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osteophyte formation, ligamentous laxity, weakening of periarticular muscles and, in some cases, synovial inflam- mation. These changes may occur as a result ...
Osteoporos Int (2013) 24 (Suppl 1):S69–S86 DOI 10.1007/s00198-013-2310-0

European Congress on Osteoporosis and Osteoarthritis (ESCEO13-IOF): ESCEO Symposia Abstracts

# International Osteoporosis Foundation and National Osteoporosis Foundation 2013

SE1 INCIDENCE AND BURDEN Cyrus COOPER1 1 MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, Oxford, UK OA is a joint disorder involving the cartilage and many of its surrounding tissues. In addition to damage and loss of articular cartilage, there is remodelling of subarticular bone, osteophyte formation, ligamentous laxity, weakening of periarticular muscles and, in some cases, synovial inflammation. These changes may occur as a result of an imbalance in the equilibrium between the breakdown and repair of the joint tissue. Primary symptoms of OA include joint pain, stiffness and limitation of movement. Disease progression is usually slow but can ultimately lead to joint failure with pain and disability. OA may develop in any joint, but most commonly affects the knees, hips, hands, facet joints and feet. In 2005, it was estimated that over 26 million people in the USA had some form of OA. The prevalence of OA, however, varies greatly depending on the definition used, age, sex and geographical area studied. A radiographic case definition of OA results in the highest reported prevalence. The incidence of hand, hip and knee OA increases with age, and women have higher rates than men, especially after the age of 50 years. A levelling off or decline occurs at all joint sites around the age of 80 years. The age- and sexstandardised incidence rate from the Fallon Community Health Plan in Massachusetts (USA) was highest for knee OA 240/100,000 person-years, with intermediate rates for hand OA (100/100,000 person-years) and lowest observed rates for hip OA (88/100,000 person-years). Prevalence rates for knee OA, based on population studies in the USA, are comparable to those on Europe. These studies report that severe radiographic changes affect 1 % of people

aged 25–34 and this figure increases to nearly 50 % in those 75 years and above. Among participants aged over 45 years in the Framingham Study, the prevalence of radiographic knee OA was 19.2 % and, in those over 80 years, the figure rose to 43.7 %. According to data produced by the Dutch Institute for Public Health, the prevalence of knee OA in those aged 55 and above was 15.6 % in men and 30.5 % in women. The prevalence of symptomatic knee OA is significantly lower: just 12.1 % in NHANES III and 16.3 % in participants aged 55–64 of Johnston County Osteoarthritis Project. Disease progression is usually slow but can ultimately lead to joint failure with pain and disability. OA of the hips and knees tends to cause the greatest burden to the population as pain and stiffness in these large weightbearing joints often leads to significant disability requiring surgical intervention.

SE2 NATURAL HISTORY AND OUTCOMES Flavia CICUTTINI1 1 School of Public Health and Preventive Medicine/Monash University/Alfred Hospital, Melbourne, Australia Osteoporosis (OP) and osteoarthritis (OA) are both major public health problems that are associated with aging. Over recent decades, significant progress has been made in understanding the natural history of bone changes and how they relate to osteoporosis and subsequent risk of fracture. This has enabled the development of effective preventive and therapeutic interventions for OP. There are significant lessons to be learnt from OP as we tackle OA, where effective disease modifying interventions are still limited. Although the hallmark of disease progression in OA is progressive articular cartilage loss, it is increasingly clear that OA is a disease of the whole joint. Thus the focus of

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work examining outcomes in OA, as well as including methods of assessment of articular cartilage, has expanded to include measures of bone including shape and bone marrow lesions, as well also changes associated with inflammation such as synovitis and joint effusion. Much of this new work has been possible through the advent of novel, noninvasive methods for assessing joints, in particular MRI. Through the use of MRI, it is possible to examine joints in a validated, sensitive way from normal through to disease and to measure disease progression. This has paved the way for greater understanding of the natural history of OA and the potential mechanism of action of modifiable risk factors for OA such as physical activity and obesity. The important role of bone in OA is highlighted by the interesting new developments in OA whereby a number of therapies used in OP are being found to be effective in reducing disease progression in OA. These two diseases which for so long have been examined in parallel clearly have significant overlap.

SE3 HUMAN GENETICS OF OSTEOARTHRITIS AND OSTEOPOROSIS Ana M. VALDES1 1 Dept of Twin Research, King's College London, and Dept of Academic Rheumatology, University of Nottingham, Nottingham, UK Osteoarthritis (OA) and osteoporosis (OP) are a major cause of morbidity and mortality in European population requiring a sustained medical management. Both diseases are characterised by abnormalities of skeletal biology and physiology. In OA there is involvement of the articular cartilage and underlying bone. For OP involvement of both the peripheral and axial skeleton occurs. Both diseases are also clearly associated with ageing with important clinical consequences, and both have a substantial genetic contribution. Using genomewide approaches numerous genetic loci have been associated with both OA and OP. To date at least 56 loci have shown robust association with BMD containing an even larger number of candidate genes potentially underlying these genetic signals. Many of these variants map in the vicinity of genes of unknown function (representing cutting edge new biology), while several other factors cluster within critical biological pathways relevant for bone biology like Wnt signaling, OPG-RANK-RANKL and mesenchymal cell differentiation. Thus far, these genes identified by genomewide association scan (GWAS) studies incorporate variants which together explain 3-4 % of the variation in BMD. GWAS Studies for OA have identified 13 loci associated with OA of the hip or the knee, some of them involved in known pathways for skeletal development, such as DOT1L in the Wnt signalling pathway and the growth differentiation

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factor from the bone morphogenetic protein family. The role in OA of many other genes remains to be elucidated. Most genes contribute only modestly to disease risk individually (odds ratios 95 linguistically validated alternate languages for hip and knee OA, has also been developed in 57 linguistically valid alternate language forms in prehip fracture and posthip fracture formats. Interpretation of the response of individual patient's response to treatment and their attained health state requires clinical benchmarking against published standards. In contrast to OP, the development of clinical benchmarks is more advanced in OA where there are responder criteria (OMERACT-OARSI, MCII, MPCI, WOMAC 20-50-70, AUSCAN 20-50-70), state-attainment criteria (PASS, BLISS) and age-and gender-specific general-populationbased normative values for the WOMAC NRS3.1 and AUSCAN NRS3.1 Indices. Finally the evolution from traditional paper-based to electronic methods of data capture is advancing, and experience with telephone interview, computer, hand-held device, webbased and mobile phone-based approaches to capturing patient responses is rapidly expanding. The opportunity to performing repeated, remote independent data capture of the patient's health status using validated mobile phone based applications has been confirmed in OA using the WOMAC NRS3.1 Index.

