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Byline: G. Isaia (1), R. Giorgino (2), G. B. Rini (3), M. Bevilacqua (4), D. Maugeri (5), S. Adami (6) Keywords: Hip fracture; Osteoporosis; Secondary hyperparathyroidism; Vitamin D Abstract: In order to evaluate the prevalence, risk factors, and clinical consequences of hypovitaminosis D in elderly Italian women a multicenter study of 43 osteoporosis centers from all regions of Italy was carried out. Study population included 700 women aged 60--80 years in whom blood was taken for 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) measurements. All subjects were also questioned to assess the prevalence of several risk factors for hypovitaminosis D, osteoporotic fractures and activities of daily living (ADL). Values of 25OHD lower than 5 ng/ml were found in 27% of the women and lower than 12 ng/ml in 76%. 25OHD and PTH levels were negatively correlated (r=-0.38, after logarithmic transformation of both variables). 25OHD levels significantly declined with advancing age and number of pregnancies and were positively correlated with educational level (years spent at school), dairy calcium intake, and days spent on holiday by the sea. In a multivariate model including all these variables, the only one that remained significant was the level of education. The lowest age-adjusted 25OH D levels were found in smokers or in women living in central Italy as compared with those living in northern or southern Italy. The mean (+-SD) age-adjusted 25OH D values were significantly lower in women who sustained a hip fracture (7.1+-2.2 versus 11.0+-9.9). Women with low 25OHD levels (&lt 12 ng/ml) had worse scores for ADL and mobility ADL (move outdoors, use stairs, walk at least 400 m, carry a heavy object). Vitamin D deficiency is extremely common among elderly Italian women. Women with lower educational level, living in central Italy, smokers or with lower intake of dairy products are at greater risk. Hypovitaminosis D is associated with worsening of the ability to perform activities of daily living and higher hip fracture prevalence. This finding should lead to an urgent population-based strategy to remedy this condition. Author Affiliation: (1) Department of Internal Medicine, University of Turin, Italy (2) Procter and Gamble, Rome, Italy (3) Internal Medicine, University of Palermo, Italy (4) Endocrine Unit, Ospedale Sacco, Milan, Italy (5) Internal Medicine, University of Catania, Italy (6) Rheumatologic Rehabilitation, University of Verona, Ospedale di Valeggio, 37067 Valeggio, Verona, Italy Article History: Received Date: 30/08/2002 Accepted Date: 20/01/2003 Online Date: 11/07/2003 Article note: Local participants in the study (name and Italian town of study site): S. Adami, Verona M. Bevilacqua, Milano E.M. Bibolotti, Piombino F. Cantini, Prato S. Coaccioli, Terni R. Conca, Milano D. Costi, Parma G. D'Avola, Catania O. Di Munno, Pisa M. Ferraris, Vercelli P. Filipponi, Perugia C.M. Francucci, Ancona G. Gandolini, Milano S. Gatto, Napoli P. Gigliotti, Cosenza T. Gismondi, Bari S. Gnudi, Bologna E. Grimaldi, Trieste G. Isaia, Torino G. La Montagna, Napoli G. Lojacono, Bari R.V. Lovato F. Luparelli, Taranto U. Martorana, Palermo A. Mathieu, Cagliari D. Maugeri, Catania S. Minisola, Roma S. Miozzi, Roma G. Occhipinti, Livorno R. Pellerito, Torino D. Policicchio, Avellino M. Portigliatti Barbos, Torino G.B. Rini, Palermo G. Rosa, Napoli D. Schinella, Pordenone M. Sfrappini, Tronto P. Simonetta, Reggio Calabria L. Sinigaglia, Milano S. Stisi, Benevento A. Tarroni, Rimini F. Trotta, Ferrara F. Versace, Savona

