Osteoporos Int (2015) 26 (Suppl 1):S65–S69 DOI 10.1007/s00198-015-3059-4

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Meet-the-Expert Sessions

# International Osteoporosis Foundation and National Osteoporosis Foundation 2015

MTE1 SEQUENTIAL/COMBINED THERAPIES IN OSTEOPOROSIS S. Ferrari1 1 Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland The ability of any single osteoporosis drug to fully restore bone mass and microstructure in both trabecular and cortical compartments and to prevent fragility fractures throughout the skeleton is limited. Moreover in high-risk patients at immediate risk of fracture, the antifracture efficacy of these drugs, particularly on nonvertebral fractures, may be delayed. Eventually, the benefits-risk ratio of antiresorptive therapy declines with long-term exposure, particularly with bisphosphonates (BPs). Because of these limitations and by analogy with the approaches undertaken in other chronic disorders, such as hypertension and diabetes, sequential and even combined therapy approaches for osteoporosis need to be (re)considered. For instance several studies have now demonstrated that transitioning from a BP to denosumab increases aBMD further compared to another BP. Although some early trials with alendronate and PTH(1–84) or teriparatide had shown “no additive effects”, most animal models and recent new combinations of teriparatide and zoledronate, as well as teriparatide and denosumab, have shown clear additive effects on aBMD, particularly at the hip. Interestingly, these trials revealed that the profile of bone turnover markers with these combinations may be quite different, but in any case consistent with a more positive bone mineral balance than each single agent alone. In this session we will therefore discuss the opportunities and limitations of Sequential/combined therapies in osteoporosis.

MTE2 MONITORING OF OSTEOPOROSIS TREATMENTS J. D. Adachi1 1 Medicine, McMaster University, St. Joseph’s Healthcare, Hamilton, Canada Objective: In an ideal world all therapies would be highly effective without side effects and all patients would be adherent to their medication. Unfortunately pharmacologic therapies are less than perfect and patients do forget to take their medications or forget to take them correctly. As a result it is important to monitor individuals to make sure that there is a positive response and not a lack of response to treatment Material and Methods: A history of falls or fractures is important. Ongoing fractures after a year of therapy would be considered treatment failure. Loss of height is one of the earliest signs of spine fractures. Occiput wall distance increases and rib-pelvis distance decreases with thoracic and lumbar spine fractures. Biochemical markers of bone turnover are particularly helpful when performed in a qualified lab. Early reductions in serum CTX and P1NP represent a reduction in bone turnover and suggest response to antiresorptive treatment. Increases in both with teriparatide, suggest treatment response. BMD may be followed from 1 to 3 years from baseline depending upon the expected change in BMD. For treatment where large changes in BMD are expected, a repeat BMD at 1 year may be performed. Where small changes are expected, a repeat BMD may be better done at 2–3 years. Stable or increases in BMD both are associated with reductions in fracture risk, while declines are associated with an increase in fracture risk. X-rays are still useful in detecting fractures in the presence of back pain and height loss. Results: Bone markers and BMD have been considered in determining treatment failure. Others have looked at monitoring FRAX scores. These are all open to debate and much of it based on expert opinion rather than science. There is


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increasing talk of treating-to-target. Just what that target is, is open to debate. Conclusion: Monitoring therapy is important in optimizing patient outcomes. Further guidance will be forthcoming as we learn more about what constitutes treatment success.

MTE4 EPIDEMIOLOGY AND MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN LATIN AMERICA P. Clark1 1 Clinical Epidemiology Unit, Hospital Infantil Federico Gomez-Faculty of Medicine UNAM, Mexico City, Mexico

MTE3 EXERCISE, NUTRITION, BONE AND MUSCLES B. Dawson-Hughes1 1 USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States