SE9 OSTEOPOROSIS AND OSTEOARTHRITIS: SIMILARITIES AND DIFFERENCES Jonathan D. ADACHI1 1 Department of Medicine Michael G. Degroote School of Medicine St Joseph's Healthcare - McMaster University, Hamilton, ON, Canada Today most individuals are interested in 'Quality of Life' and not quantity. They would like to enjoy the life they have rather than living in misery and as a result are interested in those interventions that will improve their quality of life. This is very true for those suffering from either osteoporosis or osteoarthritis. In the early years both are quiescent with the odd ache or self-limited pain. As both progress these aches and pains play an increasing role in day to day living until the end stages of advanced disease where pain is a constant reminder of the underlying condition.

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Health related quality of life (HRQoL) has increasing been recognized as an important outcome in clinical trials of osteoporosis and osteoarthritis. Both conditions have trials utilizing health utilities either in the form of the EQ-5D or the Health Utilities Index, or a generic instrument like the Rand Short Form-36 (SF-36) Both have disease specific instruments such as the WOMAC for osteoarthritis of the knee and Auscan for osteoarthritis of the hand and the QUALEFFO, OPAQ or miniOQLQ for osteoporosis. Indeed in osteoarthritis it is not enough to demonstrate that joints may be preserved, but it is equally important to demonstrate reduction in pain to receive drug approval. In osteoporosis HRQoL has been incorporated in clinical trials to demonstrate therapeutic efficacy. In osteoporosis, hip and clinical vertebral fractures are well recognized as fractures that play a major role in reducing HRQoL, however all recent work suggests that all fractures have an effect on HRQoL. For incident clinical vertebral fractures the impact is immediate and may get progressively worse with time particularly in terms of pain and physical function. Of importance, but poorly recognized is the reduction in HRQoL associated with non-vertebral, non-hip fractures. Emotional well being is also affected. There is a measurable decline in overall health with increased mortality being associated with vertebral fractures, in addition to hip fractures. Similar to osteoporosis, with osteoarthritis there is a decline in physical function and emotional health particularly as it relates to osteoarthritis of the knee. An often overlooked cause of reduced HRQoL is osteoarthritis of the hand and its influence has clearly been underestimated. Indeed when compared to a recognized cause of pain and dysfunction like rheumatoid arthritis, those with osteoarthritis have pain which is similar in magnitude with a reduction in function that is not quite as severe as seen in patients with rheumatoid arthritis. Exercise has long been promoted as a benefit in health related quality of life for subjects with both osteoarthritis and osteoporosis. However adherence with an exercise program is often poor, given the ongoing pain and symptoms, and the confusion around the best forms of exercise, the amount and the duration. Supervised and group programs seem to have better adherence, with individualized programs presumably having the best results. Most who participate do recognize the benefits including reduction in pain and an overall sense of well being. In summary HRQoL is an often overlooked outcome in osteoporosis and osteoarthritis. Significant reductions in HRQoL affect patient well being. It is not about 'quantity' but 'quality of life'. Those with osteoporosis and osteoarthritis understand this well.

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SE10 CONVENTIONAL RADIOGRAPHY IN ASSESSMENT OF OSTEOPOROSIS AND OSTEOARTHRITIS IN CLINICAL RESEARCH Harry K. GENANT1 1 University of California, San Francisco, CA, USA Osteoporosis and osteoarthritis are two of the most common, debilitating and costly disorders afflicting our aging populations. The two conditions contrast sharply in their demographics, manifestations and management, as discussed by other speakers in this symposium. Conventional radiography is commonly used in diagnosing and monitoring osteoporosis and osteoarthritis, but for differing reasons and rationale. In the context of clinical research, radiography provides important parameters for establishing the presence and severity of disease and for monitoring progression as a function of age, disease and intervention. For osteoporosis clinical research radiography is applied for detecting and classifying fracture, the most important c o n s e q u e n c e o f th i s o t h e r w i s e s i l e n t d i s e a s e . Radiography is a good method for diagnosing vertebral fractures, being easy and quick to perform, widely available and of relatively low cost. In randomized clinical trials (RTCs) of osteotrophic agents, radiography often serves as a primary efficacy endpoint, whether in detecting asymptomatic or symptomatic vertebral fractures or in documenting the occurrence of nonvertebral fractures. Since the latter evaluation is generally straightforward, this section on radiography in osteoporosis RTCs focuses on vertebral fracture assessment. Although there is no universally accepted definition of what constitutes a vertebral fracture, there is wide agreement that a vertebral fracture involves a distinct change in morphology along with a decrease in anterior, middle and/or posterior vertebral height. In an effort to produce definable, reproducible and objective radiographic methods for assessing vertebral fracture in RTCs, several approaches have been developed and refined. These radiographic methods can be broadly considered as either semiquantitative (SQ) or quantitative morphometric (QM). The former visually grades vertebrae as normal (0) or mild (1), moderate (2) or severe (3) fracture, with minimum vertebra height reductions of approximately 20 %, 25 % and 40 %, respectively. The quantitative morphometric approaches encompass placement of 4–6 points on the vertebral margins, generally using computer-based software and manual or semiautomated procedures applied to lateral digital images. For both SQ and QM approaches the intra- and inter-reader agreement amongst trained readers is good to excellent with kappa scores of 0.80-

