Thermal balneotherapy in Antsirabe-Madagascar: water analysis and its applications in an African context.

The Orthopaedic Rehabilitation Centre of Madagascar can be found in the city of Antsirabe. The health care facility is equipped with 2 thermal sources of bicarbonate water used for post-operative rehabilitation and for the ailment of chronic degenerative illnesses. The aim of this study, which derives from the cooperation between the School of Specialization in Thermal Therapy of the University of Parma and Antsirabe Orthopaedic Hospital, is to analyze the real properties of thermal waters utilized in this centre and to do an overview of its possible applications in this particular African context.

Analytical Evaluation of Free Testosterone and Cortisol Immunoassays in Saliva as a Reliable Alternative to Serum in Sports Medicine.

BACKGROUND: This study was aimed to investigate whether measurement of free testosterone and cortisol in saliva is a reliable alternative to their assessment in serum for monitoring physical fitness in professional athletes. METHODS: We studied 25 members of the soccer team Parma F.C., playing in Italian major football league. Blood and saliva samples were collected at fasting, before a regular training session. Cortisol, total and free testosterone, as well as the ratio between free testosterone and cortisol, were assessed in paired serum and saliva samples, and their results were compared. RESULTS: An excellent correlation was found between serum and saliva cortisol (r = 0.751; P < 0.001). A significant correlation was also observed between free testosterone in serum and saliva (r = 0.590; P = 0.002), whereas no significant correlation was found between total testosterone in serum and saliva (r = 0.181; P = 0.387). A significant correlation was found for the free testosterone to cortisol ratio in serum and saliva (r = 0.43; P = 0.031). All athletes (25/25; 100%) declared that they would feel more comfortable to have saliva rather than blood serially collected. CONCLUSIONS: The results of this study suggest that measurement of free testosterone and cortisol in saliva may be seen as a reliable alternative to their assessment in serum.

Impact of XIAP protein levels on the survival of myeloma cells.

BACKGROUND: XIAP is the best characterized and the most potent direct endogenous caspase inhibitor and is considered a key actor in the control of apoptotic threshold in cancer cells. In this report, we specifically addressed XIAP regulation and function in myeloma cells. DESIGN AND METHODS: XIAP and its endogenous inhibitor XAF-1 protein levels and their regulation were assessed by immunoblot analysis in myeloma cell lines or primary myeloma cells. XIAP knockdown by RNA interference was used to evaluate XIAP impact on in vitro drug sensitivity and in vivo tumor growth. RESULTS: Our results indicate that myeloma cells expressed high levels of XIAP protein that were tightly regulated during growth factor stimulation or stress condition. Of note, an increased XIAPlevel was evidenced during the blockade of the canonical cap-dependent translation by the mTOR inhibitor rapamycin, supporting the hypothesis of a functional IRES sequence in XIAP mRNA. In addition, caspase-mediated XIAP cleavage correlated to an apoptotic process occurring upon cell treatment with the proteasome inhibitor bortezomib. Importantly, XIAP knockdown using RNA interference enhanced drug sensitivity and decreased tumor formation in NOD/SCID mice. Finally, myeloma cells also expressed the XIAP inhibitor XAF-1 that interacted with XIAP in viable myeloma cells. CONCLUSIONS: Altogether, our data argue for a delicate control of XIAP function in myeloma cells and stimulate interest in targeting XIAP in myeloma treatment.

Prevalence and significance of hypoalbuminemia in an internal medicine department.