The Latin American Region (LatAm) includes 20 countries and 20 Caribbean Islands, with a total population over 600 million. The people over 70 years old in the region shows the largest increases, many countries will be incrementing their eldest population in as much as 300 % by the year 2050, therefore chronic diseases as OP are anticipated to increase in the near future. Three countries within the region (Brazil, Cuba and Mexico) have taken the dimension of osteoporosis at the national level. Regarding the epidemiology of fractures, available Information indicates that the incidence of hip fractures varies from intermediate to low incidence with rates that goes from the highest in Argentina to the lowest in Ecuador (264 and 55 per/100 000, respectively). Projections for hip fractures reported for Mexico will increase from 85 thousand in 2010 to over 110 thousand by the year 2050 (431 %). Less variability is found in the epidemiology of vertebral fractures. The prevalence of vertebral fractures within the LatAm region reported from the LAVOS study was similar in all five countries, increasing from 6.9 % in women aged 50–59 years to 27.8 % in those 80 years and older. The risk factors for fractures are common to all groups were older age, positive history of prior fractures and self-reported height loss for vertebral fractures; for hip fractures older age, positive story of prior fractures and positive history of falls. Guidelines for management and treatment for postmenopausal OP have been published in 10 countries by national societies; their governments have endorsed some of them. All of them include a compressive review of OP and the guidelines for treatment. Information gather from the LatAm audit indicate that bisphosphonates are available in every audited country with reimbursement policy differing in each country. Access to other osteoporosis medications (SERMs, strontium ranelate, hormone replacement therapy, PTH) is variable among the Audit countries. Vitamin D studies are also limited in this region, but the available evidence reveals an abundance of hypovitaminosis D throughout Latin America with no clear guidelines regarding supplementation of vitamin D.

Throughout life bone and muscle mass are tightly coupled. Both organs respond similarly to exercise by increasing their mass and both organs lose mass with disuse. Muscle has been thought to be the primary stimulus for bone tissue since 1977 when Harold Frost put forward, the ‘mechanostat’ theory. The mechanisms by which muscle promotes influences bone mass are less well understood, but they are thought to include exercise induced production in muscle of cytokines that stimulate bone. Other potential mechanisms include growth factor/IGF-1, FGF-23, and myostatin axes which involve bone as well as muscle. Less is known about the anabolic effect of bone on muscle and this is an area of active investigation. Factors known to increase risk of sarcopenia include decreased physical activity, increased catabolic cytokine activity, decreased circulating anabolic hormone levels, and genetic factors. Nutrition and exercise are important approaches to preventing muscle and bone wasting. Vitamin D insufficiency has been associated with decreased muscle performance and increased risk of falling and also with increased rates of bone loss and fractures. Supplementation has been shown to increase myocyte crosssectional area, through activation of vitamin D receptors in muscle tissue. Supplementation with vitamin D in amounts of 800 IU per day appears to provide protection from falls. This is also the intake recommended by the IOM for older adults to reduce fracture risk. Dietary protein intake is important for bone and muscle and protein intake has been positively associated with both muscle mass and BMD in older adults. The favorable effect of dietary protein appears to be amplified by the concurrent ingestion of foods that are metabolized to alkali, such as fruits and vegetables. Weight bearing exercise is important for bone and strength and balance training are important strategies to reduce risk of falling. Exercise for 30 min or more per day is recommended for older adults. References: Bonewald LF et al. JBMR 2013;28:1857.

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MTE5 GENETIC MARKERS FOR THE PREDICTION OF FRAGILITY FRACTURES F. Rivadeneira1 1 Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands With the advent of genomewide association studies (GWAS) the number of genetic discoveries has increased dramatically for all complex diseases, and such is the case for osteoporosis. To date ~100 BMD loci have been identified by GWAS as robustly associated with BMD and several other osteoporosisrelated traits. Many of the identified 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, among others. These variants identified by GWAS together explain about 5–6 % of the variation in BMD and less for fracture susceptibility, limiting thus far the application for meaningful clinical risk prediction. On the other hand, these discoveries have allowed us to advanced our understanding of the underlying molecular mechanisms leading to fracture. Further, there is large potential for translating GWAS discoveries into novel therapeutic applications for the treatment of osteoporosis, as most (if not all) current medications, target factors in known pathways, which have been reidentified with the GWAS approach. The main question is what comes next?—after this recent successful streak of GWAS discoveries; particularly, which techniques and methodological approaches are expected to yield the most efficient leaps towards clinical translation, particularly at the level of fragility fracture risk prediction, risk stratification and personalized medicine approaches. During this session, a glimpse will be taken into the future of new GWAS and next generation sequencing approaches for the identification of genetic determinants of fragility fracture.