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0.90 for prevalent or incident fractures. Finally, with estimated 1-2 % annual incident vertebral fracture rates in older postmenopausal women, and with reasonably accurate and precise radiographic assessment, the primary efficacy endpoint of reducing osteoporotic vertebral fracture has served well in facilitating approval of the many currently prescribed osteotrophic agents. This experience contrasts sharply with that of imaging in drug approval for reduction of joint structural damage in osteoarthritis. For osteoarthritis clinical research, where chronic symptomatic joint destruction is the hallmark of disease, radiography is applied as a tool for detecting, classifying and monitoring joint damage. Since knee OA represents the commonest debilitating form of osteoarthritis and has received the most attention in RTCs, this section focuses on radiography of the knee, particularly on measuring joint space narrowing (JSN). Radiographic assessment generally utilizes the Kellgren/Lawrence visual scoring system, a composite grading of osteophytes and JSN, or the Altman-OARSI visual scoring, a separate grading of JSN, osteophytes, sclerosis and attrition. However, since progressive cartilage destruction is characteristic of OA, indirect assessment of cartilage loss by measurement of joint space width (JSW) potentially provides the most meaningful radiographic endpoint. Indeed, guidelines of the US and European Regulatory Agencies currently recommend JSN measurement as the gold standard imaging endpoint for assessing disease modifying osteoarthritis drugs (DMOADs). Over the past 15 years, various semiflexed and standardized radiographic protocols have been developed to improve the accuracy, precision and sensitivity to change of JSN assessment in RTCs. Moreover, automated or semiautomated JSW measurements using digitized image analysis software have been documented to be more sensitive and reproducible than manual methods using a ruler or a magnifying lens. Accordingly, medial JSN progression assessed by serial radiography in well controlled studies is generally found to be~0.1-0.2 mm/yr with modest standard deviations of~ ±0.4-0.6 mm/yr. Further, with excellent training, intra- and inter-reader reproducibility (ICCs) of ≥0.90 for JSW, smallest detectable differences (SDDs) of ~ 0.5-0.8 mm and standardized response means of~0.4-0.8 have been found in longitudinal studies. However, despite the care in acquiring images and in conducting these radiographic analyses in knee OA RTCs, the very small longitudinal progression of JSN and the variances observed in the recruited populations have resulted in considerable challenges for the development and approval of potential DMOADs. To date, very few candidate drugs have met the regulatory bar of reduced cartilage damage evidenced radiographically by reduction in JSN, and no DMOAD has yet received approval from the major Regulatory Agencies.

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SE11 ASSESSMENT OF STRUCTURAL OUTCOMES WITH IMAGING Jean-Pierre RAYNAULD1 1 Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Canada This lecture will review the different aspects of clinical imaging of osteoarthritis (OA) and osteoporosis (OP), exploring common features and differences that specifically characterize both diseases. With the advent of osteodensitometry, relatively small changes in bone mass can be detected and early diagnosis can be established. This outcome tool opened the door to clinical research on new therapies to slow or prevent bone mass loss. It is common knowledge and widely accepted that these medications had positive impacts on osteoporosis outcomes, such as the rate of fractures. Emerging imaging techniques, such as microCT scan, may yield additional and independent predictors of OP progression. Quantitative MRI (qMRI) assessment of cartilage thickness and volume and other structural changes in OA can objectively evaluate the disease course and evaluate treatment that may slow down disease progression (DMOAD agents). Subchondral bone marrow lesions (BMLs) also seen on MRI, are often characterized in the early stage of OA by excessive local bone resorption leading to focal areas of 'osteoporotic' changes. The mechanisms by which these subchondral bone remodelling changes can influence the OA cartilage lesions are likely related to both biomechanical and biochemical changes. The presence and change over time of BMLs may represent a potential connection between OP and OA and provide a rationale for the use of agents that can reduce bone resorption to treat both conditions. However, clinical studies have yet to provide any conclusive evidence of the possible relationship between the two diseases. Recent advances in imaging techniques of OA and OP provide new and interesting insight into a possible relationship between periarticular bone remodelling and the development/progression of OA.

SE12 THE COUPLING OF BONE AND CARTILAGE TURNOVER IN OSTEOARTHRITIS: OPPORTUNITIES FOR BONE ANTIRESORPTIVES AND ANABOLICS AS POTENTIAL OA TREATMENTS? Claus CHRISTIANSEN1, Morten A. KARSDAL1 1 Nordic Bioscience, Herlev, Denmark Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the

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entire joint, including bone and cartilage, thereby affording multiple alternative approaches for treatment. This lecture will summarize emerging observations from cell biology to preliminary clinical trials, describing interactions between the bone and cartilage components. We speculate whether a treatment for OA would be possible without targeting the bone compartment. Bone and cartilage health seem to be tightly associated. Ample evidence is found for bone changes during progression of osteoarthritis, including, but not limited to, increased turnover in the subchondral bone, under mineralization of the trabecular structure, osteophyte formation, bone marrow lesions and sclerosis of the subchondral plate. In addition, a range of investigations has described secondary positive effects on cartilage health when bone resorption is suppressed, or deterioration of the cartilage when resorption is increased. An optimal treatment for OA likely includes targeting both the bone and cartilage compartments of the joint and possibly the synovium; estrogens, selective estrogen receptor modifiers (SERMs), bisphosphonates, calcitonin and PTH may provide OA therapeutic options due to their multifaceted tissue actions.

SE13 PHARMACOLOGICAL MANAGEMENT : OSTEOPOROSIS AND OSTEOARTHRITIS, SIMILARITIES AND DIFFERENCES Jean-Yves REGINSTER1 1 Department of Public Health Sciences, University of Liège, Liège, Belgium Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and an alteration of bone microarchitecture leading to decreased bone strength and increased fracture rates. Osteoarthritis (OA) is a degenerative disease characterized by a loss of articular cartilage, affecting the entire joint tissues, including subchondral bone. Several investigations were designed in order to assess whether drugs active in osteoporosis may have beneficial effects on the symptomatic or structural management of osteoarthritis. In preclinical studies, several antiresorptive agents exhibited an ability to reduce cartilage degradation and joint space narrowing. This was true for bisphosphonates, selective estrogen receptor modulators, salmon calcitonin and cathepsin K inhibitors. Peptides derived from the parathyroid hormone family were also suggested to have positive effects on animal cartilage. Strontium ranelate (SR), a drug known to concomitantly inhibit bone resorption and stimulate bone formation has also shown to have beneficial effects on cartilage and on subchondral bone, in cellular and animal models. In clinical trials, involving human osteoarthritic subjects, risedronate

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decreased biochemical markers of cartilage degradation but did not decrease symptoms or slow radiographic progression of knee osteoarthritis. Zoledronic acid reduced knee pain and bone marrow lesions, assessed by MRI over a short period of time (six months to one year). Salmon calcitonin decreased biochemical markers of cartilage degradation and increased cartilage volume, assessed by MRI. However, it did not reduce progression of knee osteoarthritis assessed by X-rays. In osteoporotic patients treated with 2 g/day of SR, the proportion of patients with worsening of spinal OA score was reduced by 42 % compared with those receiving a placebo. In patients with knee OA, randomly allocated to SR or placebo, treatment with SR was associated with smaller degradation in joint space than with placebo (both 1 g/day and 2 g/day). Fewer radiological progressors were observed with SR. There were greater reduction in total WOMAC score, pain subscore, physical function subscore and knee pain with SR 2 g/day compared to placebo. In conclusion, whereas several antiosteoporosis medications have, so far, shown ability to interfere with cartilage or subchondral bone metabolism, in cellular or animal models, the only drug which showed a significant effect on symptoms and structure modification of human knee osteoarthritis is SR at the dose of 2 g/day, i.e., the dose currently marketed for the management of osteoporosis.

