Interleukin-18 (IL-18) and matrix metalloproteinase-9 (MMP-9) in post-menopausal osteoporosis.

This survey covered 60 post-menopausal women with osteoporosis. The patients were divided into three equal groups, and each group was treated with one of the three so-called anti-resorptive drugs, namely alendronate (10 mg/day) risedronate (5 mg/day) and raloxifene (60 mg/day) for 12 months. The Elisa technique was used to measure circulating IL-18 and MMP-9. Lumbar bone mineral density (BMD) levels were determined by using dexa mineralometry (Lunar DPX) at baseline and after 12 months of treatment. The results showed comparable responses of the patients treated with alendronate or risedronate, being a significant increase in BMD, an increase in circulating IL-18, and only slight modifications in circulating MMP-9 levels. After 12 months of treatment with raloxifene, there were minimal, non-significant increases in BMD, slight modifications in IL-18 levels, and a significant reduction in circulating MMP-9 levels. The conclusions can be drawn that all three drugs, albeit through different mechanisms, can be considered valid treatments for post-menopausal osteoporosis. Although measurements of circulating IL-8 and MMP-9 levels allowed us to differentiate the effects of the three drugs used, as of today, they have no real role in the diagnosis and/or follow-up of osteoporosis.

Cardiovascular aging and psychometric performances: correlations in a group of ultraseptagenarian elderly.

Aging of the Italian population resulted in a net increase of the cardiovascular pathologies, and the correlated disabilities. In addition, the cardiovascular diseases represent actually in Italy the most frequent cause of death. With advancing age, both the heart and the blood vessels undergo numerous morphological and functional modifications, which are reducing the functional reserves of these organs. The present study looked for correlation between the cardiac functionality and the cognitive, as well as affective functions. Furthermore, we evaluated the functional variations of the autonomy and autosufficiency of the same patients. We had 171 enrolled subjects (108 women and 63 men), all above the age of 70 years. Based on the classification of the New York Heart Association (NYHA), 85 of these patients (35 men and 50 women) had a II class (Group A), and 86 of them (28 men and 58 women) a III NYHA class of heart function (Group B). We included only patients who did not have any cerebrovascular event yet, and were not bed-ridden. The psychometric performance has been evaluated by using the mini-mental state examination (MMSE), the geriatric depression scale (GDS), the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales. Cardiac functions have been measured by Doppler echocardiography, in M-mode. The Group A (of mean age 71 +/- 3 years) displayed ventricular ejection fraction (VEF) values in average of 43 +/- 4%, MMSE scores 27 +/- 2; GDS scores 14 +/- 3; IADL 6 +/- 1, and ADL = 6, i.e., maintained a complete autosufficiency. The Group B (mean age 74 +/- 4 years) displayed VEF values in average of 26 +/- 3%, MMSE scores 23 +/- 4; GDS scores 22 +/- 3; IADL 4 +/- 2, and ADL = 4 +/- 1, i.e., had a reduced autosufficiency. These results confirm that also the heart pays a toll for aging: the myocardial contractility becomes significantly altered, meaning the loss of cardiac functions itself. These morpho-functional heart alterations are accompanied by decreased psychometric performances during aging, with consequent reductions of cognitivity, affectivity, autosufficiency and autonomy, involving a complex decrease of the quality of life.

Antiresorption therapy and reduction in fracture susceptibility in the osteoporotic elderly patient: open study.

