The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT).

This study shows for the first time that long-term immobilized patients present hypersclerostinemia associated with reduced bone formation, and suggests that sclerostin could be a link between mechanical unloading and disuse osteoporosis in humans.

These results show for the first time that T2DM patients have serum concentrations of β-catenin lower than controls. The negative association of β-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM.

Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients ≥80 years of age.Introduction: About 25-30% of the population burden of all fragility fractures in the community arise from women Ն80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly. Materials and Methods: An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. Results: Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p ‫ס‬ 0.002), 41% (p ‫ס‬ 0.027), and 37% (p ‫ס‬ 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p ‫ס‬ 0.013), 31% (p ‫ס‬ 0.011), and 22% (p ‫ס‬ 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. Conclusions: Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis Ն80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.

Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.

KEYWORDSDoppler ultrasound; Ischemic nephropathy; Renal artery stenosis; Renovascular disease.Abstract Renovascular disease is a complex disorder, most commonly caused by fibromuscular dysplasia and atherosclerotic diseases. It can be found in one of three forms: asymptomatic renal artery stenosis (RAS), renovascular hypertension, and ischemic nephropathy. Particularly, the atherosclerotic form is a progressive disease that may lead to gradual and silent loss of renal function. Thus, early diagnosis of RAS is an important clinical objective since interventional therapy may improve or cure hypertension and preserve renal function. Screening for RAS is indicated in suspected renovascular hypertension or ischemic nephropathy, in order to identify patients in whom an endoluminal or surgical revascularization is advisable. Screening tests for RAS have improved considerably over the last decade. While captopril renography was widely used in the past, Doppler ultrasound (US) of the renal arteries (RAs), angio-CT, or magnetic resonance angiography (MRA) have replaced other modalities and they are now considered the screening tests of choice. An arteriogram is rarely needed for diagnostic purposes only. Color-Doppler US (CDUS) is a noninvasive, repeatable, relatively inexpensive diagnostic procedure which can accurately screen for renovascular diseases if performed by an expert. Moreover, the evaluation of the resistive index (RI) at Doppler US may be very useful in RAS affected patients for predicting the response to revascularization. However, when a discrepancy exists between clinical data and the results of Doppler US, additional tests are mandatory.Sommario La malattia nefrovascolare è un disordine complesso e le cause più comuni sono la malattia aterosclerotica e la displasia fibromuscolare. Classicamente si presenta in una delle seguenti tre forme: stenosi dell'arteria renale (SAR) asintomatica, associata a ipertensione nefrovascolare e/o con nefropatia ischemica. La SAR su base aterosclerotica è una malattia progressiva che può determinare in maniera asintomatica o paucisintomatica perdita graduale della funzione renale. Per tale motivo, la diagnosi precoce di SAR è un obiettivo clinico importante poiché la terapia interventistica può migliorare o curare l'ipertensione e preservare la funzione renale. Lo screening per SAR è indicato nel sospetto di ipertensione nefrovascolare o di nefropatia ischemica al fine di identificare i pazienti in cui è indicato un intervento di rivascolarizzazione. I test di screening per SAR sono migliorati considerevolmente durante l'ultimo decennio. Mentre la scintigrafia con test al captopril è stata utilizzata quasi esclusivamente nel passato, l'ecocolorDoppler delle arterie renali, l'angioTC e/o l'angioRM hanno sostituito le altre modalità di screening in molti centri. Per tale motivo l'arteriografia riveste sempre più un ruolo interventistico e solo di rado diagnostico. L'ecocolorDoppler è una procedura diagnostica non invasiva, ripetibile e relativamente economica che negli ultim...

Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/-0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4 micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs 0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG-RANKL system.

The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/β-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of β-catenin activity in the vascular cells.