Byline: R. P. Heaney (1), T. M. Zizic (2), I. Fogelman (3), W. P. Olszynski (4), P. Geusens (5), C. Kasibhatla (6), N. Alsayed (6), G. Isaia (7), M. W. Davie (8), C. H. Chesnut III (9) Keywords: Key words:Bone mineral density -- Osteoporosis -- Risedronate -- Vertebral fracture Abstract: Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =--3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90% P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90% P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96% P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Author Affiliation: (1) Creighton University, Omaha, Nebraska, USA, US (2) Chesapeake Medical Research, Baltimore, Maryland, USA, US (3) Guy's Hospital, London, UK, GB (4) Midtown Medical Center, Saskatoon, Saskatchewan, Canada, CA (5) Limburg University Center, Diepenbeek, Belgium, and University Hospital, Maastricht, The Netherlands, NL (6) Procter &amp Gamble Pharmaceuticals, Cincinnati, Ohio, USA, US (7) University of Turin, Turin, Italy, IT (8) Charles Salt Centre, Oswestry, Shropshire, UK , GB (9) University of Washington, Seattle, Washington, USA, US Article note: Received: 12 September 2001 / Accepted: 11 December 2001

Background: Hip fracture is a common event in older adults, leading to an increased risk of mortality, disability, and higher healthcare costs. Early in-hospital rehabilitation after surgery within orthogeriatric units may improve outcomes with limited incident complications even in the oldest old. We aimed to determine the prevalence and predictors of non-adherence to early rehabilitation in the orthogeriatric unit of an Italian tertiary hospital and its impact on outcomes and setting at discharge., Methods: Retrospective observational single-centered cohort study. Patients aged ≥ 65 years admitted to the orthogeriatric unit for hip fracture who underwent surgery between April 2019 and October 2020 were considered eligible if able to walk autonomously or with assistance and independent in at least 2 Basic Activities of Daily Living. Along with sociodemographic and geriatric variables, characteristics of surgery and rehabilitation, in-hospital complications and functional outcomes at discharge were collected. The primary outcome was non-adherence to the early in-hospital rehabilitation program., Results: Among 283 older patients (mean age 82.7 years, 28.6% male), non-compliance with physical therapy was assessed in 49 cases (17.3%), characterized by worse pre-fracture clinical, cognitive, and functional status and showing worse outcomes in terms of mobilization at discharge. After multivariable analysis, non-adherence was independently associated with the onset of delirium (OR 5.26, 95%CI 2.46-11.26; p < 0.001) or infections after surgery (OR 3.26, 95%CI 1.54-6.89; p < 0.001) and a systolic blood pressure at admission < 120 mmHg (OR 4.52, 95%CI 1.96-10.43, p < 0.001)., Conclusions: Pre-fracture poor cognitive and functional status, along with lower systolic blood pressure, seem to make some patients more vulnerable to in-hospital complications (mainly delirium and infections) and negatively affect the adherence to physical therapy and, by consequence, clinical outcomes of rehabilitation., (© 2024. The Author(s).)

This review critically assessed the existence of presbygeusia, i.e., the impairment in taste perception occurring in the elderly, as a natural part of the aging process and its potential clinical implications. Several factors might contribute to age-related taste alterations (TAs), including structural changes in taste buds, alterations in saliva composition, central nervous system changes, and oral microbiota dysbiosis. A comprehensive literature review was conducted to disentangle the effects of age from those of the several age-related diseases or conditions promoting TAs. Most of the included studies reported TAs in healthy elderly people, suggesting that presbygeusia is a relatively frequent condition associated with age-related changes in the absence of pathological conditions. However, the impact of TAs on dietary preferences and food choices among the elderly seems to be less relevant when compared to other factors, such as cultural, psychological, and social influences. In conclusion, presbygeusia exists even in the absence of comorbidities or drug side effects, but its impact on dietary choices in the elderly is likely modest., (© 2024. The Author(s).)