The identification of risk factors for osteoporosis has been an essential step towards the understanding of the onset of the disease as well as of the osteoporosis-related fractures due to bone fragility. The present study has been aimed at assessing whether a correlation may exist between the increment in bone mass, consequent to an antiresorption therapy, and the reduction in the incidence of fractures. Moreover, the possibility that such a reduction might result from the action of other factors, such as the changes in bone microstructure, has been investigated. A total of 2,000 osteoporotic women (mean age: 68 +/- 9 years) were enrolled in the study and divided at random into 4 treatment groups. Each group received one of the following treatments: Alendronate 10 mg/daily (1,000 patients), Clodronate 100 mg/weekly i.m. (800 patients), Risedronate 5 mg/dailt (100 patients), and Raloxifene 60 mg/daily (100 patients). Clinical evaluation was based on bone mineral density (BMD) assay on lumbar vertebrae (L1-L4) by means of a DEXA (Lunar DPX) mineralometer, as well as on the incidence of fractures following both 12- and 24-month treatment periods. The results showed an overlapping pattern in patients treated with Alendronate or Risedronate, namely a significant increment in BMD after a 24-month treatment period, whereas such an increment in BMD was less evident in patients receiving either Clodronate or Risedronate after a 24-month treatment period. In addition, a total of 18 osteoporosis-related fractures were observed during the entire study period; 10 out of 18 fractures occurred in the Alendronate treated group, whereas the remaining 8 fractures were observed in the Clodronate treated group. Fourteen fractures were detected in patients over 80-year old, whereas the remaining 4 occurred in patients aged from 70 to 79 years and appeared to be independent of both the T-score assigned and the BMD increment obtained as a result of the therapy. Such findings suggest that the plain monitoring of BMD appears not to be adequate to anticipate clearly the danger of the probable onset of additional fractures, while the higher incidence of fractures in patients over 80-year old evidences that "old age" has to be considered the most serious risk factor for osteoporosis, since it is also the real responsible factor for changes taking place in bone microstructure.

Oxidative stress and aging: studies on an East-Sicilian, ultraoctagenarian population living in institutes or at home.

The role of the free radicals in aging has been in center of research for long years. It is assumed that with advancing age, damaging effects of oxygen free radicals might be accumulated in the organisms on all components, especially on the DNA and the mitochondria. In addition, because of the decreased efficiency of the antioxidant systems, the oxidative mechanisms prevail in numerous age-dependent diseases, such as the arterio -sclerosis, Parkinson and Alzheimer diseases. The present study was aimed at revealing an eventual correlation between the free radical levels and the psychophysical health state of an ultraoctagenarian East-Sicilian population living in institutes or at home. Our study population consisted of 125 ultraoctagenarian subjects, 62 of them were institutionalized and 63 living outside the institutes. The free radical effects were measured by using the free radical analytical system (FRAS) assessing the derivatives of reactive oxygen metabolites(D-ROMs). The results are expressed in units of Caratelli (U-CARR). The psycho-physical state of the subjects was estimated by means of the mini mental state examination(MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). The nutritional state and the physical activity of the subjects were evaluated through the mini nutritional assessment (MNA) and the physical performance test (PPT). All studied parameters underwent a correlation analysis of Pearson. Statistically significant negative correlation was found between the free radical levels and the cognitive performance (p < 0.0001), as well as the levels of autonomy and autosufficiency,the physical activity in the total population (p < 0.01). These correlations were even more expressed in the institutionalized subjects. Statistically significant positive correlation seems to exist between the free radical levels and the nutritional status (p < 0.001). These studies revealed some important differences between the institutionalized and noninstitutionalized population. The levels of oxygen free radicals were higher in the former group, indicating a stronger oxidative stress, influencing the psychophysical state of the elderly subjects. This may have negative consequences on the quality and duration of the life. It is difficult to define the exact role of free radicals in the determination of aging pattern,but they may be considered without any doubt as true "markers" of an enhanced oxidative stress, accompanying a non-successful aging process.

The leptin, a new hormone of adipose tissue: clinical findings and perspectives in geriatrics.