SE14 NONPHARMACOLOGICAL MANAGEMENT Olivier BRUYÈRE1 1 Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium Besides pharmacological and surgical therapies, nonpharmacological therapies, including but not limited to education and self-management, regular telephone contact, referral to a physical therapist, aerobics, muscle strengthening and water-based exercises, weight management, walking aids, braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation or acupuncture, could be of potential interest in the management of osteoporosis and osteoarthritis. The predominance of evidence on the effects of rehabilitation interventions for both osteoporosis and osteoarthritis suggests that they enable modest health related quality of life relief, reduced disability, and improved function. In both osteoporosis and osteoarthritis, nonpharmacological interventions could be of potential interest in primary (i.e., before the disease), secondary (i.e., at the early stage of the disease) or tertiary prevention (i.e., after fracture in osteoporosis or joint replacement in osteoarthritis). Obviously, there are major differences in the nonpharmacological management of these two diseases. Some treatment modalities could have opposite effects (e.g., weight reduction) or could have different effects depending on the stage of the disease (e.g., active

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weight bearing exercises in painful or normal joint). More researches are needed to identify the modalities (e.g., doses, volume, duration, type, combination) of nonpharmacological treatment that could be the most effective to improve quality of life and functional performance in subjects with osteoporosis and/or osteoarthritis. The combination and the potential added value of pharmacological and nonpharmacological treatment also need to be better investigated.

SE15 SURGICAL MANAGEMENT OF OSTEOPOROSIS COMPARED TO OSTEOARTHRITIS Jörg GOLDHAHN1 1 Institute for Biomechanics of ETH, Zurich, Switzerland Although the underlying pathophysiology differs significantly, the surgical management shows some similarities. In both conditions is the goal of surgical intervention restoration of full function and in both cases joint replacement is a valid option to achieve this goal. However, there are major differences in the surgical pathways of both indications. Whereas joint replacement due to osteoarthritis is an elective procedure, where the complete schedule from presurgical planning to postsurgical rehabilitation can be optimized; hip fracture treatment is always an acute scenario without preplanning. Therefore, more interdisciplinary work, especially with geriatricians, is required to optimize patients for surgery, adapt postsurgical rehabilitation and prevent next fractures, e.g., via falls prevention. The differences in patient characteristics, functional demands but also in surgical pathways result in two distinct entities, which prevent pooling and generalizing both indications.

SE16 QUALITY OF LIFE IN SARCOPENIA AND FRAILTY René RIZZOLI1, Jean-Yves REGINSTER2, Jean-François ARNAL 3 , Ivan BAUTMANS 4 , Heike BISCHOFFFERRARI 5 , Emmanuel BIVER 1 , Steven BOONEN 6 , Maria Luisa BRANDI 7 , Arkadi CHINES 8 , Cyrus C O O P E R 9 , S y n n e v e D A H L I N - I VA N O F F 1 0 , S o l EPSTEIN11, John A. KANIS12, Roger A. FIELDING13, Bret GOODPASTER 14 , Andrea LASLOP 15 , Vincenzo MALAFARINA16, Leocadio RODRIGUEZ MAÑAS17, Bruce MITLAK 1 8 , Richard O. OREFFO 1 9 , Jean PETERMANS 20 , Kieran REID 21 , Yves ROLLAND 22 , Avan Aihie SAYER23, Yannis TSOUDEROS24, Marjolein VISSER25, Olivier BRUYÈRE2 1 Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland, 2Department of Public Health, Epidemiology and Health Economics, University of Liege, Belgium, 3Inserm Research Unit

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1048, Faculty Of Medicine, University Of Toulouse And Chu Of Toulouse, Toulouse, France, 4Gerontology and Frailty in Ageing Research Department, Vrije Universiteit Brussel, Brussels, Belgium, 5Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland, 6Department of Cardiology, Ziekenhuis Oost-Limburg, Gent, Belgium, 7 Department of Internal Medicine, University of Florence, Italy, 8Amgen Inc., USA, 9MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, UK, 10 Vårdalinstitutet, The Swedish Institute for Health Sciences, Universities of Gothenburg and Lund, Sweden, 11 Division of Endocrinology Mount Sinai School of Medicine, New York, USA, 12WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, 13 Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, USA, 14Department of Health and Physical Activity, University of Pittsburgh, Pittsburgh, PA, USA, 15Head of Unit Science and Information at AGES PharmMed Vienna, Austria, 16Department of Geriatrics, Hospital San Juan de Dios, Pamplona, Spain, 17Foundation for Biomedical Research, University Hospital of Getafe, Madrid, Spain, 18Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA, 19 Bone and Joint Research Group, Institute of Developmental Sciences, University of Southampton Medical School, Southampton, UK, 20Service of Geriatrics, CHU of Liege, Belgium, 21 Human Nutrition Research Center on Aging, Tufts University, Boston, USA, 22Gérontopôle of Toulouse, University of Toulouse III, CHU Purpan, Toulouse, France, 23MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, 2 4 Institut de Recherches Internationales Servier, Suresnes, France, 25 Department of Epidemiology and Biostatistics at the EMGO Institute for Health and Care Research of the VU University Medical Centre, Amsterdam, Netherlands The reduced muscle mass and impaired muscle performance that defines sarcopenia in older individuals is associated with increased risk of physical limitation and a variety of chronic diseases. It may also contribute to clinical frailty. A gradual erosion of quality of life (QOL) has been evidenced in these individuals, although much of this research has been done using generic QOL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting, presents the current definitions of these geriatric syndromes (sarcopenia and frailty) and what is known concerning QOL decline with these conditions. It then briefly summarised QOL concepts and specificities in older populations examines the relevant

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domains QOL in an evaluation and calls for a clearer definition of the construct of disability. It is argued that a diseasespecific QOL instrument for sarcopenia/frailty would be an asset for future research and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade off study could be appropriate.

