M Nuzzo

Università degli Studi di Brescia, Brescia, Lombardy, Italy

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Publications (23)85.34 Total impact

  • Clinical and experimental rheumatology 05/2014; · 2.97 Impact Factor
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    ABSTRACT: Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the child's immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mother's antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.
    Annals of the rheumatic diseases 05/2012; 72(2). DOI:10.1136/annrheumdis-2011-201167 · 10.38 Impact Factor
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    ABSTRACT: Anti-β2 GPI are a formal laboratory criterion for the antiphospholipid syndrome (APS). They were demonstrated to be a risk factor for thrombosis and fetal losses but can also be detected in patients with systemic autoimmune disease (SAD), in healthy adults individuals and pre-school children. It has been suggested that different subpopulations of anti-β2GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identified in patients with non-thrombotic conditions. We studied 48 patients with SAD (32 systemic lupus erythematosus, 16 undifferentiated connettive tissue disease), 64 patients with APS, 57 one-year-old healthy children born to mother with SAD, 33 children with atopic dermatitis. All subjects were IgG anti-β2 GPI positive. The specificity of anti-β2 GPI was investigated using ELISA research products containing recombinant β2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-β2 GPI were tested at a validated home-made ELISA routinely performed in our laboratory. No thrombotic events were recordered in patients with SAD and in both groups of children. Patients with SAD and APS showed prevalent reactivity for D1 while children in both groups preferentially recognize D4/5. IgG anti-β2 GPI against D1 seem to cluster in patients with systemic autoimmune conditions. Their pathogenic potential in determine APS manifestations may be mitigated by adequate prophylaxis.
    Reumatismo 09/2011; 63(2):91-6. DOI:10.4081/reumatismo.2011.91
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    ABSTRACT: To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy. A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared. The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies. It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.
    Rheumatology (Oxford, England) 06/2011; 50(9):1684-9. DOI:10.1093/rheumatology/ker139 · 4.44 Impact Factor
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    ABSTRACT: Anti-β₂-glycoprotein-I (anti-β₂GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β₂GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions. To evaluate the fine specificity of anti-β₂GPI in adults and infants. Three groups were examined-group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS. were selected based on positive anti-β₂GPI IgG results. Serum samples were tested for anti-β₂GPI IgG D1 and D4/5 using research ELISAs containing recombinant β₂GPI domain antigens. Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B. The specificity for D4/5 suggests that anti-β₂GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the 'innocent' profile of such antibodies.
    Annals of the rheumatic diseases 10/2010; 70(2):380-3. DOI:10.1136/ard.2010.137281 · 10.38 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate the prevalence, clinicopathologic features, and outcome of renal involvement in a large cohort of patients with primary antiphospholipid syndrome (PAPS). We retrospectively examined medical records of 160 patients with a diagnosis of PAPS of two general hospitals of northern Italy between 1985 and 2008. There were 140 women and 20 men. Mean age was 35+/-12 yr. PAPS was characterized by thrombotic events in 41.2%, fetal loss in 39.4%, and both in 19.4%. Signs of renal abnormalities were present in 14 (8.7%) patients. All patients had proteinuria, in the nephrotic range in five; four patients had moderate chronic renal insufficiency, and one had end-stage kidney disease (ESKD). Two patients presented with acute renal failure and one with nephritic syndrome. Ten patients underwent a renal biopsy, which showed a membranous glomerulonephritis in four, proliferative glomerulonephritis in two, thrombotic microangiopathy in two, and vascular lesions consistent with chronic antiphospholipid antibodies nephropathy in two. Patients with renal involvement were older (41.8 versus 34.3 years; P=0.0269), more frequently lupus anticoagulant positive (92.3 versus 48.9%; P=0.0068), and had hypocomplementemia (P<0.05). Renal abnormalities are present in approximately 9% of patients with PAPS. In addition to APS nephropathy, the prevailing picture is membranous nephropathy. Outcome and long-term follow-up usually are good. Not all of the clinical manifestations of PAPS can be ascribed to thrombotic mechanisms. The heterogeneity of renal involvement confirms the presence of a continuum between systemic lupus erythematosus and PAPS.
