Overview of Osteoporosis: Why Be Concerned About Osteoporosis?

Lecture 1
Overview of Osteoporosis
IOF / ISCD Clinician Course
Why Be Concerned about Osteoporosis?
• Major public health problem worldwide

• Osteoporosis = increased risk for fractures
• Fractures lead to:
• Disability1,2
• Dependence1,2
• Delirium & dementia3,4,5
• Death2,6,7,8
1https://osteoporosis.foundation/educational-hub/material/thematic-reports
2Cooper C, et. al., Am J Epidemiol 1993;137:1001; Harvey et al., Nat Rev Rheumatol. 2010;6(2):99-105
3Gustafson et al. . J Am Geriatr Soc 1988;36:525–530.
3Givens et al J Am Geriatr Soc. 2008 Jun;56(6):1075-9
4Tsai C et al, Medicine 2014 93(26) :1-7
5Marcantonio et al J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S282-8
6Panula et al BMC Musculoskeletal Disorders 2011, 12:105
7Tran et al., J Clin Endocrinol Metab. 2018 Sep 1;103(9):3205-3214
8Tran T et al J Bone Miner Res. 2017 Sep;32(9):1802-1810
Why DXA?
DXA may be helpful to select patients for treatment 1
• Guidelines rely on DXA for treatment thresholds2

• DXA screening: cost effective for quality-adjusted life year (QALY)
outcomes (<$50K QALY)3
• Risedronate showed hip fracture risk reduction only when patients
were selected by DXA4
• Hormone therapy is the exception that benefited pts. selected by
clinical risk factors alone with normal BMD (WHI study)5,6
1Gluer CBone 2017; 104: 7-12; Kanis J et al., Osteoporos Int. 2019;30:3-44
2Dawson-Hughes B, et al Osteoporos Int 2008;19:449 – 458.
3Tosteson AN, et al Osteoporos Int 2008;19: 437– 447
4McClung et al N Engl J Med. 2001 Feb 1;344(5):333-40
5Rossouw JE, et al JAMA. 2002 Jul 17;288(3):321-33
6Anderson GL, JAMA. 2004 Apr 14;291(14):1701-12
1
Why Quality DXA?
• DXA widely utilized bone health technology1

• Low cost
• Low radiation exposure
• Excellent accuracy and reproducibility
• DXA errors can affect diagnosis and management2,3,4,5,8,9
• Recent series: 90% of DXA presented at least one error6
• Most common error: degenerative dz & false elevation of BMD
• Errors: false negative screening; the antithesis of screening test.7
1 Maricic M Curr Rheumatol Rep 2014; 16)436:1-7

2Watts NB, Osteoporos Int 2004; (15): 847–854
3Lewiecki, EM, et al. J Clin Densitom, 2006;(9):388-392
4Lewiecki EM, Lane N E, Nature Clin Pract Rheum December 2008; (4 ) 12: 667-674
5Garg MK, Kharb S , Indian J Endocrinol Metab 2013; 17(2):203–210
6Messina et al Eur Radiol 2015;(25):1504-1511
7The American Heritage® Stedman's Medical Dictionary. Retrieved July 12, 2015, from Dictionary.com
website: http://dictionary.reference.com/browse/screening test

8Karahan A et al ACTA MEDICA 2016; 59 (4): 117-123
9Licata A et al Endoc Prac 2018;24(2) :220-229
IOF-ISCD Learning Objectives
• State definitions and classification of osteoporosis

• Summarize the pathophysiology of osteoporosis
• Explain the prevalence and incidence of osteoporosis and fractures
• Describe types of fracture and the morbidity and mortality related to
osteoporotic fractures
• List the economic costs of osteoporosis
• Compare the incidence, prevalence, morbidity, mortality, and cost of
osteoporosis with other chronic diseases
• Explain the value of bone densitometry for diagnosis of osteoporosis,
fracture risk estimation and monitoring
Learning Objectives

