Osteoporos Int (2015) 26 (Suppl 1):S381–S386 DOI 10.1007/s00198-015-3066-5
World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Satellite Symposia Abstracts
# International Osteoporosis Foundation and National Osteoporosis Foundation 2015
ESCEO Algorithm for Osteoarthritis: from treatment guidelines to real life Sponsor: MEDA AB SY1 BIOLOGICAL AND CLINICAL EFFECTS OF INTRAARTICULAR HYALURONIC ACID: META-ANALYSES AND REAL-LIFE PATIENT STUDIES T. Conrozier1 1 Nord-Franche Comté hospital, Belfort, France Knee osteoarthritis is the first cause of consultations for osteoarthritis (OA) related symptoms. Its current management requires the combination of pharmaceutical and non-pharmacological strategies, including intra-articular injections of hyaluronic acid (HA) that are aimed to decrease pain and improve joint function. This concept named “viscosupplementation” (VS) has been developed to the finding that the visco-elastic nature characterizing the healthy synovial fluid was altered in OA and that these changes were directly related to the quantitative and qualitative HA decline in the synovial fluid. Indeed HA plays a major role in cartilage lubrication and shock absorption, through the visco-elastic behavior of SF.In OA joints, SF visco-elasticity, and consequently ability to protect cartilage, are dramatically lowered when compared with healthy SF as a result of a decrease of both HA MW and concentration. However the therapeutic effects of HA are likely much more complex and are not fully clarified. They are probably mediated through several mechanisms such as promotion of endogenous HA production, interaction with pain receptors, and various anti-inflammatory effects. Most of these effects could be mediated through interactions between HA and its receptors CD44 and RHAMM. After more than 20 years of use, VS is usually recognized by rheumatologists and orthopedic surgeons as an effective treatment of knee OA in most cases (effect-size similar or higher than that of other therapeutic modalities) and a well
tolerated modality, although the actual level of the benefit/ risk/cost ratio and the precise indications remain subject to controversy. This is mainly due to conflicting results of meta- analyses which may arise from methodological differences but also from possible differences in efficacy between products. There are also increasing evidence on a structuremodifying effect of HA injections. Beyond its moderate but certain efficacy, VS should be now considered as a first line therapy for mild and moderate knee OA, thanks to both its excellent safety and its potential chondroprotective effects. SY2 PR EV E NT I ON AN D T RE ATM E NT OF K NE E OSTEOARTHRITIS WITH GLUCOSAMINE SULFATE: FROM CLINICAL STUDIES TO REAL LIFE L. C. Rovati1 1 University of Milano-Bicocca and Rottapharm Biotech, Monza, Italy Glucosamine is among the most commonly prescribed medications in osteoarthritis (OA) thanks to its good safety, efficacy as a Symptomatic Slow Acting Drug in OA (SYSADOA), with firm hints of disease modification over long-term treatments in knee OA. However, such features were confirmed only with the original formulation of prescription crystalline glucosamine sulfate, as also acknowledged in the recent ESCEO algorithm recommendations. Such preparation is the only one employed in successful glucosamine trials as assessed in several recent meta-analyses, beside having a well characterized pharmacokinetic and pharmacological profile as compared to the more erratic characteristics of glucosamine over-the-counter formulations. Such differences have been lately confirmed in a real-life patient study. The PharmacoEpidemiology of GonArthroSis (PEGASus) study is a cohort experiment of patients with knee OA pain with dynamic exposure to all available SYSADOA in France (namely
crystalline glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, avocado soybean unsaponifiables and diacerein), aimed to assess the impact of such medications on non-steroidal antiinflammatory drugs (NSAIDs) consumption. Overall, the study involved over 6.000 patients. Crystalline glucosamine sulfate was the only SYSADOA able to decrease the use of NSAIDs over treatment up to 24 months [OR=0.64 (95 % CI: 0.45-0.92) in the protocol primary analysis]. Remarkably, glucosamine hydrochloride did not decrease NSAID consumption either, confirming the different efficacy profile than glucosamine sulfate as previously emerged from clinical trials. Real-life observations also confirmed the postulated diseasemodifying effect of crystalline glucosamine sulfate. While two 3-year randomized, placebo-controlled trials in knee OA suggested that the drug is able to delay radiological joint space narrowing, a prospective observation of patients receiving at least 12 months of treatment in the studies and followed for up to 5 years after trial completion, showed that those who received glucosamine sulfate decreased their risk of undergoing total joint replacement compared to former placebo patients [RR=0.43 (95 % CI: 0.20-0.92)]. Since crystalline glucosamine sulfate proved to be particularly effective in mild knee OA, the logical question was whether the drug might even prevent the development of the disease in high-risk subjects. New results from the 30-month PRevention of knee Osteoarthritis in Overweight Females (PROOF) study suggest that glucosamine sulfate may prevent the disease compared with no intervention or a diet and exercise program. SY3 HOW CAN WE HELP IMPLEMENTING ESCEO ALGORITHM IN REAL LIFE? J.