Background: Since the occurrence of the SARS-COV2 pandemic, there has been an increasing interest in investigating the epidemiology of delirium. Delirium is frequent in SARS-COV2 patients and it is associated with increased mortality; however, no information is available on the association between delirium duration in SARS-COV2 patients and related outcomes., Aims: The aim of this study is to investigate the association between the duration of delirium symptoms and in-hospital mortality in older patients with SARS-COV2 infection., Methods: Retrospective cohort study of patients 65 years of age and older with SARS-CoV 2 infection admitted to two acute geriatric wards and one rehabilitation ward. Delirium symptoms duration was assessed retrospectively with a chart-based validated method. In-hospital mortality was ascertained via medical records., Results: A total of 241 patients were included. The prevalence of delirium on admission was 16%. The median number of days with delirium symptoms was 4 (IQR 2-6.5) vs. 0 (IQR 0-2) in patients with and without delirium on admission. In the multivariable Cox regression model, each day with a delirium symptom in a patient with the same length of stay was associated with a 10% increase in in-hospital mortality (Hazard ratio 1.1, 95% Confidence interval 1.01-1.2; p = 0.03). Other variables associated with increased risk of in-hospital death were age, comorbidity, CPAP, CRP levels and total number of drugs on admission., Conclusions: The study supports the necessity to establish protocols for the monitoring and management of delirium during emergency conditions to allow an appropriate care for older patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hospital at Home (HaH) has been proposed as a solution to relieve pressure on hospital beds during the COVID-19 pandemic; however, caregivers' feelings of inadequacy and concerns on the need for tighter clinical monitoring might lead to unnecessary and potentially harmful hospital admissions in frail older patients with mild or atypical COVID-19. Here we report the case of a 91-year old woman with severe dementia and atypical COVID-19 that could be successfully managed by our HaH thanks to her highly motivated caregivers and the support of a telemedicine solution (TMS) to provide caregiver training and support as well as supplementary telemonitoring. Despite some well-known issues on TMS use, the hybrid in-person and tele-visit approach of TMS-assisted HaH could help to create a "secure" environment, empowering caregivers to manage frail older adults with COVID-19 at home, avoiding unnecessary admissions to closed wards and their negative physical, functional and psychological outcomes.

In the search for factors affecting incidence and lethality of the current COVID-19 pandemic, recent association studies explored the possible role of vitamin D deficiency. Altogether, these studies, in most cases based on cross-sectional analyses, could not yet provide a convincing demonstration of a cause-effect relationship. In this editorial, the authors describe the scientific evidence underlying a possible role of vitamin D in the prevention and development of the pandemic, considering its immunomodulatory role and antiviral effects. They conclude that further studies are needed to (1) better explore possible associations between vitamin D deficiency and COVID-19 morbidity and lethality, and (2) assess if compensating such deficiency could avoid or mitigate the worst manifestations of COVID-19. They highlight the need for public health campaigns to promote consumption of vitamin D-rich foods and proper sunlight exposition or, when this is not possible, controlled pharmaceutical supplementation, especially in countries with high prevalence of hypovitaminosis D.

Background: Blood pressure variability (BPV) may have prognostic implications for cardiovascular risk and cognitive decline; however, BPV has yet to be studied in old and very old people., Aims: Aim of the present study was to evaluate the extent of BPV and to identify variables associated with BPV among older subjects., Methods: A retrospective study of patients aged ≥ 65 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) was carried out. Three different BPV indexes were calculated for systolic and diastolic blood pressure (SBP and DBP): standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Demographic variables and use of antihypertensive medications were considered., Results: The study included 738 patients. Mean age was 74.8 ± 6.8 years. Mean SBP and DBP SD were 20.5 ± 4.4 and 14.6 ± 3.4 mmHg. Mean SBP and DBP CV were 16 ± 3 and 20 ± 5%. Mean SBP and DBP ARV were 15.7 ± 3.9 and 11.8 ± 3.6 mmHg. At multivariate analysis older age, female sex and uncontrolled mean blood pressure were associated with both systolic and diastolic BPV indexes. The use of calcium channel blockers and alpha-adrenergic antagonists was associated with lower systolic and diastolic BPV indexes, respectively., Conclusions: Among elderly subjects undergoing 24-h ABPM, we observed remarkably high indexes of BPV, which were associated with older age, female sex, and uncontrolled blood pressure values.

Purpose: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women., Methods: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX ® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA., Results: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX ® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed., Conclusions: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX ® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

Unlabelled: The patients' adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective., Purpose: Several drugs are currently available for the treatment of osteoporosis, but the patients' compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study)., Methods: A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm)., Results: In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance., Conclusions: Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients' perceived risk of fracture are warranted.