2
Osteoporosis Can Be Defined by the
Presence or History of a Fracture
Vertebral Fracture Hip Fracture
Definition of Osteoporosis
• Osteoporosis is a skeletal disorder

characterised by low bone mass and
microarchitectural deterioration of
bone tissue, resulting in increased bone
fragility
• Bone strength reflects the integration of
two main features: Normal Bone*
• Bone density (can be measured e.g.
DXA )
• Bone quality (difficult to quantify)
There are no symptoms from low bone

mass unless fracture occurs
(WHO) Consensus development conference: diagnosis, prophylaxis, and treatment of

osteoporosis. Am J Med 1993;94(6):646-50
Osteoporotic Bone*
*Images used with permission of David Dempster, PhD. Copyright 2001
WHO Densitometric Definition of

Postmenopausal Osteoporosis
• The T-score compares an individual’s BMD with the mean value for
young normals and expresses the difference as a standard deviation
score
T-score (SD)
Normal Equal to -1.0 or higher
Low Bone Mass (Osteopenia) Between -1.0 and -2.5
Osteoporosis Equal to -2.5 or lower
Severe Osteoporosis Equal to -2.5 or lower with fracture
World Health Organization. Technical Report Series 843; WHO, Geneva.1994.

Kanis JA et al. J Bone Miner Res. 1994;9:1137.
3
Some Are Suggesting that “Osteoporosis” be
Diagnosed by Elevated Fracture Risk
• This approach is controversial and may be country specific (vs. WHO

BMD T-score definition: T-score ≤ -2.5)
• It is important to distinguish the diagnosis from intervention thresholds
at which treatment is indicated
• Treatment may be indicated in many countries by:
• Occurrence of a spine or hip fragility fracture
• Estimated fracture risk (e.g FRAX)
Siris E, et. al, Osteoporos Int; 2014, 25:1439-1443

Wright NC, et. al, Osteoporosis Int;. 2017 ,Nov;28(11):3283-3284l
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Learning Objectives

11
Functions of the Skeleton
• Supports the body

• Protects internal organs
• Muscles attached for movement
• Cavities for blood formation
• Reservoir for minerals
Bilezikian J et al. Principles of Bone Biology 2008, San Diego, CA :Academic Press
12
4
DXA Terminology:
The Skeleton Has Different Regions
• Central skeleton (axial skeleton plus hips and

shoulders):
• Spine, ribs, pelvis, hips, shoulders
• Peripheral skeleton (appendicular skeleton
minus hips and shoulders):
• Extremities (arms and legs)
Bilezikian J et al. Principles of Bone Biology 2008. San Diego, CA: Academic Press
13
Different Skeletal Regions Have

Different Type of Bone
• Cortical or compact bone Cortical Bone Venous sinus
makes up the outer Periosteum

envelope of all bones and
the shafts of the long bones Haversian canal
(appendicular skeleton) Canaliculus
• Cancellous or trabecular
bone makes up the inner Nerve
parts of the bones, Artery Endosteum

particularly bones of the
Trabecular Bone
axial skeleton
14
Cancellous and Cortical Bone Differences

in Mass, Surface Area and Turnover
Surface Turnover
Mass
area each year*
Cancellous 20% 80% 25%
Cortical 80% 20% 3%
*Up to 10% of the adult skeleton is being remodeled at any one time
(remodeling rates can be affected by age and diseases)
Parfitt M, Osteoporosis 2nd ed; 2001, 433-447
15
5
Bone Modeling and Remodeling
• Modeling: Change in size and shape of bone during growth and in

response to ageing and loading
• Remodeling: Mature bone is renewed through a process called
remodeling
• Involves replacement of old bone with new bone
• Occurs in response to fatigue damage, micro-fractures, and other
factors
Parfitt AM,J Cell Biochem. 1994 Jul;55(3):273-86

Seeman E , Crit Rev Eukaryot Gene Expr 2009 (19): 219-233
16
Bone Remodeling is Coupled and Regulated by Many