BACKGROUND: Serum albumin is commonly measured in hospitalized patients. It has habitually been included among the parameters used for nutritional assessment, and recently its use has become even more widespread. Yet, no data are available in the literature about the prevalence and clinical significance of hypoalbuminemia in patients hospitalized in an internal medicine ward. The aim of this study was to investigate the prevalence and clinical significance of hypoalbuminemia in in-hospital internal medicine patients. METHODS: We retrospectively evaluated the albumin level of patients admitted to the Department of Internal Medicine and Biomedical Sciences of the University of Parma during the year 2000. We then evaluated sex, age, nutritional status, some laboratory parameters, associated diseases, and length of hospitalization in hypoalbuminemic patients in comparison with a group of patients without hypoalbuminemia. RESULTS: Hypoalbuminemics (46.5% of patients) were older, more frequently anemic, and had a higher erythrocyte sedimentation rate (ESR) and longer hospitalization; they were mostly normal weight or overweight. These patients also had chronic liver (18.6% vs. 4.5%), onco-hematological (33.8% vs. 12%), and infectious diseases (13.4% vs. 2.3%) and nephropathies (6.3% vs. 2%) more often than patients without hypoalbuminemia. The presence of onco-hematological diseases was related to anemia (O.R.=5.73; 95% CI: 3.184-10.310), lymphopenia (O.R.=2.76; 95% CI: 1.584-4.801), and hypoalbuminemia (O.R.=2.5; 95% CI: 1.178-5.307). CONCLUSIONS: Hypoalbuminemia is very frequent in an internal medicine ward. In this setting, serum albumin is related to the length of hospitalization and to other parameters with a well-known prognostic value (age, hemoglobin) and clinical usefulness (ESR). It may also play a role in the evaluation of the possible association of onco-hematological diseases.

Idiopathic hypogonadotropic hypogonadism in selective human gonadotropin deficiency in adult man: a case report.

We report a rare case of idiopathic hypogonadotropic hypogonadism in an adult male (31-year-old), who underwent an endocrinological examination because of erectile dysfunction and suspected infertility. Laboratory data showed isolated gonadotropin deficiency. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary unit showed no tumoral expansions. The patient was tested with gonadotropin releasing hormone (Gn-RH) (100 microg as an i.v. bolus injection). No significant LH and FSH responses were observed. Idiopathic hypogonadotropic hypogonadism is usually caused by hypothalamic lesions, however, since Gn-RH was unable to stimulate LH and FSH secretions, we supposed that our patient was affected by defective gonadotropin secretion at pituitary level.

A translocation t(4; 13)(q21;q14) as single clonal chromosomal abnormality in a parathyroid adenoma.

Most of the information about the genetic composition of parathyroid tumors has been obtained by comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies, whereas only few conventional cytogenetic investigation results are available. We have performed cytogenetic analysis of short-term cultures from 3 parathyroid adenoma tissue samples. Two cases showed a normal karyotype in all the metaphases obtained from independent primary cultures. In one case 5 metaphases (in a total of 25) from 2 independent cultures showed a nonrandom translocation t(4;13)(q21;q14), which was therefore accepted as clonal. To our knowledge this is the second clonal translocation described in this tumor type. Further conventional cytogenetic analysis of more parathyroid tumor specimens would be necessary to identify other specific abnormalities and the involved genes with a potential important role in the diagnosis, prognosis and pathogenesis of parathyroid tumors.

Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-alpha therapy for hepatitis C virus-related hepatitis.

OBJECTIVE: Thyroid autoimmunity is a common side effect of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C. There are currently no reliable parameters to predict the occurrence of thyroid dysfunctions in patients undergoing IFN-alpha therapy. CXC chemokine ligand 10 (CXCL10) is a chemokine known to play a role in both thyroid autoimmune disease and hepatitis C virus (HCV) hepatitis. DESIGN: The aim of this study was to evaluate serum CXCL10 levels in HCV patients treated with IFN-alpha in relation to the occurrence of thyroid dysfunctions. Serum CXCL10 levels were assayed in 25 HCV patients (proven to be negative for serum thyroid antibodies) before and during IFN-alpha therapy (2, 4 and 6 months) and in 50 healthy controls. HCV patients were retrospectively selected according to the occurrence of IFN-alpha-induced thyroid dysfunction and were assigned to two groups. Group I included 15 patients who did not develop thyroid antibody positivity or dysfunction; group II included ten patients who showed the appearance of serum thyroid antibodies, followed by clinically overt thyroid dysfunction. RESULTS: Patients with HCV, regardless of the development of thyroid dysfunctions, had significantly higher serum CXCL10 than controls (261.6+/-123.4 vs 80.4+/-33.6 pg/ml; P<0.00001). Pretreatment mean serum CXCL10 levels were significantly higher in Group I versus Group II (308.6+/-130.7 vs 191.1+/-69.4 pg/ml; P<0.05). Groups I and II showed different rates of favourable response to IFN-alpha treatment (33 and 90% respectively). CONCLUSION: Our results suggest that measuring serum CXCL10 before IFN-alpha treatment may be helpful for identifying those patients with higher risk to develop thyroid dysfunction, and require a careful thyroid surveillance throughout the treatment.

