Osteoporosis: Measuring the Problem Dr. Tuan V. Nguyen Associate Professor Bone and Mineral Research Program Garvan Institute of Medical Research Sydney, Australia

Measuring osteoporotic fractures Magnitude of the problem Consequences Undertreated, underdiagnosed and what to do?

Increase in life expectancy WHO. Human Population: Fundamentals of Growth World Health, 2000.

The ageing of population Percent of population aged 65+ ABS and US Bureau of Census, 1996.

Osteoporosis – shift in definitions “Low bone mass, microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk” (Consensus Development Conference, 1991) “[…] 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 285:785-95; 2001)

Shift in thinking Osteoporosis Fracture Bone Bone Bone Quality Mineral RISK FACTOR OUTCOME Osteoporosis Fracture Bone Quality Bone Mineral Density Bone Strength and Architecture Turnover rate Damage accumulation Degree of mineralization Properties of the collagen/mineral matrix

BMD and fracture T < 2.5 osteoporosis

14-year risk of fractures in WOMEN aged 60+ Osteoporosis 345 (27%) Non-osteoporosis 942 (73%) Fx = 137 (40%) No Fx = 208 (60%) Fx = 191 (20%) No Fx = 751 (80%) 42%

14-year risk of fractures in MEN aged 60+ Osteoporosis N = 90 (11%) Non-osteoporosis 731 (89%) Fx = 27 (30%) No Fx = 63 (70%) Fx = 91 (12%) No Fx = 640 (88%) 23%

Magnitude of the Problem

Incidence of all-limb fractures

Annual fracture incidence in Australia 1996-2051 Projected annual number of all-limb fractures in Australia aged 35+ (Sanders et al, MJA 1999)

Hip, vertebrae, and Colles fractures 2006 2051 Hip 20,700 60,000 Vertebrae 14,500 31,700 Colles 11,900 23,000 Humerus 7,500 16,300 Pelvis 4,100 9,800 Projected annual number of all-limb fractures in Australia aged 35+(Sanders et al, MJA 1999)

Lifetime risk of some diseases - women Any osteoporotic fracture Hip fracture Clinical vertebral fracture Cancer (any site)* Breast cancer* Lung/bronchus* Coronary heart diseases Diabetes Mellitus *, from birth (from the age of 50)

Lifetime risk of some diseases - men Any osteoporotic fracture Hip fracture Clinical vertebral fracture Cancer (any site)* Prostate cancer* Lung/bronchus* Coronary heart diseases Diabetes Mellitus *, from birth (from the age of 50)

Ten-year and lifetime risk of fractures 10-y risk Lifetime risk  with advancing age  with advancing age

Ten-year and lifetime risk of fractures Normal T-scores >-1.0 Osteopenia -2.5 < T-scores < -1.0 Osteoporosis T-scores < -2.5 Lifetime risk Age free-of-fracture (y) 10-y risk Age free-of-fracture (y)

Ten-year and lifetime risk of any fracture by BMD and age FNBMD 10-year risk Lifetime risk (T-score) Age free of fracture (y) 60 70 80 WOMEN > -1.0 3.6 13.2 13.0 23.4 22.6 -2.4 to -1.1 25.4 25.3 25.7 55.7 44.3 33.0  -2.5 35.8 40.1 42.3 72.2 64.9 54.8 MEN 9.7 7.6 15.1 25.1 18.4 9.3 10.3 35.3 23.7 30.0 29.8 29.2 56.4 44.8 36.5

Consequences of Osteoporotic Fractures

Survival probability in those with and without fracture Nguyen et al, 2005

Risk of death from hip fracture 50-year old women: Lifetime risk of mortality from: Hip Fracture: 2.8% Breast Cancer: 2.8% Endometrial Cancer: 0.7% Cummings et al. Arch Intern Med 1989; 149: 2445-8

Impact of hip fractures 25% die within 6 months (*) 60% have restricted mobility (*) 25% remain functionally more dependent Cardiac (8%) and pumonary complication (4%) Transient heart attacks Non-union and avancular necrosis (*) Data from the Dubbo Osteoporosis Epidemiology Study

Impact of vertebral fractures Symptomatic fx : Lifetime risk 1/4 women, 1/8 men Asymptomatic fx prevalence: 20-30% Back pain, functional limitation Rib-against-pelvis (RAP) syndrome Costoiliac impingement syndrome Decrease vital lung capacity Pongchaiyakul C et al, J Bone Miner Res 2005

Asymptomatic vertebral fracture increases risk of subsequent fractures 300 m+w 66 V # 234 No V # 29 Fx 37 no fx 54 Fx 180 no fx 44% 23% Pongchaiyakul C et al, J Bone Miner Res 2005

Asymptomatic vertebral fracture increases risk of death 300 m+w 66 V # 234 No V # 20 deaths 46 survived 25 deaths 209 survived 30% 11% Pongchaiyakul C et al, J Bone Miner Res 2005

Impact of wrist fracture More common in women in their 50s Post-traumatic arthritis Account for 39% of all physical therapy sessions Reduced daily living activies Melton LJ, J Bone Miner Res 2003

Utility loss associated with fracture

Under-treated & Under-diagnosis

What the experts say? “All women and men with a history of fragility fractures should be considered for treatment of osteoporosis to reduce their risk of future fracture.” (Seeman and Eisman, MJA 2004) “Initiate therapy to reduce fracture risk in postmenopausal women with BMD T-scores by DXA below -2 in the absence of risk factors and in women with T-scores below -1.5 if one or more risk factors are present.” (NOF 2003)

What the experts say? “Recommend BMD testing to postmenopausal women who have suffered a fragility fracture to confirm the diagnosis and determine disease severity.” (NOF 2003)

Levels of treatment in fractured women in primary care settings Eisman JA, et al, J Bone Miner Res 2004

Level of treatment in outpatients 157 low-trauma fx Prior fx: 76 No prior fx: 81 BMD: 35 (45%) Any Rx: 14 (18%) BMD: 18 (22%) Any Rx: 3 (10%) Bliuc D, et al, Osteoporosis Int 2004

Level of treatment – experience in the US 502 hospitalised hip-fracture patients: only 14% had BMD scans 13% received calcium and/or vitamin D 18% received HRT, calcitonin, or bisphosphonates. Harrington JT, et al. Arthritis Rheum 2002; 47: 651-654

Risk factor modifications for fracture Intervention Estimated change in fx risk Bisphosphonates, HRT, SERMs ~30-50% Quit smoking -38% Treat impaired vision -50% Stop sedatives -40% Hip protectors -50%?

Summary In individuals aged 60+: 25% women and 11% men are osteoporosis (eg low BMD) Lifetime risk of fracture (from the age of 50): 1/3 men and 1/2 women. With the presence of osteoporosis, lifetime risk increase to 1/2 men and 7/10 women

Summary Fracture, particularly hip fracture, is a serious public health problem in the elderly. Increase mortality risk, reduced quality of life, incurred health care costs Osteoporosis is both under-treated and under-diagnosed.