Osteoporos Int (2015) 26 (Suppl 1):S35–S56 DOI 10.1007/s00198-015-3067-4
World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Oral Communication Abstracts # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
OC1 ODANACATIB ANTIFRACTURE EFFICACY AND SAFETY IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: RESULTS FROM THE PHASE III LONG-TERM ODANACATIB FRACTURE TRIAL (LOFT) M. R. McClung1, B. Langdahl2, S. Papapoulos3, K. G. Saag4, S. Adami5, H. G. Bone6, T. De Villiers7, D. P. Kiel8, A. Kung9, P. Kumar KM10, S.-K. Lim11, X. Ling12, K. Lippuner13, C. Mautalen14, T. Nakamura15, J.-Y. Reginster16, I. R. Reid17, J. A. Rodrίguez-Portales18, C. Roux19, J. Walliser20, N. B. Watts 21, J. Zanchetta 22 , C. A. F. Zerbini 23, A. RybakFeiglin24, D. Cohn24, C. A. DaSilva24, R. Massaad25, A. C. Santora24, B. B. Scott24, K. D. Kaufman24, N. Verbruggen25, A. Leung26, A. Lombardi24 1 Oregon Osteoporosis Center, Portland, OR, United States, 2 Aarhus University Hospital, Aarhus, Denmark, 3Leiden University Medical Center, Leiden, Netherlands, 4University of Alabama at Birmingham, Birmingham, AL, United States, 5 University of Verona, Verona, Italy, 6Michigan Bone & Mineral Clinic, Detroit, MI, United States, 7Stellenbosch University, Stellenbosch, South Africa, 8Institute for Aging Research, Hebrew Senior Life, Harvard Medical School, Boston, MA, United States, 9University of Hong Kong, Pokfulam, Hong Kong, 10Bangalore Diabetes Hospital, Bangalore, India, 11Yonsei University, Seoul, Republic of Korea, 12Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China, 13Bern University Hospital, Bern, Switzerland, 14 Centro de Osteopatίas Médicas, Buenos Aires, Argentina, 15University of Occupational & Environmental Health, Fukuoaka, Japan, 16 CHU-Centre Ville, Policliniques BRULL, Liège, Belgium, 17 University of Auckland, Auckland, New Zealand, 18 Pontificia Universidad Católica de Chile, Santiago, Chile, 19 Paris Descartes University, Cochin Hospital, Paris, France, 20 Bone Metabolism Clinic, Hospital Angeles del Pedregal, Mexico City, Mexico, 21Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, United States, 22IDIM Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 23 Centro Paulista de Investigações Clinicas, São Paulo, Brazil,
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Merck & Co., Inc., Whitehouse Station, NJ, United States, MSD Europe Inc., Brussels, Belgium, 26Formerly Merck & Co., Inc., Whitehouse Station, NJ, United States
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Objective: The Phase III Long-Term Odanacatib (ODN) Fracture Trial (LOFT; NCT00529373) is a randomized, double-blind, placebo-controlled, event-driven trial evaluating the efficacy and safety of ODN, an oral selective inhibitor of cathepsin K, in reducing osteoporotic fracture risk. Material and methods: Postmenopausal women ≥65 years with BMD T-score≤−2.5 at total hip (TH) or femoral neck (FN), or with prior radiographic vertebral fracture (VFx) and T-score≤−1.5 at TH or FN, were randomized to ODN 50 mg/ week or placebo. Patients received vitamin D (5600 IU/week), plus calcium to achieve intake of 1200 mg/d. Primary endpoints were: new/worsening morphometric VFx; hip fractures; nonvertebral fractures. Secondary endpoints included clinical VFx; BMD; bone turnover markers. Safety/ tolerability measures included independent adjudication of adverse events (AEs) of special interest. Results: 16,713 women were randomized; 16,071 were included in analysis. Mean age was 72.8 years; 46.5 % had prior radiographic VFx. Mean BMD T-scores were: TH −2.4; FN −2.7; lumbar spine (LS) -2.7. Mean follow-up was 34.5 months. Versus placebo, ODN treatment resulted in relative risk reductions of: 54 % for new/worsening morphometric VFx; 47 % for hip fractures; 23 % for nonvertebral fractures; 72 % for clinical VFx (p Conclusion: ODN significantly reduced osteoporotic fracture risk versus placebo in women with postmenopausal osteoporosis. Acknowledgments: This study was sponsored by Merck & Co., Inc. Author conflicts of interest: Awards/grants: Amgen (MRM, BL, KGS, HGB, IRR, CAFZ), Bongrain (CR), Lilly (BL, DPK, CR, CAFZ), Merck (MRM, BL, KGS, HGB, DPK, XL, IRR, JAR-P, NBW, CAFZ), MSD (CR), Novartis (IRR, CAFZ), NPS (NBW), Pfizer (CAFZ), Roche (CAFZ). Speakers’ bureaux: Amgen (BL, NBW), GSK (JZ), Lilly (BL), Merck (BL, NBW, CAFZ), Pfizer (TdV, CAFZ). Consulting fees: AbbVie (NBW), Abiogen (SA), Amarin
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(NBW), Amgen (MRM, BL, SP, KGS, SA, HGB, TdV, DPK, KL, TN, CR, NBW), Asahi-Kasei (TN), Axsome (SP), BMS (NBW), Chugai (TN), Corcept (NBW), Endo (NBW), GSK (SP), Imagepace (NBW), Janssen (NBW), Lilly (MRM, BL, KGS, SA, DPK, KL, IRR, CR, NBW, CAFZ), Merck (MRM, BL, SP, KGS, SA, HGB, TdV, DPK, CM, IRR, JAR-P, CR, NBW, JZ, CAFZ), MSD (KL, TN), Novartis (SP, HGB, DPK, IRR, NBW), Noven (NBW), Pfizer (NBW), Radius (NBW), Roche (SA), Sanofi-Aventis (NBW), Servier (CM), UCB (KL, CR). Speakers’ fees: Amgen (MRM, HGB), Merck (MRM, HGB). Royalties: Kluwer Wolter (DPK). Holds stocks and bonds: OsteoDynamics (NBW). J-YR unspecified support from MSD, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GSK, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee, Pharma, Zodiac, Danone, Will Pharma, Amgen. Member of Board of Trustees for the International Osteoporosis Foundation (SP). Employee: Merck & Co., Inc (AR-F, DC, CADS, RM, AS, BBS, KDK, NV, ALo, Ale [at time of study]). Nothing to disclose: AK, PK, S-KL, JW. OC2 THE BMD RESPONSE TO BLOSOZUMAB IS INDEPENDENT OF INITIAL AGE, BODY MASS INDEX, AND BMD IN POSTMENOPAUSAL WOMEN WITH LOW BMD: RESULTS OF A PHASE 2 RANDOMIZED CLINICAL TRIAL B. Mitlak1, A. Chiang1, F. Marin2, J. Krege1, C. Benson1 1 Eli Lilly and Company, Indianapolis, United States, 2Lilly Europe, Windlesham, United Kingdom Objective: In a recent double-blind study of women with low BMD, 52 weeks of treatment with blosozumab, a humanized antibody targeted to sclerostin, increased lumbar spine (LS) and total hip BMD.1 BMD decreased after stopping treatment, but remained significantly higher than placebo after 52 weeks of follow-up in the prior blosozumab 270 mg every 2 weeks (Q2W) and 180 mg Q2W groups.2 In the same cohort, we evaluated the relationship between treatment effect and the patient’s initial age, BMI, and BMD. Material and Methods: Patients were randomized in parallel to blosozumab 180 mg Q4W, blosozumab 180 mg Q2W, blosozumab 270 mg Q2W, or placebo. BMD was assessed by DXA after 52 weeks of treatment. Absolute change in spine and total hip BMD from baseline to 52 weeks was evaluated within each treatment group for women above and below the median age and BMI, and above and below a LS T- score of −2.5 for the overall cohort, as predefined in the study protocol. Statistical analyses were conducted using a repeated measures model with Dunnett’s multiplicity adjustment. Results: Of 120 randomized patients, 108 had efficacy measures at 52 weeks. The median baseline age was 65.9 y (range 50.2-83.5 y); BMI was 23.0 kg/m2 (range 14.8-40.5 kg/m2);
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and LS T-score was −2.76 (range −4.03 to −1.52). The effect of blosozumab to increase spine and total hip BMD at 52 weeks was similar for women above and below the median age and BMI, and a LS T-score −2.5 (each interaction p>0.10). Conclusion: In this phase 2 study cohort, blosozumab increased spine and total hip BMD similarly across a range of age, BMI, and disease severity. References: 1. Recker et al., J Bone Miner Res 2014; doi:10. 1002/jbmr.2351. 2. Benson et al., J Bone Miner Res 2014;29(Suppl 1). Disclosures: The study was funded by Eli Lilly and Company. B Mitlak, A Chiang, F Marin, J Krege, and C Benson are employees and shareholders of Eli Lilly and Company. Acknowledgements: The authors acknowledge Jennifer Harris, Pharm.D., an employee of Eli Lilly and Company, for assistance with abstract preparation and submission. OC3 RESULTS OF 2 YEARS OF ROMOSOZUMAB T R E AT M E N T F O L L O W E D B Y 1 Y E A R O F DENOSUMAB OR PLACEBO IN POSTMENOPAUSAL WOMEN WITH LOW BONE MINERAL DENSITY M. R. McClung1, A. Chines2, J. P. Brown3, A. Díez-Pérez4, H. Resch5, J. Caminis6, M. A. Bolognese7, S. Goemaere8, H. G. Bone9, J. R. Zanchetta10, J. Maddox2, O. Rosen2, S. Bray11, A. Grauer2 1 Oregon Osteoporosis Center, Portland, United States, 2 Amgen Inc., Thousand Oaks, United States, 3 Laval University and CHU de Québec Research Centre, Quebec City, Canada, 4Autonomous University of Spain, Barcelona, Spain, 5St. Vincent Hospital, Vienna, Austria, 6UCB Pharma, Raleigh, United States, 7 Bethesda Health Research Center, Bethesda, United States, 8Ghent University Hospital, Ghent, Belgium, 9 Michigan Bone and Mineral Clinic, Detroit, United States, 10Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 11Amgen Ltd., Cambridge, United Kingdom Objective: Romosozumab (Romo) increased BMD and bone formation, and decreased bone resorption after 1 yr in postmenopausal women with low BMD (McClung NEJM 2014). Here, we report results of 2 yrs of Romo treatment, followed by 1 yr of denosumab (DMAb) or placebo (pbo). Methods: This study enrolled 419 postmenopausal women with a lumbar spine (LS), total hip (TH), or femoral neck Tscore≤−2.0 and≥−3.5. For the results here, women received Romo (70 mg QM, 140 mg QM, 210 mg QM, 140 mg Q3M, or 210 mg Q3M) or pbo for 2 yrs. After 2 yrs, eligible women entered a 1-yr extension and were re-randomized within their original groups to DMAb or pbo. Results: Romo led to rapid and marked increases in BMD during yr 1 and continued increases through yr 2. Largest gains were observed with Romo 210 mg QM, with increases of 15.7 % (LS) and 6.0 % (TH) (Figure). Women receiving
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Romo 210 mg QM who transitioned to DMAb continued to accrue BMD at a rate similar to that in the 2nd yr of Romo; in those transitioned to pbo, BMD returned toward pretreatment levels. Romo induced rapid stimulation of bone formation (P1NP) and decreased bone resorption (CTX). Increases in P1NP were transitory, returning toward baseline (BL) within 6–12 months and remaining below BL through yr 2. CTX remained below BL through yr 2. For those receiving Romo 210 mg QM who transitioned to DMAb, P1NP and CTX decreased; for those transitioned to pbo, P1NP gradually returned to BL, while CTX initially increased above BL and gradually returned toward BL. Adverse events were balanced between the Romo and pbo groups during the first 2 yrs of the study (except for injection site reactions, most reported as mild) and during yr 3. Conclusion: The treatment effects observed with Romo are further augmented by follow-on treatments like DMAb.