Background and Aims: Frailty is a common situation that often influences clinical outcomes, disability or institutionalization. The present study aims to evaluate the weight of hand grip strength (HGS) reduction in terms of death or re-hospitalizations, at 3-month and 1-year follow-up., Methods: Observational study performed on hospitalized patients aged 65 years or more. The HGS was measured twice: at hospital admission and discharge. The statistical analysis was performed using SPSS, version 18 for Windows. The χ (2) test was used to evaluate the relationship between HGS and different variables. Three-month and 1-year survival and hospital re-admissions have been analyzed using Kaplan-Meier's curves. The analyses have been adjusted for age and gender., Results: A total of 201 hospitalized patients have been recruited. Of them, 76 were males. The mean age was 81.79 ± 7.409 years. Of all the patients enrolled, 66.2 and 45.3 % did not show any impairment performing activities of daily living and instrumental activities of daily living, respectively. Moreover, patients were not cognitively impaired [SPMSQ (short portable mental status questionnaire ) m ± SD = 1.47 ± 0.794]. At 3-month follow-up patients with strength reduction had a relative risk of death more than seven times higher than the others (p = 0.047). Same results were observed at 1-year follow-up (95 % CI = 1.85-9.84; p = 0.000). There was no significant relationship between HGS and hospital re-admissions., Conclusions: Effects of strength reduction occurring during a period of hospitalization could produce effects even after hospitalization itself. This increases the relevance of maintaining usual physical performance of patients even during hospitalization.

Background and Aims: Caregiving can be extremely stressful, especially when patients' ability to communicate is impaired. While the stress undergone by relatives assisting their loved ones has been widely investigated, fewer data can be found about the stress in healthcare professionals. The aim of this study is to evaluate whether a specific training course could be related to a reduction in the levels of stress of professional care-givers working with patients suffering from dementia., Methods: Work-related levels of stress of study participants were evaluated with the Staff Stress Measure Dementia Care Scale, at baseline and four months after completion of an eight-month training course., Results: We found no significant correlation between care-givers' age, gender, marital status, years of employment or perceived economic status, and their stress levels at baseline. Patients' characteristics were not related with care-givers' stress at baseline. The mean level of stress was significantly reduced (34.64±4.15 vs 26.64±3.82, p<0.001) between baseline and the study endpoint., Conclusions: Increased knowledge of management of patients affected by dementia could help professional care-givers to reduce their work-related stress. Our results add to the evidence of the benefit of personnel support in reducing levels of stress at work.

Background: Osteoporosis is a highly prevalent disease and fractures are a major cause of disability and morbidity., Aim: The purpose of this study was to characterize post-menopausal women attending osteoporosis centers in Italy, to evaluate physician management, and to determine the incidence of first osteoporotic fracture., Subjects and Methods: PROTEO-1 was an observational longitudinal study with a 12-month follow-up. Data were collected from women attending osteoporosis centers. Women without prevalent fracture were eligible to enter the 1-yr follow-up phase: the clinical approach to patients according to their fracture risk profile and the incidence of fracture were recorded., Results: 4269 patients were enrolled in 80 centers in the cross-sectional phase; 34.2% had an osteoporotic fracture at baseline. Patients with prevalent fractures were older and more likely to be treated compared with non-fractured patients. The incidence of vertebral or hip fracture after 1 yr was 3.84%, regardless of the calculated risk factor profile, and was significantly higher in patients with back pain at baseline (4.2%) compared with those without back pain (2.2%; p=0.023). Generally, physicians prescribed more blood exams and drugs to patients at higher risk of fracture. Among fractured patients only 24% were properly treated; the rate of non-responders to treatment was about 4%., Conclusions: In a large, unselected sample of post-menopausal women attending osteoporosis centers, those without previous fracture were at substantial risk of future fracture, regardless of their theoretical low 10-yr fracture risk. The presence of back pain in women without previous fracture warrants close attention.

Introduction: The use of hospital care increases significantly with age. Older people coming to the emergency department have three to seven times higher rates of hospitalization than younger people. Hospitalization can lead to loss of independence and also need for long-term care at discharge., Methods: A prospective observational non-randomized study of elderly patients admitted to the Department of Geriatric Medicine, University of Torino, Italy, between October 2006 and May 2007., Results: The mean age of 123 subjects was 82.2±7.3 years. Among patients with dependence two weeks before admission, as reported by their caregivers, bathing, toileting and dressing were the most compromised ADL functions. In the same patients, shopping and transportation were reported as the most frequent IADL functions lost. Functional decline before hospitalization was significantly associated with a worsening in functional decline during the length of stay (RR 2.2, CI 1.05-4.66) and with discharge to a long-term facility (RR 2.1, CI 1.04-4.44)., Conclusions: As functional decline two weeks before hospitalization influences hospital discharge and functional outcomes, it is certainly interesting to evaluate the impact of a dedicated early rehabilitation program for elderly patients. A well-structured program involving geriatricians, physiatricians and physiotherapists could be helpful for better short-term prognoses.