SE17 WHAT IS THE VALUE OF BIOMARKERS FOR DRUG DEVELOPMENT IN OSTEOARTHRITIS? Martin LOTZ1, Johanne MARTEL-PELLETIER2, Claus CHRISTIANSEN3, Francis BERENBAUM4, Maria Luisa BRANDI5, Olivier BRUYÈRE6, Roland CHAPURLAT7, Julien COLETTE8, Cyrus COOPER9, Dick HEINEGARD10, John A. KANIS11, V. KRAUS12, Andrea LASLOP 1 3 , Willem LEMS 1 4 , S. LOHMANDER 15 , I. MEULENBELT16, Jean-Pierre PELLETIER2, Jean-Pierre RAYNAULD 2 , Susan REITER 17 , René RIZZOLI 18 , L. SANDEL19, Tim SPECTOR20, Willem E. VAN SPIL21, Jean-Yves REGINSTER22 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA, 2 Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada, 3 Nordic Bioscience A/S, Herlev, Denmark, 4 Department of Rheumatology, AP- HP, Saint-Antoine Hospital, Pierre and Marie Curie University, Paris, France, 5 Department of Internal Medicine, University of Florence, Italy, 6Department of Public Health, Epidemiology and Health Economics, University of Liege, Belgium, 7 INSERM UMR 1033 and Université de Lyon, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Lyon, France, 8Department of Biomedical and Preclinical Science, University of Liège, Belgium, 9MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, UK, 10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden, 11 WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK, 12 Duke University Medical Center, Division of Rheumatology, Department of Medicine, Durham, NC, USA, 13Austrian Agency for Health and Food Safety, Vienna, Austria, 14 Department of Rheumatology, VU University Medical Centre, Amsterdam, Netherlands, 15 University Hospital, Lund, Sweden, 16Leiden University Medical Centre, Section of Molecular Epidemiology, Leiden, Netherlands, 17Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany, 18Division of

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Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland, 19 Department of Cell Biology and Physiology, Washington University, St Louis, MO, USA, 20St Thomas' Hospital, Kings College London, London, UK, 21University Medical Center Utrecht, Utrecht, Netherlands, 22Dpt of Public Health Epidemiology and Health Economics, University of Liège, Liège, Belgium Osteoarthritis affects the whole joint structure with progressive degradation of cartilage, synovial inflammation, and subchondral bone changes. Biomarkers are being developed to measure dynamic and quantitative changes in joint remodelling and disease progression. This paper was prepared following a European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working meeting convened to discuss the value of biomarkers in drug development in osteoarthritis. The best candidate biomarkers are structural molecules or fragments linked to cartilage, bone, or synovium, and may be specific to one type of joint tissue or common to them all. Many are associated with collagen metabolism in cartilage or subchondral bone, or aggrecan metabolism in cartilage. Other biomarkers are related to noncollagenous proteins, inflammation, or fibrosis. Biomarkers in osteoarthritis can be categorized using the five-point BIPED classification scheme (burden of disease, investigative, prognostic, efficacy of intervention, and diagnostic). There are a number of promising candidates, most notably urinary CTX-II and serum COMP, though none is sufficiently discriminating to aid diagnosis or predict prognosis in individuals with or without osteoarthritis, or performs so consistently that it could function as a surrogate outcome in clinical trials. Future avenues for research include further exploration of underlying mechanisms of disease and development of new biomarkers; technological development (assays, standardization, and calibration) and design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic tests; and further investigation into the relationship between biomarkers and prognosis and risk.

SE18 ASSESSMENT OF TISSUE TURNOVER AND QUALITY IN RHEUMATOLOGY C l a u s C H R I S T I A N S E N 1 , A . C . B AY- J E N S E N 1 , D.J. LEEMING1, Morten KARSDAL1 1 Nordic Bioscience, Herlev, Denmark Osteoarthritis (OA) and osteoporosis (OP) share some common pathological features. However, they are also very distinct; cartilage erosion, subchondral bone formation and synovial fibrosis are common features of OA, in contrast to

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the elevated levels of both bone formation and bone resorption in osteoporosis, albeit with resorption that outstrips bone formation leasing to a net negative tissue balance and bone loss. Importantly, specific biochemical markers of tissue turnover may provide insight both into pathogenesis of disease, but also assist in the identification and development of novel therapeutic. The dysregulation of proteolytical activity is key in the development of both OA and OP, and the result of this dysregulation is an increased tissue turnover including both tissue formation and tissue degradation. The outcome is a net loss of the extracellular matrix of the different bone and joint compartments - as well as changes in the structural components leading to altered matrix quality. Consequently, it is important to investigate both tissue formation and tissue degradation of key proteins. Bone resorbing cells, osteoclasts, express cathepsin K, which degrade type I collagen of the bone, resulting in the release of small, specific carboxy-terminal fragments of type I collagen (CTX-I) released to the circulation, where it can be measured as a biomarkers of bone resorption. Interestingly, there are two different forms of CTX-I, an alpha and beta form, which are derived from resorption of newly formed and old bone, respectively. When used as biomarkers these fragments may distinguish between subchondral bone resorption seen in OA (α-CTX-I) and trabecular bone resorption seen in OP (βCTX). We have shown that α-CTX-I was predictive of joint space narrowing in OA, and that β-CTX is an efficacy marker for antiresorptive treatments such as bisphosphonates. Cathepsin K specific fragments of type I collagen is one example on how proteolytic processes can be used to profile disease events. These biomarkers are referred to as 'Protein Fingerprint', and are gaining increase interest for use in clinical research for 1) prognostic identification of fast progressions and those that are in most need of treatment, 2) diagnostic identification of patients, and lastly 3) early identification of efficacy. Importantly, a marker that may be the best diagnostic marker may not be a prognostic marker, emphasising the need for understanding the exact context and question asked for each individual marker.

SE19 STATE OF THE ART OF A COMPLEX JOINT DISEASE (TREATMENT OF OSTEOARTHRITIS: PRESENT AND FUTURE) Flavia CICUTTINI1 1 School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Australia Abstract not available.

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SE20 JOINT STRUCTURE ASSESSMENT IN THE DIAGNOSIS OF OSTEOARTHRITIS Jean-Pierre RAYNAULD 1 , Jean-Pierre PELLETIER 1 , Johanne MARTEL-PELLETIER1 1 Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada Attempts to evaluate cartilage, bone, and other structural changes related to knee osteoarthritis (OA) and its progression remain a major challenge. This review will define the role of medical imaging and biochemical markers of bone and cartilage turnover in the assessment of the progression of OA structural changes, especially in the context of clinical trials. Joint space width (JSW) as assessed by standardized radiographs has been used for many years and is considered a reliable outcome to assess knee OA progression. Recent clinical trials revealed that knee OA progression may be slowed down by a DMOAD using JSW as an outcome correlated with symptom improvement. MRI allows precise visualization of important joint structures such as cartilage and subchondral bone as well as co-factors of disease progression including changes in the synovium, menisci and ligaments. Quantitative MRI (qMRI) is also capable of measuring accurately the progression of OA changes in several knee structures. Quantitative assessment of cartilage volume/thickness (qMRI) with fat- suppressed gradient echo sequences and digital post-processing techniques displays high accuracy and adequate precision for cross-sectional and longitudinal studies in OA patients. Data on precision, reliability and sensitivity to change of quantitative parameters of cartilage morphology in OA will be reviewed. Longitudinal studies in knee OA suggest a decrease in cartilage volume of about 5 % per year, predominantly in the medial compartment. This decrease in cartilage tissue detected by both JSW and qMRI is strongly associated with the occurrence of a total knee replacement. Moreover, biomarkers of bone (CTX-I) and cartilage (CTX-II) degradation as well as inflammation (CRP, IL-6) have also been shown to be sensitive to the DMOAD impact on disease progression. In knee OA patients, it is now feasible, with the use of imaging techniques and biomarker measurement, to detect the impact of medications (DMOADs) that may slow down disease progression.

SE21 IMPROVING JOINT STRUCTURE IN OSTEOARTHRITIS TREATMENT. NEW PERSPECTIVES

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Cyrus COOPER1 1 MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, UK Abstract not available.

SE22 HEALTH ECONOMICS IN OSTEOARTHRITIS Mickaël HILIGSMANN 1 , Cyrus COOPER 2 , Nigel ARDEN3, Marteen BOERS4, Jaime BRANCO 5, Maria Luisa BRANDI6, Olivier BRUYÈRE7, Francis GUILLEMIN8, Marc HOCHBERG9, David HUNTER10, John A. KANIS11, Tore KVIEN12, Andrea LASLOP13, Florence PETIT-DOP14, Jean-Pierre PELLETIER15, Daniel PINTO16, Susanne REITER17, René RIZZOLI18, Lucio C. ROVATI19, Hans SEVERENS20, Stuart SILVERMAN21, Yannis TSOUDEROS14, Peter TUGWELL22, Jean-Yves REGINSTER7 1 Department of Public Health, Epidemiology and Health Economics, University of Liège, Belgium and CAPHRI School for Primary Care and Public Health, Maastricht University, Netherlands, 2MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, 3 Rheumatic Diseases, Musculoskeletal Epidemiology and Biobank, University of Oxford and Southampton, UK, 4 Department of Epidemiology and Biostatistics, VU Medical Center, Amsterdam, Netherlands, 5 Faculdade Ciências Médicas, da Universidade Nova de Lisboa, and Serviço de Reumatologia, do CHLO,EPE/ Hospital Egas Moniz, Lisboa, Portugal, 6 Department of Internal Medicine, University of Florence, Italy, 7Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium, 8School of Public Health, Faculty of Medicine, University of Nancy, France, 9 Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, USA, 10Medicine, Northern Clinical School, University of Sydney, Sydney, Autralia, 11 Academic Unit of Bone Metabolism, WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK, 12 Dpt of Rheumatology, University of Oslo and Head of the Dpt of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 1 3 Unit Science and Information, AGES PharmMed, Vienna, Austria, 14 Institut de Recherches Internationales Servier, Suresnes, France, 15Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada, 16 Dpt of Physical Therapy and Human Movement Sciences, Feinberg Medical School, Northwestern University,

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Chicago, USA, 17 Bundesinstitut für Arzneimittel und Medizinprodukte, Germany, 18Division of Bone Diseases, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, 19Rottapharm/Madaus, Monza, Italy, 20 Institute of Health Policy and Management, Erasmus University Rotterdam, Netherlands, 21Cedars-Sinai Bone Center of Excellence UCLA School of Medicine, Los Angeles, CA, USA, 22Ottawa Hospital Research Institute, Ottawa, Canada Osteoarthritis is an increasingly frequent debilitating disease in industrialised countries. This represents a major and increasing burden on healthcare expenditure because of the high costs involved with treatment reduced productivity. It is therefore important to be able to evaluate therapeutic approaches in terms of cost-effectiveness as well as efficacy. Pharmacoeconomic studies in this field are rare and in those that do exist, considerable heterogeneity of methodological approaches makes interstudy comparisons problematic. This review and report of an expert working group, presents the epidemiological evidence for the increasing concern for the economic impact of this disease and reviews the current state-of-the-art in health economic investigation in this field. It then examines the relevant outcome measures and discusses the necessity of a definition of a reference case in osteoarthritis (for each of the main affected joints), i.e., the optimal minimal care of patients who are not receiving an active treatment in a controlled study.