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Disclosures: Amgen Inc and UCB Pharma sponsored this study. MR McClung (Research grants, consulting fees, and/ or speakers bureau - Amgen, Eli Lilly, and Merck); A Chines, J Maddox, O Rosen, S Bray, and A Grauer (Employees and stock/stock options - Amgen); JP Brown (Research grants, advisory boards, and/or conferences - Abbott, Amgen, BMS, Eli Lilly, Merck, sanofi-aventis, Novartis, Pfizer, Roche, Servier, Takeda, and Warner Chilcott); A Diez-Perez (Stock options or bond holdings, consulting fees, and/or speakers bureau - Active Life Scientific, Amgen, Eli Lilly, MSD, and Novartis); H Resch (Research grants and speaker fees Amgen, Eli Lilly, MSD, and Novartis; Advisory boards - Eli Lilly, Amgen, and MSD); J Caminis (Employee and stock/ stock options - UCB); MA Bolognese (Research grants and/ or advisory boards - Amgen, Eli Lilly, Genentech, NOF, and VIVUS); S Goemaere (Research grants and speaker fees Amgen, Eli Lilly, MSD, and Novartis; Advisory boards - Eli Lilly and UCB); HG Bone (Research grants, advisory council, consulting fees, and/or speakers bureau - Amgen, Merck, Novartis, and Tarsa); JR Zanchetta (Research grants and/or consulting fees - Amgen, Eli Lilly, GSK, MSD, Pfizer, and Radius) OC4 DENOSUMAB TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS FOR UP TO 9 YEARS: RESULTS THROUGH YEAR 6 OF THE FREEDOM EXTENSION S. Papapoulos 1 , C. Roux 2 , H. G. Bone 3 , P. Dakin 4 , E. Czerwiński5, D. Frey6, D. Kendler7, E. M. Lewiecki8, J. Malouf9, D. Mellström10, J.-Y. Reginster11, H. Resch12, N. S. Daizadeh4, A. Wang4, M. Gavin4, R. B. Wagman4, M. L. Brandi13 1 Leiden University Medical Center, Leiden, Netherlands, 2 Paris Descartes University, Paris, France, 3 Michigan Bone & Mineral Clinic, Detroit, United States, 4Amgen Inc., Thousand Oaks, United States, 5 Krakow Medical Center, Krakow, Poland, 6University Hospital of Zurich, Zurich, Switzerland, 7University of British Columbia, Vancouver, Canada, 8New Mexico Clinical Research & Osteoporosis Center, Albuquerque, United States, 9Universitat Autònoma de Barcelona, Barcelona, Spain, 10Sahlgrenska University Hospital, Göteborg, Sweden, 11University of Liège, Liège, Belgium, 1 2 St. Vincent Hospital, Vienna, Austria, 13 University of Florence, Florence, Italy Objective: To report the results through year 6 of the FREEDOM open-label Extension (Ext), representing up to 9 years of continued denosumab (DMAb) for the treatment of postmenopausal osteoporosis. Material and Methods: During the Ext, all women received 60 mg DMAb every 6 months, and daily calcium and vitamin D. At Ext year 6, bone turnover markers, nonvertebral fracture
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incidence, and adverse events were evaluated. In these analyses, women in the long-term group received up to 9 years of DMAb (3 years in FREEDOM and up to 6 years in the Ext); women in the cross-over group received up to 6 years of DMAb (3 years of placebo in FREEDOM and up to 6 years of DMAb in the Ext), allowing replication of results from the long-term group. Results: Of the women who enrolled in the Ext, 3,098 (68 %) were still on study at the beginning of year 6, with a mean age of 79 years (range 68–98 years). In both groups, serum CTx and P1NP were similarly reduced after each DMAb dose. The characteristic attenuation was observed through each dosing period and reductions were sustained through Ext year 6. The yearly incidences of nonvertebral (Figure) and major nonvertebral fractures remained low in both groups. Rates of adverse events and serious adverse events were consistent with previously reported Ext data. In Ext year 6, 2 events were adjudicated positive for ONJ in the cross-over group; there were no cases of atypical femoral fracture in either group.
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Conclusion: In this aging population, DMAb treatment for up to 9 years maintained reduced bone turnover and was associated with continued low incidence of nonvertebral and major nonvertebral fractures. The benefit/risk profile remained favorable. Disclosures: S Papapoulos: Consultant/Advisory activities Amgen Inc., Axsome, Gador, GSK, Merck, Novartis, UCB; Board membership - IOF. C Roux: Grant/Research support Bongrain, Lilly, MSD; Consultant/Advisory activities Amgen Inc., MSD; Board membership - Amgen Inc., MSD, UCB. HG Bone - Grant/Research support - Amgen Inc., Merck, Novartis; Consultant/Advisory activities - Amgen Inc., Merck, Mission, Novartis. P Dakin, NS Daizadeh, A Wang, M Gavin, and RB Wagman: Company employee Amgen Inc.; Stock/Stock options - Amgen Inc. E Czerwiński: Grant/Research support - Amgen Inc. D Frey: Grant/Research support - Abbott, Amgen Inc., DaiichiSankyo, Novartis, UCB; Consultant/Advisory activities Amgen Inc., Meda, Takeda. D Kendler: Grant/Research support - Amgen Inc., Astalis, Astra Zeneca, Eli Lilly, GSK,
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Novartis; Consultant/Advisory activities - Amgen Inc., Eli Lilly, GSK, Merck, Pfizer; Speaker’s bureau - Amgen Inc., Eli Lilly, Novartis. EM Lewiecki: Grant/Research support - Amgen Inc., Lilly, Merck; Consultant/Advisory activities - AgNovos, Alexion, Amgen Inc., Lilly, Merck, NPS, Radius Health; Board membership - National Osteoporosis Foundation, ISCD. J Malouf and D Mellström: Nothing to disclose. J-Y Reginster: Grant/Research support - Amgen Inc., Bristol Myers Squibb, GSK, Lilly, Merck Sharp & Dohme, Novartis, Roche, Rottapharm, Servier, Teva. Consultant/Advisory activities - Amgen Inc., GSK, Lilly, Merckle, Negma, Novartis, NPS, Nycomed, Roche, Servier, Theramex, UCB, Wyeth. Lecture fees - Analis, Ebewee Pharma, Genevrier, GSK, IBSA, Lilly, Merck Sharp & Dohme, Nolver, Novartis, Novo-Nordisk, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Zodiac. H Resch: Grant/Research support - Amgen Inc., Lilly; Consultant/Advisory activities - Amgen Inc., Lilly, MSD; Speaker’s bureau - Amgen Inc., Lilly, MSD, UCB. ML Brandi: Grant/Research support - Abiogen, Alexion, Amgen Inc., Bruno Farmaceutici, Eli Lilly, MSD, NPS, Servier, Shire, SPA; Consultant/Advisory activities - Abiogen, Alexion, Amgen Inc., MSD, NPS, Servier, Shire, SPA; Board membership: Alexion, Servier. OC5 THE POSITION OF STRONTIUM RANELATE IN TODAY’S MANAGEMENT OF OSTEOPOROSIS J.