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Introduction: Poor adherence to prescribed treatments is widespread in clinical practice and this can lead to potentially life-threatening events. This problem is apparently very common for osteoporosis treatment but the causes of discontinuation and low compliance are complex and poorly defined. Methods: Global adherence to osteoporosis treatment was specifically addressed in a nation-wide survey carried out in 9851 postmenopausal women referred to 141 Italian centres for osteoporosis management for a follow-up assessment, at least one year after having been prescribed a treatment with one of the following drugs: calcium [+ or -] vitamin D supplements alone (CaVitD), hormone replacement therapy (HRT), raloxifene 60 mg (RLX), intramuscular clodronate 100 mg/7-14 days (CLOD), risedronate 5 mg/day (RIS) and alendronate 10mg/daily (ALN10) or 70 mg once weekly (ALN OW). Results: Overall 19.1% of the patients discontinued the prescribed drug before attending the bone mass reevaluations, more than half of them within the first 6 months. The discontinuation rate was significantly different between the treatments. The medications most frequently interrupted within one year were CLOD (28.7%; p Keywords Adherence * Compliance * Osteoporosis * Persistence * Treatment

Byline: M. Pedrazzoni (1), G. Girasole (2), F. Bertoldo (3), G. Bianchi (2), C. Cepollaro (4), A. Del Puente (5), S. Giannini (6), S. Gonnelli (4), D. Maggio (7), C. Marcocci (8), S. Minisola (9), E. Palummeri (10), M. Rossini (11), L. Sartori (6), L. Sinigaglia (12) Keywords: Bone densitometry; Diagnosis; DXA; Osteoporosis; Reference values Abstract: Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2--L4) and proximal femur in 1,622 women aged 20--79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66) the BMD values between 20--45 in premenopausal women (mean 1.036 SD 0.109 g/cm.sup.2) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm.sup.2). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS. Author Affiliation: (1) Dipartimento di Medicina Interna e Scienze Biomediche, Universita di Parma, Via Gramsci 14, 43100 , Parma, Italy (2) Divisione di Reumatologia, Dipartimento Apparato Locomotore, ASL 3 Genovese, Genova, Italy (3) Dipartimento di Scienze Biomediche e Chirurgiche, Universita di Verona, Verona, Italy (4) Dipartimento di Medicina Interna, Scienze Endocrino-Metaboliche e Biochimica, Universita di Siena, Siena, Italy (5) Reumatologia, Universita 'Federico II', Napoli, Italy (6) Dipartimento di Scienze Mediche e Chirurgiche, Universita di Padova, Padova, Italy (7) Gerontologia e Geriatria, Universita di Perugia, Perugia, Italy (8) Dipartimento di Endocrinologia e Metabolismo, Universita di Pisa, Pisa, Italy (9) Dipartimento di Scienze Cliniche, Universita di Roma 'La Sapienza', Roma, Italy (10) Dipartimento Interaziendale di Geriatria, ASL 3--Ospedali Galliera, Genova, Italy (11) Centro Osteoporosi, Universita-ASL di Verona, Verona, Italy (12) Servizio Malattie Osteometaboliche, Dipartimento di Reumatologia, Istituto G. Pini, Milano, Italy Article History: Received Date: 14/02/2003 Accepted Date: 05/09/2003 Online Date: 03/10/2003

Byline: S. Giannini (1), M. Nobile (1), M. Ciuffreda (1), R. M. Iemmolo (1), L. Dalle Carbonare (1), N. Minicuci (1), F. Casagrande (1), C. Destro (1), G. E. Gerunda (1), L. Sartori (1), G. Crepaldi (1) Keywords: Key words:Bone turnover -- Immunosuppressive drugs -- Liver disease -- Liver transplant -- Osteoporosis Abstract: We determined bone density and metabolism in 46 patients (35 males, 11 females) who had undergone liver transplantation 1--48 months previously. Twenty-one patients were then followed for the next 24 months. At each visit, blood and urine samples for bone and liver metabolism parameters, as well as spinal and femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal and femoral density was low (p&lt 0.001). Patients with pre-transplant cholestatic diseases had lower spinal density than all the other subjects (p&lt 0.05) and the cumulative methylprednisolone intake was an independent negative predictor of total hip density (p&lt 0.02). At baseline, urinary hydroxyproline and N-telopeptide were at the upper normal level and decreased only after 24 months of follow-up (p&lt 0.05). During the first year of follow-up, femoral density decreased (p&lt 0.05) and a partial recovery was observed for both spine and femur after 24 months. After 12 months, femoral bone density was negatively associated with serum cyclosporin A levels (p&lt 0.005) and cumulative methylprednisolone intake (p&lt 0.05), while the percent decrease in spinal density after the first 12 months was negatively predicted by mean daily methylprednisolone intake (p&lt 0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal density increased after the first (p&lt 0.05) and second year (p&lt 0.05), respectively. In patients with previous post-necrotic cirrhosis, femoral density decreased after 12 months (p&lt 0.05) and was still lower than baseline after 24 months (p&lt 0.05). However, at the end of the study the cumulative percentage of femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of spinal and femoral osteoporosis is present even many years after liver transplantation, with immunosuppressive treatment and pre-transplant liver disease being the most important pathogenetic factors. Author Affiliation: (1) Department of Medical and Surgical Sciences, University of Padua and National Research Council, Centre for Aging Studies of Padua, Italy, IT Article note: Received: 15 April 1999 / Accepted: 29 October 1999

Purpose: Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences., Methods: The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits., Results: During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%., Conclusions: We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes., (© 2024. The Author(s).)

Introduction: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management., Methods: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice., Results and Conclusion: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released., (© 2024. The Author(s).)

Purpose: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity)., Methods: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ)., Results: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people., Conclusions: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT., (© 2023. The Author(s).)

