Osteoporos Int (2015) 26 (Suppl 1):S387–S396 DOI 10.1007/s00198-015-3062-9

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Non-sponsored Symposia Abstracts

# International Osteoporosis Foundation and National Osteoporosis Foundation 2015

NS1 APPLICATION OF SHAPE AND APPEARANCE MODELS IN OSTEOPOROSIS AND OSTEOARTHRITIS T. Cootes1 1 Imaging Sciences, Population Health, University of Manchester, Manchester, United Kingdom Many objects of interest in medical images can be represented as deformed versions of some average structure. This talk will describe methods of constructing statistical models of the variation in shape and appearance of such structures from annotated sets of medical images, with a particular focus on bones. The shape of an object is represented with a set of ‘landmark’ points, each defining the position of a particular part, and thus the correspondences across a set of example images. Statistical analysis of the sets of points leads to a model of the shape variation, which has been shown to be a powerful approach and is now widely used in both medical image analysis and in studies of the ways in which bones change during disease. The talk will include an overview of efficient approaches for matching such models to new images, including Active Appearance Models and a powerful recent technique which uses Random Forest regression to vote for the most likely position of each model point. This latter technique has been shown to lead to robust, accurate delineation of the outline of bony structures and opens the way to automated analysis of large image datasets. A range of examples will be included, focusing on the analysis of radiographs and DXA images.

NS2 APPLICATION OF SHAPE AND APPEARANCE MODELS IN OSTEOPOROSIS AND OSTEOARTHRITIS K. Poole1,2 1 HEFCE Senior Lecturer, Honorary Consultant in Metabolic Bone Disease and Rheumatology, Department of Medicine, University of Cambridge, Cambridge, United Kingdom, 2 Cambridge NIHR Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom CT technology has been used to image bone structure and pathology for more than 40 years. There is a growing interest in combining the 3D imaging capabilities of modern multislice CT scanners with advanced image processing techniques and statistical methodology. Such techniques allow the study of bone anatomy and in particular allow researchers to pinpoint the differences between groups of living patients’ bones in health, disease and in response to treatment. By making reasonable assumptions about both the anatomy and the imaging blur, cortical thickness can be measured to superresolution accuracy across the entire proximal femur, by fitting a model to the data at many thousands of surface points, distributed uniformly across, and passing through, the bone isosurface. The methodology has been validated against thickness measurements obtained from high resolution Xtreme CT scans of cadaveric femurs. We have used cortical thickness mapping to explore differences between women with and without recent hip fracture and identified generalised thinning of the femoral cortex in fracture patients. More intriguingly, we also discovered focal differences manifest as several welldefined patches of markedly thinner femoral cortex in hip fracture patients compared to controls. Since osteoporosis is defined as microarchitectural deterioration of bone tissue, we


described these areas of focally thinner bone as patches of focal osteoporosis. The patches were evident at common sites involved in fracture, the most severe being a thumbnail-sized patch of up to 30 % thinner bone at the head-neck junction in patients with femoral neck fracture. Focal osteoporosis at the head-neck junction may play an important role in fractures associated with falls, and might even be involved in ‘spontaneous’ hip fracture on rare occasions. Several groups have also identified focal differences in trabecular bone using parametric mapping technology, and our own best prospective predictors of eventual hip fracture required a model including cortical and trabecular bone as well as overall bone size.