Factors Including Estrogen and Cytokines
Cytokines (+)
IL-1, TNF-α
IL-6, M-CSF, PGE2 ....
-
Osteoblast Osteoclast
Precursor Precursor
Estrogens
+ -
OPG - Cytokines +
TGFβ - RANK-L +
Lining cells
Osteoblast
Osteoclast
Adapted from Riggs B.L., et al. Endocr Rev. 2002; 23:279

Manolagas S et al.Gondal Steroids.Primer on Metabolic Bone.8th ed.2013
17
Bone Remodeling Cycle After Menopause is Uncoupled:

Bone Loss Occurs When Resorption > Formation
Formation:
Resting / quiescent
osteoblasts
Resorption:
10-12 weeks;
osteoclasts
Activation7-10mineralization
Deficit
days
Adapted from Watts NB. Clin Chem. 1999;45:1359.
18
6
Peak Bone Mass
• Peak bone mass is the maximum bone mass or density achieved during
a lifetime
• It is reached when the growth in the size of bones and accumulation of
bone mineral has stabilized (consolidation)
• Different skeletal sites peak at different times
• Trochanter BMD: Mid-teens (14.2  2.0)
• Femoral neck BMD: Late teens (18.5  1.6)
• Spine BMD: Early 20s (23.0  1.4)
Lin Y-C et al, Bone. (2003);32:546.

Baxter-Jones et al. (2011) J Bone Miner Res, 26: 1729-1739
Harvey et al. J Bone Miner Res. 2014;29(9):1917-25
Ferrari S et al., Osteoporos Int. 2012;23:2735-2748
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Factors Influencing Peak Bone Mass
• Heredity/Genetics (~60-80%) • Mechanical factors

• Gender • Physical activity
• Nutrition • Body weight
• Energy intake • Smoking
• Protein intake • Alcohol
• Calcium intake • Early life environment
• Vitamin D
• Endocrine factors
• Sex steroids
• Calcitriol
Rizzoli R. et al, J Molec Endocrinol. 2001; 26:79
• GH─IGF-1 axis Eisman J, Endocrine Rev, 1999; 20:788-804
Baxter-Jones AD, et al Bone. 2008 Dec;43(6):1101-7
Liang X et al, Bone 2018 Nov;116:301-306.
Ferrari S et al., Osteoporos Int. 2012;23:2735-2748
Rizzoli R and Bonjour JP, in Osteoporosis, eds Leder B and Wein N 2020
20
Changes in Bone Density with Age
White Women
Peak bone mass

1.2
Plateau maintained
Age-related bone loss (~0.5%-1.0% per year)
Spine BMD 1.0 Bone loss accelerates with

by DXA
menopause (~1%-2% per year)
(g/cm2)
Age-related bone loss
resumes
0.8
Increase with adolescence
Eventually back to
pre-adolescent levels
0.6
10 20 30 40 50 60 70 80 90
Sambrook P and Cooper C, Lancet. 2006;367(9527):2010-8
Ferrari S et al., Osteoporos Int. 2012;23:2735-2748 Age (years)
Rizzoli R and Bonjour JP, in Osteoporosis, eds Leder B and Wein N 2020
21
7
Influence of Sex on BMD
On average, men have higher BMD as measured by DXA than women
1.5
Spine
BMD
by DXA 1.0 White Men
(g/cm2)
White Women
0.5
10 20 30 40 50 60 70 80 90
Age (years)
Adapted from A. Looker et al. Osteoporos Int 1998;8:468–489
22
Influence of Ethnicity on BMD
On average, blacks have higher BMD as measured by DXA than whites
1.5 1.5
Spine BMD (g/cm2)
Black Men
1.0 Black Women 1.0
White Men
White Women
0.5 0.5
10 20 30 40 50 60 70 80 90 10 20 30 40 50 60 70 80 90
Age (years) Age (years)
Adapted from A. Looker et al. Osteoporos Int 1998;8:468–489