Background and Aims: The most recent guidelines suggest treating patients whose FRAX 10-year fracture risk scores are ≥ 20%. However, this method of evaluation does not take into account parameters that are nonetheless relevant to the therapeutic choice. Our aim was to compare the therapeutic choices for treatment based on a wider assessment (real-world practice) with those based on FRAX scores, taking 20% as the cut-off score., Methods: We obtained the medical history, bone mineral density (BMD) values, and the presence of major fragility fractures in a sample of 856 postmenopausal women. The 10-year FRAX risk of major osteoporotic fracture was calculated, and patients were grouped into risk classes ("FRAX < 20%" = low, "FRAX ≥ 20%" = high); we then compared the treated and untreated patients in each class. After an average interval of 2.5 years, changes in lumbar and femoral BMD and appearances of new fragility fractures were recorded., Results: 83% of high-risk patients and 57% of low-risk patients were treated. The therapeutic decision was based mainly on densitometric values and the presence of vertebral fractures. At the 2.5 year follow-up, lumbar spine and femur BMD had decreased in the untreated group; 9.9% of the treated patients developed new vertebral fragility fractures, compared with 5.3% of the untreated patients., Discussion and Conclusions: Our wider assessment designated as at high fracture risk a group of patients who had not been identified by the FRAX assessment. FRAX could underestimate the risk of fracture in older people, for which the therapeutic choice should consider a broader approach, also based on individual patient's needs., (© 2022. The Author(s).)

Background: A low calcium intake is a well-known factor that influences the bone mineral density (BMD) maintenance. In the presence of inadequate calcium intake, secondary hyperparathyroidism develops, leading to an increased bone turnover and fracture risk., Aims: To assess the dietary calcium intake in relation with osteoporosis and fragility fracture in a cohort of Italian individuals evaluated for low BMD., Methods: A 7-day food-frequency questionnaire was administered to 1793 individuals, who were consecutively referred at the Centers of the Italian Society for Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) for low BMD., Results: In 30.3% and 20.9% of subjects, the calcium intake was inadequate (< 700 mg/day) and adequate (> 1200 mg/day), respectively. As compared with patients with adequate calcium intake, those with inadequate calcium intake were younger (65.5 ± 10.8 vs 63.9 ± 11.5 years, p = 0.03) and they more frequently reported adverse reactions to food (3.2% vs 7.2% p = 0.01) and previous major fragility fractures (20.8% vs 27.0%, p = 0.03). Patients with calcium intake < 700 mg/day showed a higher prevalence of diabetes mellitus, idiopathic hypercalciuria and food allergy/intolerance (8.1%, 5.1%, 7.2%, respectively) than patients with calcium intake > 700 mg/day (5.3%, 3.0%, 4.1%, respectively, p < 0.04 for all comparisons), also after adjusting for age, gender and body mass index. In 30.3% of fractured subjects, the calcium intake was < 700 mg/day., Discussion: In Italy, a low calcium intake is highly prevalent in individuals at risk for low BMD. Importantly, an inadequate calcium intake is highly prevalent even in patients with history of fragility fractures., Conclusions: Only about a fifth of patients being assessed for low BMD in an Italian SIOMMMS referral Centre have an adequate calcium intake., (© 2021. The Author(s).)

Rapid intensive observation (RIO) units have been created to guarantee high standards of care in a sustainable health-care system. Within short stay units (SSUs), which are a subgroup of RIOs, only rapidly manageable patients should be admitted. Physicians are unable to predict the length of stay (LOS) as objective criteria to make such a prediction are missing. A retrospective observational study was carried out to identify the objective criteria for admission within a cardiovascular care-oriented SSU. Over a period of 317 days, 340 patients (age 69.4 ± 14.7 years) were admitted to a pilot SSU within our internal medicine department. The most frequent diagnoses were chest pain (45.9%), syncope (12.9%), and supraventricular arrhythmias (11.2%). The median LOS was 4 days (quartile 1:3; quartile 3:7). Predictors of LOS ≤ 96 h were age < 80, hemoglobin > 115 g/L, estimated glomerular filtration rate > 45 mL/min/1.73 m 2 , Charlson Comorbidity Index < 3, Barthel Index > 40, diagnosis of chest pain, syncope, supraventricular arrhythmias, or acute heart failure. The HEART (history, ECG, age, risk factors, troponin) score was found to be excellent in risk stratification of patients admitted for chest pain. Blood tests and anamnestic variables can be used to predict the LOS and thus SSU admission. The HEART score may help in the classification of patients with chest pain admitted to an SSU., (© 2021. The Author(s).)

Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality., Methods and Results: A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09])., Conclusions: PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE., Registration Number: PROSPERO-CRD42018087640.

Background and Aims: Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DM patients on HD, compared to HD patients without DM, and their association with vascular and bone disease., Methods: 387 HD patients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan-Meier., Results: Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabetic patients. In univariate Cox regression analysis, DM patients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13-2.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients., Conclusions: HD patients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HD patients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway.

Background: The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation., Methods: A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug., Results: Of the 113 trials fulfilling the inclusion criteria, 19 did not report information on atrial fibrillation, whereas 63 reported zero events in all treatment groups. In the remaining trials (enrolling 17,966 and 15,305 patients in GLP-1 RA and comparator arms, respectively, 55.3% women, with a mean age of 57.0 ± 3.8 years), treatment with GLP-1 RA was not associated with a significant increase in the incidence of atrial fibrillation [Mantel-Haenszel OR (95% CI) 0.87 (0.71-1.05), p = 0.15]., Conclusions: In conclusion, available data suggest that GLP-1 RA is not associated with atrial fibrillation, with the only possible exception of albiglutide. Newly onset atrial fibrillation deserves to be investigated as an event of special interest in future trials with GLP-1 RA.