-Y. Reginster 1 , M. L. Brandi 2 , J Cannata-Andia 3 , C. Cooper 4 , B. Cortet 5 , J. M. Feron 6 , H. K. Genant 7 , S Palacios8, J. D. Ringe9, R. Rizzoli10 1 University of Liège, Liège, Belgium, 2 University of Florence, Florence, Italy, 3University of Oviedo, Oviedo, Asturias, Spain, 4 MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom, 5Department of Rheumatology, Roger Salengro Hospital, CHU Lille, Lille, France, 6Service de Chirurgie Orthopédique et Traumatologique, Hôpital Saint Antoine, GHU Est, AP-HP, Paris, France, 7University of California, San Francisco, United States, 8Instituto Palacios, Salud y Medicina de la mujer, Madrid, Spain, 9West German Osteoporosis Center (WOC), Klinikum Leverkusen, University of Cologne, Leverkusen, Germany, 10Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland Osteoporosis accounts for about 3 % of total European healthcare spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost-saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible and without contraindications including uncontrolled
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hypertension, established, current, or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today’s evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today’s management of osteoporosis, with a positive benefit-risk balance provided the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible, and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis. OC6 TRACKING OF 25-HYDROXYVITAMIN D STATUS DURING PREGNANCY R. J. Moon 1 , S. R. Crozier 1 , E. M. Dennison 1 , S. M. Robinson1, H. M. Inskip1, K. M. Godfrey1, C. Cooper1, N. C. Harvey1 1 MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom Objective: When assessed in pregnancy studies, 25(OH)D is usually measured only once. However, it is unknown whether the ranking of an individual’s 25(OH)D is maintained across pregnancy, which crosses several seasons. We therefore assessed the tracking of 25(OH)D from early to late pregnancy in a prospective mother-offspring study, the Southampton Women’s Survey. Material and Methods: At 14 and 34 weeks gestation, serum 25(OH)D was measured, and diet and lifestyle questionnaires completed. We modelled seasonal variation in 25(OH)D separately for each gestation using Fourier transformations, and then calculated the difference between actual 25(OH)D and the modelled value corresponding to the sampling date for each individual [denoted 25(OH)Ddev]. We used Spearman’s rank correlation to test tracking of 25(OH)Ddev from 14 to 34 weeks gestation. Multivariate linear regression was used to determine factors associated with changes in 25(OH)Ddev ranking. Results: 25(OH)D was available in 2060 and 2332 women at 14 and 34 weeks, respectively, with 1756 women included at both gestations. 25(OH)Ddev tracked moderately from 14 to 34 weeks (r=0.57, p80 years). The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages. OC35 REDUCED FRACTURE RISK IN DANISH WOMEN WITH POLYCYSTIC OVARY SYNDROME: A NATIONAL REGISTER-BASED COHORT STUDY K. H. Rubin1, D Glintborg2, M. Nybo3, M. Andersen4, B. Abrahamsen5 1 Odense Patient Data Exploratory Network, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark, 2 Department of Endocrinology, Odense University Hospital, Odense, Denmark, 3 Clinical Biochemistry, Odense University Hospital, Odense, Denmark, 4 Department of Endocrinology M, Odense University Hospital, Odense, Denmark, 5OPEN, Institute of Clinical Research, University of Southern Denmark, Glostrup, Denmark Objective: To investigate fracture risk in patients with polycystic ovary syndrome (PCOS). We hypothesized that fracture risk could be lower in patients with PCOS than in healthy controls due to hyperandrogenemia and obesity. Material and Methods: Women with PCOS or hirsutism (ICD-10 codes L680 and E282) were identified in the Danish National Patient Register (NPR) from 1995–2012. Three age-matched controls were included per patient and were assigned the same index date as their matched PCOS
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case. Subjects with a history of hyperprolactinemia, acromegaly, Cushing’s disease, adrenogenital syndrome, and Turner syndrome were excluded. We identified incident fractures by ICD10 codes and used conditional Cox regression analysis to compare fracture risk. We focused on overall fracture risk and fractures of the appendicular skeleton rather than fractures of the spine or hip, which are rare in the age group. Results: We included 19,199 patients with PCOS and 57,483 control subjects. The mean (range) age was 30.6 (12–60) years. The overall risk of fractures was significantly lower in PCOS (HR 0.74; 95%CI 0.70-0.78, p Conclusion: This study demonstrates that women with PCOS have a substantially reduced risk of fractures, in particular of the appendicular skeleton, which could perhaps be accounted for by hyperandrogenism or obesity. However, the reduced incidence of fractures of the face and hands may also suggest a difference in the exposure to direct trauma such as for example in contact sports. Additional research is needed to determine the mechanism behind the risk reduction. OC36 IMPACT OF HIP FRACTURE ON HOSPITAL CARE COSTS: A POPULATION BASED STUDY J. Leal1, A. M. Gray1, M. K. Javaid2, D. Prieto-Alhambra2, N. K. Arden2, C. Cooper3, A. Judge2 1 Health Economics Research Centre, University of Oxford, Oxford, United Kingdom, 2 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom, 3MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom Objective: Hip fracture is a major public health problem with the majority of sufferers being old, female and vulnerable. Understanding its costs is essential to aid decisions about improvements to health and social care services. We aim to estimate UK hospital costs of hip fracture up to two years post fracture and compare costs before and after the index fracture. Material and Methods: A cohort of patients with hip fracture were identified from the Hospital Episode Statistics database and followed until death or administrative censoring. All records (inpatient stay, day cases, outpatient consultations, emergency attendances, and critical care) between 2003 and 2013 were extracted before and after index admission and valued using 2012/13 unit costs. Non-parametric censoring methods were used to adjust for censoring when estimating average annual costs and a generalised linear model was used to examine the main variables associated with cost variations. Results: 33152 patients were identified as having a hip fracture. Mean age was 83 years (SD 8.2) with women
