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Osteoporosis is a common non-communicable disease with enormous societal costs. Antiosteoporosis medications have been proven efficacious in reducing the refracture rate and mortality; moreover, we have now convincing evidence about the cost-effectiveness of antiosteoporotic medications. However, albeit preventable and treatable, osteoporosis has been somehow neglected by health authorities. Drugs approval has been unnecessarily lengthy, especially when compared with other non-communicable diseases. Herein, we discuss the issue of procrastinating drug approval in osteoporosis and future implications.

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by multiple comorbid conditions including cardiovascular comorbidities, diabetes, obesity and osteoporosis. Little is known about body composition in patients with PsA and no data are available regarding body composition changes under DMARDs.Objectives:We investigated the effects of ustekinumab (UST), a humanized anti-interleukin 12/23 antibody, on body composition, bone mineral density (BMD) and bone remodeling markers in patients treated for PsA.Methods:Thirty patients with active PsA treated with UST were included in a 6 months open follow-up study. Body mass index, DAS28-CRP, bone remodeling markers, serum levels of leptin, BMD and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 months of treatment. At baseline, PsA patients were compared with 60 non-PsA controls matched for age, sex and body mass index.Results:Compared with controls, we observed lower total and appendicular lean mass (53.1 ±13.1 vs. 56.7 ±11.9 kg, p=0.013 and 21.6 ±6.3 vs. 23.4 ±5.0 kg, p=0.010 respectively) and greater fat mass in PsA (32.5 ±10.8 vs. 25.2 ±8.9 kg, p2, p=0.061). In contrast, a decrease in total lean mass was observed (-1.57 ±3.10 kg, p=0.046) without a significant change in appendicular lean mass and skeletal muscle mass index. No changes for bone remodeling markers, leptin and BMD were observed at 6 months.Conclusion:Patients with active PsA required biologic therapy had increased fat mass and decreased lean mass. Moreover, ustekinumab might worsen the decrease in lean mass with no significant change in fat mass.Disclosure of Interests:Julien Paccou Grant/research support from: Janssen, Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi, UCB, Wallis Bavière: None declared, Roland Chapurlat: None declared, Elisabeth Sornay-Rendu: None declared, Pawel Szulc: None declared, Bernard Cortet Consultant of: Aptissen, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi

ObjectivesPatients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women.MethodsThe Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60 393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, ‘Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?’, and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status.ResultsOf 51 386 women followed for a median of 2.9 years (interquartile range 2.1–3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; pConclusionsPostmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.

Objectives A new high-resolution peripheral quantitative CT (HR-pQCT) system allows for in vivo assessment of bone microarchitecture and volumetric bone mineral density (vBMD) with an 82 µm isotropic resolution. With this device, the microarchitecture impairment was evaluated in patients with rheumatoid arthritis (RA) in comparison with healthy controls and measured the erosion volume at metacarpal heads (MCPs). Methods In this cross-sectional study, the reproducibility was first assessed by 3 HR-pQCT exams with repositioning in 14 patients with late RA and 14 healthy subjects. Then, HR-pQCT parameters were measured in a group of 93 patients with RA and 31 healthy controls. Two RA subgroups were distinguished: early RA (disease duration ≤2 years) (n=36) and late RA (n=57) and compared them to healthy controls. Results The precision of the HR-pQCT volumetric measurements as assessed with coefficient of variation ranged from 0.7% to 1.8% in patients with late RA and from 0.6% to 1.4% in healthy subjects at MCPs. Total and trabecular vBMD and trabecular thickness were significantly decreased in patients with RA compared to healthy subjects and were significantly correlated to disease activity. The erosion volume was highly correlated to a semiquantitative assessment using the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system applied to the HR-pQCT slices. Conclusions This study demonstrated the good reproducibility of the HR-pQCT volumetric measurements at MCPs and confirmed the involvement of trabecular compartment in periarticular osteopoenia. Thus, HR-pQCT appears interesting to simultaneously assess differences in bone volumetric density, microarchitecture and erosions.