Purpose: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women., Methods: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement., Results: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively)., Conclusions: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Reconstruction of bone defects is a challenge for all orthopedic surgeons worldwide; to overcome this problem there are different options: the use of autografts, allografts and bone substitutes (BSs) to enhance and accelerate bone repair. Autografts have excellent biological properties but are associated with morbidity of the donor site and are restricted in volume. Allografts are available in adequate quantity but concerns still remain about the risk of infections, moreover they do not have osteogenetic properties. Bone substitutes have different indications and are very attractive for orthopedic surgeons. The present paper briefly reviews the advantages and disadvantages of autografts, allografts and BSs for bone reconstruction.

Improving rehabilitation strategies after lower limb fractures among elderly patients is an urgent public health challenge due to the increasing proportion of older population and therefore the raised number of falls and fractures. Due to their strategic positioning, physiatrists should aim not only to improve functional outcomes after acute fracture treatment but also to address the underlying osteoporotic condition in order to prevent the devastating socioeconomic consequences of osteoporotic fractures.

The incidence of ankle fractures (AFs) in the elderly is rising due to the increase in life expectancy. Rather than directly related to osteoporosis, AFs are a predictor of osteoporotic fractures in other sites. In women AFs are associated with weight and BMI. AFs are difficult to categorize; therapeutic options are non-operative treatment with plaster casts or surgical treatment with Kirschner's wires, plates and screws. The choice of treatment should be based not only on the fracture type but also on the local and general comorbidity of the patient. Considering the new evidence that postmenopausal women with AFs have disrupted microarchitecture and decreased stiffness of the bone compared with women with no fracture history, in our opinion low-trauma AFs should be considered in a similar way to the other classical osteoporotic fractures.

The present-day patients have complex diseases that are responsible for the great increase of medical interventions, overcrowding in emergency departments and access to the wards, increased waiting times and length of stay, difficult discharge, increased readmission rate and finally increased mortality. By breaking the steps of the patients pathways it allows us to simplify the problems and to face the individual aspects of the complexity related to the management of patients in the hospital. One solution that has been growing in popularity is the rapid intensive observation of the patients in acute hospital setting within Internal Medicine wards. This model has been otherwise defined with different terminology, but the most widely used name is Acute Medical Unit (AMU). We describe the model of an AMU within an Internal Medicine department as proposed and adopted in Anglo-Saxon countries, the methods of clinical approach and the practical organisation of the units in close collaboration with the ED ward. Finally we report our experience at an Internal Medicine department in Padova and the initial results obtained during the first 4 months of the project. Our approach of intensive rapid observation of intermediate risk patients admitted from the ED led to a significant reduction in the duration of hospitalization, without increasing readmission rate after discharge and fatality rate. Factors significantly associated to a short hospital stay were a preserved function and a lower number of previous admissions to the hospital. Several gray zones in the realisation and management of the project were identified and the possible solutions are still matter of discussion and debate.

Vitamin K denotes a group of lipophilic vitamins determining post-translational modification of proteins. There are 2 main forms of vitamin K: vitamin K1 (phylloquinone, found in vegetables); vitamin K2 (menaquinone, produced by bacteria in the intestine and in fermented foods). Vitamin K stores are limited in humans, but it can be recycled. Vitamin K1 is principally transported to the liver, regulating the production of coagulation factors. Vitamin K2, instead, is also transported to extra-hepatic tissues, such as bone and arteries, regulating the activity of matrix Gla-protein (MGP) and osteocalcin [bone Gla-protein (BGP)]. In patients with chronic kidney disease (CKD), cardiovascular mortality is the first cause of death. Some pathogenetic mechanisms of vascular calcification (such as hyperparathyroidism, hyperphosphatemia, hypercalcemia, role of vitamin D) have been widely investigated, but the potential role of vitamin K is still uncertain. Vitamin K could play a key role, as it transforms glutamic acid residues into γ-carboxyglutamic acid, through a carboxylation process, makings both MGP (cMGP) and BGP (cBGP) biologically active. cMGP inhibits vascular calcifications (VC), while cBGP has an important role for a proper mineralization process. Uncarboxylated MGP and BGP (ucMGP and ucBGP) concentrations are indirect markers of vitamin K2 deficiency. The purpose of this review is to analyze the current literature to understand the relationship between vitamin K2 status, fragility fractures and VC in CKD patients. This analysis could be of help in planning investigations of Vitamin K status and its possible supplementation in CKD patients to avert fragility fractures and VC.

Elderly osteoporotic patients with a femoral neck fractures should undergo hip prosthesis replacement. Nevertheless, there is still debate about the best choice of treatment (Total Hip Replacement (THR) vs HemiArthroplasty (HA)). The aim of our study is to compare functional results of new polycarbonate- urethane (PCU) cup coupled with large diameter femoral head THR and bipolar HA. To verify our hypothesis, a consecutive series of 60 patients were randomized either to receive a bipolar HA or a THR. No statistically significant difference was found between the two groups in terms of age, surgical time and blood loss. Splitting the Harris Hip Score into two categories, pain and function, a trend for a better functional score was found in THR either at 3 and 12 months when compared to HA. Our study suggests that the use of a PCU acetabular cup with large diameter femoral head is an effective solution for osteoporotic patient and may provide a better hip function to this patient population. These positive results should be confirmed at a longer follow-up in a large cohort of patients.

The occurrence of metabolic bone disease in patients with renal dysfunction is due to the key role played by the kidney in regulating calcium-phosphate metabolism. The incidence of hip fractures in end-stage renal disease is 3- to 4-fold higher than the general population, while poor data about vertebral fractures show similar prevalence. Bone health has been mainly evaluated in the general population through bone mass density (BMD) measurements, while in Chronic Kidney Disease (CKD) patients, bone turnover (low or high turnover) has been considered the most relevant parameter. Indeed, in CKD patients, the association between BMD and fractures is unclear, and even studies on established risk factors (body mass index, PTH, and vitamin D) for fractures have contrasting outcomes. Recently, an important association has been found between bone disorders and vascular calcifications in CKD patients that has changed the denomination of renal osteodystrophy in CKD mineral and bone disorder. In this article, a poorly investigated subject, vertebral fractures in CKD patients, is addressed, as it is underestimated despite its remarkable clinical relevance.