NS3 APPLICATION OF SHAPE AND APPEARANCE MODELS IN OSTEOPOROSIS AND OSTEOARTHRITIS T. Neogi1 1 Medicine and Epidemiology, Clinical Epidemiology Unit, Boston University Schools of Medicine and Public Health, Boston, United States Osteoarthritis is the most common form of arthritis, and knee osteoarthritis in particular is a leading cause of disability among older adults worldwide. There are presently no therapies proven to prevent the onset of osteoarthritis or its progression, with treatment development partly hampered by use of insensitive radiographs to identify incidence and progression of disease. While osteoarthritis had traditionally been considered a disease of primarily cartilage degeneration, it is now understood to involve all joint tissues, with both active anabolic and catabolic processes. Knee osteoarthritis itself is considered to be a largely mechanically-driven disease. As bone adapts to mechanical loads by remodeling, bone alterations likely play an important role in OA development and progression. The normal functioning of diarthroidal joints is dependent upon stability provided by ligaments, tendons and musculature; appropriate load distribution across the joint surfaces, which is dependent upon the geometry and material properties of the articulating joint tissues; and joint congruity. Joint geometry has a clear role in predisposition to hip osteoarthritis due to developmental hip dysplasia and to a lesser extent due to femoroacetabular impingement. More recently, bone morphology has begun to be recognized as a possible risk factor in knee osteoarthritis. Advanced imaging modalities are being utilized to develop 3D bone shape of the knee with statistical shape modeling as a potential imaging biomarker that may provide a more sensitive means of identifying and monitoring changes in knee osteoarthritis than that afforded by tracking the relatively slow changes that occur in cartilage. Indeed, MRI-based 3D bone shape was recently shown to predict the onset of radiographic knee osteoarthritis

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several years later. Studying the patterns of 3D bone shape changes of the knee through use of statistical shape modeling will provide opportunities to gain further insight into biomechanical and other pathophysiologic influences in the pathogenesis of knee osteoarthritis.

NS4 APPLICATION OF SHAPE AND APPEARANCE MODELS IN OSTEOPOROSIS AND OSTEOARTHRITIS O. Museyko1 1 Institute of Medical Physics, University of Erlangen, Erlangen, Germany Statistical shape and appearance models describe a mean shape and intensity image and main variations around the mean for the study population. Models of this type proved effective at segmentation of unseen images coming from the same population, with various applications in bone imaging including rather complex shapes like that of the vertebral column in DXA images. Another application of statistical models is the shape/appearance classification problem. There are few publications devoted to the classification of bone structures, namely fracture prediction, in particular for proximal femur. Here, we analyzed the performance of statistical shape and appearance models for the problem of discrimination between subjects with and without acute osteoporotic femur fracture in 3D QCT. To be able to evaluate the performance of the models, we compared it with the results of fracture discrimination by other methods, such as voxel-wise comparison (voxel- and deformation-based morphometry) and some conventional integral parameters (total hip BMD, neck cortical thickness, etc.). The results highlighted a certain weakness of statistical shape and appearance models when applied to the fracture discrimination which we discuss in more detail.

NS5 OSTEOARTHRITIS, COMORBIDITY AND FUNCTIONAL LIMITATIONS IN THE EPOSA COHORTS S. Maggi1 1 CNR, Neuroscience Institute - Aging Branch, Padova, Italy The objective of the present work is to evaluate the relationships between osteoarthritis (OA) and functional limitations in the EPOSA cohorts and to analyze the role of comorbidity and pain. The baseline data of 2942 men and women between 65 and 85 years of age were analyzed, outcomes included selfreported physical function measured by the WOMAC index and walking test. A clinical diagnosis of hip/knee OA was performed. Pain was evaluated by WOMAC. Comorbidities

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included: obesity, cognitive impairment, anxiety, depression, self-reported chronic lung, cardiovascular and peripheral artery diseases, diabetes, stroke, cancer and osteoporosis. Participants with the worst WOMAC scores or walking times were older, mostly women, least educated, with higher prevalence rates of all diseases. Adjustment for age, sex, education, country, comorbidities did not affect the significant association between hip/knee OA and physical functional limitations. Pain was only a partial mediator in the association between OA and selfreported functional limitations (OR=1.63, CI=1.05-2.52), while it was a complete mediator in the association between OA and the walking test (OR=1.38, CI=0.971.96). Obesity, anxiety, depression, and cardiovascular diseases were associated to worst WOMAC scores, while obesity, cognitive impairment, depression, peripheral artery disease, and stroke were associated to worst walking times. These findings demonstrate that OA and comorbidity play an important and independent role in determining physical functioning, and pain has a complex mediator role.