-Y. Reginster1 1 Department of Public Health and Health Economics, University of Liège, Liège, Belgium Most osteoarthritis (OA) treatment guidelines analyze the evidence behind each proposed treatment, but the intervention strategies are not prioritized in the way which would meet the need of everyday clinical practice. This apparent “gap” results from the fact that few clinical trials have been designed to study the effect of a given treatment in patients in whom initial therapies have failed and/or how new treatments should be introduced. As a consequence, treatments are sometimes based on individualized patient’s assessment and the physicians’ subjective interpretation of the (often contradicting) evidence. An accurate analysis of the evidence, by an international task force of 10 rheumatologists (from Europe and North America) and 2 clinical epidemiologists experienced in the performance, analysis and interpretation of RCTs in OA,
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allowed to prioritize interventions into logical steps and to develop the ESCEO algorithm recommendation, with the purpose to adapt current global or other guidelines to the European situation. The ESCEO algorithm has been presented and discussed in 2014 at both OARSI and EULAR Congresses, and it is now a published document which we consider an easy-to- follow and evidence-based advice on how and when establishing treatment flow in patients with knee OA. Patient education with an appropriate exercise program, together with weight reduction when necessary, represent the background non-pharmacological treatment, to be joined early by pharmacological treatment represented by paracetamol for rescue analgesia and/or continuous prescription glucosamine sulfate (and/or other SYSADOA) for long-term symptom control and for delaying joint damage progression. In case of symptom persistence, the choice of a NSAID may consider not only the option “COX-2 selective or nonselective in combination with a proton pump inhibitor”, but also evaluations about overall safety and absence of negative interaction with the cartilage metabolism. In case of persistent pain, use of weak opioids, particularly in slow-release formulations with smooth PK curves, could represent a suitable option. Implementation of the ESCEO algorithm recommendations in real life may represent a framework for the development of new international guidelines for the management of OA and other rheumatological conditions. Dairy products & bone health : turning facts and beliefs into clinical practice Sponsor: CERIN/CNIEL, EMF, GDP SY4 THE ACID-ASH HYPOTHESIS AND BONE HEALTH T. Fenton1 1 Department of Community Health Sciences, Faculty of Medicine, University of Calgary, Calgary, Canada Many books and websites currently state that the modern diet causes many diseases through an accumulation of acids and that this produces whole body acidification. These promotions state that this acid from the modern diet cause the bones to demineralize to buffer the whole body acidosis. People are encouraged to measure their urine pH as an assessment of how well they are doing at alkalinzing themselves and achieving a better health status. These claims are based on the acid-ash hypothesis that was developed between 1907 and 1920. The main claims of the acid-ash hypothesis, that the body becomes acidified by the modern diet and that urine pH reflects whole body acidification are simply not true. While many studies have examined the changes in urine pH with diet changes, these studies have
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uniformly found that diet or supplement changes can change urine pH, however, the studies that examined both urine and blood pH found that the diet changes does not change blood pH. In fact, acidic urine shows that kidneys are effective at excreting acid. Although claims are made that Western industrialized nations suffer from problems caused by acidification, because both modern lifestyle and the modern diet promote acidification of the body, evidence does not support these claims. While many diseases have been claimed to be caused by the acid-producing modern diet, the only disease process that has been comprehensively studied regarding this topic is the maintenance of bone health. A systematic review by our group of all of the studies that could be located on the topic of the alkaline diet and bone health (including randomized control trials, as well as observational, and cellular mechanism studies) found no evidence of benefit of the alkaline diet or alkaline supplements on bone health. SY5 DAIRY PRODUCTS & BONE HEALTH: TURNING FACTS AND BELIEFS INTO CLINICAL PRACTICE O. Bruyère1 1 University of Liège, Liège, Belgium Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy- free diet. The recommended consumption is 3 servings of dairy products per day (for example, 1 glass of milk, 1 portion of cheese, 1 yogurt) - an amount that provides most of the RDI of calcium for the general population. Regarding bone health, there is growing evidence that the consequences of age-related or postmenopausal bone loss on fracture risk depends on the level of peak bone mass achieved during childhood and adolescence. Interestingly, it has been shown that adequate dietary calcium and protein intakes are essential to achieve optimal peak bone mass during skeletal growth and to prevent bone loss in the elderly. Current European guidance on osteoporosis incorporates nutritional recommendations for bone health, including at least 1000 mg/d calcium and 800 IU/d vitamin D. The available data show a positive association between dairy food intake and markers of bone health (i.e., bone mineral density, bone turnover markers), although data on the relationship with fracture risk are currently limited. SY6 DAIRY PRODUCTS: FACTS AND FICTION J.-J. Body1 1 Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