Background: Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer., Aim: Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells., Material and Methods: We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis., Results: Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression., Conclusion: Zol may affect cancer cells also by targeting the gene expression of STEAP.

Background: To investigate the impact on bone and muscle of pathological conditions involving only one of the upper limbs, it is important to know the physiological differences due to the dominance effect., Aim: To evaluate any physiological differences between dominant and non-dominant upper limbs in terms of bone mineral density (BMD), muscle mass, and muscle density at different levels., Subjects and Methods: The study considered 60 right-handed healthy adults, 30 men and 30 women. Cortical BMD, muscle area, and muscle density were investigated by pQCT-XCT-3000 Stratec at the proximal radius, trabecular and total BMD at the distal radius, and trabecular and cortical BMD at the second phalanx of the third finger. Hand grip strength was also measured., Results: No significant differences in BMD were found between the dominant and non-dominant upper limbs at any of the sites considered, in men or women. Muscle density was also similar on the two sides, whereas muscle area at the proximal radius was significantly lower on the non-dominant side in both men [4177.5+/-475.1 vs 4009.3+/-552.7 mm2; Delta%: 4.1%; 95% confidence interval (CI) 1.7%-6.5%] and women (2903.9+/-470.9 vs 2720.3+/-411.7 mm2; Delta%: 6.1%; 95%CI 4.3%-7.9%). Hand grip strength proved greater on the right side in both men (48.5+/-8.8 vs 45.2+/-8.7 kg; Delta% 7.1; p<0.001) and women (29.1+/-4.3 vs 27.0+/-5.1 kg; Delta% 7.1; p<0.001)., Conclusion: The dominance effect does not seem to influence trabecular or cortical BMD at any of the sites in the upper limb. Muscle density is not modified by dominance, while muscle area is reduced on the non-dominant side and this should be borne in mind when the effect of pathological conditions on the body composition of a single forearm is investigated.

Background: Viscosupplementation, with hyaluronan derivates injected into the intra-space of osteoarthritic joints, is now widely used for the treatment of knee osteoarthritis. This study evaluates the results in terms of pain and disability of intra-articular injections of hyaluronan derivates into the ankle joint in patients suffering from grade II primary or secondary osteoarthritis of the ankle., Methods: Twenty-one patients with a painful ankle and radiographic evidence of grade II osteoarthritis had three weekly intra-articular injections of 2 ml of hylan G-F 20 (10 mg/ml) into the ankle joint. The primary clinical outcome measurement was the ankle osteoarthritis score (AOS) at the baseline, and at 6, 12 and 18 months., Results: Significant improvement of the AOS from baseline was seen after 6 months (p=0.0001). This improvement was maintained over time with no further changes at 12- and 18-month follow-ups. Regarding pain, the AOS improved over time from the baseline to the 18-month follow up and became statistically significant at the 12- and 18-month follow-ups (p<0.05).

Primary hyperparathyroidism (PHPT) is a common endocrine disease. High levels of PTH cause demineralization of bone and increased risk of fracture. On the other hand, the effect of PHPT on bone structure is more ambiguous. The aim of this study was to evaluate the effect of PHPT on cancellous bone volume, structure, and microarchitecture. Thirteen transiliac biopsy specimens taken in untreated post-menopausal women aged 65+/-5 yr with primary hyperparathyroidism were compared with 13 biopsies taken in normal women aged 66+/-6 yr. None of the patients presented any other disorder affecting bone metabolism. In these samples we evaluated the direct and indirect histomorphometric parameters of bone microarchitecture using an image analysis system consisting of an epifluorescent microscope (Leica DMR) connected to an analogic 3 CCD camera (Sony DXC 390P) and a computer equipped with specific software for histomorphometric analyses. No significant differences between PHPT patients and controls in cancellous bone volume, trabecular thickness, and number were found. Two-dimensional parameters showed a preserved microarchitecture in PHPT patients. On the other hand, indirect parameters of microarchitecture [Marrow Star Volume (MSV) and Trabecular Bone Pattern Factor (TBPf)] showed a significant compromising of microarchitecture in these patients. PHPT patients have similar structural parameters to normal subjects. Concerning microarchitecture, indirect approach by MSV and TBPf shows a significant compromising of connectivity. These results can explain trabecular fragility observed in clinical studies on PHPT.

The treatment of large (6 cm) segmental bone defects, especially in areas associated with soft tissue damages and exposure, is challenging. Massive bone allografts are widely used in reconstructive surgery to replace missing bone parts such as critical size defects, nevertheless, early vascular invasion is a critical factor in bone allograft incorporation and in the consequent success of the surgery. Unfortunately, it has been proven that only slow and incomplete bone integration is possible by using frozen allografts in the treatment of large bone defects. An allogenic frozen bone graft was engineered with bone marrow mononuclear cells (BMMCs) to repair a large ulna defect in a male patient. When infection and sinus developed at the graft site 4 months after implantation, the partially reabsorbed graft was removed and send to the lab for examination. The histological and immunohistochemical analysis performed on a graft removed from the central zone of the defect demonstrated areas of neo-vascularisation, indicating that a remodelling process was actively occurring even in an area not usually repopulated with the conventional techniques. For these reasons, we may hypothesise that the use of BMMCs has a role in the re-building of large segmental defects.

Rupture of the tibialis posterior tendon may occur during a trauma in pronation-external rotation of the foot or, less commonly, during a direct trauma of the ankle. When an isolated fracture of the medial malleolus is present, it is more likely that a direct trauma has occurred. A 36-year-old man with a non-displaced medial malleolar fracture was evaluated. Repair of the tendon and reduction of the fracture were performed. Twenty-four months after the operation, the fracture was completely healed, the patient was asymptomatic, he had a normal ankle range of motion, and the function and strength of the tibialis posterior tendon were equal to those on the contralateral side. Early surgical repair of the tibialis posterior tendon combined with malleolar fracture reduction is recommended to avoid progression to a plano-valgus foot.