MTE6 ROLE OF NUTRACEUTICALS IN THE MANA GEMENT OF OSTEOARTHRITIS G. Herrero-Beaumont1 1 Fundacion Jimenez Diaz Hospital - IDC, Madrid, Spain Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive cartilage degradation, loss of joint architecture, and, finally, joint failure leading to significant pain and disability. The guidelines for the treatment of knee OA include losing weight, muscle strengthening and analgesics. However, real-life data suggest that NSAIDs,


paracetamol, and opioids are mostly used in daily clinical practice. Chronic use of NSAIDs is associated with gastrointestinal complications, myocardial infarction and acute kidney failure. The side effects of NSAIDs counter-indicate their use in some patients, who turn out to be regular users of opioids with a large amount of side effects including increased functional limitations and poor self-reported health outcomes. In turn, compounds of the symptomatic slow-acting drugs for OA (SYSADOA) class include nutraceuticals such as glucosamine-containing compounds, chondroitin sulphate, and others. Despite strong controversies about their use, these agents are commonly used for the control of OA symptoms in all European countries as well as in America. We will discuss the updated evidence of nutraceuticals compounds for OA treatment. Most practice guidelines analyze the evidence behind each proposed treatment, but do not prioritize the interventions. Furthermore, few clinical trials have been designed to study the effect of a given treatment in patients with history of previous therapeutic failure, and/or how new treatments should be introduced. In this sense, the algorithm recommendation of ESCEO for the management of knee OA puts all proposed treatments in logical sequence suggested by the available evidence, including the SYSADOAs. In the near future, and due to few current pharmacologic alternatives in OA treatment, other therapeutic targets should be considered. In this regard, innate immune responses have been suggested to play a key role in OA development; therefore, it is necessary to fully discern it and particularly to explore the role of toll like receptors in this process. In fact, several factors associated with TLR4 activation may be relevant biomolecules in cartilage inflammatory responses and in the development and progression of cartilage degradation. The most active ginger derivative, 6-shogaol, shows a potent anti-inflammatory and antidegradative effects in human OA chondrocytes, by blocking TLR4 signaling. New molecules of the SYSADOA group may come to the OA field.

MTE7 DIAGNOSIS AND TREATMENT OF SARCOPENIA M. Visser1 1 VU University and VU University Medical Center, Amsterdam, Netherlands Sarcopenia is an aging concept that receives increasing attention in the geriatric world. The concept was launched in 1998 by Dr. Rosenburg and was originally defined as the agerelated loss of muscle mass. The operationalization of sarcopenia has changed and broadened over time. First, persons with a low muscle index (appendicular muscle mass (kg) divided by height (m) squared) were considered sarcopenic.


Later, poor muscle strength was also included in the definition, although some researchers prefer to call this dynapenia and treat it as a separate aging phenomenon. More recently, according to several consensus definitions, measures of physical functioning such as gait speed have also been included. Advantages and disadvantages of the different operationalizations will be discussed during this session. Also, consequences of the different operationalizations for diagnosis and prognostic value will be discussed. Finally, the preferred methodology to assess the different components of sarcopenia will be reviewed.

MTE8 PHYSICAL REHABILITATION IN MUSCULOSKELETAL CONDITIONS: WHICH METHOD? O. Bruyère1 1 University of Liège, Liège, Belgium Disability is strongly associated with musculoskeletal conditions, such as low back pain, osteoporosis- related fracture, osteoarthritis and sarcopenia. These conditions can have long-term impacts on patients’ quality of life. Rehabilitation (i.e. the process of managing the consequences of disease) aims to maximize physical, functional, psychological, social and role status. The burden of these musculoskeletal conditions may become exponentially high in the absence of rehabilitation. Indeed, musculoskeletal-related disability is amenable to rehabilitation and there is evidence to suggest that multidisciplinary forms of rehabilitation programs are effective in improving clinical and quality of life outcomes. Communitybased programs, as an extension of rehabilitation, have also shown clinical effects in people with musculoskeletal conditions. Interestingly, some recent studies have suggested that home-based rehabilitation may be an effective alternative and that the Internet may be successfully used as a medium for providing community based self- management and rehabilitation interventions. However, the exact modalities of rehabilitation need to be defined as they depend on the disease and on the stage of its management (primary, secondary or tertiary prevention).