NS6 TARGETING OSTEOSARCOPENIA: A PRACTICAL APPROACH FOR THE PREVENTION OF FALLS AND OSTEOPOROTIC FRACTURES G. Duque1, N. Binkley2, C. Alonso3, B. Buering2 1 University of Sydney, Sydney, Australia, 2University of Wisconsin, Madison, Wisconsin, United States, 3Hospital Getafe, Madrid, Spain Sarcopenia and osteoporosis affect older adults around the world and many times have devastating complications that affect their well being and quality of life. Analysis of the pathophysiologic pathways of sarcopenia and osteoporosis reveal several overlapping features. These conditions are age-related, both are multifactorial processes and both are characterized by progressive loss of tissue mass. Additionally, physical inactivity, vitamin D deficiency and poor nutrition accelerate the progression of both conditions. Despite these similarities, most interventions to date target these conditions separately. In this symposium we will review the current state of knowledge about sarcopenia and osteoporosis and will analyze preventive measures and therapeutic interventions that can benefit both conditions simultaneously. We intend to go over the translational aspects of sarcopenia and osteoporosis research and highlight expected outcomes from different interventions for both conditions. We will initially review the mechanisms contributing to sarcopenia and osteoporosis including metabolic and cell signaling changes. For example, we will analyze how changes in protein and amino acid intake affect muscle and bone metabolism. Next, we will discuss the benefits and limitations of current diagnostic schemes for both conditions. For instance, the benefits and limitations of DXA as a diagnostic and research


tool will be analyzed. Then, we will discuss evidence-based diagnostic and therapeutic interventions that pose promising opportunities for both conditions, which include the review of nutritional, physical activity and pharmacologic interventions. Finally we will translate this information into practical approaches that can improve older adult care.

NS7 PHYSICAL PERFORMANCE IN LATER LIFE AND ITS RELATIONSHIP WITH OSTEOARTHRITIS M.H. Edwards1, A. Litwic1, K. A. Jameson1, D. J. Deeg2, C. Cooper1, E. M. Dennison1 1 MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom, 2Department of Epidemiology & Biostatistics, VU University Medical Centre, Amsterdam, Netherlands

Objective: Poor physical performance (PP) is associated with disability, lower quality of life and higher mortality rates. In this study we examined relationships between hip and knee osteoarthritis (OA) according to self-report or clinical American College of Rheumatology (ACR) definition and PP, before and after adjustment for pain scores, in a cohort representing 6 European countries. Material and Methods: The EPOSA study comprises 2942 men and women from the Netherlands, Germany, Sweden, Spain, Italy and the United Kingdom. Participants completed a questionnaire detailing self-reported OA, demographics, lifestyle and WOMAC. Clinical OA was defined based on ACR criteria. PP was determined from assessments of walking speed, chair stands and balance (tandem stand) to create a composition score (0–12); low PP was defined as ≤9. Results: The mean(SD) age of the study population was 74.2(5.1) years. Advanced age, female gender, lower educational attainment, alcohol consumption, and higher BMI were independently associated with low PP. Having clinical knee OA, hip OA, or both were associated with a higher risk of low PP; OR(95%CI) 2.93(2.36,3.64), 3.79(2.49,5.76), and 7.22(3.63,14.38) respectively, with relationships robust to adjustment for the confounders above and WOMAC pain score. Self-reported OA was also associated with low PP, but relationships were attenuated after adjustment for confounders, and relationships were not observed at the knee in Sweden. Low PP correlated well with low self-reported WOMAC physical function score (p vertebral fractures by 70 % (10.9 % vs. 3.3 %, p relative risk reductions of 68 % (7.2 % vs. 2.3 %, p reduced vertebral fractures by 41 % (32.8 % vs. 20.9 %, p vertebral fractures of 65 % (14 % vs. 5 %, p Side Effects: Bisphosphonates (Alendronate, Ibandronate, Risedronate and Zoledronic Acid): Side effects for all the bisphosphonates