Unlabelled: Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1., Control: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 mug/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 microg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31+/-1 vs 35+/-1%, p<0.05; Tb.Th: 43+/-2 vs 50+/-3 microm, p<0.01; Ac.f: 1.8+/-0.2 vs 1.6+/-0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.

Endothelial cells (EC) play a role in many diseases including diabetes mellitus. EC share common functions, such as angiogenesis and vascular remodeling both regulated by proliferation and apoptosis, anti-thrombotic properties, regulation of vascular tone, control in the passage of nutrients and secretion of peptides and growth factors. However, EC are characterized by site-specificity so their characteristics depend on the organs and tissues where they are. The IGF system induces important growth factors that control cell growth in different microvascular EC (mEC). This family includes IGF-I and IGF-II peptides, their receptors and regulatory proteins IGF-binding proteins (IGFBP-1 to IGFBP-6). The IGFBP modulate their interaction with the IGF membrane receptors and might be regulated at a transcriptional and post-transcriptional level, thus determining the biological IGF-dependent effects on target cells. The IGF system is also a mediator of vascular diseases, and its altered balance might contribute to endothelial dysfunction with the development and evolution of diabetic microangiopathy. We reported here the reviewed literature of IGFBP production from various sources of mEC, showing that they predominantly express IGFBP-2 through IGFBP-5 mRNA. The different pattern of IGFBP secretion depends on the anatomical district and on the species of the tissues. Nevertheless, based on our and other experimental observations, we suggested that a common mechanism of IGFBP regulation in mEC could be hypothized. In retinal and glomerular EC the IGFBP4/IGFBP5 ratio controls the response of these cells to IGF-I and high levels of glucose, in terms of cellular growth.

In brain mitochondria, phosphate- and Ca(2+)-dependent cytocrome c (cyt c) release reveals pools that interact differently with the inner membrane. Detachment of the phosphate-dependent pool did not influence the pool released by Ca(2+). Cyt c pools were also detected in a system of cyt c reconstituted in cardiolipin (CL) liposomes. Gradual binding of cyt c (1 nmol) to CL/2-[12-(7-nitrobenz- 2-oxa-1,3-diazol-4-yl)amino]dodecanoyl-1-hexadecan oyl-sn-glycero-3-phosphocholine (NBDC(12)-HPC) liposomes (10 nmol) produced NBD fluorescence quenching up to 0.4 nmol of added protein. Additional bound cyt c did not produce quenching, suggesting that cyt c-CL interactions originate distinct cyt c pools. Cyt c was removed from CL/NBDC(12)-HPC liposomes by either phosphate or Ca(2+), but only Ca(2+) produced fluorescence dequenching and leakage of encapsulated 8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis-pyridinium bromide. In mitochondria, complex IV activity and mitochondrial membrane potential (Deltapsi(m)) were not affected by the release of the phosphate-dependent cyt c pool. Conversely, removal of cyt c by Ca(2+) caused inhibition of complex IV activity and impairment of Deltapsi(m). In a reconstituted system of mitochondria, nuclei and supernatant, cyt c detached from the inner membrane was released outside mitochondria and triggered events leading to DNA fragmentation. These events were prevented by enriching mitochondria with exogenous CL or by sequestering released cyt c with anti-cyt c antibody.

The human cytochrome P450s constitute an important family of monooxygenase enzymes that carry out essential roles in the metabolism of endogenous compounds and foreign chemicals. We present here results of a fusion between a human P450 enzyme and a bacterial reductase that for the first time is shown does not require the addition of lipids or detergents to achieve wild-type-like activities. The fusion enzyme, P450 2E1-BMR, contains the N-terminally modified residues 22-493 of the human P450 2E1 fused at the C-terminus to residues 473-1049 of the P450 BM3 reductase (BMR). The P450 2E1-BMR enzyme is active, self-sufficient and presents the typical marker activities of the native human P450 2E1: the hydroxylation of p-nitrophenol (KM=1.84+/-0.09 mM and kcat of 2.98+/-0.04 nmol of p-nitrocatechol formed per minute per nanomole of P450) and chlorzoxazone (KM=0.65+/-0.08 mM and kcat of 0.95+/-0.10 nmol of 6-hydroxychlorzoxazone formed per minute per nanomole of P450). A 3D model of human P450 2E1 was generated to rationalise the functional data and to allow an analysis of the surface potentials. The distribution of charges on the model of P450 2E1 compared with that of the FMN domain of BMR provides the ground for the understanding of the interaction between the fused domains. The results point the way to successfully engineer a variety of catalytically self-sufficient human P450 enzymes for drug metabolism studies in solution.

Background and Aims: Vitamin D deficiency is a well-known risk for hip fracture, and vitamin D insufficiency is so frequent in the elderly that population-wide preventive intervention would be useful. The objective of the study was to evaluate the efficacy of vitamin D bolus on hip fracture incidence in elderly women., Methods: All women aged > 65 years registered at Health District 20 of the Regione Veneto, Italy, were eligible for this quasi-experimental, prospective community intervention study. A vial containing 400,000 IU vitamin D2 (Ostelin 800, Teofarma, Italy) was offered for oral administration to all women in the winters of 2000-2001 and 2001-2002. The only exclusion criteria for treatment were age and gender, and the control group included women who did not participate in the Health District initiative. Analysis of hip fracture incidence was carried out for 4 years, from 1999 to 2002. Patients with incident hip fracture were identified as soon as they were admitted to one of the 3 hospitals of the health district and interviewed regarding their participation in the vitamin D preventive intervention program. In 120 of the women (age range 68-90 years), serum concentrations of 25-OH vitamin D were measured from October to June, both before and 1 and 4 months after vitamin D administration., Results: 23,325 and 24,747 women received the vitamin D bolus during winters 2000-2001 and 2001-2002 respectively, i.e. 45-47% of eligible women. The proportion of women who accepted the bolus declined with advancing age, from 50-55% in women aged 60-70 years to 22-26% in those aged > 90 years. The two-year intervention on the community decreased the incidence of fracture by 10% (p = 0.050) in comparison with the previous two years. The age-adjusted risk reduction (RR) of hip fracture during 2001 and 2002 in women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) respectively. The RR was considerably greater and statistically significant over both 2001 and 2002 in the cohort aged > 75 years. 25-OH vitamin D concentrations, in the subset of women in whom it was measured, rose significantly (p < 0.0001) by 9 ng/ml over 4 months after administration., Conclusion: Despite several obvious limitations due to its nature, this study sufficiently documents that yearly vitamin D bolus supplements, given as primary prevention to elderly Caucasian women, may decrease the incidence of hip fracture. For its probable safety and excellent feasibility and cost-effectiveness, this primary intervention has a great potential for generalisability.