    Clinical Journal of the American Society of Nephrology 07/2010; 5(7):1211-7. DOI:10.2215/CJN.00460110 · 5.25 Impact Factor
  • Current Rheumatology Reviews 02/2010; 6(1):18-24. DOI:10.2174/157339710790827713
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    ABSTRACT: Anti-β₂glycoprotein I antibodies (a-β₂GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-β₂GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a-β₂GPI in different clinical situations. We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-β₂GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-β₂GPI positive. IgG a-β₂GPI were performed by homemade ELISA, while IgG a-β₂GPI D1 and D4/5 were tested on research ELISAs containing recombinant β₂GPI domains antigens. One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-β₂GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-β₂GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children. A-β₂GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the "innocent" profile of a-β₂GPI in children.
    Reumatismo 01/2010; 62(3):189-94. DOI:10.4081/reumatismo.2010.189
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    A Tincan · M Nuzzo · M Motta · A Lojacono
    Nephrology Reviews 06/2009; 2(10). DOI:10.4081/hmr.v2i10.453
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    ABSTRACT: To asses risk factors for a first thrombotic event in antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of prophylactic treatments. Recruitment criteria were age 18-65 years, no history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM anticardiolipin antibody (aCL) on > or =2 occasions at least 6 weeks apart. Demographic, laboratory and clinical parameters were collected at enrolment and at the time of the thrombotic event. 370 patients/subjects (mean (SD) age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of 59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event during follow-up. Hypertension and medium/high levels of IgG aCL were identified by multivariate logistic regression analysis as independent risk factors for thrombosis. Thromboprophylaxis during high-risk and long-term periods was significantly protective. Hypertension or medium/high titres of IgG aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers and primary prophylaxis is protective.
    Annals of the rheumatic diseases 10/2008; 68(3):397-9. DOI:10.1136/ard.2008.096669 · 10.38 Impact Factor
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    ABSTRACT: Recommendations for the treatment of aPL-positive patients with pregnancy morbidity are based on a limited number of well-designed clinical trials. However, the management of pregnant aPL-positive women still displays several open questions. To determine the practice patterns of experienced physicians in the management of the controversial aspects of aPL pregnancies. A questionnaire reproducing debated conditions was initially sent to the Advisory Board members (ABMs) of the 12th Congress of aPL and the Fifth Conference on Sex Hormones, Pregnancy and Rheumatic Diseases (Florence, Italy, April 2007), and then the same questionnaire was posted at the Hospital for Special Surgery (www.hss.edu) website and all attendees (ATS) of the above meetings were invited to participate via e-mail. Answers have been collected and analysed in a descriptive fashion and responses of the two groups evaluated by Chi-square or Fisher's exact test. As a whole 75 responses from the ABMs and ATS were included in the analysis. In general, there was no significant difference between the opinions of two groups. Management recommendations displayed reasonable consistence: (i) for the use of low-dose aspirin and low-molecular weight heparin during pregnancy and during ovarian stimulation for in vitro fertilization; (ii) against oestrogen-containing oral contraceptives; and (iii) for the use of anticoagulants in the post-partum period.
    Rheumatology (Oxford, England) 07/2008; 47 Suppl 3(Supplement 3):iii23-7. DOI:10.1093/rheumatology/ken181 · 4.44 Impact Factor
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    ABSTRACT: To verify the occurrence of learning disabilities (LDs) in the offspring of women with primary antiphospholipid syndrome (APS) as a consequence of fetal exposure to maternal antiphospholipid antibodies (aPL), and to evaluate the impact of maternal chronic disease on children's development. We studied 17 children of mothers with primary APS using a standardized intelligence test (Wechsler Intelligence Scale for Children, Revised), a specific LD battery of tests (Sartori, MT groups' test for reading ability, MT groups' test for math skills), and a questionnaire on behavioral and social characteristics (Child Behavior Checklist [CBCL]). Mothers were interviewed about their pregnancy and motherhood experience. All children had a normal intelligence level (full-scale intelligence quotient >85); 15 pregnancies occurred in mothers with IgG aPL. LDs were diagnosed in 4 children (26.7%), 2 boys and 2 girls. One of these children was born premature, with a brother also affected. Four children (26.7%) showed a higher risk to present problems on the CBCL total competence scale and 2 children (13.3%) on the CBCL total behavior scale. Two children were described as hyperactive (1 had an LD). All families had a good socioeconomic status and educational level. Besides prematurity and genetic and environmental factors, the genesis of LDs may also include in utero exposure to aPL, in agreement with described experimental models and patients with systemic lupus erythematosus. Socioeconomic status does not seem to influence the occurrence of LDs. A long-term multidisciplinary followup may improve quality of life in patients with primary APS and their children.
    Arthritis & Rheumatology 03/2008; 59(3):345-51. DOI:10.1002/art.23311 · 7.87 Impact Factor
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    ABSTRACT: To evaluate the efficacy and the safety of anti-TNF alfa treatment in elderly patients (>/=65 years old) with active rheumatoid arthritis (RA), in comparison with younger (17-65 years old). We considered retrospectively 295 patients, affected by RA and treated with anti-TNF alfa drugs. They were divided in two groups, according to their age, and followed up for two years: over-65-years old patients (190) and under-65-years old patients (105). Effectiveness of drugs was assessed analyzing RA disease activity (DAS28, DAS44, SDAI), functional status (HAQ) and serological parameters (CRP) before and after anti-TNF alfa therapy. Safety was studied considering discontinuation rate of biological disease-modifying antirheumatic drugs, and collateral events rate. At baseline, elderly patients showed higher disease activity's score (DAS 28, DAS44, SDAI, HAQ) with important loss of articular function (worse quality of life, HAQ) than younger patients (p<0.05). During the therapy, improvement in clinical parameters was observed (DAS28, DAS44 and SDAI) with no significant difference between the two groups. In elderly patients disability index, on the contrary, improved less than in younger (p<0.05). After treatment, also CRP decreased less in elderly patients (p<0.05). During the follow-up, 74 over-65-years old patients (38.95%) and 116 under-65-years old patients (38.05%) discontinued anti-TNF alfa therapy because of loss of efficacy (20.52% vs 11.42%), severe adverse events (17.34% vs 25.67%), voluntary discontinuation or good clinical response (1% vs 0.95%). No differences were shown about the frequency and reasons of anti-TNF alfa withdrawal (p>0.05). Anti-TNF alfa treatment was efficacious and safe in both groups of patients. These drugs induced improvement in disease activity, apart from the age. No functional improvement was observed in HAQ, showing the irreversible loss of articular function and the incomplete recovery in elderly patients. Age doesn't interfere with the possibility to treat elderly patients with anti-TNF alfa drugs.
    Reumatismo 01/2008; 60(1):41-9. DOI:10.4081/reumatismo.2008.41
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    A Tincani · M Nuzzo · A Lojacono · M Cattalini · A Meini
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    ABSTRACT: In the management of adolescents with systemic lupus erythematosus (SLE), sexual activity and prevention of unwanted pregnancies are important topics. Many contraceptive methods are available nowadays. Oral contraceptives (OCs) are the preferred choice among adolescents in general. However, the use of these medications in adolescents with SLE raises serious concerns, particularly the risk of thrombotic events from estrogen exposure and the impact of these medications on lupus activity. In this article, different contraceptive methods available are reviewed and their application in adolescents with SLE is discussed. In conclusion, OCs are the methods of choice in adolescents with stable disease and no antiphospholipid antibodies (aPL) detected. In patients with aPL, fewer options are available, and the selection of the preferred form of contraception should be made on an individual basis.
    Lupus 02/2007; 16(8):600-5. DOI:10.1177/0961203307078074 · 2.48 Impact Factor
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    ABSTRACT: Since the 1960s, antiphospholipid antibodies have been known to be associated with repeated miscarriages and fetal losses. Other complications of pregnancy, such as preterm birth, with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome. The titer, isotype or antigen specificity of the antibodies may be important in risk determination. The pathogenesis of pregnancy failures is not only linked to the thrombophilic effect of antiphospholipid antibodies but also to a direct effect of antibodies on trophoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of antiphospholipid antibodies both in lupus-prone and -naive mice. The classification of pregnant antiphospholipid syndrome patients as being at a 'high risk' has completely changed their prognosis due to obstetric monitoring and the application of effective therapy. In fact, despite the high rates of complications and preterm delivery, a successful outcome can now be achieved in a large majority of cases.
    Women s Health 11/2006; 2(6):873-80. DOI:10.2217/17455057.2.6.873
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    ABSTRACT: In women who suffer from rheumatic diseases (RDs) the risk of repeated fetal loss, intrauterine growth restriction, and preterm birth remains higher than in the general population. Antiphospholipid antibodies are frequently observed in patients with systemic lupus erythematosus (SLE). They are associated with recurrent pregnancy losses that may occur at any age of gestation. The cause of fetal death is believed to be intraplacental thrombosis, although other pathologic mechanisms have been described. A recent study has described the increased frequency of learning disabilities in the offspring of SLE patients; case reports of neonatal thrombosis are very rare. Transplacental passage of IgG anti-Ro/SS-A antibodies is linked to neonatal lupus (2%). The main manifestation is congenital heart block (CHB) due to the binding of anti-Ro/SS-A antibodies to cardiac conduction tissue and to the consequent inflammatory/fibroid reaction. Neonatal lupus also includes cutaneous, hematologic, and hepatobiliary manifestations, which are typically transient. Incomplete CHB can be treated with fluorinated corticosteroids to prevent the progression and decrease inflammation. Intravenous immunoglobulin, decreasing the tranplacental passage of anti-Ro/SS-A, has been proposed as prophylactic therapy in patients who had one or more child with CHB. Transplacental passage of antiplatelet antibodies, in about 10% of mothers with SLE, can induce thrombocytopenia in the fetus or the neonate. Patients with RD have a higher incidence of anxiety and depression compared to the general population, interfering with parenthood and the upbringing of children.
    Annals of the New York Academy of Sciences 07/2006; 1069:346-52. DOI:10.1196/annals.1351.032 · 4.31 Impact Factor
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    ABSTRACT: This cross-sectional study shows that a high number of untreated adult patients with GHD develop radiological vertebral deformities. Patients undergoing GH replacement treatment showed a significantly lower prevalence of vertebral deformities versus treated patients in the presence of similar BMD, as assessed by DXA. In this cross-sectional study, we investigated whether the prevalence and degree of spinal deformities in adults with growth hormone deficiency (GHD) were related to the age of patients, degree of bone turnover, BMD, and recombinant human GH (rhGH) replacement therapy. One hundred seven adult hypopituitary patients (67 males and 40 females; mean age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39 males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At study entry, 65 patients were on replacement therapy with rhGH, whereas 42 patients had never undergone rhGH. Vertebral fractures were significantly more frequent in GHD patients versus control subjects (63.6% versus 37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture number, was significantly higher in untreated versus treated patients (78.6% versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not show any significant difference in median T score. In untreated GHD patients, the prevalence of vertebral deformities was correlated with T score (p = 0.002) and duration of disease (p = 0.003). In treated GHD patients, the prevalence of spinal deformities was correlated only with the timing of the beginning of rhGH replacement. This cross-sectional study reports high prevalence of vertebral radiological deformities in adult patients with untreated GHD. The replacement treatment of GHD leads to a significant decrease in fracture rate.
    Journal of Bone and Mineral Research 04/2006; 21(4):520-8. DOI:10.1359/jbmr.060112 · 6.59 Impact Factor
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    ABSTRACT: The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares.
    Lupus 02/2006; 15(11):801-7. DOI:10.1177/0961203306071005 · 2.48 Impact Factor
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    ABSTRACT: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.
    Journal of Bone and Mineral Research 11/2005; 20(10):1837-44. DOI:10.1359/JBMR.050603 · 6.59 Impact Factor
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    ABSTRACT: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics. The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31-64 years) receiving chronic (>6 months) therapy with glucocorticoids (daily dosage >7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects. Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process. In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3+/-0.74 vs 8.8+/-1.4 pg/ml per min in controls, P = 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42+/-8.2 vs 18.3+/-3.9 pg/ml per min, P = 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects. These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.
    European Journal of Endocrinology 03/2005; 152(2):199-205. DOI:10.1530/eje.1.01841 · 3.69 Impact Factor