1. Prof.Emeritus Khunying Kobchitt Limpaphayom Past President Thai Osteoporosis Foundation (TOPF) President of Thai Menopause Society (TMS) Prof.Emeritus Khunying Kobchitt Limpaphayom Past President Thai Osteoporosis Foundation (TOPF) President of Thai Menopause Society (TMS)

2. Physical sequelae Height loss… Back pain… Limited ventilation… Narrow abdominal cavity… Abdominal skin infection… Problem with gait & balance Mental sequelae Poor self esteem… Social isolation… Depression…

3. One year after hip fracture 20% Death… 30% Permanent disability 40% Can’t walk independently 80% Can’t do 1 ordinary activity Rene Rizzoli, 2006

5. Male Female Female/Male Ratio US (white) 187 535 2.9 Hong Kong 180 459 2.4 Singapore 164 442 2.6 Malaysia 88 218 2.4 Thailand 114 269 2.8 * Adjusted to the 1989 US white population by direct standardization, and presented with US white incidence data for 1988 -1989. Asian Osteoporosis Study Group, 1998.

6. Patients (%) Death within One year Permanent disability Unable to carry out at least one independent activity of daily living Unable to walk independently One year after a hip fracture: 20% 30% 40% 80% Cooper C., Am J Med. 1997;103(2A):12s-19s

7. Age (yrs.) 90807060504030 1.4 1.2 1.0.8.6.4.2 Bone Mineral Density at Lumbar Spine (g/cm 2 ) Osteopenia 27.63% Osteoporosis 19.75% Osteopenia Osteoporosis 0.847 0.682 Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 : 65-69.

8. Bone Mineral Density at Femoral neck (g/cm 2 ) 1.4 1.2 1.0.8.6.4.2 Age (yrs.) 90807060504030 0.716 0.569 Osteopenia Osteoporosis Osteopenia 37.4% Osteoporosis 13.6% Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 : 65-69.

9. HIP FX 269/100,000 Osteoporosis 1.8 m. Woman> 55 yr 6.2 m Woman 31.8 m Thai Population 63 m. National Statistic Office 2003

10. Phadungkiat S, et al J Med Assoc Thai 2002;85:565 Age (yrs) Age-adjusted incidence (per 100,000) 0 150 300 450 600 750 900 51-5455-5960-6465-6970-74>75

11. 1970 1980 1990 2000 2010 2020 2030 2040 2050 Total population Aging population Total population Aging population United Nations World Population Prospects, The 1998 Revision, Vol. 1,New York: Dept. of Economic and Social Affairs, Population Division, 1999. United Nations World Population Prospects, The 1998 Revision, Vol. 1,New York: Dept. of Economic and Social Affairs, Population Division, 1999. AP / TP ~ 1 / 3 AP / TP ~ 1 / 12 AP / TP ~ 1 / 20

13. Estrogen deficiency Rene Rizzoli, 2006

14. Osteoclast lineageOsteoblast lineage Rene Rizzoli, 2006

15. RANKL OPG StimulationDexametasone17 β-Estradiol 1 α,25-(OH 2 )D 3 PTH PGE 2 Inhibition17 β-EstradiolHydrocortisone 1 α,25-(OH 2 )D 3 PTH PGE 2 Aubin J., Osteoporosis Int. 2000;11(11):905-13

16. Increased OC formation Increased OC activity Increased OC lifespan Decreased OB lifespan Decreased O ’ cyte lifespan Increased OC formation Increased OC activity Increased OC lifespan Decreased OB lifespan Decreased O ’ cyte lifespan Estrogen deficiency

17. Decreased OC formation Decreased OC activity Decreased OC lifespan Increased OB lifespan Increased O ’ cyte lifespan Decreased OC formation Decreased OC activity Decreased OC lifespan Increased OB lifespan Increased O ’ cyte lifespan Estrogen therapy Estrogen deficiency

18. Normal bone Osteoporosis Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95

19. Normal: BMD is within +1 or -1 SD of the young adult mean. Osteopenia (low bone mass): BMD is between -1 and -2.5 standard deviations below young adult mean. Osteoporosis: BMD is -2.5 SD or more than the young adult mean. Severe (established) osteoporosis: BMD is more than -2.5 SD and one or more osteoporotic fractures have occurred. *based on DXA measurement at hip or spine

20. Bone Strength NIH Consensus Statement 2000 Bone Quality Bone Strength and Architecture and geometry Turnover/ remodeling rate Degree of Mineralization Damage Accumulation Properties of collagen/mineral matrix Bone Density NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95

24. Cooper 1992 3250 Total number of hip fractures 1990 = 1.6 millions 2050 = 6.3 millions (n x1000)

25.  Dietary calcium intake  Vitamin D intake and synthesis  Calcium absorptionEstrogen deficiency  Plasma calcium  PTH secretion  Bone turnover and resorption

26. Low peak bone mass Postmenopausal Bone loss Age related bone loss LOW BONE MASS Other risk factors Non skeletal Factors (propensity to fall) FRACTURE = Fall + Low BMD Poor bone Quality (architecture) LOW BMD =  PMB or  Loss Adapted from Melton LJ & Riggs BL. Osteoporosis : Etiology, Diagnosis and Management Raven Press, 1988, pp155-179

27. With socio-economic development in many Asian countries and rapid ageing of the Asian population, osteoporosis has become one of the most prevalent and costly health problems in the region. Unsurprisingly, Asia is the region expecting the most dramatic increase in hip fractures during coming decades; by 2050 one out of every two hip fractures worldwide will occur in Asia.