Du y et al. Osteoporosis Int. 2017 May;28(5):1699-1709
Jain RK et al Osteoporosis Int. 2017 Mar;28(3):917-923
Looker AC et al. Osteoporosis Int. 2012 Apr;23(4):1351-60
23
Cancellous and Cortical Bone Loss Occurs at

Different Times and Different Rates
Percent
of peak
bone Wrist
mass Fractures
Spine Hip
Fractures Fractures
Age
Adapted from Watts NB. Am Fam Physician. 1988;38:193
24
8
Trabecular Bone – Age Related Loss
Differs Between Men and Women
Women Men
Resorption >> Formation Resorption > Formation
Perforation Thinning
Adapted from Seeman E., J Appl Physiol 2003; 95:2142
25
Summary: Bone Mass and Bone Loss
• Women have lower peak bone mass than men

• Whites have lower peak bone mass than blacks
• Bone loss occurs
• With advancing age
• Because resorption is greater than formation
• As bone loss occurs, there is loss of quality as well as quantity
26
Learning Objectives

27
9
Prevalence
Prevalence
• “Snapshot” of disease at a single point in time
• Number with disease  number at risk at that moment
• Often expressed as percent, or number cases per 1,000 people
• Example: 30% of women over age 50 have osteoporosis
• In order to determine prevalence you need to :

• Define the disease
• Define the population being studied
28
Determining the Prevalence of Osteoporosis
• Recognize that DXA BMD determined T-scores, and thus osteoporosis

classification, varies according to:
• Anatomic site(s) used for definition*
• Age
• Race
• Examples on next slides:
* The WHO definition uses the lowest T-score at lumbar spine, total hip, femoral
neck or 33% radius
29
Osteoporosis Prevalence Increases With Age

The Most Common Site That Determines It Varies With Age Also
In older age, prevalence based on

hip is higher than based on spine
Overall, prevalence
At younger ages, at spine and hip are
% of prevalence based on similar
women spine is higher than
based on hip
All women
50 and older
T-score –2.5 or below

** “Hip” was either femoral neck or intertrochanteric region, whichever was lower
which is different from WHO Total Hip site
Kanis J et al., Osteoporos Int. 2019;30:3-44
Kanis J et al., Osteoporos Int. 2013;24:23-57
Data from Melton LJ III et al. J Bone Miner Res. 1995;10:175.
30
10
Osteoporosis Prevalence Differs by Ethnicity
USA Data
Caucasian reference data used for all
60%
52% 50%
49%
50%
40% 35%
30%
20% 18%
20%
10%
10% 5%
0%
White Black Mexican All races
Osteopenia Osteoporosis
Adapted from Looker et al. J Bone Miner Res. 1997;12:1761

Barrett-Conner et al. J Bone Miner Res 2005 Feb;20(2):185-94
31
Incidence
• Incidence
• New cases of disease over a specific period of time (rate)
• New cases within the period of time  number at risk
• Often expressed as number of cases per person-years
• Example: the incidence of hip fractures in an elderly population is 12 per
1000 person-years
32
Incidence of Radiographic Vertebral

Fractures Is Greater In Women Than Men
Adapted from European Prospective Osteoporosis Study
(follow-up mean 3.8 years)
Incidence of vertebral fractures
per 1000 patient-years
Age (years)
Data from the EPOS Study Group, J Bone Miner Res. 2002;17:716-24
Kendler, et. al., Am J Med. 2016 Feb;129(2):221.e1-10
33
11
Osteoporosis Prevalence and Incidence Worldwide
• Prevalence: Over 200 million people worldwide have osteoporosis

• Incidence: Hip fractures projected to increase substantially by 2050:
• 240% in women
• 320% in men
• Even if no increase in the age-adjusted hip fracture rate, the number of
hip fractures will increase from 1.7 million in 1990 to 6.3 million in
2050
https://osteoporosis.foundation/health-professionals/about-osteoporosis/epidemiology
Cooper C et al., Osteoporos Int. 1992;2:285-289
Odén A et al., Osteoporos Int. 2015;26:2243-8
34
Burden of High Fracture Risk Globally
Total at high risk