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accounting for 75 % of the sample. Mean censoradjusted 1- and 2-year hospital costs after index hip fracture were £14,163 (95%CI: £14,008 to £14,317) and £16,302 (95%CI: £16,097 to £16,515) respectively. Index admission due to hip fracture accounted for 60 % (£8613; 95%CI: £8565-£8661) of total 1-year hospital costs, and index hip fracture and refracture (second) costs were very similar. In the year of hip fracture, the mean annual hospital costs increased by £10,964 compared to the year pre-event (p
World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Oral Communication Abstracts # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
OC1 ODANACATIB ANTIFRACTURE EFFICACY AND SAFETY IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: RESULTS FROM THE PHASE III LONG-TERM ODANACATIB FRACTURE TRIAL (LOFT) M. R. McClung1, B. Langdahl2, S. Papapoulos3, K. G. Saag4, S. Adami5, H. G. Bone6, T. De Villiers7, D. P. Kiel8, A. Kung9, P. Kumar KM10, S.-K. Lim11, X. Ling12, K. Lippuner13, C. Mautalen14, T. Nakamura15, J.-Y. Reginster16, I. R. Reid17, J. A. Rodrίguez-Portales18, C. Roux19, J. Walliser20, N. B. Watts 21, J. Zanchetta 22 , C. A. F. Zerbini 23, A. RybakFeiglin24, D. Cohn24, C. A. DaSilva24, R. Massaad25, A. C. Santora24, B. B. Scott24, K. D. Kaufman24, N. Verbruggen25, A. Leung26, A. Lombardi24 1 Oregon Osteoporosis Center, Portland, OR, United States, 2 Aarhus University Hospital, Aarhus, Denmark, 3Leiden University Medical Center, Leiden, Netherlands, 4University of Alabama at Birmingham, Birmingham, AL, United States, 5 University of Verona, Verona, Italy, 6Michigan Bone & Mineral Clinic, Detroit, MI, United States, 7Stellenbosch University, Stellenbosch, South Africa, 8Institute for Aging Research, Hebrew Senior Life, Harvard Medical School, Boston, MA, United States, 9University of Hong Kong, Pokfulam, Hong Kong, 10Bangalore Diabetes Hospital, Bangalore, India, 11Yonsei University, Seoul, Republic of Korea, 12Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China, 13Bern University Hospital, Bern, Switzerland, 14 Centro de Osteopatίas Médicas, Buenos Aires, Argentina, 15University of Occupational & Environmental Health, Fukuoaka, Japan, 16 CHU-Centre Ville, Policliniques BRULL, Liège, Belgium, 17 University of Auckland, Auckland, New Zealand, 18 Pontificia Universidad Católica de Chile, Santiago, Chile, 19 Paris Descartes University, Cochin Hospital, Paris, France, 20 Bone Metabolism Clinic, Hospital Angeles del Pedregal, Mexico City, Mexico, 21Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, United States, 22IDIM Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 23 Centro Paulista de Investigações Clinicas, São Paulo, Brazil,
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Merck & Co., Inc., Whitehouse Station, NJ, United States, MSD Europe Inc., Brussels, Belgium, 26Formerly Merck & Co., Inc., Whitehouse Station, NJ, United States
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Objective: The Phase III Long-Term Odanacatib (ODN) Fracture Trial (LOFT; NCT00529373) is a randomized, double-blind, placebo-controlled, event-driven trial evaluating the efficacy and safety of ODN, an oral selective inhibitor of cathepsin K, in reducing osteoporotic fracture risk. Material and methods: Postmenopausal women ≥65 years with BMD T-score≤−2.5 at total hip (TH) or femoral neck (FN), or with prior radiographic vertebral fracture (VFx) and T-score≤−1.5 at TH or FN, were randomized to ODN 50 mg/ week or placebo. Patients received vitamin D (5600 IU/week), plus calcium to achieve intake of 1200 mg/d. Primary endpoints were: new/worsening morphometric VFx; hip fractures; nonvertebral fractures. Secondary endpoints included clinical VFx; BMD; bone turnover markers. Safety/ tolerability measures included independent adjudication of adverse events (AEs) of special interest. Results: 16,713 women were randomized; 16,071 were included in analysis. Mean age was 72.8 years; 46.5 % had prior radiographic VFx. Mean BMD T-scores were: TH −2.4; FN −2.7; lumbar spine (LS) -2.7. Mean follow-up was 34.5 months. Versus placebo, ODN treatment resulted in relative risk reductions of: 54 % for new/worsening morphometric VFx; 47 % for hip fractures; 23 % for nonvertebral fractures; 72 % for clinical VFx (p Conclusion: ODN significantly reduced osteoporotic fracture risk versus placebo in women with postmenopausal osteoporosis. Acknowledgments: This study was sponsored by Merck & Co., Inc. Author conflicts of interest: Awards/grants: Amgen (MRM, BL, KGS, HGB, IRR, CAFZ), Bongrain (CR), Lilly (BL, DPK, CR, CAFZ), Merck (MRM, BL, KGS, HGB, DPK, XL, IRR, JAR-P, NBW, CAFZ), MSD (CR), Novartis (IRR, CAFZ), NPS (NBW), Pfizer (CAFZ), Roche (CAFZ). Speakers’ bureaux: Amgen (BL, NBW), GSK (JZ), Lilly (BL), Merck (BL, NBW, CAFZ), Pfizer (TdV, CAFZ). Consulting fees: AbbVie (NBW), Abiogen (SA), Amarin