Objective To assess the association between atrial fibrillation and flutter and use of bisphosphonates for osteoporosis among women. Design Population based case-control study, using medical databases from Denmark. Setting Northern Denmark. Participants 13 586 patients with atrial fibrillation and flutter and 68 054 population controls, all with complete hospital and prescription history. Main outcome measure Adjusted relative risk of atrial fibrillation and flutter. Results 435 cases (3.2%) and 1958 population controls (2.9%) were current users of bisphosphonates for osteoporosis. Etidronate and alendronate were used with almost the same frequency among cases and controls. The adjusted relative risk of current use of bisphosphonates compared with non-use was 0.95 (95% confidence interval 0.84 to 1.07). New users had a relative risk of 0.75 (95% confidence interval 0.49 to 1.16), broadly similar to the estimate for continuing users (relative risk 0.96, 95% confidence interval 0.85 to 1.09). The relative risk estimates were independent of number of prescriptions and the position of the atrial fibrillation and flutter diagnosis in the discharge record, and were similar for inpatients and outpatients. Conclusion No evidence was found that use of bisphosphonates increases the risk of atrial fibrillation and flutter.

Background Osteoporosis is an important chronic disease, requiring prolonged treatment. Long-term efficacy and safety data are therefore of great importance. Denosumab (DMAb) is used in over 80 countries or administrative districts worldwide for the treatment of postmenopausal women with osteoporosis. The effects of DMAb treatment for up to 10 years have been evaluated in the 3-year FREEDOM study and its 7-year extension. Objectives Report results through the final year of the FREEDOM extension, representing up to 10 years of continued DMAb treatment. Methods During the extension, all subjects were to receive 60 mg DMAb every 6 months and calcium and vitamin D daily. In this analysis, the long-term group received 10 years of DMAb treatment (3 years in FREEDOM and 7 years in the extension), and the cross-over group received 7 years of DMAb treatment (3 years of placebo in FREEDOM and 7 years of DMAb in the extension). Results Of the 4,550 subjects who entered the extension, 2,784 (61%) continued to participate at the beginning of year 10. Of these, 2,212 (80%) have completed their final 10-year visit, 120 (4%) discontinued, and 452 (16%) were ongoing at the time of this submission. In the long-term group, further significant increases in BMD occurred with mean cumulative 10-year gains of 21.6% (lumbar spine) and 9.1% (total hip) from FREEDOM baseline. The cross-over group had mean cumulative 7-year gains of 16.3% (lumbar spine) and 7.3% (total hip) from the extension baseline (Figure 1; all P Conclusions DMAb treatment for up to 10 years was associated with persistent reduction of bone turnover, continued increases in BMD without therapeutic plateau, and low fracture incidence. The benefit/risk profile for DMAb in an aging population of postmenopausal women remains favorable. Acknowledgement Amgen funded Disclosure of Interest H. Bone Grant/research support from: Amgen, Merck, Consultant for: Amgen, Merck, Graunenthaler, Speakers bureau: Amgen, M. Brandi Grant/research support from: Alexion, Abiogen, Amgen, Bruno Farmaceutici, Eli Lilly, MSD, NPS, Shire, SPA and Servier., Consultant for: Alexion, Abiogen, Amgen, Bruno Farmaceutici, Eli Lilly, MSD, NPS, Shire, SPA and Servier., J. Brown Grant/research support from: Amgen, Eli Lilly, Novartis, Consultant for: Amgen, Eli Lilly, Speakers bureau: Amgen, Eli Lilly, R. Chapurlat Grant/research support from: Pfizer, Chugai-Roche, Consultant for: Pfizer, Amgen, Bioiberica, S. Cummings Consultant for: Amgen, E. Czerwinski Grant/research support from: Amgen, Speakers bureau: Amgen, A. Fahrleitner-Pammer Grant/research support from: Roche, Consultant for: EliLilly, Speakers bureau: Amgen, EliLilly, Pfizer, MSD, D. Kendler Grant/research support from: Amgen, Lilly, Astrazenica, Astallis, Consultant for: Pfizer, Merck, Lilly, Amgen, Speakers bureau: Lilly, Amgen, GSK, K. Lippuner Consultant for: Amgen, J.