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(alendronate, ibandronate, risedronate and zoledronic acid) may include bone, joint or muscle pain. Side effects of the oral tablets may include nausea, difficulty swallowing, heartburn, irritation of the esophagus (tube connecting the throat to the stomach) and gastric ulcer. Side effects that can occur shortly after receiving an IV bisphosphonate include flu-like symptoms, fever, headache and pain in muscles or joints. Inflammation of the eye (called uveitis) is a rare side effect of all bisphosphonates. Bisphosphonates are not recommended for people with severe kidney disease or low blood calcium. People with certain problems of the esophagus may not be able to take the oral tablets. There have been rare reports of osteonecrosis (death of bone cells or tissue) of the jaw (ONJ) with bisphosphonate medicines. Although quite unusual, patients treated with the bisphosphonate tablets, alendronate (Fosamax®), ibandronate (Boniva®) and risedronate (Actonel®), for osteoporosis prevention or treatment have also been reported to have developed ONJ. There have also been recent reports of unusual fractures of the upper femur (thigh bone) in people taking bisphosphonate medicines. If you have been taking bisphosphonate medicines for several years or longer and have an unusual ache or pain in your hip or thigh bone, it’s important to tell your healthcare provider. There have been reports of people having an ache or pain, sometimes for several weeks or even months, before having an unusual break in the thigh bone. Patients taking the oral bisphosphonate tablets should stop taking the drug and contact their healthcare provider immediately when experiencing chest pain, new or worsening heartburn, or difficult or painful swallowing. Adverse effects: Zoledronic acid: Symptoms including fever, myalgia, influenza-like symptoms, headache, nausea and arthralgia occur for 1–3 days. Giving paracetamol shortly after the infusion reduces these symptoms. Zoledronic acid may also increase serum creatinine concentrations, particularly in patients with pre- existing renal impairment. In postmenopausal women with osteoporosis, the incidence of serious atrial fibrillation was increased versus placebo (1.3 % vs. 0.5 %, p Denosumab: The most common adverse reactions include musculoskeletal pain, hypercholesterolaemia and eczema, and discontinuation should be considered if the latter is severe.13 Hypocalcaemia may rarely occur, especially in patients with stage 5 chronic kidney disease. Pancreatitis has also been reported. Denosumab has the potential to increase the risk of infection and neoplasia. Increased rates of serious skin infections, predominantly cellulitis, have been observed in trials and patients should seek prompt medical attention if they develop signs and symptoms of


infection. No significant increases in malignancy rates have been noted to date. Atypical fractures and delayed fracture healing have not been observed in trials. Osteonecrosis of the jaw has rarely been reported (two cases) and a routine oral examination is recommended before starting treatment.17 In patients with bone metastases from breast or prostate cancer, osteonecrosis of the jaw may be associated with denosumab treatment, suggesting decreased bone turnover may be an important contributing factor. Strontium ranelate: The annual incidence of venous thromboembolism over 5 years was 0.9 % with strontium ranelate versus 0.6 % with placebo (relative risk of 1.4).23 Strontium has also been associated with rare and potentially fatal cases of hypersensitivity reactions with eosinophilia and systemic symptoms. The incidence of this adverse reaction is extremely low, estimated at 1:54 000 patient-years of treatment. Patients should be warned of the possibility of a rash and it may be prudent to stop strontium if this occurs within the first 6–8 weeks of treatment. Diarrhoea and nausea also occur. Initiating treatment every second day for 1 month may reduce these adverse effects. Teriparatide: Adverse reactions reported during phase III trials with teriparatide generally have been mild. The most frequent events were dizziness, headache and leg cramps in fewer than 10 % of patients. Injection site hypersensitivity occurred in a small number of patients. Allergic reactions, including dyspnoea, urticaria and chest pain, occurred in less than one in 1000 patients. 31 About 5 % of recipients experienced mild transient hypercalcaemia which resolved within 24 h. If hypercalcaemia occurs, it is generally recommended to reduce calcium intake to 1000 mg daily or less or to decrease the frequency of injections. Monitoring of serum calcium is not routinely needed, however it may be worth measuring serum calcium at baseline and after a month of therapy. A recent study evaluating the effect of teriparatide on urinary calcium at one, 6 and 12 months 27, 28 showed small increases in urinary calcium excretion, with less than 1 % of the participants requiring a dose change in calcium or teriparatide due to hypercalciuria. Osteosarcoma was reported in a rat oncogenicity model. However, only two cases have been reported in patients during postmarketing studies of approximately one million patients to date. This frequency is less than anticipated for people aged over 60 years. Each patient commencing teriparatide must sign a consent form acknowledging they are aware of this risk and treatment should be avoided in patients at increased baseline risk for osteosarcoma, such as children, and those with Paget’s disease, unexplained elevations in alkaline phosphatase, or prior radiation therapy involving the skeleton.