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(NBW), Amgen (MRM, BL, SP, KGS, SA, HGB, TdV, DPK, KL, TN, CR, NBW), Asahi-Kasei (TN), Axsome (SP), BMS (NBW), Chugai (TN), Corcept (NBW), Endo (NBW), GSK (SP), Imagepace (NBW), Janssen (NBW), Lilly (MRM, BL, KGS, SA, DPK, KL, IRR, CR, NBW, CAFZ), Merck (MRM, BL, SP, KGS, SA, HGB, TdV, DPK, CM, IRR, JAR-P, CR, NBW, JZ, CAFZ), MSD (KL, TN), Novartis (SP, HGB, DPK, IRR, NBW), Noven (NBW), Pfizer (NBW), Radius (NBW), Roche (SA), Sanofi-Aventis (NBW), Servier (CM), UCB (KL, CR). Speakers’ fees: Amgen (MRM, HGB), Merck (MRM, HGB). Royalties: Kluwer Wolter (DPK). Holds stocks and bonds: OsteoDynamics (NBW). J-YR unspecified support from MSD, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GSK, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee, Pharma, Zodiac, Danone, Will Pharma, Amgen. Member of Board of Trustees for the International Osteoporosis Foundation (SP). Employee: Merck & Co., Inc (AR-F, DC, CADS, RM, AS, BBS, KDK, NV, ALo, Ale [at time of study]). Nothing to disclose: AK, PK, S-KL, JW. OC2 THE BMD RESPONSE TO BLOSOZUMAB IS INDEPENDENT OF INITIAL AGE, BODY MASS INDEX, AND BMD IN POSTMENOPAUSAL WOMEN WITH LOW BMD: RESULTS OF A PHASE 2 RANDOMIZED CLINICAL TRIAL B. Mitlak1, A. Chiang1, F. Marin2, J. Krege1, C. Benson1 1 Eli Lilly and Company, Indianapolis, United States, 2Lilly Europe, Windlesham, United Kingdom Objective: In a recent double-blind study of women with low BMD, 52 weeks of treatment with blosozumab, a humanized antibody targeted to sclerostin, increased lumbar spine (LS) and total hip BMD.1 BMD decreased after stopping treatment, but remained significantly higher than placebo after 52 weeks of follow-up in the prior blosozumab 270 mg every 2 weeks (Q2W) and 180 mg Q2W groups.2 In the same cohort, we evaluated the relationship between treatment effect and the patient’s initial age, BMI, and BMD. Material and Methods: Patients were randomized in parallel to blosozumab 180 mg Q4W, blosozumab 180 mg Q2W, blosozumab 270 mg Q2W, or placebo. BMD was assessed by DXA after 52 weeks of treatment. Absolute change in spine and total hip BMD from baseline to 52 weeks was evaluated within each treatment group for women above and below the median age and BMI, and above and below a LS T- score of −2.5 for the overall cohort, as predefined in the study protocol. Statistical analyses were conducted using a repeated measures model with Dunnett’s multiplicity adjustment. Results: Of 120 randomized patients, 108 had efficacy measures at 52 weeks. The median baseline age was 65.9 y (range 50.2-83.5 y); BMI was 23.0 kg/m2 (range 14.8-40.5 kg/m2);
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and LS T-score was −2.76 (range −4.03 to −1.52). The effect of blosozumab to increase spine and total hip BMD at 52 weeks was similar for women above and below the median age and BMI, and a LS T-score −2.5 (each interaction p>0.10). Conclusion: In this phase 2 study cohort, blosozumab increased spine and total hip BMD similarly across a range of age, BMI, and disease severity. References: 1. Recker et al., J Bone Miner Res 2014; doi:10. 1002/jbmr.2351. 2. Benson et al., J Bone Miner Res 2014;29(Suppl 1). Disclosures: The study was funded by Eli Lilly and Company. B Mitlak, A Chiang, F Marin, J Krege, and C Benson are employees and shareholders of Eli Lilly and Company. Acknowledgements: The authors acknowledge Jennifer Harris, Pharm.D., an employee of Eli Lilly and Company, for assistance with abstract preparation and submission. OC3 RESULTS OF 2 YEARS OF ROMOSOZUMAB T R E AT M E N T F O L L O W E D B Y 1 Y E A R O F DENOSUMAB OR PLACEBO IN POSTMENOPAUSAL WOMEN WITH LOW BONE MINERAL DENSITY M. R. McClung1, A. Chines2, J. P. Brown3, A. Díez-Pérez4, H. Resch5, J. Caminis6, M. A. Bolognese7, S. Goemaere8, H. G. Bone9, J. R. Zanchetta10, J. Maddox2, O. Rosen2, S. Bray11, A. Grauer2 1 Oregon Osteoporosis Center, Portland, United States, 2 Amgen Inc., Thousand Oaks, United States, 3 Laval University and CHU de Québec Research Centre, Quebec City, Canada, 4Autonomous University of Spain, Barcelona, Spain, 5St. Vincent Hospital, Vienna, Austria, 6UCB Pharma, Raleigh, United States, 7 Bethesda Health Research Center, Bethesda, United States, 8Ghent University Hospital, Ghent, Belgium, 9 Michigan Bone and Mineral Clinic, Detroit, United States, 10Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 11Amgen Ltd., Cambridge, United Kingdom Objective: Romosozumab (Romo) increased BMD and bone formation, and decreased bone resorption after 1 yr in postmenopausal women with low BMD (McClung NEJM 2014). Here, we report results of 2 yrs of Romo treatment, followed by 1 yr of denosumab (DMAb) or placebo (pbo). Methods: This study enrolled 419 postmenopausal women with a lumbar spine (LS), total hip (TH), or femoral neck Tscore≤−2.0 and≥−3.5. For the results here, women received Romo (70 mg QM, 140 mg QM, 210 mg QM, 140 mg Q3M, or 210 mg Q3M) or pbo for 2 yrs. After 2 yrs, eligible women entered a 1-yr extension and were re-randomized within their original groups to DMAb or pbo. Results: Romo led to rapid and marked increases in BMD during yr 1 and continued increases through yr 2. Largest gains were observed with Romo 210 mg QM, with increases of 15.7 % (LS) and 6.0 % (TH) (Figure). Women receiving
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Romo 210 mg QM who transitioned to DMAb continued to accrue BMD at a rate similar to that in the 2nd yr of Romo; in those transitioned to pbo, BMD returned toward pretreatment levels. Romo induced rapid stimulation of bone formation (P1NP) and decreased bone resorption (CTX). Increases in P1NP were transitory, returning toward baseline (BL) within 6–12 months and remaining below BL through yr 2. CTX remained below BL through yr 2. For those receiving Romo 210 mg QM who transitioned to DMAb, P1NP and CTX decreased; for those transitioned to pbo, P1NP gradually returned to BL, while CTX initially increased above BL and gradually returned toward BL. Adverse events were balanced between the Romo and pbo groups during the first 2 yrs of the study (except for injection site reactions, most reported as mild) and during yr 3. Conclusion: The treatment effects observed with Romo are further augmented by follow-on treatments like DMAb.