-Y. Reginster Grant/research support from: Bristol Myers Squibb,Merck Sharp & Dohme, Rottapharm, Teva, Roche, Amgen, Lilly, Novartis, GlaxoSmithKline, Servier, Pfizer, Theramex, Danone, Organon, Therabel, Boehringer, Chiltern, Galapagos, Consultant for: Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed-Takeda, NPS, I BSA-Genevrier, Theramex, UCB, Asahi Kasei, Endocyte, Speakers bureau: Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee Pharma, Zodiac, Danone, Will Pharma, Amgen., E. Vittinghoff: None declared, N. Daizadeh Shareholder of: Amgen, Employee of: Amgen, A. Wang Shareholder of: Amgen, Employee of: Amgen, P. Dakin Shareholder of: Amgen, Employee of: Amgen, R. Wagman Shareholder of: Amgen, Employee of: Amgen, S. Papapoulos Consultant for: Amgen, Axsome, Merck & Co, Novartis, UCB, Speakers bureau: Amgen, Merck & Co, UCB

Background In the ADAMO trial in men with low BMD, DMAb treatment for 1 yr significantly increased BMD and reduced bone resorption vs placebo (Pbo) (Orwoll, JCEM 2012). Transiliac bone biopsies from women with postmenopausal osteoporosis (PMO) treated with DMAb for up to 5 yrs had normal bone quality and decreased remodeling at the tissue level (Reid, JBMR 2010; Brown, JBMR 2012) Objectives To confirm bone histology and histomorphometry effects of DMAb among men treated for 1 yr in men Methods Following labeling with tetracycline or demeclocycline, transiliac bone biopsy was performed as a substudy of the ADAMO trial ≤30 d before the yr-1 visit. For biopsies with only single labels in trabecular bone within the measurable field (20mm 2 ), mineral apposition rate was imputed as 0.3μm/d Results Among 29 subjects (17 DMAb; 12 Pbo) in the bone biopsy substudy, mean (SD) time from last DMAb dose to first label dose was 5.0 (0.5) months. Qualitative bone histology, assessed in all samples, showed normally mineralized lamellar bone. Structural indices, including cancellous bone volume and trabecular number and surface, were similar between treatment groups Consistent with the mechanism of action, bone remodeling was decreased in DMAb-treated subjects; 12/17 (71%) DMAb- and all Pbo-treated subjects had specimens with double labels in trabecular and/or cortical compartments; 6 DMAb- and 12 Pbo-treated subjects were evaluable for dynamic trabecular bone parameters. Static and dynamic remodeling indices were lower in DMAb- than Pbo-treated subjects, consistent with reduced bone turnover with DMAb. Conclusions DMAb for 1 yr in men with low BMD resulted in qualitatively normal bone with reduced bone turnover. These findings are consistent with those from women with PMO treated with DMAb for 1, 2, 3 or 5 yrs. Acknowledgements Study sponsor and abstract preparation Amgen/GSK Disclosure of Interest D. Dempster Consultant for: Amgen, D. Kendler Grant/research support: Amgen, Eli Lilly, Novartis, Pfizer, GSK, J&J, Consultant for: Amgen, Eli Lilly, Novartis, Pfizer, Warner Chilcott, S. Boonen Grant/research support: Amgen and Novartis, M. Bolognese Grant/research support: Amgen, Eli Lilly, GenenTech, Consultant for: Eli Lilly, NOF, VIVUS, R. Chapurlat Grant/research support: Merck, Consultant for: Novartis, Amgen, Roche, Pfizer, S. Goemaere: None declared, L. Hyldstrup Consultant for: Amgen, Novartis, Takeda, E. M. Lewiecki Grant/research support: Amgen, Lilly, Merck, Consultant for: Amgen, Lilly, Merck, Novarits, P. Miller Grant/research support: Amgen, Eli Lilly, Merck, Radius, Consultant for: Amgen, Eli Lilly, Merck, Warner-Chilcott, Y.-C. Yang Shareholder of: Amgen, Employee of: Amgen, R. Wagman Shareholder of: Amgen, Employee of: Amgen, B. Langdahl Grant/research support: Amgen, MSD, Eli Lilly, Consultant for: Amgen, MSD, Eli Lilly, Speakers bureau: Amgen, MSD, Eli Lilly DOI 10.1136/annrheumdis-2014-eular.1181