Background and Aims: The number of hospital admissions of the elderly is increasing and hospitalization often leads to functional decline. The aim of this study was to identify major risk factors for functional decline in the hospitalized oldest old., Methods: Prospective, observational, non-randomized study of patients aged >/=80 years, admitted for at least two days to the University Department of Geriatric Medicine of Torino, Italy, between November 2003 and November 2004. For detection of functional decline, the ADL scale was used, referring to the number of dependent ADL., Results: At discharge, ADL mean scores were significantly higher than on admission (2.5+/-2 vs 2.3+/-1.9, p<0.001). 23.9% of the sample lost at least one ADL function during hospitalization, and 19.2% were transferred to long-term care, compared with 5.4% of those with no functional decline. Length of hospitalization, neoplasm, low level of albumin and high number of drugs prescribed were associated with functional decline. At multivariate analysis, only in-hospital stay was an independent risk factor for functional decline (RR 1.1 per day of hospitalization, CI 1.03-1.14)., Conclusions: Hospitalization of the oldest old increases the risk of functional decline, especially if prolonged. It is important to identify patients at high risk for functional decline after hospital admission.

Background: Osteoporosis is the most common skeletal disorder in the elderly, being characterized by impaired bone strength and increased risk of fracture. Severe osteoporosis is currently defined by the threshold of bone density value below the -2.5 SDS of T-score, determined by dualenergy X-ray absorptiometry, and the presence of one or more fragility fractures. This definition does not entirely reflect the spectrum of severity of the disease that provides a variable increase in fracture risk., Methods: This manuscript reports a consensus statement on the diagnostic criteria for severe osteoporosis in real-life clinical setting, achieved in an event held by Italian physicians with expertise in osteoporosis and metabolic bone diseases., Results: The group stated that a large number of fractures occur in subjects with T-score above -2.5. In light of recent advances on the structural basis of skeletal fragility, it became clear that bone density represents only one of the contributors to bone strength and number and severity of fragility fractures. The group suggests that the condition of two or more fragility fractures should be considered as severe osteoporosis, independently of bone density., Conclusions: The consensus statement proposes a more specific definition of severe osteoporosis, which should consider not only densitometric measurements, but also the number and severity of fragility fractures. Patients' management and choice of treatment should take into consideration the type and severity of osteoporotic fractures, in addition to bone density.

Delirium usually occurs during hospitalisation. The aims of this study were to evaluate the incidence of delirium in "hospital-at-home" compared to a traditional hospital ward and to assess mortality, hospital readmissions and institutionalisation rates at 6-month follow-up in elderly patients with intermediate/high risk for delirium at baseline according to the criteria of Inouye. We performed a prospective, non-randomised, observational study with 6-month follow-up on 144 subjects aged 75 years and older consecutively admitted to the hospital for an acute illness and followed in a geriatric hospital ward (GHW) or in a geriatric home hospitalisation service (GHHS). Baseline socio-demographic information, clinical data, functional, cognitive, nutritional status, mood, quality of life, and caregiver's stress scores were collected. Of the 144 participants, 14 (9.7%) had delirium during their initial hospitalisation: 4 were treated by GHHS and 10 in a GHW. The incidence of delirium was 16.6% in GHW and 4.7% in GHHS. All delirious patients were very old, with a high risk for delirium at baseline of 60%, according to the criteria of Inouye. In GHW, the onset of delirium occurred significantly earlier and the mean duration of the episode was significantly longer. The severity of delirium tended to be higher in GHW compared to GHHS. At 6-month follow-up, mortality was significantly higher among patients who suffered from an episode of delirium. Moreover, they showed a trend towards a greater institutionalisation rate. GHHS may represent a protective environment for delirium onset in acutely ill elderly patients.