150 million 2010
300 million 2040
Oden et al., Osteoporos Int. 2015;26(9):2243-8
35
Incidence of Hip Fracture Varies Worldwide
Kanis, et. al., Osteoporos Int, 2012; 23: 2239-2256
36
12
Hip Fracture Rates Worldwide, Men and Women
Countries are color coded according to annual hip fracture incidence (if known):
red ( >250/100,000)
orange (150–250/100,000)
green(<150/100,000)
Kanis, et. al., Osteoporos Int, 2012; 23: 2239-2256
37
Projected Worldwide Increase in Hip Fracture Number

75% of world’s population live in Asia
By 2050, more than 50 % of all osteoporotic
fractures will occur in Asia Projected to reach 3250
742 3.25 million in
668
37 Asia by 2050
40
8 0
1990 2050 1990 2050
600
62
9
100
Total number of
hip fractures: 1990 2050
1990 2050
1950 = 1.66 million
2050 = 6.26 million
Estimated number of hip fractures: (1000s)

Adapted from C. Cooper et al, Osteoporos Int. 1992; 2:285-9
Cheung, et al., Osteoporos Sarcopenia, 2018; 4:16-21
Mithal A, Kaur P (2012) Osteoporosis in Asia: a call to action. Current Osteoporosis Reports 10(4):245–247.
38
Learning Objectives

39
13
Types of Fracture
• Traumatic fracture
• Pathological fracture
• Stress fracture
• Osteoporotic fracture* (sometimes called fragility fracture or
low-trauma fracture)
40
Bimodal Distribution Of Fractures
Peak in adolescence Second peak in older age

4000 Females >> males
Males >> females
Mostly long bones, trauma Mostly low trauma
3200
Annual
Incidence 2400 Females
of limb
fractures Males
per 100,000
1600
population
800
0
0-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 >85
Age (years)
Garraway WN et al. Mayo Clin Proc 1979; 54:701-707
© Mayo Clinic Foundation, used with permission
41
Pathogenesis of Osteoporotic Fracture

Low peak Postmenopausal Age related
bone mass (PBM) bone loss bone loss
Other risk
LOW BONE MASS
factors
Non skeletal Poor bone

FRACTURE =
factors quality
Fall + Low BMD
(propensity to fall) (architecture)
LOW BMD = PBM or Loss
Adapted from Melton LJ & Riggs BL. Osteoporosis: Etiology, Diagnosis & Management Raven Press, 1988, 155-179
Cauley, Jane A. Curr Opin Rheumatol. 2017 Mar;29(2):150-156.
42
14
Type of Fall Affects Fracture Site
Younger
• Intact protective mechanisms
• Fall on hand
• Forearm fracture
Older
• Compromised protective mechanisms
• Fall on side
• Hip fracture
Images are courtesy of Eis, IFR, 2011

O’Neill, Ann Rheum Dis, 53;773-775, 1994
43
Distal Forearm Fractures
4000
Women
Men
Incidence/1,000,000 person-years
3000
2000
1000
0
40 60 80
Graph adapted from Cooper C, et al. Trends Endocrinol Metab. 1992;3:224.
44
Distal Forearm Fractures
• Second most common osteoporotic fracture in US (~400,000/yr)1

• Prior forearm fracture is a marker for future fracture2
• Most are caused by fall on outstretched hand
• Most are diagnosed clinically and usually confirmed with radiography
• Complications
• Pain
• Temporary disability; difficulty dressing, toileting, meal preparation
• Degenerative arthritis
• Complex regional pain syndrome (reflex sympathetic dystrophy syndrome)
• Six months after fracture, 23% report fair to poor recovery in functional
outcome3
1 Burge R
,et al. J Bone Miner Res. 2007 ;22:465
2Klotzbuecher CM, et al. J Bone Miner Res. 2000;15:721.
3Kaukonen JP et al, Ann Chir Gynaecol. 1988;77:27.
Meena, et. al., J Family Med Prim Care 2014; 3: 325-332
45
15
Vertebral Fractures
4000
Women
Men
Wedge Crush 3000
2000
1000
Normal Endplate
0
40 60 80
Images adapted from Watts NB. Am Fam Phys. 1988;38:193.