Thiazolidinediones (TZD) [Troglitazone (TRO), Pioglitazone (PGZ), Rosiglitazone, (RGZ)] are a novel class of antidiabetic drugs for patients with Type-2 diabetes mellitus (T2DM) able to decrease blood glucose, working through a reduction of insulin resistance. The family of TZD exerts its effect specifically bound to peroxisome proliferator-activated receptor y (PPARy). This is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, together with PPARalpha and deltabeta. Although PPARgamma is essentially expressed in adipose tissue, it has also been found in endothelial cells, macrophages, vascular smooth muscle cells, glomerular mesangial cells, hepatic stellate cells and in several cancer cell lines. In these cells, the PPARgamma activation by TZD determines modulatory effects on growth factor release, production of cytokine, cell proliferation and migration, extracellular matrix remodeling and control on cell cycle progression and differentiation. In addition, TZD have been shown to have a potent antioxidant effect. This review, taking a quick look beyond the antidiabetic activity of PPARgamma, shows the dramatic ranging of medical implications that the use of TZD could have modulating the PPARgamma activity in several diseases with a strong social impact, such as insulin resistance syndrome, chronic inflammation, atherosclerosis and cancer.

The authors report their experience in the implantation of 108 posterior-stabilized cemented total knee replacements, where in 43 cases the patella was not resurfaced (group 1) and in 65 in was resurfaced (group 2). The ability to perform daily activities, the subjective function of the patello-femoral joint and the index of patient satisfaction were evaluated by means of a telephone interview; furthermore, a clinical-radiographic evaluation was carried out in 50 cases. The results of the present study indicate the need of resurfacing the patella using a posterior-stabilized prosthetic design, based on the fact that more joint excursion, a low incidence of complications on the patello-femoral joint, and improved ability to perform daily activities were demonstrated.

The term myositis ossificans (MO) means a pathology characterized by the formation of heterotopic bone tissue within the connective tissue of the muscle. Two clearly differentiated forms of the disease are described: one is generalized and one is localized or circumscribed (CMO). It is the purpose of this study to describe a case of circumscribed myositis ossificans located in the iliopsoas muscle, clinically by CT scan and followed-up after 1 and 14 years.

Factors influencing the release and anchorage of cytochrome c to the inner membrane of brain mitochondria have been investigated. Metabolic activity of mitochondria caused a decrease in the membrane potential delta psi(m), accompanied by detachment of the protein from the inner membrane. In a model system of cytochrome c reconstituted in cardiolipin (CL) liposomes, phosphate was used to breach the hydrophilic lipid-protein interactions. About 44% cytochrome c was removable when heart CL (80% 18:2n-6) was employed, whereas the remaining protein accounted for the tightly bound conformation characterized by hydrophobic lipid-protein interactions. Cytochrome c release from brain CL liposomes was higher compared to heart CL, consistent with lower polyunsaturated fatty acid content. The release was even higher with CL extracted from metabolically stressed mitochondria, exhibiting more saturated fatty acid profile compared to control (30% vs. 17%). Therefore, weakening of the hydrophobic interactions due to saturation of CL may account for the observed cytochrome c release from mitochondria following metabolic stress. Moreover, mitochondria enriched with polyunsaturated CL exhibited higher delta psi(m), compared to less unsaturated species, suggesting that CL fatty acid composition influences delta psi(m). Mitochondria incorporated exogenous cytochrome c without protease-sensitive factors or delta psi(m). The internalized protein anchored to the inner membrane without producing swelling, as monitored by forward and side light scattering, but produced delta psi(m) consumption, suggesting recovery of respiratory activity. The delta psi(m) decrease is ascribed to a selected mitochondrial population containing the incorporated cytochrome c.

First-metatarsal osteotomy is performed for an abnormal intermetatarsal angle and severe hallux valgus deformity. The metatarsal head is slid along the osteotomy and fixed with a Kirschner wire to achieve angular and linear realignment with respect to the other metatarsals. When reduction of joint subluxation is also sought, a bone wedge is removed. A mathematical model and a corresponding computer-based tool were developed for pre-operative planning of the optimum surgical solution. Standard intermetatarsal angle correction, head-to-sesamoids re-alignment, joint subluxation reduction and metatarsal length adjustment were all pursued. A standard pre-surgical dorso-plantar radiograph of the patient, with an additional metal ball for calculation of X-ray magnification, was necessary to analyse the original and final geometrical configurations. For the first time, expected bone loss and wire diameter were also considered. The angles of bone cuts and the amount of sliding along these cuts were calculated by the model according to the surgical goal. All the resulting geometrical parameters, both in the pre- and planned post- operative configuration, were provided in graphical and tabular form. In a change from former qualitative analysis of radiograms, the surgeon can now enter the operating theatre with a detailed plan of the goal to be achieved.

