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).

Summary Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. Introduction Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-oflife (QoL). Strontium ranelate (2 g/day) was shown to Osteoporos Int (2009) 20:1663-1673 DOI 10.1007 prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. Methods A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. Results Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction=0.67, p< 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p<0.001). QoL, assessed by the QUALIOST®, was significantly better (p=0.025), and patients without back pain were greater (p=0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. Conclusion In this 4-and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

SUMMARY Primary hyperparathyroidism (PHPT) is a common cause of bone loss that is modeled by continuous PTH (cPTH) infusion. Here we show that the inflammatory cytokine IL-17A is upregulated by PHPT in humans and cPTH in mice. In humans IL-17A is normalized by parathyroidectomy. In mice treatment with anti-IL-17A antibody and silencing of IL-17A receptor IL-17RA prevent cPTH induced osteocytic and osteoblastic RANKL production and bone loss. Mechanistically, cPTH stimulates conventional T cell production of TNFα (TNF), which increases the differentiation of IL-17A producing Th17 cells via TNF receptor 1 (TNFR1) signaling in CD4+ cells. Moreover, cPTH enhances the sensitivity of naïve CD4+ cells to TNF via GαS/cAMP/Ca++ signaling. Accordingly, conditional deletion of GαS in CD4+ cells and treatment with the calcium channel blocker diltiazem prevents Th17 cell expansion and blocks cPTH induced bone loss. Neutralization of IL-17A and calcium channel blockers may thus represent novel therapeutic strategies for hyperparathyroidism.

Aim:To characterize elderly medical patients and identify factors associated with prolonged length of stay. Methods:The present prospective observational study evaluated consecutive patients aged ≥65 years admitted in acute geriatric and medical wards. A comprehensive assessment including demographic, clinical, functional and cognitive variables was carried out. Delayed discharge was defined when patients were discharged later than the date they were deemed medically ready for discharge by physicians. The analysis was initially carried out on the total sample and subsequently according to whether hospital admission had been from home, or from intermediate or long-term facilities.Results: Among 1568 patients (age 81.3 ± 7.3 years, 712 men), we observed a high prevalence of functional dependence, cognitive impairment, chronic immobilization and frailty (50%, 25%, 20% and 40%, respectively). Overall, delayed discharge occurred in 442 cases -resulting in 2637 days of prolonged hospital stay -and was independently associated with impairment in activities of daily living, frailty, high comorbidity and inappropriate admission. Among patients admitted from home (roughly 90% of the sample), delayed discharge occurred in 392 patients, and was independently associated with cognitive impairment, functional dependence, low severity of comorbidity and inappropriate admission (OR 3.39). Among patients admitted from intermediate or long-term facilities, lower cognitive impairment and greater severity of functional dependence were independently associated with prolonged stay. Conclusions:Poor health conditions and high prevalence of geriatric syndromes are extremely common among older medical inpatients. Delayed discharge was mainly observed in patients admitted from home, and associated with cognitive impairment (OR 1.12) and functional dependence (OR 1.49). Geriatr Gerontol Int 2015; 16: 314-321.

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