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Disclosures: Amgen Inc and UCB Pharma sponsored this study. MR McClung (Research grants, consulting fees, and/ or speakers bureau - Amgen, Eli Lilly, and Merck); A Chines, J Maddox, O Rosen, S Bray, and A Grauer (Employees and stock/stock options - Amgen); JP Brown (Research grants, advisory boards, and/or conferences - Abbott, Amgen, BMS, Eli Lilly, Merck, sanofi-aventis, Novartis, Pfizer, Roche, Servier, Takeda, and Warner Chilcott); A Diez-Perez (Stock options or bond holdings, consulting fees, and/or speakers bureau - Active Life Scientific, Amgen, Eli Lilly, MSD, and Novartis); H Resch (Research grants and speaker fees Amgen, Eli Lilly, MSD, and Novartis; Advisory boards - Eli Lilly, Amgen, and MSD); J Caminis (Employee and stock/ stock options - UCB); MA Bolognese (Research grants and/ or advisory boards - Amgen, Eli Lilly, Genentech, NOF, and VIVUS); S Goemaere (Research grants and speaker fees Amgen, Eli Lilly, MSD, and Novartis; Advisory boards - Eli Lilly and UCB); HG Bone (Research grants, advisory council, consulting fees, and/or speakers bureau - Amgen, Merck, Novartis, and Tarsa); JR Zanchetta (Research grants and/or consulting fees - Amgen, Eli Lilly, GSK, MSD, Pfizer, and Radius) OC4 DENOSUMAB TREATMENT IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS FOR UP TO 9 YEARS: RESULTS THROUGH YEAR 6 OF THE FREEDOM EXTENSION S. Papapoulos 1 , C. Roux 2 , H. G. Bone 3 , P. Dakin 4 , E. Czerwiński5, D. Frey6, D. Kendler7, E. M. Lewiecki8, J. Malouf9, D. Mellström10, J.-Y. Reginster11, H. Resch12, N. S. Daizadeh4, A. Wang4, M. Gavin4, R. B. Wagman4, M. L. Brandi13 1 Leiden University Medical Center, Leiden, Netherlands, 2 Paris Descartes University, Paris, France, 3 Michigan Bone & Mineral Clinic, Detroit, United States, 4Amgen Inc., Thousand Oaks, United States, 5 Krakow Medical Center, Krakow, Poland, 6University Hospital of Zurich, Zurich, Switzerland, 7University of British Columbia, Vancouver, Canada, 8New Mexico Clinical Research & Osteoporosis Center, Albuquerque, United States, 9Universitat Autònoma de Barcelona, Barcelona, Spain, 10Sahlgrenska University Hospital, Göteborg, Sweden, 11University of Liège, Liège, Belgium, 1 2 St. Vincent Hospital, Vienna, Austria, 13 University of Florence, Florence, Italy Objective: To report the results through year 6 of the FREEDOM open-label Extension (Ext), representing up to 9 years of continued denosumab (DMAb) for the treatment of postmenopausal osteoporosis. Material and Methods: During the Ext, all women received 60 mg DMAb every 6 months, and daily calcium and vitamin D. At Ext year 6, bone turnover markers, nonvertebral fracture
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incidence, and adverse events were evaluated. In these analyses, women in the long-term group received up to 9 years of DMAb (3 years in FREEDOM and up to 6 years in the Ext); women in the cross-over group received up to 6 years of DMAb (3 years of placebo in FREEDOM and up to 6 years of DMAb in the Ext), allowing replication of results from the long-term group. Results: Of the women who enrolled in the Ext, 3,098 (68 %) were still on study at the beginning of year 6, with a mean age of 79 years (range 68–98 years). In both groups, serum CTx and P1NP were similarly reduced after each DMAb dose. The characteristic attenuation was observed through each dosing period and reductions were sustained through Ext year 6. The yearly incidences of nonvertebral (Figure) and major nonvertebral fractures remained low in both groups. Rates of adverse events and serious adverse events were consistent with previously reported Ext data. In Ext year 6, 2 events were adjudicated positive for ONJ in the cross-over group; there were no cases of atypical femoral fracture in either group.
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Conclusion: In this aging population, DMAb treatment for up to 9 years maintained reduced bone turnover and was associated with continued low incidence of nonvertebral and major nonvertebral fractures. The benefit/risk profile remained favorable. Disclosures: S Papapoulos: Consultant/Advisory activities Amgen Inc., Axsome, Gador, GSK, Merck, Novartis, UCB; Board membership - IOF. C Roux: Grant/Research support Bongrain, Lilly, MSD; Consultant/Advisory activities Amgen Inc., MSD; Board membership - Amgen Inc., MSD, UCB. HG Bone - Grant/Research support - Amgen Inc., Merck, Novartis; Consultant/Advisory activities - Amgen Inc., Merck, Mission, Novartis. P Dakin, NS Daizadeh, A Wang, M Gavin, and RB Wagman: Company employee Amgen Inc.; Stock/Stock options - Amgen Inc. E Czerwiński: Grant/Research support - Amgen Inc. D Frey: Grant/Research support - Abbott, Amgen Inc., DaiichiSankyo, Novartis, UCB; Consultant/Advisory activities Amgen Inc., Meda, Takeda. D Kendler: Grant/Research support - Amgen Inc., Astalis, Astra Zeneca, Eli Lilly, GSK,
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Novartis; Consultant/Advisory activities - Amgen Inc., Eli Lilly, GSK, Merck, Pfizer; Speaker’s bureau - Amgen Inc., Eli Lilly, Novartis. EM Lewiecki: Grant/Research support - Amgen Inc., Lilly, Merck; Consultant/Advisory activities - AgNovos, Alexion, Amgen Inc., Lilly, Merck, NPS, Radius Health; Board membership - National Osteoporosis Foundation, ISCD. J Malouf and D Mellström: Nothing to disclose. J-Y Reginster: Grant/Research support - Amgen Inc., Bristol Myers Squibb, GSK, Lilly, Merck Sharp & Dohme, Novartis, Roche, Rottapharm, Servier, Teva. Consultant/Advisory activities - Amgen Inc., GSK, Lilly, Merckle, Negma, Novartis, NPS, Nycomed, Roche, Servier, Theramex, UCB, Wyeth. Lecture fees - Analis, Ebewee Pharma, Genevrier, GSK, IBSA, Lilly, Merck Sharp & Dohme, Nolver, Novartis, Novo-Nordisk, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Zodiac. H Resch: Grant/Research support - Amgen Inc., Lilly; Consultant/Advisory activities - Amgen Inc., Lilly, MSD; Speaker’s bureau - Amgen Inc., Lilly, MSD, UCB. ML Brandi: Grant/Research support - Abiogen, Alexion, Amgen Inc., Bruno Farmaceutici, Eli Lilly, MSD, NPS, Servier, Shire, SPA; Consultant/Advisory activities - Abiogen, Alexion, Amgen Inc., MSD, NPS, Servier, Shire, SPA; Board membership: Alexion, Servier. OC5 THE POSITION OF STRONTIUM RANELATE IN TODAY’S MANAGEMENT OF OSTEOPOROSIS J.-Y. Reginster 1 , M. L. Brandi 2 , J Cannata-Andia 3 , C. Cooper 4 , B. Cortet 5 , J. M. Feron 6 , H. K. Genant 7 , S Palacios8, J. D. Ringe9, R. Rizzoli10 1 University of Liège, Liège, Belgium, 2 University of Florence, Florence, Italy, 3University of Oviedo, Oviedo, Asturias, Spain, 4 MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom, 5Department of Rheumatology, Roger Salengro Hospital, CHU Lille, Lille, France, 6Service de Chirurgie Orthopédique et Traumatologique, Hôpital Saint Antoine, GHU Est, AP-HP, Paris, France, 7University of California, San Francisco, United States, 8Instituto Palacios, Salud y Medicina de la mujer, Madrid, Spain, 9West German Osteoporosis Center (WOC), Klinikum Leverkusen, University of Cologne, Leverkusen, Germany, 10Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland Osteoporosis accounts for about 3 % of total European healthcare spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost-saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible and without contraindications including uncontrolled