Obesity has gained a great importance during the last decades, and this fact stimulated numerous studies regarding the genetic causes of this disease. A recently discovered new molecule, called leptin, raised a wide interest. It is a product of the adipocytes, it exerts inhibitory effects on the center of appetite and increases the energy expenditure of the organism. The present study evaluated blood leptin levels in 57 elderly subjects and searched for eventual correlations between this parameter and the age, the body mass index (BMI), the fat body mass (fat%), the waist (W) and hip (H) circumference, as well as the ratio (R) of these latter two values (WHR). Blood leptin levels do not correlate with age, body height and the WHR, but display significant positive correlations with the body weight, the BMI, the fat%, the W, H and WHR. A deeper knowledge on leptin and the correlations of this hormone with other body parameters might be helpful in a better understanding of several pathogenetic mechanisms related to aging and involved in a deterioration of the quality of life in elderly, like multiple atherosclerotic and metabolic diseases (diabetes, dyslipidemias).

Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis.

The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.

Correlation between the bone mass, psychometric performances, and the levels of autonomy and autosufficiency in an elderly Italian population above 80 years of age.

This study was aimed at evaluating the correlation between bone mineral density (BMD) and the psychophysical health status in an elderly study population (62 subjects, mean age 84+/-5 years, 21 males and 41 females), institutionalized (Group A) in various structures of Pozzallo, a marine locality of the Ragusa Province in Sicily. BMD was measured by using ultrasonography of the calcanear area (T-score, Z-score, stiffness). The alterations of the cognitive and affective spheres as well as the levels of autonomy and autosufficiency were estimated by means of psychometric scales like mini-mental state examination (MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). Other biological, social and health-related factors, such as age, sex, body weight and height, nutritional and drug-taking habits, physical activity and previous pathologies, were also considered. These variables were compared to those obtained in a similar, but non-institutionalized controls (Group B) of 63 subjects (mean age 85+/-2 years, 27 males and 36 females), being similar in number and age distribution, frequenting the Geriatric Day Center of the same locality. Statistical analysis revealed significant differences between Groups A and B: the BMD was considerably lower, but also the cognitive and affective performances were strongly reduced in Group A. These findings can be attributed to decreased psychosensorial stimuli and lost interest of the patients in Group A, resulting in a lower physical activity, accompanying the depressive state, and may represent the first signs of a decreased intellectual performance, which can later be transformed into dementia. The functional abilities and the levels of autonomy are also reduced, risking the loss of autosufficiency. Also, the drug usage was different in Group A: more sedative-hypnotics and anticoagulants were consumed. As regards the polymorbidities, arterial hypertension and consequent chronic renal failure, hepatopathies and thyreopathies were most frequent, these latter two being more frequent in the Group A.

A new method for diagnosing fever of unknown origin (FUO) due to infection of muscular-skeletal system in elderly people: leukoscan Tc-99m labelled scintigraphy.

Twenty patients affected by fever of unknown origin (FUO), due to a likely infection of the muscular or skeletal tissues, were studied by a Total Body scan with a monoclonal antibody fragment (Leukoscan) labelled with Tc-99m. The diagnostic procedure helped reach a final diagnosis in 8 out of the 20 patients because it identified the focus of the infection of the muscles or bones in joint proximity. Our data show that Leukoscan deserves to become a first line diagnostic procedure in the diagnostic algorithm for the evaluation of patients with FUO.

Leukoaraiosis, cognitivity and affectivity in elderly patients: on the lack of correlations between neurodiagnostic and psychometric findings.

Among the age-related pathophysiological alterations of the brain, the anomalies of the white matter are becoming of increasing interest at both pathological and clinical levels. Wherever specific pathologies of the white matter can be excluded, the still encountered anomalies are generally defined as leukoaraiosis (from the Greek words white and rarefaction), in order to indicate certain ill-defined, slurred subcortical areas which may be single, multiple, or confluent, representing transparent white matter regions, most probably of ischemic origin. The causes, risk factors and clinical significance of leukoaraiosis have remained so far unknown. At clinical level, it is believed to be connected with cognitive and affective disorders. This study intended to collect evidence of the presence and to estimate the extent of eventual cognitive and affective disorders in a sample of elderly patients displaying cerebral lesions like simple or associated leukoaraiosis, as well as other stabilized focal, single or multiple ischemic lesions, cerebral atrophy, lacunar state and vascular cerebropathies without leukoaraiosis. So far no significant correlations have been encountered between the neurodiagnostic and psychometric findings.

