 ± 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation. Copyright 2003, Elsevier Science (USA). All rights reserved.
Standard Infliximab infusion consists of a 2-hour intravenous administration. Recently, Infliximab shortened infusion has been included in the Infliximab label as possible maintenance regimen for ...patients tolerating Infliximab induction therapy.
To verify if accelerated 1-hour Infliximab infusions are as safe as standard administrations, in patients with Inflammatory Bowel Disease.
Seventy-four patients treated between September 2008 and November 2014 were evaluated. Patients were eligible for 1-hour infusion if they had no history of infusion reactions during the previous 2-hour infusions.
Twenty-three patients received 2-hour infusions, 16 patients received 1-hour infusions, 35 patients received 2-hour infusions followed by 1-hour infusions. A total of 1,123 Infliximab infusions were administered. The proportion of patients experiencing infusion reaction was: 4% over the 1-hour infusions and 9% over the 2-hour (P = 0.318). Adverse reaction/infusion rate was 0.55% over the 1-hour infusions and 0.66% over the 2-hour (P = 0.835). In the logistic model, accelerated infusion was the only statistically significant predictor of infusion reaction risk reduction (-90%; P = 0.024). Mean satisfaction was 8/10 (±0.84) with 1-hour regimen and 6/10 (±0.56) with 2-hour infusions (P = 0.000). The mean total cost was reduced by 47% with the 1-hour regimen (133.54€ and 250.86€ for 1-hour and 2-hour infusions, respectively).
Accelerated Infliximab infusion does not increase the acute infusion reaction incidence. In patients with inflammatory bowel disease, the 1-hour regimen should be preferred to 2-hour protocol also due to positive effects on indirect costs and patient's satisfaction.
We assessed the incidence of hip fracture and ecological correlates in residents of 14 communities in six countries of Southern Europe. Hip fracture cases were recorded prospectively in defined ...catchment areas over a 1-year interval. A retrospective questionnaire was used to assess ecological differences between communities. During a 1-year period of observation a total of 3629 men and women over the age of 50 years were identified with hip fracture from a catchment of 3 million. In all communities the fracture rate increased exponentially with age. There were large and significant differences between centres in the doubling time for hip fracture risk with age and in crude and age-standardized rates. Greater than 4-fold and 13-fold differences in age-standardized risk were found amongst men and women respectively. The lowest rates were observed from Turkey and the highest from Seville, Crete and Porto. Fractures were significantly more frequent among women than men with the exception of three rural Turkish centres. Indeed, in rural Turkey the normal female/male ratio was reserved. Variations in incidence between regions were greater than the differences within centres between sexes, and there was a close and significant correlation between incidence rates for men and those for women in the regions studied. Excess female morbidity increased progressively from the age of 50 years but attained a plateau after the age of 80 years, suggesting a finite duration of the effect of the menopause. The retrospective questionnaire completed by 80% of cases suggested that differences in incidence between the communities studied could not be explained by differences in gonadal status in women. In both men and women cross-cultural associations were found with factors related to age or socioeconomic prosperity, the majority of which disappeared after adjustment for age. We conclude that there are marked and sizeable differences in the incidence rates of hip fracture throughout Southern Europe. The reasons for these differences are not known but affect both men and women, and are likely to be related to lifestyle or genetic factors rather than to differences in endocrine status.
Adrenomedullin (ADM) is a new potent vasorelaxant peptide identified originally in extracts of pheochromocytoma, and is widely distributed within the tissue. Although histopathological studies have ...demonstrated the presence of ADM-immunoreactivity (ir-ADM) in some human neuroendocrine tumors (such as insulinoma, pituitary adenoma, and gastrointestinal neuroendocrine tumors), data on the presence of ADM in normal and pathological parathyroid gland are not available. Plasma AM concentrations were recently reported to be elevated in patients with PHP (primary hyperparathyroidism). The aim of our study was to determine tissue distribution of ir-AM in 34 patients with PHP (27 female and 7 male, mean age 50 +/- 6 years) undergoing surgery. Six normal parathyroid samples incidentally found during thyroidectomy for neoplastic diseases and ten sections of human rectus abdominis muscle tissue were used as controls (C). Adenomatous parathyroids were found in 22 PHP and hyperplastic parathyroids in twelve PHP patients. Four hyperplastic parathyroids were found in three PHP patients and three parathyroids in 10 PHP patients. Eight parathyroids revealed a prevalent diffuse growth pattern and four showed a prevalent nodular growth pattern. Immunohistochemical ADM expression was seen in seven of twelve (58.3 %) hyperplastic parathyroids and in fourteen of twenty-two (66.6 %) adenomatous glands. Parathyroid chief cells showed strong cytoplasmatic staining, whereas oncocytic cells showed a faintly aspecific cytoplasmatic staining. Normal parathyroids were negative for ir-ADM. In conclusion, we found the presence of ADM in parathyroid chief cells of PHP patients using immunohistochemistry in our study.
This investigation was undertaken to determine whether the preservation of bone mass in patients with mild primary hyperparathyroidism (PHPT) could be detected when measuring spine density in the ...lateral projection. We compared the bone mineral density (BMD) of L2-L4 utilizing the posterior-anterior (PA) and lateral projections in postmenopausal patients with PHPT and in a group of 27 postmenopausal normal women. Thirty-three consecutive postmenopausal patients with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered complications related to the disease. Based upon the criteria established by the Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25 asymptomatic patients could be considered affected by mild disease; the remaining patients were classified as having moderate disease. Patients with mild disease had mean lateral total BMD values (0.682 +/- 0.113 g/cm(2)) significantly higher than normal women (0.588 +/- 0.076, p<0.02) and patients with moderate disease (0.599 +/- 0.077, p<0.05). There were significant differences among the three groups in both PA L2-L4 and L1-L4 levels: patients with mild disease had significantly higher mean BMD values than patients with moderate disease and normal women, when either three or four vertebrae were considered. Interestingly, at this latter site, patients with moderate disease had significantly ( p<0.05) lower values than normal women. Our results indicate that patients with mild PHPT have a preservation of vertebral mass when compared with the other hyperparathyroid patients and normal women, when taking into account both the mainly trabecular portion and the whole vertebra. The finding that when the PA projection was assessed, BMD values of patients with moderate disease were significantly lower than those of normal women, might be attributed to the detrimental effect of raised parathyroid hormone levels on the cortical component of the vertebral body.
We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. ...453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.
In this paper we present the results of a 12-month double-blind clinical multicenter study assessing the effects of synthetic salmon calcitonin (CT) administration in a group of white postmenopausal ...osteoporotic women. Treated patients were given 100 MRC units of synthetic salmon CT injected i.m. in the morning every other day. Control patients received a placebo injection. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radionuclides, 241Am and 125I, with energies of about 60 keV and 30 keV respectively. Biochemical parameters of calcium-phosphorus metabolism were also measured. After 12 months of treatment a significant mean increment of BMC and nondialyzable OHPr/creatinine values and a significant decrease of total OHPr/creatinine values were observed in the treated group, while controls showed a significant decrease in BMC values. These results, together with the observation that in some patients the decrease in total OHPr/creatinine values was not accompanied by an increment of BMC, show that long-term salmon CT treatment may be of benefit in postmenopausal osteoporosis and that the effects of CT on bone mass may be due not only to the inhibition of bone resorption but also to the stimulation of bone formation.
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