MTE9 USE OF FRAX WORLDWIDE: CURRENT CHALLENGES AND SOLUTIONS J. A. Kanis1 1 Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, United Kingdom FRAX is a computer based algorithm (http://www.shef.ac.uk/ FRAX) that calculates the 10-year probability of a major fracture (hip, clinical spine, humerus or wrist fracture) and

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the 10-year probability of hip. Fracture risk is calculated from age, BMI and well validated dichotomized risk factors. Femoral neck BMD can be optionally input to enhance fracture risk prediction. Fracture probability differs markedly in different regions of the world so that FRAX is calibrated to those countries where the epidemiology of fracture and death is known (currently more than 50 countries). In addition to the web site, FRAX has been incorporated into the software of densitometers and is available as an application for the iPhone/iPod. The major clinical application of FRAX is to enhance the assessment of fracture risk to better target interventions, particularly in primary care. However, the utility of FRAX depends importantly on the development of guidance on the fracture probability at which treatment should be recommended (i.e. the intervention threshold). In Europe, risk assessment models are available in 21 of the 27 member states but a small majority (12/21) provide guidance on its application to clinical practice. The intervention thresholds that are selected vary from country to country, since they depend on the importance of osteoporosis, the heath care budget allocated, current practice guidelines, reimbursement and health economic considerations. This year, European guidelines have been published that incorporate FRAX which may stimulate a more cohesive approach to risk assessment and the targeting of treatment. The targeting of treatment by fracture probability has stimulated the evaluation of treatment responses as a function of FRAX. Treatment with teriparatide, raloxifene and strontium ranelate appears to be equally effective over a wide range of fracture probabilities. By contrast, treatment efficacy (relative risk reduction) is enhanced in patients at high fracture probability with clodronate, bazedoxifene and denosumab. Such treatment interactions need to be explored with all therapeutic interventions because of important implications for meta-analysis, effective targeting of treatment and health economic consequences.

MTE10 EPIDEMIOLOGY AND MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN THE MIDDLE EAST AND AFRICA L. Zakraoui1, S. Jemmali1 1 Mongi Slim Hospital, La Marsa School of Medicine, University of Tunis El Manar, Tunis, Tunisia Postmenopausal osteoporosis (PMO) is an under recognized disease and its characteristics vary among regions. Genetic and environmental factors play a major role. Objective: To gather data on epidemiology of PMO and fragility fractures (fx) and to study their management in countries in the Middle East and Africa (ME&A) as well

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as to study the particularities of this disease in this region in order to deliver policy for health care improvement. Methods: The resources of our research included Personal communication and a review of PubMed electronic database using the following terms: “Fractures, postmenopausal Osteoporosis, BMD, Middle East and Africa ” up to September 2014. Results: The prevalence of PMO based on BMD is quite comparable across ME&A countries, and was close to 30 % in several studies. Hip fx incidence ranged between 100 and 295 per 100,000 person/year. Radiographic vertebral fractures VF were detected in 1/4 of asymptomatic women with low BMD. A large number of women are unaware of osteoporosis (OP) risk factors: Sixty percent of women identified low calcium intake, 39 % lack of exercise and 22 % a family history of OP as risk factors of OP. The prevalence of hypovitaminosis D in the ME&A has been estimated to range between 50 and 90 %. The availability of DXA machines is estimated to


be less than 5/million population. National OP guidelines are available in five countries. Only 4 countries in ME&A have an online FRAX® calculator. Most approved antiresorptive drugs were available in the majority of countries, whereas PTH analogs were in only half. Reimbursement for diagnostics and therapeutics varied widely. Information on social costs and quality of life are rare. Discussion: The health burden of PMO in the ME&A is significant. The prevalence of PMO, fragility fx incidence and risk factors should be more widely and rigorously evaluated. Multiparity, skin pigmentation, clothing style are possible predictors of hypovitaminosis D. Access to care and the availability of equipment are variable depending on economic conditions. Conclusion: Considerable support for research is required to face the explosive growth in osteoporotic fracture due to the steady growth of the ageing population in the ME&A.

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Meet-the-Expert Sessions.

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