SE23 OSTEOPOROSIS IN EUROPE Cyrus COOPER1 1 MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, Oxford, UK Osteoporosis constitutes a major public health problem through its association with age related fractures. These fractures typically occur at the hip, spine and distal forearm. It has been estimated from incidence rates derived in North America that the lifetime risk of a hip fracture in caucasian women is 17.5 %, with a comparable risk in men of 6 %. Age- and sexadjusted hip fracture rates are generally higher in Caucasian than in Asian populations. Furthermore, the pronounced female preponderance in fracture incidence observed in white populations is not seen amongst blacks or Asians in whom age-adjusted female to male incidence ratios approximate unity. Life expectancy is increasing around the globe and the number of elderly individuals is rising in every geographic region. Assuming constant age-specific incidence rates for fracture, the number of hip fractures occurring worldwide among people aged 65 years and over will rise from 1.66

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million in 1990 to 6.26 million in 2050. Studies performed in the United States, Scandinavia, and the United Kingdom, between 1930 and the late 1980s, consistently reported increases in the age-adjusted incidence of hip fractures among men and women. This increase appears to have levelled off, in the northern regions of the United States, as well as more recently in Europe. Rates in Asian populations continue to show substantial rises between the 1960s and the present time. In the most recent data available from the United States, the incidence of first ever hip fracture declined by 1.37 % per year among women and 0.06 % per year among men. The cumulative incidence of a second hip fracture after 10 years was 11 % among women and 6 % among men, when death was treated as a competing risk. The reduction in hip fracture occurrence was even greater than that expected from the declining incidence of hip fractures more generally. Ageperiod-cohort models have suggested influences of all three contributors to these secular trends. Among current risk factors for low bone density and trauma (low BMI, cigarette smoking, alcohol consumption, physical inactivity and dietary calcium intake) the trends are best explained by physical inactivity. Developmental contributors to peak bone and muscle mass, for example maternal nutrition and lifestyle, also appear capable of contributing to cohort effects. Finally, debate continues on the role of more aggressive osteoporosis risk assessment and therapeutic strategies in contributing to the secular decline in hip fracture rates generally. Although pharmacologic intervention might be efficacious, only a minority of hip fracture patients remain so treated, and the scope for even greater reductions in incidence remains an enticing prospect.

SE24 ASSESSMENT OF OSTEOPOROSIS: EUROPEAN GUIDANCE FOR THE DIAGNOSIS, ASSESSMENT AND TREATMENT OF OSTEOPOROSIS Eugene McCLOSKEY1 1 Academic Unit of Bone Metabolism University of Sheffield, Sheffield, UK Whereas BMD provides the cornerstone for the diagnosis of osteoporosis, the use of BMD alone is less than optimal as an assessment of osteoporotic fracture risk or intervention for several reasons. Firstly, the fracture risk varies markedly in different countries, but the T-score varies only by a small amount. Secondly, the significance of any given T-score to fracture risk in women from any one country depends on age and the presence of clinical risk factors. Intervention thresholds will also be determined in part by the cost and benefits of treatment. Whereas assessment guidelines have traditionally been based on BMD, the limitations above have stimulated the development of risk engines that

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integrate several risk factors for fracture. These include the Garvan fracture risk calculator, QFracture (UK only) and FRAX. The use of tools such as FRAX in clinical practice demands a consideration of the fracture probability at which to intervene, both for treatment (an intervention threshold) and for BMD testing (assessment thresholds). For many reasons, including reimbursement issues, health economic assessment, willingness to pay for health care in osteoporosis and access to DXA, it is not possible or desirable to recommend a unified threshold. The new guidance describes a strategy based on currently applied approaches in Europe in the context of postmenopausal osteoporosis, but takes account that access to DXA varies markedly in different European countries(1). It provides a platform on which specific guidelines can be developed for national use. Reference: 1. Kanis JA, McCloskey EV, Johansson H, et al. Osteoporos Int 2013;24:23.

SE25 MANAGEMENT OF OSTEOPOROSIS René RIZZOLI1 1 Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland The decrease in bone mass and the alterations in bone microstructure, which characterize osteoporosis, i.e., mechanical incompetence, lead to an increased bone fragility and a higher risk of fracture. Low energy fractures results also from a stress that a fragile bone cannot withstand, ie mechanical overload. General management include sufficient calcium and protein intakes, vitamin D supplements and regular physical exercises, particularly resistance training and weight-bearing physical activities, which are targetting both components of fracture risk, ie mechanical incompetence and mechanical overload. Most drug therapies are effective in increasing areal BMD, but several decrease the risk of vertebral fracture. Alendronate, basedoxifene, denosumab, ibandronate, intranasal calcitonin, parathyroid hormones, raloxifene, risedronate, hormone replacement therapy, strontium ranelate and zoledronate decrease vertebral fracture risk. For hip fracture, alendronate, denosumab, risedronate, strontium ranelate and zoledronate reduce the risk in women with osteoporosis, hormone replacement therapy in postmenopausal women, and calcium and vitamin D in institutionalized patients. The amino-terminal fragment of PTH as well as the full length molecule stimulate bone remodeling, with a positive bone balance at the BMU level and an increase in volumetric density. This is associated with a marked decrease in vertebral and nonvertebral fracture risk.

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SE26 ESA LIFE SCIENCES PROGRAM Thu Jennifer NGO-ANH1 1 Human Research Unit, Directorate of Human Spaceflight and Operations (HSO-USH), European Space Agency, Noordwijk, Netherlands This presentation will give an overview of recent achievements within ESA's life science programme, and will cover ESA's activities on-board the ISS focusing on human physiology. Understanding of the effects of gravity on physiological functions in humans, as well as elucidation of the basic mechanisms by which these effects occur, are of direct benefit to understanding the impact of, and providing countermeasures for long-term exposure of humans to the microgravity of space flight and the partial gravity of Moon and planetary bases. The results of these studies will also have applications in clinical medicine, especially in pathological conditions related to rehabilitation, ageing, and a sedentary lifestyle.

SE27 BONE TISSUE AND SPACE ENVIRONMENT Laurence VICO1 1 INSERM U1059, Université Jean Monnet, Saint-Etienne, France Space is an extreme environment and a challenge for humans. Crew members are healthy, physically fit and they follow a training program during their mission. Despite this training often vigorous, associated to attempts to ensure an adequate diet, losses of mass and function occurred in the muscles and bones with antigravity functions. We will focus on bone loss and discuss the skeletal effects of microgravity and potential other confounding factors. Bone alteration still remains a key concern for long-term exposure and effective countermeasures have to be developed. We will also focus on the long-term post flight recovery that leaves astronauts unadapted for life with gravity. The abnormal physiology that manifests itself in healthy humans during their adaptation to the microgravity of space has features of accelerated aging. The loss of functional capacities of the mechanoskeletal system that results in space is estimated to be 10 times faster than in the course of aging. Both adaptation to space and aging do not merely parallel but converge as disorders of mechanotransduction. The convergence of the disciplines of aging, along with gravitational and space physiology is advancing the understanding and prevention of modern lifestyle medical disorders.