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hypertension, established, current, or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today’s evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today’s management of osteoporosis, with a positive benefit-risk balance provided the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible, and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis. OC6 TRACKING OF 25-HYDROXYVITAMIN D STATUS DURING PREGNANCY R. J. Moon 1 , S. R. Crozier 1 , E. M. Dennison 1 , S. M. Robinson1, H. M. Inskip1, K. M. Godfrey1, C. Cooper1, N. C. Harvey1 1 MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom Objective: When assessed in pregnancy studies, 25(OH)D is usually measured only once. However, it is unknown whether the ranking of an individual’s 25(OH)D is maintained across pregnancy, which crosses several seasons. We therefore assessed the tracking of 25(OH)D from early to late pregnancy in a prospective mother-offspring study, the Southampton Women’s Survey. Material and Methods: At 14 and 34 weeks gestation, serum 25(OH)D was measured, and diet and lifestyle questionnaires completed. We modelled seasonal variation in 25(OH)D separately for each gestation using Fourier transformations, and then calculated the difference between actual 25(OH)D and the modelled value corresponding to the sampling date for each individual [denoted 25(OH)Ddev]. We used Spearman’s rank correlation to test tracking of 25(OH)Ddev from 14 to 34 weeks gestation. Multivariate linear regression was used to determine factors associated with changes in 25(OH)Ddev ranking. Results: 25(OH)D was available in 2060 and 2332 women at 14 and 34 weeks, respectively, with 1756 women included at both gestations. 25(OH)Ddev tracked moderately from 14 to 34 weeks (r=0.57, p80 years). The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages. OC35 REDUCED FRACTURE RISK IN DANISH WOMEN WITH POLYCYSTIC OVARY SYNDROME: A NATIONAL REGISTER-BASED COHORT STUDY K. H. Rubin1, D Glintborg2, M. Nybo3, M. Andersen4, B. Abrahamsen5 1 Odense Patient Data Exploratory Network, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark, 2 Department of Endocrinology, Odense University Hospital, Odense, Denmark, 3 Clinical Biochemistry, Odense University Hospital, Odense, Denmark, 4 Department of Endocrinology M, Odense University Hospital, Odense, Denmark, 5OPEN, Institute of Clinical Research, University of Southern Denmark, Glostrup, Denmark Objective: To investigate fracture risk in patients with polycystic ovary syndrome (PCOS). We hypothesized that fracture risk could be lower in patients with PCOS than in healthy controls due to hyperandrogenemia and obesity. Material and Methods: Women with PCOS or hirsutism (ICD-10 codes L680 and E282) were identified in the Danish National Patient Register (NPR) from 1995–2012. Three age-matched controls were included per patient and were assigned the same index date as their matched PCOS
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case. Subjects with a history of hyperprolactinemia, acromegaly, Cushing’s disease, adrenogenital syndrome, and Turner syndrome were excluded. We identified incident fractures by ICD10 codes and used conditional Cox regression analysis to compare fracture risk. We focused on overall fracture risk and fractures of the appendicular skeleton rather than fractures of the spine or hip, which are rare in the age group. Results: We included 19,199 patients with PCOS and 57,483 control subjects. The mean (range) age was 30.6 (12–60) years. The overall risk of fractures was significantly lower in PCOS (HR 0.74; 95%CI 0.70-0.78, p Conclusion: This study demonstrates that women with PCOS have a substantially reduced risk of fractures, in particular of the appendicular skeleton, which could perhaps be accounted for by hyperandrogenism or obesity. However, the reduced incidence of fractures of the face and hands may also suggest a difference in the exposure to direct trauma such as for example in contact sports. Additional research is needed to determine the mechanism behind the risk reduction. OC36 IMPACT OF HIP FRACTURE ON HOSPITAL CARE COSTS: A POPULATION BASED STUDY J. Leal1, A. M. Gray1, M. K. Javaid2, D. Prieto-Alhambra2, N. K. Arden2, C. Cooper3, A. Judge2 1 Health Economics Research Centre, University of Oxford, Oxford, United Kingdom, 2 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom, 3MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom Objective: Hip fracture is a major public health problem with the majority of sufferers being old, female and vulnerable. Understanding its costs is essential to aid decisions about improvements to health and social care services. We aim to estimate UK hospital costs of hip fracture up to two years post fracture and compare costs before and after the index fracture. Material and Methods: A cohort of patients with hip fracture were identified from the Hospital Episode Statistics database and followed until death or administrative censoring. All records (inpatient stay, day cases, outpatient consultations, emergency attendances, and critical care) between 2003 and 2013 were extracted before and after index admission and valued using 2012/13 unit costs. Non-parametric censoring methods were used to adjust for censoring when estimating average annual costs and a generalised linear model was used to examine the main variables associated with cost variations. Results: 33152 patients were identified as having a hip fracture. Mean age was 83 years (SD 8.2) with women
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accounting for 75 % of the sample. Mean censoradjusted 1- and 2-year hospital costs after index hip fracture were £14,163 (95%CI: £14,008 to £14,317) and £16,302 (95%CI: £16,097 to £16,515) respectively. Index admission due to hip fracture accounted for 60 % (£8613; 95%CI: £8565-£8661) of total 1-year hospital costs, and index hip fracture and refracture (second) costs were very similar. In the year of hip fracture, the mean annual hospital costs increased by £10,964 compared to the year pre-event (p