Use of alendronate in treatment of secondary osteoporosis from hypopituitarism: a case report.

The authors report a case of hypogonadotropic and hypothyrotropic partial hypopituitarism, being treated for over sixteen years with a substitution therapy consisting of estroprogestogenal hormones and L-thyroxine, presenting severe secondary osteoporosis, detected by densitometric examination (DEXA) of the medial and ultradistal sites of the non dominant radius. The patient was treated with alendronate (10 mg/die) for two years, in addition to the estroprogestogen therapy, resulting in a significant recovery of bone mass, equal to 16% compared to initial values, reaching near normal bone density values. On analysing the mechanisms of action of the bisphosphonates, the estrogens and the L-thyroxines, the authors suggest a synergic mechanism between the estrogen and the alendronate, which act on the bone turn-over at different times. Also, the alendronate would seem to antagonise the osteopenia of L-thyroxine, though this mechanism is still unknown.

ED hemodialysis for treatment of renal failure emergencies.

Patients with chronic renal failure (CRF) are at risk for unique medical emergencies, many of which require hemodialysis for their definitive treatment. This study describes the use of emergency department (ED) hemodialysis in the management of CRF patients. A retrospective chart review was conducted of patients who underwent ED hemodialysis at a regional dialysis center between April 1994 and September 1996. Data were collected on presenting complaint, ED diagnosis, indication for hemodialysis, ED pharmacologic treatment, ED airway management, cardiovascular stability, and disposition. Fifty episodes of ED hemodialysis were identified in 37 different patients. Presenting complaints included: shortness of breath, 38 (69%); weakness, 8 (15%); chest pain, 3 (5%); and other, 6 (11%). ED diagnoses included: congestive heart failure, 36 (65%); hyperkalemia, 13 (24%); and other, 6 (11%). Indications for hemodialysis included: cardiovascular instability, 33 (38%); respiratory distress, 22 (26%); cardiac monitoring, 16 (19%), timing, 13 (15%); and other, 2 (2%). Predialysis stabilization included: nitroglycerin, 29 (26%); sublingual captopril, 17 (15%); calcium chloride, 13 (11%); sodium bicarbonate, 12 (11%); insulin/dextrose, 11 (10%); none, 12 (11%); and other, 18 (16%). Airway support included: noninvasive pressure support ventilation (NPSV), 9 (18%); and endotracheal intubation, 6 (12%). NPSV was provided with a bilevel positive airway pressure system. Three of the endotracheal intubation patients were weaned to NPSV during dialysis, and all NPSV patients were weaned from respiratory support during their hemodialysis in the ED. Some patients had more than one problem. Sixteen patients (32%) were admitted, while 34 (68%) were discharged, including 3 NPSV patients and 22 initially unstable patients. ED hemodialysis in conjunction with additional medical care is a useful emergency medicine technique that can prevent hospital admission in patients with acute renal emergencies.

Electroionotherapy in acute arthrorheumatic pain.

The authors evaluated the efficacy of an electronic treatment for pain, using an ion flow generator, BE-101 model by Bio-Ejt, on 19 patients suffering from acute pain of an arthrorheumatic nature. Each patient was treated for two weeks every other day (6 sittings), each sitting lasting 20 minutes at an intensity of about 30 microAmper for both transducers. The results demonstrated that this technique is very effective in curing the pain.

Thyroid hormones and lipid metabolism in a group of patients over seventy.

Numerous studies have suggested a marked correlation between thyroid functionality indices and lipid metabolism. In this trial we assessed the functional parameters of 165 individuals over 70, 87 women and 78 men, correlating the serum values of T3, T4, FT4, TSH with cholesterol, triglycerides, HDL, Apo-A and Apo-B levels. The correlation was performed over the whole population studied and subsequently, after dividing the population by sex and age (3 age groups: A, 70-75; B, 76-80; C, over 80) in the individual groups. In the population as a whole, we have observed a statistically significant correlation between T4/cholesterol (P=0.0001); T3/cholesterol (P=0.06); T4/triglycerides (P=0.0001); T3/triglycerides (P=0.09); T4/HDL (P=0.0001); T4/Apo-A (P= 0.02); T3/Apo-A (P=0.008); T4/Apo-B (P=0.0001). Analysis by gender shows a statistically significance between the female and male sexes in the correlation between T3/cholesterol (P=0.001); T3/triglycerides (P=0.06); T4/cholesterol (P=0.0001) and T4/triglycerides (P=0.0001). When the data were analyzed by age, in Group A (75-80) there was no statistically significant correlation, whereas in Group B (76-80) there has been an increase in significance in the correlation between T3/cholesterol (P=0.006); T3/triglycerides (P=0.001); T3/Hdl (P=0.08); T3/Apo-A (P=0.0001); T3/Apo-B (P=0.08); T4/cholesterol (P=0.00001) and ); T4/Apo-A (P=0.0001). On the other hand in the Group C age group (over 80) this significance is considerably lower. Maybe this decrease of correlations should be attributed to a global savings of the older organisms, or to a process of natural selection.

The NTX assay in the follow-up of the osteoporotic patients: 3 years of alendronate treatment.

These studies were conducted on 38 female patients treated with alendronate (10 mg/day, per os) for 3 years, because of osteoporosis. Of these patients, 29 were in the menopausal age longer than 10 years, and the remaining nine patients were in menopausa shorter than 10 years. Urine sample were taken at the start of the treatment and every 6 months afterward for 3 years, and crosslinked N-telopeptides of type I collagen (NTx) have been measured in them by means of an ELISA technique. Bone mineral density (BMD) has been recorded at the ultradistal (UDBMD) and mediodistal (MDBMD) region of radius of the non-dominant side. Body mass index (BMI) of the subjects has also been determined each time. The baseline values of NTx varied very much, scattered in a range of 11-215 nanomoles bone collagen equivalent/millimoles creatinine (nM BCE/mM Cr), in average 59+/-46; those of UDBMD and MDBMD amounted to 258+/-63 and 587+/-112 mg/cm(2), respectively. NTx, the BMD values and the menopausal age does not correlate with cach other. Both BMD values increased almost linearly in the total study pool during the 3-years-long treatment, being 3.0-9.2 and 0.8-2.5% higher in terms of UDBMD and MDBMD, respectively. Urine NTx concentrations decreased during the same time 30-35%. It is concluded that monitoring of urine NTx levels may be very useful during antiosteoporotic treatments, because a reduction of NTx is an indicator of the slowing down of bone turnover and the bone losses, as was observed during the alendronate therapy.

Assessment of cognitive and affective disorders in an elderly population undergoing hemodialysis.

The purpose of this study was to assess the prevalence of cognitive and affective disorders in a group of elderly people suffering from chronic renal failure (CRF) and undergoing outpatient hemodialysis. Psychogeriatric assessment was performed on 39 individuals over 65 years of age suffering from CRF, and on a control group composed of 35 healthy elderly individuals. Assessment was made through Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activity Daily Living (ADL) and Instrumental Activity Daily Living (IADL) shortly before hemodialysis. A number of blood parameters were determined for both groups to evaluate the state of metabolic compensation. The elderly people undergoing hemodialysis did not seem to present a greater decline in cognitive capacity than their healthy peers, even if this is closely related to the level of anemia present in hemodialysis patients. On the other hand, affective disorders were widely observed, although in mild form, and seem to depend on factors other than age. There is certainly a reactive element deriving from the hemodialysis condition itself and the problems related to it, whereas an organic element linked to CRF cannot be excluded, and which seems to be related to anemia. Finally, the level of independence does not seem to be compromised in hemodialysis patients.

Estrogens and euosteogenesis in men.