28. OsteoclastOsteoblast Russell RGG, et al. Current Opinion in Rhematology 2006;18:S3-10. EstablisheddrugsEstablisheddrugsPotentialinhibitorsPotentialinhibitors Bisphosphonates Estrogens SERMs Calcitonin Strontium Blocking RANKL system Cathesin K inhibitor Mevalonate inhibitor Other inhibitors & antagonists EstablisheddrugsEstablisheddrugsPotentialstimulatorsPotentialstimulators PTHStrontium PGsFluoride Vitamin D Sclerostin inhibitors Androgen (SERMs) BMP-2Etc.

29. Enhance PBM Fall prevention Prevent bone loss Prevent bone loss HealthylifestyleHealthylifestyleAvoiding Health risks Avoiding LifestylemodificationLifestylemodification PharmacologicalinterventionPharmacologicalintervention SelfimprovementSelfimprovement EnvironmentaladaptationEnvironmentaladaptation

30. Estrogen Bisphosphonates Raloxifene Calcitonin Parathyroid hormone Strontium ranelate ~ 50% Risk reduction!

31. Sambrook P, et al. Lancet 2006;367:2010-18.

32. Fall & balance Environmental & family factor! Physical & mental strengthening

33. Age Impaired gait or balance; lower body muscle weakness Poor vision; cataracts Malnutrition; excessive alcohol intake Certain medical conditions, e.g. arthritis, diabetes, postural hypotension, cognitive impairment, peripheral neuropathy Polypharmacy; certain medications, e.g. psychoactive medications, antihypertensives Footwear with slippery soles, high heels Factors in the home, e.g. poor lighting, loose rugs, loose cabling, uneven or wet surfaces, bathtubs without handrails or bath mat, clutter at floor level, stepping over pets Environmental factors, e.g. wet or cracked paving or steps, ice or snow

34. 1. Lighting : ample, easy switchs, walkways 2. Obstruction 3. Floors & carpets 4. Furniture : chairs, bed height 5. Storage : accessible height 6. Bathroom : grab bars, chairs, toilet seat, nonskid 7. Stairways & halls : handrails, steps, nonskid 8. Human factor : heartfelt care, wheel chair 9. Medication : sedatives NAMS. Position Statement. Management of Osteoporosis in postmneopausal women 2006. Menopause 2006;13:340-67.

36. Kannus P, et al. N Engl J Med 2000;343:1506-13.

40. 0 10 20 30 40 50 60 70 80 90 100 020406080100 Age (years) % full health Road traffic accident Colles ’ fracture Vertebral fractures

41. NORMAL HEALTH FRACTURE PARTIAL RECOVERY DEATH Structure bone density microarchiecture Structure / Function Activities / Participation Mobility walking, using transport Interactions & relationships spousal, family, work Symptoms pain loss of movement OSTEOPOROSIS Self care washing, dressing Domestic life shopping, meals, house FURTHERFRACTURE

42. Following first distal forearm fracture Cuddihy et al Osteoporosis Int 1999 uhip fracture 1.4 fold in women 2.7 fold in men uvertebral fracture5.2 fold in women 10.7 fold in men Prevalent vertebral fracture and new vertebral fracture in next year Lindsay et al JAMA 2001  1 prevalent fracture RR 2.6  1 RR 5.1  2 RR 7.3 Prevalent vertebral fracture increases risk of hip fracture > 2 fold

43. NORMAL HEALTH FRACTURE PARTIAL RECOVERY DEATH Acute care hospitalisation rehabilitation Direct Costs Indirect Costs Attendant care Opportunity costs of family / carers Long term primary care drugs further fractures OSTEOPOROSIS Social services Institutionalisation

44. 1.Biology eg., vit D receptor gene, hip axis length 2.Mentality eg., introvert, slow down, peaceful 3.Nutrition eg., semi-vegetarian food 4.Family eg., higher priority, big family 5.Social status eg., privilege, seniority oriented

46. Perception HRT should not be used for bone protection because of its unfavorable safety profile. Official recommendations by health authorities (EMEA, FDA) limit the use of HRT to a second-line alternative. HRT could only be considered when other medications failed, were contraindicated or not tolerated, or in the very symptomatic woman. Evidence For the age group 50-59, HRT is safe and cost-effective. Overall, HRT is effective in the prevention of all osteoporosis-related fractures, even in patients at low risk of fracture. Roussow J. JAMA 2007;297:1465; Cauley JA. JAMA 2003;290:1729 Jackson RD. J Bone Min Res 2006;21:817

47. Perception HRT is not as effective in reducing fracture risk as other products (bisphosphonated, etc) Evidence Although no head-to-head studies have compared HRT to bisphosphonates in terms of fracture reduction, there is no evidence to suggest that bisphosphonates or any other antiresorptive therapy are superior of HRT.

48. Many people read only headlines or short messages: For these people, a short take-home message is the following: The target population for initiation of HRT is usually women up to age 55. HRT initiated in the early postmenopausal period in healthy women is safe. Like all medicines, HRT needs to be used appropriately, but it is essential that women in early menopause who are suffering menopausal symptoms should have the option of using HRT.