Dairy products provide a source of key nutrients that is difficult to obtain in low-dairy or dairy-free diets. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight or digestion concerns, arthritis or trying to avoid cancer. The bioavailability of calcium from milk is high. In some people, milk ingestion causes gastrointestinal symptoms due to a relative deficiency of the enzyme lactase causing undigested lactose to be fermented by the colonic bacteria. Self-diagnosis of lactase deficiency is common and often incorrect; in fact the degree of lactose tolerance varies, and drastic restrictions are usually not needed. Yogurts which contain pre-digested lactose and hard cheese which do not contain lactose are other excellent sources of dietary calcium. Meta-analyses concluded that restriction of dairy products intakes has not been reliably shown to aid in weight loss programs. Data actually suggest that consumption of dairy products reduces body fat and preserves lean body mass. Recent data from limited prospective studies suggest even that consumption of dairy products protects against the risk of overweight and obesity. Cancer is a complex and multifactorial disease and diet has received considerable attention. The abundant scientific data has been collated and interpreted by the World Cancer Research Fund (WCRF), one of the world’s most authoritative reference in that field. In their recent updates, the WCRF experts panel concluded that the evidence for any link between milk/dairy products and breast, ovarian or prostate cancer was limited whereas milk consumption probably decreases the risk of cancers of the colon and rectum. Results of ongoing trials are eagerly awaited. Studies on dairy products and arthritis are scarce but there appears to be no physiopathological reason why patients with osteoarthritis or rheumatoid arthritis should avoid dairy consumption. In conclusion, the intake of dairy products at the recommended dose of 3 servings per day as part of a balanced diet is safe, practical and affordable. Overall, the proven benefits of dairy foods on bone health greatly outweigh possible but unproven harms. Putting the Patient First: Effective Therapeutic Strategies to Reduce the Burden of Fractures Sponsor: Eli Lilly SY7 PUTTING THE PATIENT FIRST: EFFECTIVE THER APEUTIC STRATEGIES TO REDUCE THE BURDEN OF FRACTURES Eli Lilly and Company, Indianapolis, Indiana, United States
While considerable progress has been made in recent years in the management of patients with osteoporosis, many challenges remain that prevent healthcare professionals from being able to provide the right treatment to the right patient at the right time. This symposium will address three of these challenges: deficiencies in diagnosis and follow-up, assessment and treatment of the fragile osteoporotic patient, and treatment strategies in patients with secondary osteoporosis. A distinguished panel of speakers will provide their expert opinion on these key issues. The 90-minute programme will begin with a discussion of the proven benefits of implementing a Fracture Liaison Service (FLS). A series of cases of fragile patients will then be presented and best practice management strategies highlighted. Finally, the clinical benefits of anabolic therapy in patients with secondary osteoporosis will be reviewed. All of these issues will be discussed in the context of “putting the patient first”. Through participation in this symposium, it is hoped that attendees will leave better equipped to: Understand how implementation of a FLS enables patients to receive timely treatment and follow- up care. Identify specific challenges encountered in fragile osteoporotic patients, and develop appropriate care pathways for the individual patient. Evaluate current therapeutic options available for secondary osteoporosis, and select the best treatment for each patient. The ultimate aim of this symposium is to help clinicians make informed decisions when presented with specific patient scenarios in practice. This symposium is sponsored by Eli Lilly and Company. Old and new treatments for bone diseases Sponsor: Abiogen SY8 VITAMIN D: ITS EXPANDING ROLE IN THE MAIN TENANCE OF BONE HEALTH M. L. Brandi1 1 Department of Surgery and Translational Medicine, University of Florence, Florence, Italy Vitamin D is a hormone with a key role in calcium and phosphate metabolism and bone health. Even though in the last decade Vitamin D has been the focus of research, beyond these known effects (with low Vitamin D levels being associated with neurodegenerative disorders, cancer, altered glucose metabolism, and cardiovascular diseases), its main recognized function is as a calciotropic hormone. The association of Vitamin D deficit with many non-skeletal disorders has facilitated the attention not only to the elderly people but also to younger populations, that also appear to exhibit low 25(OH)D3 curculating levels.
