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 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<.001) (ALN,256±70vs378±99,p<.001) (ALN+IND,218±90vs384± 48,p<.001). Themean%decreaseofCaU inALN+IND(−43%)and INDgroups(−46%)wassimilar (p=.699) and significantly greater compared to ALN (−30%, p<.05). BMD decreased significantly (p< .03) from baseline after 2 or 3 years of treatment with IND (at 3-year; LS:−3.2±4.4%; FN: −3.0±2.3%; TH: −2.7±2.3%), while it showed a significant increase from baseline in the other 2 groups (ALN, 3-year; LS: +5.2±5.4%; FN: +6.0±11.6%; TH: +2.3±3.9%) (ALN+ IND, 3-year; LS: +10.6±8.2%; FN: +8.5±11.1%; TH: +5.1±6.3%). Patients in the combination group showed a significantly higher increase of BMD at LS compared to ALNafter 2 (p=.03) and 3 years (p=.03). Conclusions: These results demonstrate a sustained beneficial effect on BMD andCaU, of BPs in IHC associatedwithosteoporosis. The combination therapy demonstratedover 3 years of treatment a reduction of CaU and an increase in LS BMD superior to that observedwith alendronate alone. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: A. Giusti Consulting fees from Novartis, Speaker Fees from Novartis, Roche, Abiogen, Chiesi, A. Barone: None declared, G. Girasole: None declared, M. Razzano: None declared, M. PIzzonia: None declared, E. Palummeri: None declared, M. Pedrazzoni: None declared, G. Bianchi: None declared, G. Pioli: None declared. doi:10.1016/j.bone.2011.03.490 PP360-T Teriparatide [RHPTH (1–34)] can improve the osteosynthesis results in unstable hip fractures. A series of 7 clinical cases A. Oteo-Alvaro ⁎, P. Sanz , L. Castrejon , R. Larrainzar , P. Maseres , T. Pampliega , P. Santarcangelo f a Orthopedics, Hospital General Universitario Gregorio Maranon, Madrid, Spain b Orthopedics, Hospital Universitario Infanta Cristina, Badajoz, Spain c Orthopedics, Hospital Infanta Leonor, Madrid, Spain d Orthopedics, Hospital Marina Baixa, Villajoyosa, Alicante, Spain e Orthopedics, Hospital Gutierrez Ortega, Valdepenas, Ciudad Real, Spain f Orthopedics, Hospital Nuestra Senora del Prado, Talavera de la Reina, Toledo, Spain Abstract: Purpose of the study: To describe the osteosynthesis results in 7 unstable hip fractures treated with teriparatide. Methods: A retrospective case analysis based on monthly radiological studies and pain VAS scores (numerical). Results: In each of the 6 fractures (4 subtrochanteric and 3 intertrochanteric fractures), all of a multiple-fragment and/or unstable Purpose of the study: To describe the osteosynthesis results in 7 unstable hip fractures treated with teriparatide. Methods: A retrospective case analysis based on monthly radiological studies and pain VAS scores (numerical). Results: In each of the 6 fractures (4 subtrochanteric and 3 intertrochanteric fractures), all of a multiple-fragment and/or unstable nature due to poorbonequality, a lack of bonestock, lesser trochanter rupture and/or the absence of posteromedial bony contact, an accelerating effect was observed in fracture healing after teriparatide treatment,with fillingof thebonedefect and early callusdevelopment that stabilized the fracture, accompanied by a considerable reduction of pain VAS score correlated to clinical