MISSION OSTEOPOROSIS THE FIRST DECADE: 2007-2017 Gaining awareness and getting results:

John P. Bilezikian, M.D. Professor of Medicine and Pharmacology Vice-Chair for International Education and Reseach Director, Metabolic Bone Diseases Program College of Physicians and Surgeons Columbia University, New York, NY USA

ARMENIAN HERITAGE CRUISE January 21, 2017

John P. Bilezikian, M.D.

Disclosures:

Amgen (Consultant, Advisory Board) Shire Pharmaceuticals (Consultant) Radius Pharmaceuticals (Advisory Board)

1//17 Outline

• Background- Osteoporosis in the world • Inspiration for applying knowledge to Armenia • What we knew in 2007 • What we accomplished • Where we are going

Osteoporosis

A GLOBAL PROBLEM

Projected Number of Hip Fractures

3250 Projected to reach 3.250 million in

Asia by 2050

668

742

400

Total number of 378 600 hip fractures: 1950 2050 1950 = 1.66 million 629 1950 2050 2050 = 6.26 million

1950 2050

100 1950 2050

Estimated no. of hip fractures: (1000s)

Adapted from Cooper C et al. Osteoporosis Int. 1992;2:285-289. Osteoporosis: Worldwide Prevalence

 Affects 200 million women worldwide1 - 1/3 of women aged 60 to 70 - 2/3 of women aged 80 or older

 Approximately 30 % of women over the age of 50 have one or more vertebral fractures2

1. International Osteoporosis Foundation Osteoporos Int 1996, 6:233 2. Dennison,2000 • A hip fracture occurs on average every 30 seconds, somewhere in the world! The key epidemiological message:

“Osteoporosis is one of the most dangerous diseases of the 21st century*”

*Narine Mamikonyan, Armenian Osteoporosis Association, 2015 Shuler FD, et al. Orthopedics 2012; 35:798-805

Postmenopausal Osteoporosis in the United States

• 2.0 Million Fractures Annually in the United States

• 40-50% life time risk in a typical 50 year old Caucasian woman

• Fractures occur at 3 main sites: Vertebral: 15.6% Hip: 17.5% Forearm: 16.0%

Melton LJ, et al. J Bone Miner Res 1992;7:1005-10. Looker AC, et al. J Bone Miner Res 1997;12:1761-8. National Osteoporosis Foundation. 1998, 2002. Burge et al. J Bone Miner Res, 2007

Postmenopausal Osteoporosis in Armenia

• Data relative to fractures in Armenia have become available in the past year

Human Costs of Osteoporosis • Impaired function, decreased mobility • More bone loss due to decreased activity • Compressed abdomen, reduced appetite • Reduced pulmonary function • Sleep disorders • Shortened survival • Poor self esteem

Ross PD et al. Ann Intern Med 1991;114-23. Silverman SL. Bone 1992;13 (suppl 2):S27-31. Cooper C, et al. Am J Epidem 1993;137:1001-5. Photo courtesy of the National Osteoporosis Foundation Lyles et al. Am J Med 1993;94:595-601. Schlaich C, et al. Osteoporos Int 1998;8:261-7. 10-12,000,000 Men

Women

28-32,000,000 Osteoporosis: Identifying the Problem

“ A skeletal disorder characterized by compromised bone strength Osteoporotic bone predisposing to an increased risk of fracture.”

Healthy bone

NIH Consensus Development Conference on Osteoporosis, 2000. 14 Bone Loss

Begins in 30s (women), late Women Men 40s (men)

Accelerates at menopause due to estrogen deficiency

Continues throughout life Bone Mass Active Slow Continuing

Growth Loss MENOPAUSE Loss Influenced by other factors: nutrition, diseases, 10 20 30 40 50 60 70 80 90 medications, lifestyle, etc Age

Adapted from Wasnich RD, et al. Osteoporosis: Critique and Practicum. 1989:179 Pathogenesis of Osteoporosis and Fractures

AGING MENOPAUSE OTHER RISK FACTORS

INCREASED LOW PEAK BONE LOSS BONE MASS

LOW BONE DENSITY

POOR BONE PROPENSITY QUALITY TO FALL

FRACTURES

Figure reprinted from National Osteoporosis Foundation, Physician’s Guide to Prevention and Treatment of Osteoporosis. Modified from Riggs BL, Melton LJ. Osteoporosis: Etiology, Diagnosis, and Management. New York: Raven Press; 1988. Before 1986, osteoporosis was diagnosed by clinical appearance or the fragility fracture In 1986…. • Dual energy X-ray Absorptiometry (DXA) became available as a clinical tool to assess bone mineral density in the setting of clinical medicine….. • It changed the way we think about and the way we diagnose osteoporosis Features of Bone Densitometry by DXA