Background Strontium ranelate (SrRan) has potential beneficial effects on cartilage degradation in OA, stimulating human cartilage matrix formation in vitro and decreasing the urinary C-terminal telopeptides of type II-collagen. SrRan has also been shown to reduce radiographic spinal OA progression and back pain in osteoporotic women with prevalent spinal OA. Objectives We compared the efficacy and safety of SrRan with placebo in the treatment of knee osteoarthritis in a double-blind, placebo-controlled, randomised, international study (registration number: ISRCTN41323372) designed in accordance with the European Guidelines. Methods Patients with primary knee osteoarthritis, Kellgren and Lawrence grade 2 or 3, joint space width (JSW) 2.5 to 5 mm, and knee pain intensity of at least 40 mm on a visual analogue scale during the month prior to selection, were randomly allocated to SrRan 1 or 2 g/day, or placebo using a centralised interactive voice response system. The primary endpoint was radiographic joint space narrowing measured as the mean change in the minimal JSW of the knee medial tibiofemoral compartment with a semiautomated centralised reading method. JSW was measured at inclusion, 12, 24, and 36 months on radiographs with a postero-anterior, weight-bearing, fixed-flexion acquisition technique. Main secondary endpoints were changes in algofunctional scores (WOMAC), changes in knee pain intensity, and proportion of radiological progressors (patients with knee JSN>0.5 mm). Safety was assessed by adverse events and haematology/biochemistry/haemostasis parameters. Results Detailed results will be presented. The patients were included in 113 centres in 18 countries. 558 patients were assigned to SrRan 1 g/day, 566 to 2 g/day, and 559 to placebo. Mean follow-up was 29.8±10.5 months. Mean age was 62.8±7.2 years and 69% were female. Mean BMI was 30±5 kg/m 2 , mean JSW was 3.50±0.83 mm, and 61% of randomised patients were Kellgren and Lawrence stage II. Conclusions This large randomised placebo-controlled study will establish the long-term efficacyof SrRan on structure and symptoms in patients with knee osteoarthritis. Disclosure of Interest None Declared

Background Denosumab (DMAb) is approved for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial.1 The open-label, active-treatment FREEDOM extension study is evaluating the long-term efficacy and safety of DMAb for up to 10 years. Objectives Report results from the first 3 years of the extension, representing up to 6 years of DMAb treatment. Methods In the extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For women given placebo during FREEDOM, the data here reflect 3 years of DMAb exposure (cross-over group). For women given DMAb during FREEDOM, the data reflect 6 years of DMAb exposure (long-term group). Results There were 5928 women eligible for the extension. Of these, 4550 (77%) enrolled (2207 cross-over; 2343 long-term). In the first 3 years of DMAb treatment during the extension, the cross-over group had significant gains in bone mineral density (BMD) at the lumbar spine (9.4%) and total hip (4.8%), comparable to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). In the long-term group, further significant increases in BMD occurred for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip. After the 1st (cross-over) or 7th (long-term) DMAb dose, sCTX was rapidly and similarly reduced with the characteristic attenuation at the end of the dosing period. In the cross-over group, yearly incidences of nonvertebral, new vertebral, clinical vertebral, and clinical fractures were lower than those in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb. Two subjects in each group had AEs adjudicated to ONJ. Both cases in the cross-over group healed without further complications; one subject continues to