© American Family Physician, used with permission
Graph modified from Cooper C et al. Trends Endocrinol Metab. 1992;3:224.
46
Vertebral Fractures
• Most common US osteoporotic fracture (~550,000 per yr)1

• Vertebral fracture is a marker for future fracture risk2
• Many occur with every-day activities (lifting, pushing, pulling, etc)
• Only 25% to 30% of vertebral fractures seen on x-ray are diagnosed
clinically
• Patients with clinical vertebral fractures may have severe pain and are
confirmed with x-ray
1 Burge R ,et al. J Bone Miner Res. 2007 ;22:465

2Klotzbuecher CM, et al. J Bone Miner Res. 2000;15:721.
Kendler, et. al., Am J Med. 2016 Feb;129(2):221.e1-10
47
Consequences of Vertebral Fractures
• Back pain
• Loss of height
• Deformity (kyphosis, protuberant abdomen)
• Reduced pulmonary function1
• Diminished quality of life (loss of self-esteem, distorted body image,
dependence on narcotic analgesics, sleep disorder, depression, loss of
independence)2
• Increased mortality
1Harrison, et al. J Bone Miner Res. 2007;22:447-457.

2Gold, et al. Rheum Dis Clin North Am. 2001;27:255-262
48
16
Hip Fractures
4000
Women
Men
3000
2000
1000
Femoral Neck Intertrochanteric Region

~40% ~40% 0
40 60 80
Graph modified from Cooper C et al. Trends Endocrinol Metab. 1992;3:224.
49
Hip Fractures
2nd most common fracture in many countries 4
3rd most common osteoporotic fracture US
• Approximately 400,000 per year US (2005)1
• Estimated to increase to 6.3 million annually by 2050
• Hip fracture is a marker for future fracture risk2
Most are caused by fall from standing height
• Only about 5% are “spontaneous”
• Only 1% of falls lead to hip fracture
Diagnosis
• Most are diagnosed clinically
• Often confirmed with radiography
• Most are hospitalized and require surgery
1Burge R ,et al. J Bone Miner Res. 2007 ;22:465
2 Klotzbuecher CM, et al. J Bone Miner Res. 2000;15:721
3 Cooper C, et. al, Osteoporos Int, 22; 2011:1277-88
4 Kanis JA et al, OI 2012 23: 2239-2256
50
Complications of Hip Fracture
• Up to 24-30% excess mortality within 1 year1,2

• Nearly 65,000 American women die from complications of hip fracture each
year3
• ~50% of hip fracture survivors are permanently incapacitated4
• ~20% of hip fracture survivors require long-term nursing home care5
1 Ray NF et al. J Bone Miner Res. 1997;12:24.

2 Kiebzak GM et al Arch Intern Med. 2002; 162:2217.
3 Col NF et al. JAMA. 1997; 227:1140.
4 Consensus Development Conference. Am J Med. 1993;94:646.
5 Chrischilles EA et al. Arch Intern Med. 1991;151:2026.
Dyer, et. al., BMC Geriatr. 2016; 16:158. doi: 10.1186/s12877-016-0332-0
51
17
Patients With Prior Fracture Are at High
Risk for Future Fragility Fractures
Relative Risk of Future Fractures
Prior Fracture Wrist Vertebra Hip

Wrist 3.3 1.7 1.9
Vertebra 1.4 4.4 2.5
Hip NA 2.5 2.3
Klotzbuecher CM et al. J Bone Miner Res. 2000;15:721.