Osteoporosis and atherosclerosis are degenerative disorders of old age that often present together, but recently it has been suggested that the association between osteoporosis and cardio-vascular diseases is not just due to the aging process. The osteoprotegerin (OPG)/receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL) system has been identified as a possible mediator of arterial calcification suggesting common links between osteoporosis and vascular diseases. Since the discovery of the OPG/RANK/RANKL system, much has been learned about its role in controlling skeletal biology; however, its role in the context of vascular biology is only beginning to be explored. It has been suggested that OPG might act as an autocrine/paracrine regulator of vascular calcification and might be useful as a serum marker of vascular disease. However, the exact role of OPG (or RANKL/RANK) in vascular calcification is still not completely understood. This review aims to report the recent findings on the relationship between osteoporosis and OPG/RANK/RANKL-mediated vascular disease.

Background and Aims: Osteoporotic fractures are a major public health problem notably affecting quality of life. The observational, multicenter study ICARO was designed to evaluate inadequate clinical response to antiresorptive drugs. The aim of the present study was to evaluate the impact of the clinical response to treatment on the health-related quality of life in women with postmenopausal osteoporosis., Methods: 880 osteoporotic women (mean age 68.0+/-8 years; range 53-79) in treatment with antiresorptive drugs for at least one year were analyzed. All subjects had at least 50% compliance to treatment (i.e., patients took >50% of prescribed doses). The "inadequate clinical response" (ICR), as opposed to "adequate clinical response" (ACR), was defined as the Xrays revealing evident new vertebral or non-vertebral fragility fractures at least 6 months after initiation of antiresorptive therapy. The QUALEFFO- 41 questionnaire was used to evaluate changes in quality of life prospectively., Results: 220 subjects (25%) had an ICR. Non-responders had a higher incidence of multiple vertebral fractures compared with responders. The quality of life data in the study subjects showed a significantly increased score (indicative of lower quality of life) in the total mean score (37.89+/-16.7 vs 45.84+/-18.2, p<0.01), as well as in all the domains/subdomains examined in the QUALEFFO-41 questionnaire in ICR, when compared with ACR., Conclusions: Inadequate clinical response in subjects on antiresorptive drugs is associated with increased severity of the disease and with a significant reduction in the quality of life.

Osteoporotic fractures are associated with significant morbidity and mortality. In addition, the declines in physical function and the changes in appearance due to fractures contribute to the severe reduction in patients' quality of life (HRQOL). It has been demonstrated that patients suffering subclinical fractures experience a reduction in their HRQOL. Some studies have also suggested that osteoporotic patients without fractures perceive a reduction in their quality of life. It has been suggested that anti- osteoporotic therapy is effective in increasing patients' HRQOL. In our clinical experience, treatment with teriparatide is effective in reducing back pain and in enhancing patients' activities of daily living.

Many patients are affected by metabolic bone diseases such as osteoporosis and Paget's disease, and many medical specialties such as internal medicine, orthopedics, radiology, gynecology and endocrinology are involved in their diagnosis and treatment. The most common metabolic disease of bone is osteoporosis, but osteoporosis-related fractures, mainly vertebral, are often underdiagnosed and undertreated by physicians. Thus, a Center specializing in these diseases would represent a good opportunity to improve clinical practice and guarantee proper communications between specialists in the field and general practitioners.

Bone density depends on various factors such as age, hormonal status, genetics factors and lifestyle: a balanced diet plays a fundamental role in the prevention of osteoporosis. The role of protein intake on bone health is still controversial: this review is focused on the relation between protein intake and bone metabolism.

Leptin is a cytokine-like hormone which is considered the link between fat and bone; it is produced by adipocytes and osteoblasts, regulates food intake via specific receptors located in the central nervous system (CNS) and bone mass through alternate pathways: one involving a direct stimulatory effect on bone formation; and another indirect effect through the CNS that suppresses bone formation. Leptin exerts a direct stimulatory effect on osteoblast differentiation and on bone growth if directly administered, while it exerts an inhibitory effect on bone formation if administered in the CNS. It is therefore unclear whether leptin should be considered an antiosteogenic factor or an anabolic agent for bone formation: in all probability, leptin has a broader role in human physiology and in particular its action has evolved in order to synchronize periods of bone growth, mineral accretion and fertility with periods of food availability, while it restricts growth and reproduction during periods of nutritional stress.