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The accumulated information of Vitamin D status in a wide range of ages is going to be described in detail, along with potential future interventional approaches, with a main focus to the maintenance of bone health. SY9 N E W T R E N D S I N T H E T R E AT M E N T O F ALGODYSTROPHY S. Adami1 1 Department of Rheumatology, University of Verona, Verona, Italy Complex Regional Pain Syndrome type I (CRPS-I) is a severely disabling pain syndrome for which no definite treatment has been established. Aim of this multi-centre, randomized, double-blind placebo controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I. The treatment of CRPS-I has been a medical challenge until recently. A number of therapeutic approaches have been proposed with uncertain results based on randomized controlled trials (RCTs) with methodological limitations in terms of homogeneity and size of the study samples. For long-time bisphosphonates were used off-label for the treatment of CRPS-I based on 4 RCTs and a number of small uncontrolled studies, all of them showing positive results in controlling pain, oedema and functional impairment. However, none of these trials provided sufficient data to make the use of a bisphosphonate formally indicated for the treatment of CRPS-I. This gap was fulfilled recently by a registration RCT properly powered to show efficacy on pain at either hand or foot. The included 82 patients were randomly assigned to 100 mg neridronate infused intravenously 4 times over 10 days or placebo. After 50 days the former placebo patients were given open label the same regimen of neridronate. Within the first 20 days ≥50 % reduction of the pain VAS score was seen in 73 % of patients in the neridronate group versus 32 % in the placebo group (a 40.7 % treatment difference; 95 % CI 20.8-60.5 %, P=0.0003). Reduction in pain was associated with decreased allodynia, hyperalgesia and oedema, and improvements in quality of life. Subsequent treatment of patients from the placebo group with the active medication produced similar outcomes to those in the patients initially treated with neridronate, such that in the total group, no patient had clinical features of CRPS-I at 1 year. At the study entry all patients initially had CRPS-I for less than 4 months and all showed either bone oedema at the Magnetic Resonance Imaging (RMI) or positive local over-uptake at bone scintigraphy. These features identify a sub-group of patients with CRPS-I who have active bone-related pain. Thus, the efficacy of neridronate in patients without active bone disease remain to be assessed. The persistent positive effects
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of bisphosphonates in CRPS-I challenges the most accredited theories on the pathogenesis of the disease. It is worth mentioning also that the doses of nitrogen-based bisphosphonates required to treat CRPS-I are considerably higher than those normally used to treat Paget’s disease of bone. The results accumulated so far provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I. SY10 ADHERENCE TO TREATMENT IN OSTEOPOROSIS: CHALLENGES AND NEW SCENARIOS N. Napoli1 1 Divisione di endocrinologia, Università Campus Bio-Medico di Roma, Rome, Italy Bisphosphonates are key players for the treatment of osteoporotic patients. Data available have shown a clear, strong, effect on preventing both vertebral and femoral fractures up to 10 years. Nevertheless, fractures prevalence in Europe is still alarming and many patients, even after a fragility fracture, do not receive an appropriate treatment. Bisphosphonates are generally safe although concerns have been raised in the last years because of the onset of osteonecrosis of the jaw (ONJ) or atypical femur fractures (AFF). Alendronate treatment, the most studied and commonly prescribed bisphosphonate, may be limited by gastro-esophageal discomfort that may affect up to 10 % of treated patients. Clinical evidences show that the onset of upper intestinal discomfort is, in many cases, a reason to stop bisphosphonates. Therefore, if from one side, the fear for rare events like AFF or ONJ are a barrier to start an appropriate treatment, adherence to treatment is the new burden for bone specialists. A new available alendronate formulation has shown promising results, improving esophageal transit and lowering the risk of side effects. Empowerment of patients remains a main challenge for health professionals but new available formulations may offer new promising scenarios to improve adherence to anti-osteoporotic treatment. Managing Long-Term Osteoporosis : New Insights Sponsor: Amgen SY11 MANAGING LONG-TERM OSTEOPOROSIS: NEW INSIGHTS Amgen This educational symposium sponsored by Amgen is entitled “Managing long-term osteoporosis: new insights” and will be chaired by Serge Ferrari and Ego Seeman. During the 90-minute programme, the following topics will be covered:
Efficacy and safety of long-term therapy with denosumab Socrates Papapoulos The extension study of the 3-year randomised placebocontrolled FREEDOM trial evaluates the long-term safety and efficacy of denosumab treatment for up to 10 years in women with postmenopausal osteoporosis1. This presentation will summarise long-term efficacy and safety data for up to 8 years of denosumab treatment from the ongoing study. It will also provide perspectives on long-term data of other currently used therapies. Target for osteoporosis therapy: Supportive evidence from the FREEDOM extension Serge Ferrari The concept of treat-to-target has been employed for many years in various chronic diseases and recently has been increasingly discussed with regards to the management of osteoporosis 2 . Bone mineral density (BMD) gains with denosumab have been shown to explain a considerable proportion of the fracture risk reduction demonstrated with this drug3. This presentation will review the opportunities and challenges of a treat-to-target concept and will provide some new evidence supporting this concept, based on data on up to 8 years of continuous denosumab therapy in over 1500 subjects from the FREEDOM extension study. Explaining the differences in long-term BMD gain across therapies Ego Seeman Many approved and experimental osteoporosis therapies have been shown to increase BMD at sites such as the lumbar spine, femoral neck and total hip; however, while short-term BMD gains during the first few years of therapy are roughly comparable, there are notable differences in BMD increases in the long term1,4–6. This presentation will consider a number of hypotheses for the continuous long-term increase in BMD with denosumab. Factors such as secondary mineralisation7, reduced cortical porosity8,9, the transient increase in parathyroid hormone levels after each denosumab injection10, as well as modeling- based bone formation in the presence of markedly reduced bone resorption11 will be discussed. References 1. Bone HG, et al. J Clin Endocrinol Metab 2013;98: 4483–92 2. Lewiecki EM, et al. J Clin Endocinol Metab 2013;98: 946–53 3. Austin M, et al. J Bone Miner Res 2012;27:687–93 4. Black DM, et al. J Bone Miner Res 2012;27:243–54 5. Langdahl B, et al. J Bone Miner Res 2012;27:2251–8 6. Miller PD, et al. Osteoporos Int 2012;23:1747–56 7. Bolognese MA, et al. J Clin Densitom 2013;16:147–53
8. McClung MR, et al. J Clin Densitom 2013;16:250–6 9. Seeman E, et al. J Bone Miner Res 2010;25:1886–94 10. Seeman E, et al. J Bone Miner Res 2011;26(Suppl 1): abstract 1064 11. Ominsky MS, et al. J Bone Miner Res 2013;28(Suppl 1): abstract LB-MO30 Hypophosphatasia: a rare disease with heterogeneous presentation Sponsor: Alexion
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of disease in patients with hypophosphatasia and the diagnostic challenges associated with the heterogeneous presentation of this rare genetic disease, focusing on distinguishing it from other musculoskeletal diseases. A case study will also be presented, in which several members of a family share the same genetic mutation but experience differing manifestations of hypophosphatasia. Calcium and vitamin D – Fact and fiction Sponsor: Takeda
SY12 HYPOPHOSPHATASIA: A RARE DISEASE WITH HETEROGENEOUS PRESENTATION Alexion Pharmaceuticals
Abstract not available.
Supported by Alexion Pharmaceuticals Inc., the aim of this 90-minute symposium is to raise awareness of hypophosphatasia among healthcare professionals and researchers. A panel of internationally recognised experts, cochaired by Professor Maria Luisa Bianchi and Professor Maria Luisa Brandi, comprising Professors Thomas Weber, Francesco Conti and Christian Roux, will discuss the burden
Abstract not available.
Evolving Strategies for Management of Osteoporosis Sponsor: MSD
Management of severe osteoporosis: personalized medicine in practice Sponsor: Servier Abstract not available.