Gehlbach, et. al., J Bone Miner Res. 2012; 27: 645-653.
52
Survival Rates After Fractures
Expected
Observed
100 100
80 80
%
60 60
Survival
Hip Fracture Vertebral Fracture
40 (relative survival = 0.82) 40 (relative survival = 0.81)
20 20
0 0
1 2 3 4 5 1 2 3 4 5
Time after fracture (years)
Adapted from Cooper C, et al. Am J Epidemiol. 1993;137:1001. © Johns Hopkins University School of Hygiene and Public Health,
used with permission
Lau, et. al., J Bone Joint Surg Am. 2008; 90:1479-86
Lee, et. al., J Clin Endocrinol Metab. 2014; 99:97-100
53
Fractures Reduce Quantity AND Quality of Life.

Loss of Independence
https://osteoporosis.foundation/educational-hub/material/thematic-reports
Abimanyi-Ochom, et. al., Osteoporosis Int. 2015; 26: 1781-1790
54
18
Fractures Cause Dependency:
Older Adults Value Independence
• Phone survey: ~800 older US adults in 2007

• What do you fear most?
• Loss of independence: 26%
• Moving out of home into nursing home: 13%
• Giving up driving: 11%
• Loss of family/friends: 11%
• Death: 3%
Fracture Prevention Maintains Quality of Life
www.slideshare.net/clarityproducts/clarity-2007-aging-in-place-in-america-2836029
55
In Summary: Hip Fractures

Have a Devastating Toll
• Mortality rate exceeds breast cancer 1,2

• ~20% excess mortality in the first year (higher for
men)3,4,5
• ~50% incapacitation3
• ~20% of women need assisted living or nursing
home3
• ~80% of older adults preferred death to living in a
nursing home6
1Forsen L Osteoporos Int. 1999;10:73

2http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/acessed12/16/16
3Cooper C, et. al., Am J Epidemiol 1993;137:1001
4Melton LJ J Bone Miner Res. 2003 Jun;18(6):1139-41
5Hawkes et al J Gerontol A Biol Sci Med Sci. 2006 May;61(5):495-9.
6Salkeld G et al . BMJ. 2000 Feb 5;320(7231):341-6
56
Learning Objectives

57
19
Cost of Osteoporosis & Fractures
• EU: economic burden of osteoporosis is 37 billion EUR/ year
• USA: 19 billion USD /year
• Costs are projected to rise dramatically with increased osteoporosis prevalence
• Fractures: 40% of osteoporotic fractures worldwide occur in people of working age

• Direct fracture costs in Canada, Europe and USA of working age osteoporotic people is
48 billion USD/year
• Does not include indirect costs such as disability, loss of productivity
Total Annual Cost in USA

In-patient
Long-term
$5.1 billion care
$9.6 (30%)
$16.9 Billion billion
(57%)
$2.2 b
(13%)
Outpatient
Adapted from Burge, et. al., J Bone Min Res 2007; 3:465-475
Blume SW and Curtis JR., Osteoporos Int 2011; 22:1835-1844
Hernlund et al., Arch Osteoporos. 2013;8:136
https://osteoporosis.foundation/
58
Learning Objectives

59
Prevalence and Economic Impact of Osteoporosis
Annual economic cost of treating osteoporosis in the USA is similar to that

of treating cardiovascular disease and asthma
Prevalence Annual direct cost including

Disease
(millions) hospitalization (US$ billion)
Cardiovascular disease 4.6 20.3
Osteoporosis 10 13.8
Asthma 15 7.5
Information supplied by National Heart, Lung & Blood Institute, National Osteoporosis
Foundation, American Heart Association
60
20
Fracture Incidence Compared With Other
Common Diseases
Predicted incidence per year, women ages 50-79
Number per 10,000
Adapted from Cauley, et. al., Osteoporos Int 19:1717, 2008
61
Fragility Fractures Cause Disability
IOF, Broken Bones, Broken Lives. 2019 https://osteoporosis.foundation/educational-hub/topic/epidemiology
62
Learning Objectives

