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Much work has been directed at establishing the impact of osteoporosis and related fragility fractures in rheumatic diseases. Several cross-sectional studies reported that disability and reduced motility that are due to functional impairment are among the most important determinants of bone loss in different rheumatic diseases. At the same time, longitudinal studies have confirmed the detrimental effect of uncontrolled disease activity on bone density. In this perspective, the suppression of inflammation probably remains the main concern when considering treatment options. Besides these variables, pharmacologic agents that are used commonly in the treatment of these conditions probably have an adjunctive effect on bone loss in rheumatic patients. Large epidemiologic studies have demonstrated clearly that patients who have RA, SLE, or AS are at an increased risk for fragility fractures. Further studies are required to investigate the effective impact of osteoporosis and fragility fractures in other rheumatic diseases, and to define the relationship between OA and osteoporosis. A better appreciation of the impact and mechanisms of osteoporosis in rheumatic diseases by rheumatologists represents a clinical challenge; however, a greater understanding of this frequent complication will improve the quality of health care and the lives of patients who have rheumatic diseases.

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

A well-known in vivo mouse model for postmenopausal osteoporosis is the ovariectomized (OVX)mousemodel, commonly used to study the effect of treatments. Although many studies have investigated the treatment of osteoporosis with parathyroid hormone (PTH), some information is lacking about several histomorphometric parameters, non-collagen protein expression, Ca/P ratio, and mechanical properties in this particular model. The aim of this study was to investigate the effect of PTH through histological, biochemical, histomorphometric and mechanical analyses in OVX mice. To simulate postmenopausal osteoporosis, forty C57BL/6 female mice (15 w old) were ovariectomized. A subcutaneous injection of PTH (hPTH 1–34, Bachem AG, Switzerland) or just vehicle was administered daily. To explore structural changes and bone loss with time in vivo, microtomographic scans of the sixth caudal vertebra (C6) were performed from the day of surgery till the end of the experiment. Histomorphometric, histological, western blotting (wb), immunohistochemical and energy dispersive X-ray (EDX) analyses were performed on one femur to investigate trabecular and cortical thickness, the mineral apposition rate (MAR), osteoid and osteoclast surface, osteocytes apoptosis, osteopontin (OP) and osteocalcin (OC) expression and Ca/P ratio. On the contralateral bone one 4-point bending tests were performed to determine the mechanical stiffness in four directions and the failure strength of the diaphysis. Furthermore, a fracture test of the femoral neck was performed. Comparing the PTHgroup to thevehicle: themicroCTanalysis demonstratedaweak increase over time only in trabecular thickness in the C6, up to ~10% at the time of sacrifice; histology and histomorphometry revealed significant increase in trabecular and cortical thickness (~45% and ~15%, respectively), the MAR increased (~20%), the osteoid surface strongly increased (~60%) together with the osteoclast surface and the number of apoptotic osteocytes greatly decreased (~60%); wb showed no significant difference in OP content, while immunohistochemistry revealed a strong increase of OC (~80%); EDX showedno significant variation in Ca/P content. All mechanical properties significantly increased (10–20%). These findings demonstrate that PTH treatment positively affects biochemical, histomorphometric and mechanical properties of this mouse model. This work was funded by the European Community (project no.: FP7-223865, acronym VPHOP). This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.489 PP359-M Sustained increase in bone mineral density with alendronate in combination with indapamide in postmenopausal women with idiopathic hypercalciuria associated to osteoporosis: A 1-year randomized trial followed by a 2-year extension A. Giusti ⁎, A. Barone , G. Girasole , M. Razzano , M. Plzzonia , E. Palummeri , M. Pedrazzoni , G. Bianchi , G. Pioli d a Gerontology, Galliera Hospital, Genoa, Italy b Rheumatology, La Colletta Hospital, Arenzano, Italy c Internal Medicine, Parma University, Parma, Italy d Geriatrics, ASMN Hospital, Reggio nell'Emilia, Italy Abstract: Introduction: A recent 1-year randomized trial (Giusti A et al., NDT 2009) demonstrated the beneficial effect of alendronate (ALN)+indapamide (IND) in the treatment of women with idiopathic hypercalciuria (IHC) and associated bone loss. Methods: To evaluate the effect of ALN alone or in combination with IND on bone mineral density (BMD) and 24-hour urinary calciumexcretion (CaU), 77 postmenopausalwomenwith CaU>4mg/ kg/die and low BMD were randomized to receive for 1-year: indapamide 2.5 mg/daily alone (24 patients, IND group), alendronate 70mg/weekly alone (27 patients, ALN group) or the combination therapy (26 patients, ALN+IND group). 50 women (IND: 14, ALN: 17, ALN+IND: 19) who completed the first yearandconsented toparticipatewereenrolled ina2-yearextension.All subjects received daily calcium supplements to maintain a daily input of 1000mg, and were instructed to increase water intake up to 2000ml daily. The percentage change of BMD at lumbar spine (LS), femoral neck (FN) and total hip (TH) after 3-year, and the variation of 24-hour CaU from baseline at 2-year were the primary outcomes. Serum calcium, PTH and bone alkaline phosphatase were also measured. Results: After 2-year CaU values significantly decreased from baseline in all groups (IND, 210±89vs382±54,p

To study the short-term effects on mineral and bone metabolism of a recently introduced amino-diphosphonate (4-amino-1-hydroxybutylidene-1,1-diphosphonate or ABDP), 10 patients suffering from active Paget's disease were examined. Each subject received intravenously 5 mg/day of ABDP for 4 days and the effects of treatment were monitored for 12 days. ABDP administration was followed by an early and significant decrease of the urinary hydroxyproline and calcium excretion, of the theoretical renal threshold for phosphate of the serum calcium. Serum phosphate also decreased, while its urinary excretion increased. Intact parathyroid hormone levels at the end of treatment were four times higher than basal levels. Total and bone alkaline phosphatase tended to decrease only slightly at the end of the observation, whereas serum osteocalcin, tended to increase. These findings indicate that the earlier effect of ABDP is a profound inhibition of bone resorption, which brings about a compensatory parathyroid hormone response. The decrease of urinary hydroxyproline follows an exponential curve, with a calculated half-life of 2.2 days, suggesting an approximate equivalency of 5 mg/day ABDP to slightly more than 30 mg/day 3-amino-1-hydroxypropylidene-1,1-diphosphonate. Bone formation seems scarcely influenced in the short-term, but osteoblastic indices show a contrasting behaviour, which may reflect a different biological origin and/or significance.