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SE28 NUTRIENT INTAKE AND BONE TURNOVER IN SPACEFLIGHT Martina HEER1, Scott M. SMITH2 1 University of Bonn and Profil Neuss, Germany, 2NASA JSC, Human Adaptation and Countermeasures Division, TX, USA Reduced mechanical loading, which occurs in spaceflight and immobility, causes increased bone resorption, resulting in an adaptive response of lowering BMD. This effect is exacerbated by inadequate nutrient intake, such as high intake of protein or sodium chloride, both of which most likely induce a low- grade metabolic acidosis. In an attempt to mitigate acidosis, multiple experiments have been carried out in microgravity or in analog environments (head-down-tilt bed rest) to examine the effect of decreasing the ratio of animal protein to potassium in the diet or supplementing a high-protein or high sodium chloride diet with potassium bicarbonate. Results from these experiments have clearly shown that the increase in bone resorption markers seen with high protein intake can be almost fully compensated. On the other hand, when a diet high in sodium chloride is supplemented with potassium bicarbonate to compensate for the increased metabolic stress, excretion of N-telopeptide, one of the bone resorption markers, was only 8 % less than with high sodium chloride intake alone. In all studies calcium supply was adequate. We conclude from these results that in spaceflight adequate nutrient supply is of particular importance to maintain bone health. These results also indicate that either the mechanisms by which high protein and high sodium chloride intake induce exacerbated bone resorption are different, or the effects of supplementary potassium bicarbonate on high sodium chloride or protein intake are not easily identified. Acknowledgements: Studies described here were funded by the DLR Space Program, Germany and NASA Human Research Program, USA

SE29 SYMPTOMATIC MANAGEMENT OF OSTEOARTHRITIS: ANALGESICS VS. NONSTEROIDAL ANTI INFLAMMATORY DRUGS (NSAIDS) Jean-Pierre PELLETIER1 1 Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada Osteoarthritis (OA) is the most common arthritis condition leading to disabling symptoms and severe incapacity. This

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lecture will review the treatment of disease symptoms including nonpharmacologic intervention and pharmacologic agents. Among the pharmacologic agents, analgesics and antiinflammatory drugs including NSAIDs and coxibs are the most commonly used. Non-narcotic analgesics such as acetaminophen/paracetamol are often recommended as first line of treatment because of their good long-term safety profile. However, recent warning about the maximum dosage to be used should be heeded to avoid drug toxicity, particularly in older patients. Moreover, recent meta-analyses have reported that acetaminophen has very low effect size for OA symptom treatment. Narcotic analgesics should be used as a very last resort and with great caution, as they have been shown to be associated with increased morbidity and mortality in OA patients. NSAIDs are very commonly used to treat OA symptoms. In a number of clinical surveys, patients have expressed preference for NSAIDs over non-narcotic analgesics for symptom relief. These findings were corroborated in clinical trials. Moreover, chronic use of NSAIDs (coxibs) was found more effective than intermittent treatment. However, the significant gastroinestinal, renal, and cardiovascular morbidity/mortality of NSAIDs/coxibs must be taken into account when establishing the risk/benefit of an OA treatment strategy. Appropriate measures should be taken, particularly in high risk patients, to minimize the occurence of such side effects. Local treatment with corticosteroids is an effective and safe way to control inflammatory OA flares. A number of pharmacologic agents are effective for the treatment of OA symptoms. However, the choice of drug to be used by the physician should take into consideration the safety/efficacy of the treatment on a case by case basis to ensure maximum therapeutic benefit for the patient.

SE30 ROLE OF NUTRACEUTICALS IN THE SYMPTOMATIC AND STRUCTURAL MANAGEMENT OF OSTEOARTHRITIS Olivier BRUYÈRE1 1 Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium The use of nutraceuticals in the treatment of OA is common, and scientific studies examining the effects of nutraceuticals on the pathogenesis and treatment of OA are increasing. Currently, some clinical data (positive or negative) are available for glucosamine (hydrochlorate or sulphate), chondroitin sulphate, collagen hydrolysates, avocado-soybean unsaponifiables (ASU) but also for vitamin D and polyphenols. It is important to note that several nutraceuticals have been carefully investigated for the symptomatic and structural management of osteoarthritis, whereas some have only

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been tested for their symptomatic effects. It has also to be acknowledged that some products are considered as drugs in some countries. Significant improvements in pain, function and structural outcomes have been shown for some of the treatment arms or subgroups of patients, but the effects are not consistent across the studies (i.e., the results demonstrate significant heterogeneity). To date, the most compelling evidence of potential for inhibiting the structural progression of osteoarthritis (i.e., an effect on the symptoms and the structure) has been obtained with glucosamine sulphate and chondroitin sulphate, while some evidence of efficacy to reduce pain and improve function has been shown with ASU, and suggestive evidence of efficacy has been demonstrated with vitamin D and collagen hydrolysate. The safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance. Given the good safety profile of nutraceuticals, the marginal efficacy of conventional treatments, the high prevalence and rate of disability of OA and the possible benefit of nutraceuticals for patients with OA, the use of nutraceuticals in selected patients could be appropriate. Future studies should focus on standardization of symptomatic and structural outcome measures, be of longer duration and pay careful attention to the content of the investigational products. At last, an important issue is that most of the conclusive studies with such chemical entities resulted from the use of prescription medicines, and not over-the-counter pills or food supplements.

SE31 ARE ANTIOSTEOPOROTIC DRUGS EFFECTIVE IN THE MANAGEMENT OF OSTEOARTHRITIS? Cyrus COOPER1 1 MRC Lifecourse Epidemiology Unit, University of Southampton and Institute of Musculoskeletal Science, University of Oxford, Oxford, UK Osteoarthritis is the commonest joint disorder in western populations, and symptomatic osteoarthritis in the lower limb joint affects as many as 40 % of men and women aged 65 years and over in the general population. Current management strategies for osteoarthritis focus on relieving symptoms and improving function through nonpharmacological and pharmacological approaches; when these efforts fail, surgical arthroplasty provides the mainstay. Pharmacological approaches include analgesics, antiinflammatory agents, intra-articular glucocorticoid, glucosamine sulphate and chondroitin sulphate; however, none of these are registered as structure modifying drugs. Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium Ranelate Efficacy in Knee Osteoarthritis Trial evaluated its

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effect on radiological progression of knee osteoarthritis. Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: 0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95 % CI 0.05-0.23, p