63
21
Clinical Utility of Bone Densitometry (DXA)
• Diagnosis
• WHO T-score classification
• Prognosis
• Facilitates fracture risk assessment
• Monitoring
• Requires knowledge of precision and least significant change (LSC)
These topics will be discussed in detail in later sections
64
Caveats of Diagnosis Based on BMD
• Diagnosis of osteoporosis by DXA is based on the WHO classification as

a T-score of -2.5 or below
• Some patients with T-score –2.5 or below do not have osteoporosis
• Some patients with T-score above –2.5 may be diagnosed with
osteoporosis
• T-scores may differ at different skeletal sites
• Patients with a diagnosis of osteoporosis may have substantially
different fracture risk
• Diagnosis of osteoporosis does not explain etiology
65
IOF-ISCD Learning Objectives

66
22

Overview of Osteoporosis: Why Be Concerned About Osteoporosis?

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Overview of Osteoporosis: Why Be Concerned About Osteoporosis?

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Lecture 1

Why Be Concerned about Osteoporosis?

• Major public health problem worldwide

• Guidelines rely on DXA for treatment thresholds2

• DXA widely utilized bone health technology1

1 Maricic M Curr Rheumatol Rep 2014; 16)436:1-7

website: http://dictionary.reference.com/browse/screening test

IOF-ISCD Learning Objectives

• State definitions and classification of osteoporosis

• State definitions and classification of osteoporosis

Vertebral Fracture Hip Fracture

• Osteoporosis is a skeletal disorder

There are no symptoms from low bone

(WHO) Consensus development conference: diagnosis, prophylaxis, and treatment of

WHO Densitometric Definition of

Normal Equal to -1.0 or higher

Low Bone Mass (Osteopenia) Between -1.0 and -2.5

Osteoporosis Equal to -2.5 or lower

Severe Osteoporosis Equal to -2.5 or lower with fracture

World Health Organization. Technical Report Series 843; WHO, Geneva.1994.

• This approach is controversial and may be country specific (vs. WHO

Siris E, et. al, Osteoporos Int; 2014, 25:1439-1443

• State definitions and classification of osteoporosis

Functions of the Skeleton

• Supports the body

• Central skeleton (axial skeleton plus hips and

Different Skeletal Regions Have

• Cortical or compact bone Cortical Bone Venous sinus

makes up the outer Periosteum

parts of the bones, Artery Endosteum

Cancellous and Cortical Bone Differences

Parfitt M, Osteoporosis 2nd ed; 2001, 433-447

• Modeling: Change in size and shape of bone during growth and in

Parfitt AM,J Cell Biochem. 1994 Jul;55(3):273-86

Bone Remodeling is Coupled and Regulated by Many

Adapted from Riggs B.L., et al. Endocr Rev. 2002; 23:279

Bone Remodeling Cycle After Menopause is Uncoupled:

Adapted from Watts NB. Clin Chem. 1999;45:1359.

Lin Y-C et al, Bone. (2003);32:546.

Factors Influencing Peak Bone Mass

• Heredity/Genetics (~60-80%) • Mechanical factors

Changes in Bone Density with Age

Peak bone mass

Age-related bone loss (~0.5%-1.0% per year)

Spine BMD 1.0 Bone loss accelerates with

On average, men have higher BMD as measured by DXA than women

Adapted from A. Looker et al. Osteoporos Int 1998;8:468–489

Influence of Ethnicity on BMD

On average, blacks have higher BMD as measured by DXA than whites

Adapted from A. Looker et al. Osteoporos Int 1998;8:468–489

Cancellous and Cortical Bone Loss Occurs at

Adapted from Watts NB. Am Fam Physician. 1988;38:193

Adapted from Seeman E., J Appl Physiol 2003; 95:2142

Summary: Bone Mass and Bone Loss

• Women have lower peak bone mass than men

• State definitions and classification of osteoporosis

• In order to determine prevalence you need to :

Determining the Prevalence of Osteoporosis

• Recognize that DXA BMD determined T-scores, and thus osteoporosis

• Examples on next slides:

Osteoporosis Prevalence Increases With Age

In older age, prevalence based on

T-score –2.5 or below