Structure and microarchitecture are determinant aspects of bone strength and essential elements for the assessment of bone mechanical properties. The main structural determinants of bone mechanical strength include width and porosity in the cortical bone; shape, width, connectivity, and anisotropy in the trabecular bone. There are several methods to assess bone architecture, particularly at the trabecular level. Two different approaches can be identified. The first is based on the use of optical microscopy and on the principles of quantitative histology, which evaluate microarchitecture two-dimensionally. The second applies the most modern diagnostic techniques, employing computed tomography and magnetic resonance to obtain and analyze three-dimensional images. From a clinical point of view, microarchitecture is an interesting aspect to study and define specific patterns, such as glucocorticoid-induced osteoporosis, or to evaluate bone alterations in transplanted patients. Microarchitecture seems to be a determinant of bone fragility independent of bone density. Moreover, bone microarchitecture seems to be important to understand the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) showed important findings on the effects of different treatments on microarchitecture. Bisphosphonates and parathyroid hormone seemed to preserve or even improve microarchitecture. These observations can provide an additional interpretation for the anti-fracture effect of drugs from a structural viewpoint. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods in use today.

Although change in bone mineral density was the outcome most commonly measured in early clinical trials of osteoporosis therapies, it is now understood that the most clinically important outcome is reduction in the risk of fractures. Of currently available osteoporosis therapies, the bisphosphonates have been most thoroughly investigated in studies with fracture risk as the primary outcome. The most widely studied bisphosphonates include etidronate, alendronate and risedronate. Alendronate and risedronate have the most compelling evidence for vertebral and non-vertebral fracture reduction. This review provides a comprehensive overview of the anti-fracture efficacy of bisphosphonates at the spine, hip, and non-vertebral sites.

Bone response to hydroxyapatite coating on stainless steel has not been so extensively tested in animals as it happened for other metallic substrate, like Ti6Al4V. For this reason, authors performed an in vivo histomorphological electron microscopic study of hydroxyapatite coating on duplex stainless steel cylinders, to gather further evidences on the characters of bone apposition at the interface. Sixteen HA-coated cylinders were implanted in the distal femur of New Zealand White rabbits. Comparison with uncoated controls was made. Retrieval steps were at: 4, 8, 26 and 34 weeks. Specimens were analyzed in a Jeol JSM 6301F scanning electron microscope. The response to HA-coated samples has a morphological character of tight apposition between bone and coating. Osteocytic lacunae may be found few microns close to the coating and newly formed bone is extremely interlocked with it so that even an higher magnification electron-microscopy cannot resolve any discontinuity in between. Pictures of physiological bone-turnover are distinguishable at the bone-coating interface; areas of well preserved coating may be present together with areas where local exfoliation or fragmentation has already completely exposed the metallic substrate. On the opposite in uncoated samples, despite a morphological picture of properly formed bone, the largest area of the metal has no direct apposition with it.

Idiopathic pulmonary fibrosis (IPF) is characterized by the rearrangement of extracellular matrix and progressive increase in the amount of fibrotic tissue in the lung. IGF-I is a potent profibrogenic molecule and its bioavailability is dependent on at least 6 binding proteins called IGFBPs. Among these, IGFBP-3 is the most represented in serum and in different connective tissues. The purpose of this study was to identify and characterize IGFBP-3 in bronchoalveolar lavage (BAL) fluids. We studied 11 patients with IPF and 6 normal subjects by performing baseline pulmonary function test and BAL. IGF-I and IGFBP-3 were measured by RIA in BAL and serum. No significant differences were observed between serum IGF-I and IGFBP-3 from IPF patients and normal subjects. Instead, the direct measurement in BAL revealed a significant increase of IGF-I and IGFBP-3 in IPF patients compared to normal subjects. BAL IGF-I and IGFBP-3 concentrations were significantly related to inspiratory vital capacity (IVC) and carbon dioxide partial pressure (PaCO2): the higher the value of IVC and the lower the value of PaCO2, the higher the level of IGF-I and IGFBP-3. In conclusion, IGFBP3 and IGF-I could be important local mediators of IPF. Their direct measurement in BAL in IPF patients could be used as a clinical marker of the disease, since high levels of IGFBP-3 and IGF-I in BAL are associated to the initial phase of the disease.

The use of magnetic fields in medicine has obtained encouraging results and it has stimulated the research conducted so that the use of this method of treatment may be better and more widespread. A double blind study was conducted to evaluate the effectiveness of the generation of magnetic fields on edema and on pain in patients submitted to surgery for bilateral hallux valgus.

The poor results of total ankle replacement have been attributed to the inability of designers to restore adequately the critical mutual function of the ligaments and the articular surfaces. The purpose of this study was to design sagittal shapes of the articular surfaces for a new ankle prosthesis to be compatible with the geometry of the retained ligamentous structures. Several ligament-compatible pairs of articular surfaces were tested using a computerised version of a four-bar linkage model. The kinematics of the ankle when replaced by non-conforming two-component and by fully conforming three-component designs with either flat, concave or convex tibial surfaces were assessed by the model. A ligament-compatible convex-tibia fully-congruent three-component prosthesis showed the best features. The three-component prosthesis allows complete congruence over the entire range of flexion. A convex shape for the tibial arc was preferred because of the better degree of entrapment of the meniscal bearing. A 5 cm convex-tibia arc radius gave 2 mm entrapment together with 9.8 mm of tibial bone cut. Ligament elongation imposed by full congruence of the articular surfaces was less than 0.03% of the original length. The original patterns of joint kinematics and ligament tensioning are closely restored in the joint replaced by the proposed prosthesis.

Osteoporosis is characterized by impairment of bone mass and deterioration of bone microscopic structure, resulting in increased bone fragility and susceptibility to fracture. Recent reports have indicated that reduced plasma levels of IGF-I are associated with osteoporosis in both males and females. Moreover, there is accumulating clinical evidence that treatment with GH or IGF-I has beneficial effects on bone mass and bone remodeling in men with idiopathic osteoporosis, in the elderly and in hypopituitary patients. As correlative studies on IGF-I, IGF-BP3 and bone mass in the elderly are lacking, we studied the relationships between serum IGF-I, IGF-BP3, bone mineral density (BMD), body mass index (BMI), calciotropic hormones and age in 102 premenopausal and postmenopausal women. Our study indicates that the reduction of the anabolic processes mediated by IGF-I may account for the slow and progressive loss of bone mass that take place after the age of 40-50 years. In addition, nutritional caloric or proteic deficit may add to the effects of GH, age and other factors in decreasing IGF-I synthesis and therefore further contribute to the development of primary osteoporosis.

