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)

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…

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

Male Female Female/Male Ratio US (white) Hong Kong Singapore Malaysia Thailand * Adjusted to the 1989 US white population by direct standardization, and presented with US white incidence data for Asian Osteoporosis Study Group, 1998.

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

Age (yrs.) Bone Mineral Density at Lumbar Spine (g/cm 2 ) Osteopenia 27.63% Osteoporosis 19.75% Osteopenia Osteoporosis Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 :

Bone Mineral Density at Femoral neck (g/cm 2 ) Age (yrs.) Osteopenia Osteoporosis Osteopenia 37.4% Osteoporosis 13.6% Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 :

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

Phadungkiat S, et al J Med Assoc Thai 2002;85:565 Age (yrs) Age-adjusted incidence (per 100,000) >75

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, United Nations World Population Prospects, The 1998 Revision, Vol. 1,New York: Dept. of Economic and Social Affairs, Population Division, AP / TP ~ 1 / 3 AP / TP ~ 1 / 12 AP / TP ~ 1 / 20

Estrogen deficiency Rene Rizzoli, 2006

Osteoclast lineageOsteoblast lineage Rene Rizzoli, 2006

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

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

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

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):

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

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):

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

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

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, pp

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.

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.

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

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

Sambrook P, et al. Lancet 2006;367:

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

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

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 Menopause 2006;13:

Kannus P, et al. N Engl J Med 2000;343:

Age (years) % full health Road traffic accident Colles ’ fracture Vertebral fractures

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

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

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

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

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

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.

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.