• Safe • Accurate • Precise • Normative population databases • Correlates with fracture risk • A diagnostic standard • An important aspect of FRAX risk assessment system HOLOGIC Central DXA Bone Density Measurements Hologic

• Central DXA is the gold standard for diagnosis • Measures the most Norland important fracture sites (hip and spine) • Can be used to monitor response to therapy GE Lunar

NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis . 2013. www.nof.org . Interpreting T-scores (WHO)

Correlates with life time fracture risk for Caucasian Women

Low Normal Osteoporosis Bone Mass Bone Mass (Osteopenia)

-4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0 +0.5 +1.0 T-score UNITED STATES GUIDELINES FOR BONE DENSITOMETRY TESTING

Women Men NOF1/AACE2 3ISCD, 4TES Age >65 >703

Fragility fracture YES YES

Starting steroids YES YES

> 50 but <65 if > 50 but < 70 if Other risk factors • Weight <127 lbs • Low weight ? • Early menopause • Low T • Smoking • Smoking • FH of fracture • FH of fracture • Other Causes • Other causes

1 National Osteoporosis Foundation 2 AACE 3 ISCD, 2010, 4Watts et al, 2012 ARMENIA: GUIDELINES FOR BONE DENSITOMETRY TESTING

Women Men

???? Age ????

Fragility fracture ???? ????

Starting steroids ???? ????

Other risk factors ???? ????

With DXA… .Osteoporosis can be identified before the fracture occurs and plans for prevention and treatment can be implemented In 2007, 20 years after DXA became widely used throughout the world…

• There was 1 DXA machine in Armenia! The case to make available bone density density testing in Armenia was clear in 2007…

• But where did the inspiration to do something come from?

• Edgar Housepian

When the plane lands….. The case to make available bone density density testing in Armenia was clear in 2007…

• But where did the inspiration to do something come from?

• Edgar Housepian • Aram Chobanian

• Family FAMILY • Pauline and Armen Barooshian

• Sophie Bilezikian • Diana Bilezikian

• Caroline Apovian

• Other relatives who have accompanied me over the past 10 years to Yerevan!

ZABELLE APOVIAN BILEZIKIAN DXA in Armenia since 2007 . 2007: DXA placed at Markarian . 2008: Ultrasound densitometer, YSMU . 2009: DXA placed at YSMU . 2010: Major software upgrades to all DXA equipment . 2011-1014: DXA units placed in . Erebouni Hospital . Traumatology and Orthopedic Hospital . Gyumri . Stepanakert (Karabagh) . 2016: DXA units placed in Vanadzour and in Kapan

Historical View

• By 2017, Armenia has acquired enough DXA instruments, through the generosity of the Hologic Corporation in the United States, to be placed as above average in rankings for instruments per capita in the world! We brought technology and thus capabilities to diagnose osteoporosis in Armenia ... but how does one teach physicians in Armenia whose training is generally substandard and whose motivation is sometimes even less? A broader view of education in Armenia (it’s not just osteoporosis)

• in Armenia – Needs identified during the Housepian/Chobanian initiatives in the early 2000s: – Needs to address: • Teaching methods • Educational requirements • Credentialing system • Postgraduate education for specialty certification The years of Dr. Gohar Kyalyan Former Rector of Yerevan State Medical University (2006-2010)

• In collaboration with Aram Chobanian (President Emeritus of ) and the late Edgar Housepian • Change happened! The Kyalyan years circa 2006-2010

• Official affiliation between YSMU and Boston University and between YSMU and Columbia University • The entire medical curriculum of BU was made available to all medical students at YSMU • International Advisory Committee established The Kyalyan years

• The Bologna system of medical education implemented: updated course and teaching methods • Credentialling examinations • More rigorous admission and retention policies Beyond those years

• Pace of progress has continued with recognition by subsequent Rectors that there is much to be done • Good working relationships with Former Rector Mikayel Naramanyan • Active involvement of the American University of Armenia (Armen Der Kiureghian, President) Back to Mission Osteoporosis

Training and Education

• Radiologists were trained by a Hologic application specialist (Larry Mowat) in all aspects of the DXA instrument, prior to using the instrument • A “hot line” enables them to contact Hologic if any problems arise • A Hologic-trained engineer is a full-time employee at Ereubuni Hospital and, thus, is available to service and make needed repairs whenever necessary Training and Education

• Educational symposia for physicians and other health care professionals have been conducted yearly for the past 10 years

• The Tenth Symposium was held on October 6, 2016 The Osteoporosis Education Army: from the United States, UK, and Russia:

• Mariam Manoukian Tammy Martin • Samuel Badalian Elena Sagayan • Caroline Apovian Kim Hekimian • Sara Takii Nicholas Hutchings • John Kanis Richard Deckelbaum • Larry Mowat Bob Bagramian • Olga Lesynak • Noune Pashinian • Hasmik Arzumanyan

and from Armenia….

• Nara Mamikonyan Varduhi Petrosyan • Gevorg Yachjyan Georgy Okoev • Armine Horoyan Varta Babalyan • Karine Arustamyan Bagrat Lalalyan • Yelena Aghajanova Khoren Hovhannisyan • Ani Akopyan Artashes Grigoyan • Sargis Sahakyan Vachagan Ayvazyan • Nara Aslanyan • Siranoush Karagoshian

Supporting Organizations . Columbia University . Boston University . Yerevan State Medical University . American University of Armenia . Fund for Armenian Relief (FAR) . JHM Foundation . Hovnanian Foundation . International Osteoporosis Foundation Supporting Organizations -2-

• Russian Osteoporosis Association • Armenian Osteoporosis Association • Hologic Corporation Osteoporosis Symposia in Armenia 2007-2016

• In 2007, the first symposium at Markarian Hospital drew a capacity audience of about 100 people • In 2016, the 10th Annual Osteoporosis Symposium at the American University of Armenia drew over 600 attendees! 10th International

6 October 2016 10th Annual Osteoporosis Symposium Yerevan, 2016 Faculy

Tenth Annual Osteoporosis Symposium for Physicians and Health Professionals

OBJECTIVE: To review and to provide updates on the latest advances in osteoporosis, regarding: epidemiology, causes, nutrition, risk factors, and management Topics to be covered Thyroid Armenian Osteoporosis Hormone and Public Health Association Bone Initiatives

Nutrition and Major issues in Skeletal Glucocorticoid- Osteoporosis Health Induced Osteoporosis

Premenopausal Osteoporosis: Diabetes and The Perimenopausal Bone Health Obesity and woman Skeletal Health Agenda Afternoon MORNING Lunch Workshops 9:30-12:45 12:45-13:45 13:45-15:15

 Welcome and  Nutrition and Physical Activity Introductions  Armenian Osteoporosis  Topics in Osteoporosis Association  Public Health Issues  Diabetes and Obesity  Medical Issues  Epidemiology  Rheumatology and  Nutrition and skeletal Osteoporosis Health  Thyroid and Iodine Deficiency  Perimenopausal Skeletal Health The steps to recognition of osteoporosis in Armenia: How is Progress Assessed?

Acquisition of Capability to Measure Bone Mineral Density Education Hosting an International Summit Conference on Osteoporosis International Osteoporosis Summit: Central Asian and Eastern European Countries

Armenian Osteoporosis Association International Osteoporosis Foundation

Yerevan, Armenia 4 October 2016 International Osteoporosis Summit: Participating Countries*

• Armenia • Uzbekistan • Russia • Austria • Belarus • Czech Republic • Georgia • Hungary • Kazakhstan • Poland • Kyrgyz • Slovakia • Moldova • United States

*Regrets from Ukraine, Slovenia, Romania International Osteoporosis Summit: Participants and Acknowledgements*

• Armenia: Varta Babalyan, Karine Arustamyan, Lena Aghajanova, Sargis Sahakyan, Varduhi Petroysan, Armine Haroyan, Gevorg Yaghjyan

• *Acknowledgements: Levon Altunyan, Minister of Health (represented by Vartan Vartazaryan (Minister of Hospital Health Care) International Osteoporosis Summit: Participants • Russia: Olga Lesnyak,Olga Ershova, Olga Derevyanko, Evgeni Zotkin • Belarus: Emma Rudenka, Elena Rudenka, Alla Shepelkevich • Georgia: Marina Tsagarely, Medea Kopaliani, Maya Santania, Yulia Zedgenidze • Kazakhstan: Gulzhan Gabdulina, Sholpan Isaeva, Chokan Baymukchmedov, Laura Danyarova, Akmaral Nurbekova, Nurlan Turdalin • Kyrgyz: Olga Lobanchenko, Anara Mamazhunosova • Moldova: Eugeniu Russu, Victor Cazac,Angela Chicu, Oxana Odobescu • Uzbekistan: Shakirova Munavvara, Nadira Alikhanova International Osteoporosis Summit: Participants

• Austria: Heinrich Resch, Gerold Holzer • Czech Republic: Milan Bayer • Hungary: Peter Lakatos • Poland: Edward Czerwinski, Roman Lorenc • Slovakia: Juraj Payer, Peter Vanuga, Peter Jackuliak • United States: John P. Bilezikian, Nicholas Hutchings, Kim Hekimian, Mariam Manoukian, Noune Pashinan,

International Summit: Armenia 4 October 2016 International Summit: Armenia 4 October 2016 The steps to recognition of osteoporosis in Armenia: How is Progress Assessed?

Acquisition of Capability to Measure Bone Mineral Density Education Awareness

5 Leadership Round Tables on Osteoporosis in Armenia

• Gathering of the leading governmental and society leaders in Women’s Health in Armenia • Purpose: to further emphasize the importance of skeletal health, nutrition and other issues in Armenia 3rd Leadership Round Table on Osteoporosis

5th Leadership Roundtable 5 October 2016 Key points of the leadership discussion

 Capability for bone density acquired over the past 10 years  Doctors in Yerevan are more knowledgeable about osteoporosis than ever before  There is now sound epidemiological data on fracture incidence in Armenia leading to a country-specific FRAX

Key points of the leadership discussion

The challenge now is to apply these advances to improve detection, evaluation, and treatment of patients who are at risk. PROGRESS

Acquisition of Capability Education • Research Ongoing Research in Osteoporosis in Armenia

• Traumatology and Orthopedic Hospital (Nicholas Hutchings,Khoren Hovhassisyan, Artashes Grigoyan) • Ereubuni Hospital (Sargis Sahakyan) • Markarian (Karine Arustamyan) • Yerevan State Medical University (Yelena Aghajanova) • Armenian American Wellness Center (Zaha Sahradyan)

New Research being planned for 2016-2017 Iodine Deficiency and thyroid disease in Armenia • Yerevan State Medical University (Yelena Aghajanova) • American University of Armenia (Varduhi Petrosyan) • Columbia University (Nicholas Hutchings, John Bilezikian) • Stanford University (Mariam Manoukian) • Ministry of Health • UNICEF and WHO

PROGRESS

Acquisition of Capability Education Research Governmental How do we get the word out and influence governmental policy?

Ministry of Health: October 10, 2014

Ministry of Health

• Health priorities of former Minister of Health: Dr. Muradyan – Preventative Medicine • Cardiovascular • Oncology • Diabetes • Nutrition • Osteoporosis My vision for Armenia – An Osteoporosis Center that will be a central referral program for the entire region

Varta Babalyan has been named the first full-time, salaried Director of the Osteoporosis Center of Armenia!

My vision for Armenia

– An Osteoporosis Center that will be a central referral program for the entire region – A program of first rate and publishable research on the epidemiology, diagnosis, and treatment of osteoporosis

Development of a Fracture Risk Assessment Tool for Armenia (Lesynak,Sahakyan, Bilezikian, Hutchings, Manoukian et al. To be published in 2017)- My next lecture on the cruise! My vision for Armenia

– An Osteoporosis Center that will be a central referral program for the entire region – A program of first rate and publishable research on the epidemiology, diagnosis, and treatment of osteoporosis – A program of research that extends into other areas of endocrinology such as thyroid disease, obesity, and diabetes

– Hutchings N, Bilezikian JP et al. Iodine nutrition in Armenia, 2017 My vision for Armenia (cont’d)

– Ongoing educational programs to keep physicians and other health-care professionals for Armenian Health Care Professionals and others in the region

– Armenia will become the center for referrals and for education throughout the region

My vision for Armenia (cont’d)

– Government-sanctioned guidelines for screening with DXA and for treating osteoporosis will be implemented Lessons Learned in the First 10 Years…

• We can make a difference

• It takes time to make a difference

• It takes a lot of work to make a difference

• As a result, the skeletal health of the people of Armenia will be improved

• Armenia has the potential to become a center for Osteoporosis through the region Lessons Learned in the First 10 Years…

Each of us doing what we do best leads to positive results, multiplied many times over

PROGRESS

Acquisition of Capability Education Research Governmental

Shnorhagalutyun!