A 62-yr-old woman with idiopathic hypoparathyroidism was admitted to our hospital for severe anemia (Hb 5.6 gr/dl) and hypoalbuminemia (3.2 gr/dl). Hypoparathyroidism was diagnosed when she was 33 yr old, because of repeated hypocalcemic tetanic crises, low calcium and high phosphate levels. Since then she has been treated with oral calcium gluconate and calcitriol, with satisfactory clinical balance and normalization of calcium serum levels. After menopause, despite this therapy, the patient still had frequent hypocalcemic tetanic crises, resolving with iv administration, in high doses, of calcium gluconate. The anemia, for which the patient came to our attention, was hypochromic microcytic and in the past she had been treated with iron and transfusion therapy. The patient's recent history also revealed recurrent long lasting episodes of diarrhea, hyporexia and weight loss. The clinical presentation seemed related to a malabsorption syndrome: a celiac disease (CD) diagnosis was confirmed, based upon the finding, at duodenal biopsy, of a severe villous atrophy. A bone mineral density (BMD) evaluation showed a limited reduction of femoral values classified as osteopenia according to the World Health Organization (WHO) criteria. Thereafter, the patient was instructed to follow a gluten-free diet which rapidly led to an improvement of the nutritional parameters and to a reduction of calcium and vitamin D requirements. Difficult clinical and metabolic control in hypoparathyroidism patients may suggest the possible co-existence of both endocrine and extra-endocrine autoimmune diseases, such as CD. Moreover, bone density, normally reduced in celiac patients, seems to be preserved (maintained) by the lack of parathyroid secretion.

The effects of a chronic treatment with corticosteroids on bone are well known, but few data are available regarding the acute effect of these drugs on bone turnover. This study was aimed at evaluating the effects of high doses of corticosteroids administered for a short period on bone metabolism. We assessed 23 subjects (15 women and 8 men) suffering from multiple sclerosis and treated with methylprednisolone (1 g i.v. for 10 days) followed by oral prednisone for 9 days; patients affected by diseases involving bone or treated during the previous 6 months with drugs influencing bone metabolism were excluded. We observed a significant decrease of ALP and bone glia protein (BGP), in these subjects, and a significant sudden increase of urinary calcium/creatinine and urinary cross-laps after 3 days of treatment. All of these parameters, except urinary calcium/creatinine, returned to basal levels after 30 days from the beginning of treatment (11 days after the interruption of corticosteroids administration). Serum phosphorus showed a significant decrease after 3 days of treatment, but returned to basal levels after 10 days. These data suggest that high doses of corticosteroids administered for a short period are able to induce an increase of bone resorption and a decrease of bone formation; moreover, bone turnover returns to basal levels when the treatment is stopped.

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.

We performed a cross-sectional study in 147 women, 41 in premenopausal age and 106 in menopause for 1-5 years: bone mineral density (BMD) at the distal radius and annual bone loss (as shown by plasma alkaline phosphatase and osteocalcin levels, and by calcium/creatinine and hydroxyproline/creatinine in the second urine of the morning) were evaluated. A significant reduction of BMD with a significant increase of bone loss was observed with increasing duration of menopause. Furthermore, when the women were subdivided into two groups according to annual bone loss (over or under 1.7%), significant differences were found between bone mineral density in the second and third years of menopause. As this is a cross-sectional and not a longitudinal study, it confirms that, in the presence of a higher bone loss, the BMD levels are lower and consequently the theoretical definition of this parameter can allow useful information on the presumable behavior of BMD.

In this study we investigated the calcitonin (CT) pattern both in basal conditions and after calcium infusion before and one month after oophorectomy in 17 premenopausal women. In addition, 13 oophorectomized women were randomly allocated to two groups, one given hormone replacement treatment and the other untreated, and CT response to hypercalcemia was reevaluated one year later. CT response to calcium infusion was significant only before oophorectomy and one year after estrogen-progestogen treatment, whereas there was no response one month after oophorectomy or after one year without hormone replacement therapy. Our data indicate that both estrogen secretion and replacement treatment may be important factors in CT response.

Primary pigmented micronodular disease is a peculiar form of ACTH-independent Cushing's syndrome characterized by the familial occurrence, the frequent association with malformations and the pathological adrenocortical picture consisting in micronodules with cellular deposition of lipofuscinic pigment. We describe here a case occurring in a 14-year-old girl.