receive DMAb. One case in the long-term group healed, while the other continues to be followed. There were no atypical femur fractures. Conclusions DMAb treatment for 3 years in the cross-over group reproduced FREEDOM observations. DMAb treatment for 6 years (long-term group) continued to significantly increase BMD, maintained reduced bone turnover, and remained well tolerated. Fracture incidence remained low. References Cummings et al. N Engl J Med. 2009;361:756 Disclosure of Interest R. Chapurlat Grant/Research support from: Pfizer, Amgen, Servier, Consultant for: Amgen, Servier, Novartis, Roche, Lilly, S. Papapoulos Consultant for: Amgen, Eli Lilly, GSK, Merck, Novartis, J. Brown Grant/Research support from: Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Novartis, sanofi-aventis, Warner Chilcott, Speakers Bureau: Amgen, Eli Lilly, Novartis, N. Franchimont Shareholder of: Amgen, Employee of: Amgen, M. Brandi Consultant for: Amgen, Servier, MSD, Roche, Glaxo, Eli Lilly, Nycomed, NPS, Pfizer, E. Czerwinski Grant/Research support from: Amgen, AstraZeneca, Danone Research, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Servier, M.-A. Krieg: None Declared, Z. Man Grant/Research support from: Merck, Amgen, Lilly, Consultant for: Novartis, Merck, Sanofi aventis, D. Mellstrom: None Declared, S. Radominski Grant/Research support from: BMS, Pfizer, Amgen, Roche, Novartis, Speakers Bureau: Aventis, Lilly, Novartis, J.-Y. Reginster Grant/Research support from: BMS, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GSK, Amgen, Servier, Consultant for: Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GSK, Roche, Merckle, Nycomed, NPS, Theramex, UCB, H. Resch Consultant for: MSD, Lilly, Amgen, Sankyo, Roche, Servier, J. Roman Grant/Research support from: Roche, MSD, Consultant for: Actelion, Pfizer, C. Roux Grant/Research support from: Amgen, Novartis, Consultant for: Amgen, Novartis, MSD, N. Daizadeh Shareholder of: Amgen, Employee of: Amgen, M. Geller Shareholder of: Amgen, Employee of: Amgen, S. Smith Shareholder of: Amgen, Employee of: Amgen, R. Wagman Shareholder of: Amgen, Employee of: Amgen, S. Cummings Consultant for: Amgen, H. Bone Grant/Research support from: Merck, Amgen, Nordic Bioscience, Novartis, Takeda, Tarsa, Consultant for: Merck, Amgen, Takeda, Tarsa, Speakers Bureau: Amgen, Pfizer.

Background In RA, bone marrow edema (BME) is predictive of erosive progression. Bone erosions are assumed to appear through activation of local bone resorption mechanisms, reflected by periarticular osteopenia. Measurement of periarticular bone mineral density by DXA requires specific hand software limiting its application in large population, and does not assess bone texture. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis reflecting changes in trabecular bone architecture, with a very low radiation exposure. Objectives To assess the correlation between MRI bone edema and trabecular bone texture parameters in active RA. Methods Study design: cross-sectional multicenter study. Comparative MRI and high resolution X-rays of the dominant hand and wrist were obtained from 55 patients with active RA according to ACR/EULAR criteria (DAS 28 ≥3.2). Clinical examination and radiographs of the hands and feet were also performed. High resolution direct digital X-ray (BMA™, D3A Medical Systems): The fractal trabecular bone texture parameter (Hmean) was evaluated on the 2nd and 3rd metacarpal head, capitatum and lunatum. MRI: BME was scored according to the RA MRI score (RAMRIS) by two independent and experienced radiologists (central reading). BME was also specifically assessed on the 4 bones where Hmean was evaluated (BME4 score). Radiographs: plain radiographs were scored using the modified Sharp-van der Heijde method. Analysis: Inter-reader reliability: ICC. Correlation between BME and Hmean: Spearman test. Results Data from 53 patients were analyzable. The main patients characteristics