The pathogenesis of idiopathic hypercalciuria (IH) has not been elucidated yet, but a correlation between IH and altered bone metabolism has been proposed. Since nitric oxide (NO) regulates osteoclasts' bone resorption, a possible role for NO can be suggested. In this study we evaluated iNOS gene expression by reverse transcription of mRNA from monocytes, followed by polymerase chain reaction in patients with IH subdivided into fasting (FH) and absorptive (AH) hypercalciuria. Since superoxide (O2-), which metabolizes NO, is overproduced by osteoclasts during bone resorption, peroxynitrite plasma level was evaluated as index of O2-. Vertebral BMD in IH as a whole group was lower vs controls (C) (Z score=-1.78+/-0.2 vs 0.51+/-0.25, p<0.001), but only FH patients showed a reduced bone density (2.13+/-0.18 vs 0.51+/-0.25, p<0.0001). PTH and calcitriol were not different. FH showed an increase in b-ALP vs AH and C (41.1+/-2.6 vs 30.1+/-3.9 vs 26.6+/-3.6 U/l p<0.02), and higher uHP, either on NCD (17.7+/-1.6 vs 11.4+/-1.3 mg/g uCr, p<0.04) or after LCD (26.7+/-2.5 vs 16.7+/-1.9, p<0.01). Cells from FH patients, but not from both AH patients and C, expressed iNOS. Peroxynitrite plasma level was elevated in FH (0.30+/-0.07) pmol/l while not detectable in AH and C. This study confirms an altered bone metabolism only in FH which shows an abnormal NO system. The increased iNOS gene expression in FH, in fact, points toward an altered NO system's activity downstream the generation of NO. A possible interaction of NO with O2-, which breaks down NO, and the role of this interaction in the pathophysiology of IH is discussed.

An evaluation of total hip replacement patients requires objective criteria that allow for the measurement of any changes in the biomechanics of the prosthesis and the effects of these changes on clinical findings. An evaluation of loading and joint movement during walking in these patients has been dealt with by many authors. In this study 15 patients who had undergone total hip replacement for coxarthrosis primary or secondary to congenital dysplasia were examined by kinematic and kinetic gait analysis, clinical evaluation, and radiographic evaluation of the position of the neocenter of prosthetic joint rotation. The patients with prostheses in congenital dysplasia presented with a pattern of walking that was significantly modified. In agreement with what is reported in the literature proximal positioning had less influence on gait parameters as compared to lateral dislocation. Furthermore, changes in positioning observed did not seem to have negative effects on joint loading, measured indirectly by the calculation of joint moments.

The results of the surgical treatment of valgus high tibial osteotomy were studied based on clinical and radiographic assessment and gait-analysis in 21 patients affected with arthrotic varus knee. Although tibial osteotomy has been in use for some time now, the reasons for its frequent failure are still not fully understood. A statistical analysis of the clinical and biomechanical parameters taken into account in this study have shown that hypercorrection in valgus is required to unload the medial compartment and to prevent the recurrence of deformity in varus and pain. Walking with the limb extrarotated may also be a compensatory mechanism, in order to reduce the adductor moment in the knee and overloading of the medial compartment.

The joint biomechanics of the hip was studied analyzing the kinematic, kinetic, electromyographic and in vivo pressure parameters during walking, going up stairs, and getting up from a chair. The most significant clinical and biomechanical data emerged when the temporal correlation between intra-articular pressure variations and electric activity of the bi-articular muscles was studied. The presence of co-contraction of the bi-articular muscles during the support and oscillation phases was evident. The maximum joint pressure values were measured while getting up from a chair when the hip was flexed more than 100 degrees. The posterior region of the acetabulum was that most submitted to loading. This data is useful in gaining an understanding of joint physiology, in correctly setting up physio-kinesitherapeutic protocols, and in setting up pre-clinical prosthetic mechanical tests.

Very Low Calorie Diet (VLCD) is known to induce not only weight loss, but also an improvement of metabolic control, in obese type II diabetics. In order to evaluate the therapeutical efficacy of cycles of VLCD shorter than those previously described, 29 obese type II diabetics and 31 obese nondiabetic subjects were entered as inpatients and prescribed a 450 kcal/day diet for 15 days. Metabolic results obtained were similar to those achieved with longer cycles of VLCD, showing that 15 days are sufficient to induce a BMI decrease in diabetic (BMI from 35.3 +/- 4.8 to 33.3 +/- 4.6 after VLCD) and nondiabetic patients (BMI from 40.5 +/- 7.4 to 38.1 +/- 7.2 after VLCD), a desired fall of blood glucose levels and the decrease of daily insulin needs in insulin-treated patients. Glucagon tests were performed before and after VLCD in order to study possible modifications of insulin secretion. Although we did not observe any significant increase of C-peptide basal or peak levels (nM/ml) either in diabetic (basal levels before VLDC: 1.2 +/- 0.4 and peak levels 2.4 +/- 0.7; basal after VLCD 1.23 +/- 0.6 and peak 2.6 +/- 0.7) and nondiabetic patients (basal levels before VLDC 1.0 +/- 0.3 and peak levels 2.5 +/- 0.4; basal after VLCD 0.9 +/- 0.3 and peak 2.4 +/- 0.6). The rise of the C-peptide/glycemia ratio is an index of an improvement of insulin biological activity, which could be partly responsible for the therapeutical effects of VLCD.(ABSTRACT TRUNCATED AT 250 WORDS)