NS17 THE ECONOMIC IMPACT OF ANTI FRACTURE EFFICACY VERSUS SIDE OR ADVERSE EFFECTS A. Itria1,2 1 International Adviser, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, 2Health Economics and Outcomes Research, Goiania University, Goias, Brazil The economic evaluations in health, which proposes to study the more efficient allocation of resources, an expansion in the last 20 years. For osteoporosis drugs specifically (Table > Current Price of the Drugs In Brazil), there is increasing emergence of economic evaluations of treatment regimens because price increases of new drugs and the costs of the disease and anti fractures efficacy plus the side or adverse effects. In this scenario have that severe osteoporosis disease still a disorder of extreme importance in the world population with peculiar characteristics when considering events, morbidity, mortality and incidence in different regions. The susceptibility of the population, favorable climatic conditions, poor socioeconomic situation, making the primary prevention of the disease hard and requires specific interventions such as medications. There are several complications of osteoporosis disease (Table > Costs of Hip Fracture - Price of Prostheses in Brazil), mostly the sequels, as like treatments adverse effects and non responders set of patients. Brazil, through the National Program, included in its agenda for Technology Assessment in Health via the Health Surveillance Secretariat of the Ministry of Health, local economic assessments for the introduction of new drugs in national osteoporosis treatment schedule. So the purpose of this discussion is to develop a complementary study of costeffectiveness for the antifracture efficacy, the economic impact of the side or adverse effects with inclusion of supplementary estimates of additional costs for analysis of its impact on the incremental ratios found in the original study. In order to deepen the studies that measures the proportions of sequels and indirect costs, as well as the inclusion of new costs. The hypothesis suggests that the measurement and valuation of costs involved with sequelae of disease, improves the results of costeffectiveness and add additional elements in the decisions of managers. Were held in the city of Curitiba’s interviews with the patients and family questionnaires for routine expenditures and quality of life - EuroQol (EQ-5D), and inserted into the cost-effectiveness, the spending made by many families, some-

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times called “Family Expenditures”. The hypothesis resulted in the fact that better detail and inclusion of family spending in treating people who have acquired disabilities as a result of disability, has changed the cost effectiveness in the program of osteoporosis management. The sensitivity analysis showed that these data, when extrapolated result in incremental value showed closer to the ideal value of cost-effectiveness.

NS18 DRUG FOR BONE EVENT ESPECIALLY IN DISMETABOLIC PATIENTS F. Gatti De Menezes1 1 Health Economics and Outcomes Research Manager Pharm, São Paulo, Brazil Cost-effectiveness of paricalcitol in end stage chronic kidney disease secondary hyperparathyroidism patients on dialysis in Brazil. Objective: To understand from the perspective of the Brazilian National Health System (SUS) the cost- effectiveness of treating secondary hyperparathyroidism with IV paricalcitol versus IV calcitriol in dialysis patients diagnosed with end stage chronic kidney disease. Methods: A decision-analytic Markov model comparing the use of IV paricalcitol versus calcitriol. Main outcomes include parathyroidectomy, hospitalizations or death, life time costs and the results are reported as incremental cost-effectiveness ratios (ICER). The treatment costs are based on the DATASUS administrative claim database which includes individuals with an end stage chronic kidney disease secondary hyperparathyroidism diagnosis, who underwent hemodialysis at SUS, from 2009 to 2012. The main clinical outcomes are based on clinical trials or cohort studies reporting those outcomes. Results: The reference case analysis was a 5-year time horizon based on a comparison of treatment with paricalcitol versus calcitriol, of end stage chronic kidney disease secondary hyperparathyroidism dialysis patient. The use of paricalcitol leads to savings amounting R$113.999.601,06 to SUS and an increase in life-years gained (0.52 years). Paricalcitol was dominant over the comparator (calcitriol), indicating better health outcomes and lower costs. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model.

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2015): Non-sponsored Symposia Abstracts.

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