were (mean ± SD): age 57±14 years, 75% women, disease duration 8.6±9.2 years, DAS28 5.4±1.3, anti-CCP 76%, Sharp-DvdH 23.8±31.3, currently treated with DMARDs 74%, biologics 47%, corticosteroids 60% (mean daily dosage 9.1±6.6 mg). The mean ± SD [median] RAMRIS BME, BME4 and Hmean scores were 12.7±14.6 [5.0], 2.7±2.8 [1.0] and 0.60±0.06 [0.61], respectively. RAMRIS BME inter-reader reliability: ICC=0.96. Correlations between Hmean and both RAMRIS BME and BME4 scores were r=-0.31 (p=0.022) and r=-0.32 (p=0.018), respectively. When evaluated only on the 2nd and 3rd metacarpal head, Hmean was significantly correlated with the total BME score r=-0.28 (p=0.038) whereas it was not when evaluated on lunatum and capitatum (r=-0.22 – p=0.120). Conclusions This study demonstrated trabecular bone texture parameter is correlated to MRI bone edema scores. It would be interesting to assess if bone texture impairment, measured with a high resolution digital X-ray device, could predict RA radiographic progression in a wider range prospective study. Disclosure of Interest T. Pham Consultant for: Abbott, S. Trijau: None Declared, R. Chapurlat Consultant for: Abbott, D. Loeuille Consultant for: Abbott, T. Schaeverbeke Consultant for: Abbott, C. Roux Consultant for: Abbott, C. L. Benhamou Consultant for: Abbott, O. Vittecoq Consultant for: Abbott, J. Sibilia Consultant for: Abbott, F. Mistretta Consultant for: Abbott, C. Hacquard-Bouder Employee of: Abbott

Background Odanacatib (ODN) is an orally-active cathepsin K inhibitor being developed for the treatment of postmenopausal osteoporosis. Objectives This study evaluated the effects of ODN 50mg once weekly on BMD, bone turnover markers and safety in patients previously treated with alendronate (ALN). Methods This was a randomized, double-blind, placebo-controlled, 24-month study. The primary endpoint was % change from baseline at month 24 of femoral neck (FN) BMD. Postmenopausal women (n=243) ≥60 years of age with low BMD T-score at the total hip, FN or trochanter but no history of hip fracture and who have taken ALN for ≥3years were randomized to receive ODN or placebo. Patients received vitamin D3 and calcium supplementation. BMD was assessed by DXA at baseline, 6, 12 and 24 months. Biochemical markers of bone turnover (sCTx, uNTx, sBSAP and sP1NP) were measured at baseline and 3, 6, 12, 18 and 24 months. Results In the ODN group, BMD changes from baseline at 24 months were significantly increased from placebo at the femoral neck, trochanter, total hip and lumbar spine (1.7%, 1.8%, 0.8%, and 2.3%, respectively). In the placebo group, BMD at the femoral neck, trochanter and total hip declined significantly from baseline by month 24 (-0.9%, -1.4%, and -1.9% respectively). ODN significantly decreased bone resorption marker, u-NTx/Cr, and significantly increased bone formation markers, s-P1NP and s-BSAP, vs. placebo. The increase observed for the bone resorption marker s-CTx with ODN treatment was unexpected. Adverse events were comparable between the 2 treatments arms. The overall safety profile appeared similar between ODN and placebo. Image/graph Conclusions In this study ODN provided incremental BMD gains in osteoporotic women following ALN treatment. Biomarker results suggest that ODN decreases bone resorption while preserving bone formation. Disclosure of Interest S. Palacios Grant/research support from: Merck Sharp & Dohme Corp., S. Bonnick Grant/research support from: Merck Sharp & Dohme Corp., T. De Villiers Speakers bureau: Merck Sharp & Dohme Corp., R. Chapurlat Grant/research support from: Merck Sharp & Dohme Corp., Consultant for: Merck Sharp & Dohme Corp., A. Odio: None Declared, B. Scott Employee of: Merck Sharp & Dohme Corp., C. Le Bailly De Tilleghem Employee of: Merck Sharp & Dohme Corp., C. DaSilva Employee of: Merck Sharp & Dohme Corp., A. Leung Employee of: Merck Sharp & Dohme Corp., D. Gurner Employee of: Merck Sharp & Dohme Corp.