The bone mineral density (BMD) has been analyzed in 200 male patients divided in 4 groups of age as follows: (A) 40-49, (B) 50-59, (C) 60-69, and (D) 70 years and above. BMD was measured by using the DEXA technique both in the ultradistal and mediodistal region of radius of the non-dominant side. In addition, the serum levels of testosterone (Ts), dihydrotestosterone (DHT) and 17-beta estradiol (E-2) have also been measured. The data obtained have shown that bone mineral density values are decreasing also in the males with advancing age, and the positive correlation (p < 0.05) of BMD with the E-2 levels also tend to decrease. These results suggest the hypothesis that the true sexual hormones regulating the rhythm of osteogenesis may be the estrogens in the males, too.

Correlations between C-reactive protein, interleukin-6, tumor necrosis factor-alpha and body mass index during senile osteoporosis.

Serum concentrations of C-reactive protein (CRP), interleukin-6 (Il-6) and tumor necrosis factor-alpha (TNF-alpha), as well as body mass index (BMI) were measured in a series of 36 elderly subjects (18 males, 18 females) of mean age 76.8+/-4.5 years, in order to assess whether these parameters are involved in senile osteoporosis (SOP). Bone mineral density was determined, by a dual-emission X-ray absorbimetry (dexa) method on the nondominant radius, as a measure of SOP. These studies revealed the following main results: (i) the female/male ratio of SOP at this age is 4:1; (ii) overweight has a sort of protection against SOP in females; (iii) increased Il-6 and TNF-alpha serum levels when observed in either of the sexes were accompanied by SOP, indicating that these parameters may be involved in provoking and maintaining SOP; (iv) elevated serum CRP levels indicate, in most elderly subjects, the presence of inflammation in SOP which has been considered previously as a merely 'wear and tear'-induced disease.

Thyroid function in healthy centenarians.

Seven thyroid function parameters (total T3, TT3; total T4, TT4; free T3, FT3; free T4, FT4; TSH; anti-thyroglobulin antibodies, TGAb; and anti-microsomal antibodies, TMAb) were studied in a series of 20 healthy centenarians in order to evaluate their thyroid function status. Our results showed that all the parameters were within normal range, with the exception of TT4 values which were reduced in 60% of centenarians examined. Therefore, the authors believe that the production of thyroid hormones seems to decrease in advanced years, but that this may not solely depend on thyroid parenchyma involution, but also on a lower demand by the hormone sensitive tissues. Centenarians seem to be adapted euthyroid subjects who present low, nonetheless adequate, levels of circulating thyroid hormone (T4).

Use of disphosphonates in the treatment of osteoporosis in thyroidectomized patients on levothyroxin replacement therapy.

Bone mineral density at medio distal (MD-BMD) and ultra distal (UD-BMD) sites of non dominant radius were studied, using a DEXA Mineralometer (TURBOSCAN-NIM) on a series of 20 patients, over 60 years old, all thyroidectomized for thyroid carcinoma and treated with levothyroxin replacement therapy. T3 and T4 (RIA method), TSH (IRMA method) and two cardiac parameters as TPER (time peak ejection rate) and TPFR (time peak filling rate) by angiocardioscintigraphy were also determined. Results showed that 19 patients considering MD-BMD values and ten considering UD-BMD values were at risk of fractures. Circulating T3 levels were within normal range in 17 patients, elevated in two cases and reduced in one case. Circulating T4 levels were within normal range in 15 patients, increased in four cases and reduced in one case. Circulating TSH levels were within normal range in 17 patients, reduced in two cases and elevated in one case. TPER were reduced in 18 patients and normal in two cases. TPFR were reduced in six patients and normal in fourteen cases. The authors administered alendronate (10 mg/day) which seems to prevent bone loss, especially at the level of the trabecular bone. Bone loss reverted at 6 and 12 months, confirming that disphosphonates slow down this phenomenon in a situation of increased bone turnover (e.g. patients on long-term L-T4 therapy).