Endothelial dysfunction and cardiovascular risk profile in long-term withdrawing alcoholics.

BACKGROUND: Rates of cardiovascular morbidity and mortality are greater in heavy alcoholics than in either teetotallers or light-to-moderate drinkers. OBJECTIVE: On the assumption that factors leading to atherosclerotic damage remain operative even after long-term alcohol withdrawal, we studied the possible mechanisms of raised cardiovascular risk in former heavy alcoholics. METHODS: Forty-two apparently disease-free, normotensive alcoholics detoxified for 37.1 +/- 31.9 (SD) months, median 24, participated in the study. They were compared with 39 lifetime alcohol-abstaining control subjects, carefully matched for age, sex, body mass index, smoking and dietary habits, physical activity, lipids and fasting glucose. Endothelial function (flow-mediated dilation of brachial artery, high-resolution ultrasound technique), blood pressure, and some parameters of endothelial activation, oxidative stress, vascular inflammation and insulin sensitivity were measured. RESULTS: The maximal percentage of flow-mediated dilatation was reduced in detoxified alcoholics (10.1 +/- 4.6 versus 14.9 +/- 7.4, P < 0.001) who also showed significantly higher blood pressure (systolic 127.5 +/- 12.9 versus 118.2 +/- 10.7 mmHg, P < 0.001; diastolic 79.4 +/- 7.1 versus 74.6 +/- 6.4 mmHg, P < 0.01; mean 95.4 +/- 8.2 versus 89.1 +/- 7.3 mmHg, P < 0.001), uric acid (5.0 +/- 1.1 versus 4.4 +/- 0.8 mg/dl, P < 0.05), high-sensitivity C-reactive protein (2.1 +/- 2.0 versus 1.0 +/- 0.9 mg/l, P < 0.01), endothelin-1 (0.38 +/- 0.11 versus 0.17 +/- 0.10 pg/ml, P < 0.001) and fasting insulin (10.4 +/- 4.5 versus 5.6 +/- 1.6 muU/ml, P < 0.001) with abnormal homeostasis model assessment index of insulin resistance (2.3 +/- 1.1 versus 1.2 +/- 0.4, P < 0.001). CONCLUSION: Previous heavy alcoholism, in spite of long-term withdrawal, is associated with endothelial dysfunction and a wide cluster of haemodynamic, vascular and metabolic abnormalities that indicate an unfavourable cardiovascular and metabolic risk profile even in apparently disease-free former alcoholics.

Clinical management of paroxysmal nocturnal hemoglobinuria in pregnancy: a case report and updated review.

UNLABELLED: Because women with paroxysmal nocturnal hemoglobinuria (PNH) are especially vulnerable to thromboembolic phenomena, pregnancy is a time of increased risk for both mother and fetus. However, pregnancies in affected women are rare; only case reports and small studies have been reported so far. We present the case of a 20-year-old woman with PNH who, while undergoing medical tests in preparation for a bone marrow transplant, was discovered to be pregnant. We also review the obstetric literature on pregnancy complicated by PNH, which indicates that both maternal and fetal mortality is exceptionally high (11.6% and 7.2%) with the major cause of maternal mortality being thromboembolism. Major maternal complications are more frequent postpartum (30.2%) than antepartum or intrapartum (16.3%). TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that paroxysmal nocturnal hemoglobinuria (PNH) during pregnancy increases adverse events for both the mother and the fetus, state that maternal and fetal mortality are both high, and explain that the major complications occur in the postpartum period.

Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy.

BACKGROUND: In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension. This observational study was designed to evaluate the prevalence of pulmonary hypertension in hyperthyroidism and to determine the role of methimazole in regulating pulmonary vascular resistance in these patients. METHODS: We studied 114 patients, 78 women and 36 men, whose mean age was 51+/-13years. Forty-seven had Graves' disease and 67 had a nodular goiter. All subjects were ambulatory and were recruited in a consecutive order. The control group (group 2) included 20 healthy subjects matched for age and sex. Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressure (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli's equation. We performed a 120-day follow-up in the patients with pulmonary hypertension and we divided them into two subgroups: group 1A (n=33), patients treated with methimazole, and group 1B (n=17), subjects treated with partial thyroidectomy. RESULTS: We found a mild pulmonary hypertension in 50 patients in group 1 (43%) and in none of those in the control group. The mean+/-SD PAPs was 27.77+/-6.56 in group 1 and 21.32+/-2.55 in group 2. A negative correlation was found between the T.S.H. value and the level of PAPs (r=-0.85; p<0.001). During the follow-up, group 1A went from a PAPs value of 34.3+/-3.2 to 29.2+/-3.3 after 15days of therapy and group 1B from 34.3+/-3.0 to 34.1+/-2.9 (p<0.001). CONCLUSIONS: The results of the present study demonstrate a frequent association between hyperthyroidism and mild and transient pulmonary hypertension. Subjects treated with methimazole have a more rapid drop in PAPs.

Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations.

Although the prevalence of insulin resistance (IR) and compensatory hyperinsulinemia (CH) is increased in patients with nonalcoholic fatty liver disease, the role of IR/CH in regulation of hepatic fat content in healthy volunteers with normal concentrations of alanine transaminase (ALT) has not been defined. To address this issue, hepatic fat content was quantified by ultrasound in 69 (30 men, 39 women) healthy individuals, without known risk factors for liver disease and with plasma ALT concentrations of less than 30 U/L. Experimental variables quantified included body mass index, waist circumference, systolic and diastolic blood pressures, and fasting plasma glucose, fasting plasma insulin (FPI), and lipid concentrations. Subjects were classified as having no (55%), mild (27%), or moderate to severe (18%) hepatic steatosis on the basis of the ultrasound results. Statistically significant (P < .05-.001) correlations (Spearman rho values) existed between liver fat content and ALT (0.26), body mass index (0.52), waist circumference (0.50), systolic blood pressure (0.28), diastolic blood pressure (0.27), fasting plasma glucose (0.47), FPI (0.56), triglycerides (0.30), and high-density lipoprotein cholesterol (-0.35). Multivariate general discriminant analysis and multiple linear regression analysis indicated that FPI was the only independent predictor (P < .001) of both liver fat content and ALT concentrations. Fasting plasma insulin (a surrogate estimate of IR/CH) predicts hepatic fat content and ALT in healthy volunteers with normal transaminase concentrations, independently of the other anthropometric and metabolic variables measured.

Association between immune thrombocytopenic purpura and chronic lymphocytic leukemia in a patient carrier of anti-hepatitis C virus antibodies.

Immune thrombocytopenic purpura (ITP) occurs in 2-3% of chronic lymphocytic leukemia (CLL) patients, whereas autoimmune thrombocytopenia is very rare before the diagnosis of lymphoma. A 67-year-old patient, was admitted to our Department because of purpura on his inferior limbs. Family history revealed arterial hypertension, a previous presence of hepatitis C virus (HCV) antibodies, with no sign of liver damage. Physical examination showed purpura of inferior limbs. Laboratory analysis revealed: marked thrombocytopenia (platelet count 5000/microL); hypogammaglobulinemia (9%, immunoglobulin-IgG 634 mg/dL); presence of HCV antibody (negative HCV-RNA); low-titer anti-nuclear antibody and anti-smooth muscle antibody (1:80); positive cryoglobulin (polycolonal, IgG-IgM, cryocrit 0.5%). Abdomen ultrasound revealed a mild liver steatosis and bone marrow aspirate megakaryocytic hyperplasia. Platelet kinetics study showed a markedly reduced platelet half-life (<1 day) with evident splenic uptake. The patient was treated with steroids, intravenous Ig and immunosuppressive agent (cyclophosphamide) with only temporary effect; a splenectomy was therefore performed with a subsequent durable increase in the platelet count. Two years later, the patient underwent a prostatectomy for prostate cancer and within the pelvic nodal screening the histological examination unexpectedly revealed features of B-cell non-Hodgkin's lymphoma, type CCL/small lymphocytic lymphoma; a bone marrow aspirate showed a monotypic CD5+, CD19+, CD23+ B-cell proliferation confirming the diagnosis of CLL. Six months later, a computed tomography scan revealed multiple pathological node enlargements (1.5-3 cm), compatible with a malignant lymphoma. The marked thrombocytopenia may have been an early expression of the lymphoproliferative disease. Otherwise, the association between CLL and ITP might reflect the underlying role of HCV infection causing an immune dysregulation responsible for both pathologies.

Graves' disease in interferon-alpha-treated and untreated patients with chronic hepatitis C virus infection.

An association between Graves' disease (GD) and chronic hepatitis C (C-HC) has been observed both in the presence and the absence of recombinant interferon-alpha (rIFN-alpha) treatment. rIFN-alpha-induced GD is characterized by suppressed thyroid-stimulating hormone levels; normal or elevated free triiodothyronine (FT3) and free thyroxine (FT4) values; the presence of thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroid receptor antibodies; and high iodine thyroid uptake. In contrast, GD developed during C-HC without rIFN-alpha is less clearly defined. In this study, we examined two groups of patients: group A, 28 patients with C-HC treated with rIFN-alpha who developed GD after 1 to 9 months, and group B, 10 patients with C-HC who developed GD without a previous rIFN-alpha treatment. At the time of GD, both groups started methimazole therapy; thyroid function was reevaluated after 3, 6, 9, and 12 months. Group A patients continued IFN. After 12 months, all patients of group A were euthyroid, and 21 of them (75%) had already stopped methimazole treatment, whereas all patients of group B were euthyroid and only 2 (20%) had stopped methimazole. In conclusion, the data show a better course of GD, with a more precocious and significantly higher number of recoveries in patients with rIFN-alpha-induced GD than in rIFN-alpha-unrelated disease. Further studies are needed to establish whether the two types of GD differ not only from a clinical point of view but also because of different underlying pathogenetic mechanisms.

Is steroid therapy needed in the treatment of destructive thyrotoxicosis induced by alpha-interferon in chronic hepatitis C?

OBJECTIVE: Treatment with interferon (IFN) of patients affected by chronic hepatitis C (CH-C) may produce alterations in thyroid function, such as hypothyroidism, Graves'-like hyperthyroidism and destructive thyrotoxicosis (DT). IFN-induced DT is characterized by suppressed serum TSH levels, normal or elevated FT4 and FT3 concentrations, with the presence or absence of thyroid peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid receptor antibodies and radioactive iodine uptake suppressed or <5%. DESIGN: IFN-induced DT is a mild clinical disease, because thyroid-destructive processes last for a short time and involve a small portion of the gland. At present, the therapeutic approach in DT suggests IFN withdrawal and 1-2 months of methylprednisolone treatment. METHODS: In consideration of possible untoward side effects of steroid treatment in patients with CH-C, we studied two groups of patients with CH-C who developed DT after treatments with various preparations of recombinant IFN (with or without ribavirin). Patients sequentially entered the study during a 4-year period, at the time of DT diagnosis, when IFN therapy was discontinued. The first 12 subjects (group A) were treated with 8-16 mg/day methylprednisolone for 30-40 days after IFN withdrawal; in the following 15 patients (group B), IFN withdrawal was not followed by any additional treatment. All patients underwent clinical and laboratory controls of thyroid function at 1, 2, 3 and 6 months after DT diagnosis. RESULTS: The results showed restoration of euthyroidism in both group A and group B patients at 6 months after DT diagnosis, regardless of steroid treatment. CONCLUSIONS: The simple withdrawal of IFN therapy in patients with CH-C, who had developed DT, appears to be effective in the treatment of the thyroid disease. This therapeutic approach should be preferred in order to avoid possible undesired side effects of steroid therapy in patients with CH-C.

Pulmonary complications in diabetes mellitus: the role of glycemic control.

Insulin deficiency induces an increase in blood glucose levels that, in long run, becomes toxic for many organs and systems. Microangiopathy and derangements in the immune function are known consequences of hyperglycemia, but the way in which these systemic alterations may affect pulmonary function has been scarcely investigated. Although confirmation from large clinical trials is still to come, the diabetic disease seems to hit the pulmonary microcirculation as any other organ by increasing vessel wall thickness and impairing gas exchange, which leads to a measurable loss of function and respiratory efficiency. In addition, a diabetic lung is more susceptible to low respiratory tract infections by atypical microorganisms and more likely to host severe episodes of pneumonia than a normal, non-diabetic lung. This is a review of current knowledge on the impact of diabetes mellitus in lung health. We have paid special attention to the role of metabolic control in preventing damage to the lung by sustained hyperglycemia.

[Thyroid dysfunction and pulmonary hypertension]. / Distiroidismi e ipertensione polmonare.

Prior observational studies and several case reports have suggested an association between thyroid dysfunction and pulmonary hypertension. This review was designed to evaluate the prevalence and the pattern of pulmonary vasculature involvement in hyper- and hypothyroidism. We identified original research papers and reviews by going through leading journals that publish basic and clinical research in the fields of pulmonary hypertension, hyperthyroidism and hypothyroidism, by electronically searching the Medline database. We directed special attention to papers published from 1972 to 2003. Our findings indicate the presence of a frequent association between hyperthyroidism and pulmonary hypertension (35% in the largest series of cases) which decrease after achievement of a euthyroid state. A possible explanation includes an influence of thyroid hormones which affect growth and maturation of vascular cells and enhanced catecholamine sensitivity causing pulmonary vasoconstriction. Furthermore, several studies suggest a high prevalence of transient pulmonary hypertension in hypothyroidism (49% in the largest series of cases), in these cases autoimmunity play a key role.

Acute antiarrhythmic effects of bi-level positive airway pressure ventilation in patients with acute respiratory failure caused by chronic obstructive pulmonary disease: a randomized clinical trial.

BACKGROUND: Cardiac arrhythmias are common in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure (ARF) and may be life threatening. Recently, non-invasive positive pressure ventilation has been advanced as a useful tool in COPD patients with ARF. This method can affect global cardiac performance through its effects on many determinants of cardiac function and may be helpful in reducing arrhythmias. OBJECTIVE: To assess the role of bi-level positive pressure ventilation (BiPAP) in the management of cardiac arrhythmias in patients with ARF caused by COPD. METHODS: We studied 30 consecutive patients with ARF related to COPD diagnosed according to American Thoracic Society criteria. All subjects were smokers; the mean age was 68 +/- 7 years. They were randomly assigned to receive BiPAP plus standard therapy (group 1) or standard therapy alone (group 2). Patients randomized to receive BiPAP were first fitted with a nasal mask, and BiPAP was administered after 12 h of standard therapy. All subjects were studied using a computerized 24-hour Holter ECG. Blood gases, plasma electrolytes, respiratory rate and blood pressure were measured at study entry, at 30, 60 and 120 min and then every 3 h. RESULTS: Heart rate decreased from 86.08 +/- 7.86 to 74.92 +/- 5.39 in group 1 (p < 0.001) versus 82.77 +/- 8.78 to 75.82 +/- 6.76 in group 2 (p = 0.033). Ventricular premature complexes decreased from 564.38 +/- 737.36 to 166.15 +/- 266.26 in group 1 (p < 0.001) versus 523.38 +/- 685.75 to 353.54 +/- 469.93 in group 2 (p = 0.021). Atrial premature complexes decreased from 570.00 +/- 630.36 to 152.31 +/- 168.88 in group 1 (p < 0.001) versus 513.77 +/- 553.81 to 328.62 +/- 400.81 in group 2 (p = 0.021). CONCLUSIONS: Cardiac arrhythmias decreased significantly in both groups after the start of both treatments, although data obtained from group 1 revealed a more important statistical significance. Our data seem to support the hypothesis that BiPAP may be a useful tool in managing COPD patients with ARF and mild arrhythmias.

Low vitamin D status, high bone turnover, and bone fractures in centenarians.

The oldest olds, including centenarians, are increasing worldwide and, in the near future, will represent a consistent part of the population. We have studied bone status and metabolism in 104 subjects over 98 yr of age to evaluate possible interventions able to avoid fragility fractures and disability. Ninety females and 14 males not affected by any acute disease were considered. After a complete clinical assessment, blood was drawn for evaluating bone turnover markers, and performance tests together with skeletal ultrasonography (either at the phalanges or at the heel) were performed. We found that 38 subjects had sustained a total of 55 fractures throughout their lives, and 75% of these were fragility fractures. Twenty-eight fractures occurred at the proximal femur, with 14 after the age of 94 yr. Serum 25-hydroxyvitamin D was undetectable in 99 of 104 centenarians. PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of centenarians, respectively, with a trend toward hypocalcemia. Bone alkaline phosphatase levels were close to the upper limit. Serum IL-6 was elevated in 81% of centenarians and was positively correlated with PTH and negatively correlated with serum calcium. Serum creatinine was not correlated with PTH. Bone ultrasonography showed that most centenarians had low values, and ultrasonographic parameters were correlated with resorption markers. We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.