Objectives In SEKOIA, strontium ranelate 2g/day (SrRan) has shown a structure-modifying activity with significant symptomatic improvement compared to placebo in patients with knee OA. This analysis aimed to determine proportion of patients considered as symptomatic responders as per WOMAC pain sub-score and OMERACT-OARSI-like responders, as well as the number of patients reaching MPCI (Minimal Perceptible Clinical Improvement) and MCII (Minimal Clinical Important Improvement). Methods SEKOIA was a double-blind, placebo-controlled, randomized, 3-year study aiming to demonstrate effects of strontium ranelate on radiographic progression of knee OA. It included men and women over 50 years old, with symptomatic primary knee OA (at least 40 on 100 mm VAS on most days of previous month, Kellgren and Lawrence [KL] grade 2 or 3, and JSW 2.5–5mm). Symptoms were assessed every 6 months using the WOMAC questionnaire. Proportions of patients with at least 20% or 50% improvement from baseline of WOMAC pain sub-score, proportion of OMERACT-OARSI-like responders (calculated without patient’s global assessment as it was not assessed in SEKOIA) and percentages of patients reaching MPCI or MCII values, were compared between groups using a chi² test. Patients prematurely withdrawn from the study were counted as non-responding patients. Results ITT population included 1371(82%) patients. Mean±SD age was 63±7years, BMI 30±5 kg/m 2 , and WOMAC 132±62 mm. 66 % were KL grade II and 69% were female. Over 3 years, a greater percentage of patients treated with SrRan 2g were considered as symptomatic responders compared to placebo: For physical function, MCII and MPCI responders were statistically significantly greater in the SrRan 2g group compared to the placebo group from M12 (p=0.019 and p=0.027, respectively). For pain, the rate of responders was greater in the SrRan 2g group from M6 (p=0.024). Conclusions SrRan treatment is associated with greater number of patients with relevant improvement in symptoms. This can be evidenced from M6 considering MPCI pain responders. Disclosure of Interest O. Bruyere Grant/research support from: IBSA, Merck Sharp & Dohme, Nutraveris, Novartis, Pfizer, Rottapharm, Servier, Theramex, P. Richette Consultant for: Servier, Novartis, Negma, Expanscience. Wyeth Roche, Merck Sharp and Dohme, Genevrier, Menarini. Ipsen. Pfizer. Sobi. Bioiberica. Fidia. BMS, Paid instructor for: Servier, Novartis, Negma, Expanscience. Wyeth Roche, Merck Sharp and Dohme, Genevrier, Menarini. Ipsen. Pfizer. Sobi. Bioiberica. Fidia. BMS, N. Bellamy Shareholder of: Registered copyright and trademark holder of the WOMAC® Index, Consultant for: Servier, J. Brown Grant/research support from: Abbott, Amgen, Arthrolab, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Takeda and Warner-Chilcott, Consultant for: Abbott, Amgen, Arthrolab, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Takeda and Warner-Chilcott, Speakers bureau: Abbott, Amgen, Arthrolab, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Takeda and Warner-Chilcott, R. Chapurlat Grant/research support from: Merck, Amgen, Servier, Lilly, Roche, Novartis, X. Chevalier Grant/research support from: Roche for the department association, Consultant for: Expanscience, Negma, Genevriers, Merck Sharp and Dohme, Rottapharm, Fidia, Servier, Pierre Fabre, Smith Nephews, Paid instructor for: Merck Sharp and Dohme, Servier, Expanscience, Ibsa, Genzyme, E. Czerwinski E Grant/research support from: Amgen, Andromeda Biotech Ltd., AstraZeneca, Biotest AG, Eli Lilly, INC Research, Johnson&Johnson, Merck Serono, Novartis, Pfizer, Roche, Servier, Shire Movetis, J. Devogelaer Consultant for: Novartis, Paid instructor for: Merck, Sharpe & Dohme, Servier, Procter & Gamble, Roche, and Amgen, L. March Grant/research support from: Servier, MSD, Pfizer, Abbott, UCB, Paid instructor for: Servier, MSD, Pfizer, Abbott, UCB, K. Pavelka Paid instructor for: BMS, Abbott, Pfizer, MSD, Amgen, L. Punzi Grant/research support from: Abbott SpA, Menarini Spa, Fidia SpA, Sobi SpA, UCB SpA, Consultant for: Abbott SpA, Menarini Spa, Fidia SpA, Sobi SpA, UCB SpA, C. Cooper Consultant for: Amgen, ABBH, Novartis, Pfizer, Merck Sharp and Dohme, Eli Lilly, Servier, J. Reginster Grant/research support from: Bristol Myers Squibb, Merck Sharp and Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier, Consultant for: Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Paid instructor for: Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk.