1. OsteoporosIs: EpIdemIology and dIagnosIs
Endo Bridge 2013
Antalya, Turkey
OsteoporosIs: EpIdemIology and dIagnosIs
Dilek Gogas Yavuz , MD
Marmara University School of Medicine
Section of Endocrinology and Metabolism
Istanbul ,Turkey

2. Silent disease until complicated by fractures
OP is the most common bone disease and a serious health problem
osteoporosis has been termed a silent disease because until a fracture occurs symptoms are absent . Chief clinical manifestations are vertebal and hip fractures

3. Osteoporosis: silent epidemic
385 pts with fragility fractures
Have you ever heard of osteoporosis?
NO:20% YES:80%
Do you think that the fracture you have experienced could be due to fragility of your bones?
NO:73 % YES:27 %
Osteoporosis is called the silent epidemic because of  the lack of public awareness
Chavalley et al. Osteoporosis Int 2002;13:450

4. Definition of osteoporosis
NIH Consensus Development Conference, March 2000
A skeletal disorder characterized by
Compromised bone strength
An increased risk of fracture
Bone strength =bone density+ bone quality
Osteoporosis is defined as a systemic skeletal disease characterised by low bone mass and microarchitectural
deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Notice that that definition does not include a specific bone density criteria. It is an overall effect on bone health, which includes issues such as bone density, but also other issues of bone quality, not the least of which includes architectural change shown in this famous scanning electron microscopic picture from David Dempster
So it is not just less bone. It is less architecture, less connection, poor bone quality.
normal
osteoporosis
Low bone mass and microarchitectural deterioration

5. Osteoporosis is a Serious Public Health Problem
Every 3 second an osteoporotic fracture occcur
Worldwide, osteoporosis causes more than
8.9 million fractures annually
Osteoporosis affects an estimated 75 million people in Europe, USA and Japan, 2.2 million in Australia, 70 million in China
only 10 to 20% are diagnosed and treated
Osteoporosis int.2013:24;23-57

6. Prevalance of osteoporosis in men and women by gender-spesific scores
Osteoporosis is estimated to affect 200 million women worldwide
approximately one-tenth of women aged 60, one-fifth of women aged 70, two-fifths of women aged 80 and two-thirds of women aged 90
Schuit et al. Bone 2004;34:195

7. Prevalance of Osteoporosis
At age lifetime risk of fracture is
1:2 women
1:5 men
Over 50% of women and 30-45% of men over age 50 have osteopenia/osteoporosis
Men over age 60 has 25% risk osteoporotic fracture
70% over age 80 have osteoporosis
At age 50 lifetie risk of fracture is
1 of every 2 women
1 of every 5 men

8. Osteoporotic Fractures in Women: Comparison with Other Diseases*
500
1000
1500
2000
Osteoporotic
Fractures
*annual incidence all ages
† annual estimate women 29+
‡annual estimate women 30+
§1996 new cases, all ages † ‡ §
vertebral
other sites
forearm
hip
Heart
Attack
Stroke
Breast
Cancer
Annual incidence x 1000
Fractures in Women Are Common: Incidence of Chronic Diseases
This slide demonstrates that the incidence of new cases of osteoporotic fracture in women each year is far greater than the incidence of heart attack, stroke, and breast cancer combined.1–3 Hip fracture incidence alone exceeds that of breast cancer.1
This information, with the information on the previous slide, further emphasizes that osteoporosis should be considered a major health concern among postmenopausal women in the United States. The point is not to suggest that osteoporosis is more important than the other diseases but that it should be managed as routinely as are the other diseases.
incidence of new osteoporotic fracture in 1 year is greater than combined incidence of heart attack, stroke, and breast cancer.
Hip fracture incidence alone exceeds that of breast cancer.
Riggs BL, Melton LJ. Bone 1995
Heart and Stroke Facts, 1996, American Heart Association
Cancer Facts & Figures, 1996, American Cancer Society

9. Osteoporotic Fractures in Men and Women
As with women, hip fractures in men increase dramatically with age
Common sites for osteoporotic fracture are the spine, hip,
distal forearm and proximal humerus. As with women, hip fractures in men increase dramatically with age
The remaining lifetime probability in women, at menopause, of a fracture at
any one of these sites exceeds that of breast cancer (approximately 12 %), and the likelihood of a fracture at any of
these sites is 40 % or more inWestern Europe
Osteoporotic Fractures in Men and Women
.1,2
References:
1. Cooper C, Melton LJ III. Epidemiology of osteoporosis. Trends Endocrinol Metab. 1992;3:224–229.
2. Cooper C, Atkinson EJ, O’Fallon WM, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res. 1992;7:221–227.
Common sites of osteoporotic fractures
Distribution of Fractures
Cooper C, Melton LJ. Trends Endocrinol Metab. 1992;3:224–229.

11. Consequences of Fractures
All Osteoporotic fractures are associated with significant morbidity
Death
10%-20% inrease in mortality with hip fractures
Disability
hip fractures
20% of patients require long-term nursing home care
60% of patients fail to return to prefracture level of function
vertabral fractures
chronic back pain,kyphosis,height loss, impaired pulmonary function
Reduced quality of life
Loss of independence
All osteoporotic fractures are associated with significant morbidity, but both hip and
vertebral fractures are also associated with excess mortality
Clinician’s Guide To The Prevention And Treatment Of Osteoporosis
US Department Of Health And Human Sciences

12. Diagnosis of Osteoporosis
Based on T score (T Score : standart deviation by which the individual’s BMD differs from the mean value expected in young healthy individuals)
Operational definition of osteoporosis: BMD SD or more below the Young female adult mean
Reference technique :DXA
Reference site: femoral neck
Applies to men and to women
Operational definition of osteoporosis is based on t score for BMD assesed at femoral neck and its defined as a value for BMD 2.5 SD or more below the young female adult mean
Osteoporosis international 2013;24:23-57

13. WHO criteria for diagnosis of osteoporosis
T-score : Difference expressed as standard deviation compared to
young reference population
T score
normal
-1.0 and above
osteopenia
-1.0 and
osteoporosis
-2.5 and below
Severe (established) osteoporosis
-2.5 and below ,plus one or more osteoporotic fracture(s)
Operational diagnosis
Kanis et al. J Bone Mineral Res 1994;9:1137

14. WHO classification with a T-score cannot be applied to:
premenopausal women
men under age 50
children
Z score
Low Z-score (less than -2.0) has been suggested by some to increase likelihood of secondary osteoporosis

15. Who Should Have a Bone Density Test?
Women age 65 and older and men age 70 and older
Younger postmenopausal women and men ages –69 with clinical risk factors
Adults who have a fracture after age 50
Adults with a condition (e.g., rheumatoid arthritis) or taking a medication (e.g., glucocorticoids) associated with low bone mass or bone loss
Conditions, Diseases and Medications That Cause or Contribute to Osteoporosis and Fractures
Lifestyle factors
Alcohol Abuse High salt intake Falling
Low calcium intake Inadequate physical activity Excessive thinness
Vitamin D insufficiency Immobilization
Excess vitamin A Smoking (active or passive)
Genetic factors
Cystic fibrosis Homocystinuria Osteogenesis imperfecta
Ehlers-Danlos Hypophosphatasia Parental history of hip fracture
Gaucher’s disease Idiopathic hypercalciuria Porphyria
Glycogen storage diseases Marfan syndrome Riley-Day syndrome
Hemochromatosis Menkes steely hair syndrome
Hypogonadal states
Androgen insensitivity Hyperprolactinemia Premature ovarian failure
Anorexia nervosa and bulimia Premature menopause Athletic amenorrhea
Turner’s & Klinefelter’s syndromes Panhypopituitarism
Endocrine disorders
Adrenal insufficiency Cushing’s syndrome Central Adiposity
Diabetes mellitus (Types 1 & 2) Hyperparathyroidism Thyrotoxicosis
Gastrointestinal disorders
Celiac disease Inflammatory bowel disease Primary biliary cirrhosis
Gastric bypass Malabsorption
GI surgery Pancreatic disease
Hematologic disorders
Multiple myeloma Monoclonal gammopathies Sickle cell disease
Hemophilia Leukemia and lymphomas Systemic mastocytosis
Thalassemia
Rheumatologic and autoimmune diseases
Ankylosing spondylitis Lupus Rheumatoid arthritis
Other rheumatic and autoimmune diseases
Central nervous system disorders
Epilepsy Parkinson’s disease Stroke
Multiple sclerosis Spinal cord injury
Miscellaneous conditions and diseases
AIDS/HIV Congestive heart failure Muscular dystrophy
Alcoholism Depression Post-transplant bone disease
Amyloidosis End stage renal disease Sarcoidosis
Chronic metabolic acidosis Hypercalciuria Weight loss
Chronic obstructive lung disease Idiopathic scoliosis
Medications
Aluminum (in antacids) Cyclosporine A and tacrolimus Proton pump inhibitors
Anticoagulants (heparin) Depo-medroxyprogesterone (premenopausal contraception) Selective serotonin reuptake inhibitors
Anticonvulsants Glucocorticoids (≥ 5 mg/d prednisone or equivalent for ≥ 3 months) Tamoxifen® (premenopausal use)
Aromatase inhibitors GnRH (Gonadotropin releasing hormone) antagonists and agonists Thiazolidinediones (such as Actos® and Avandia®)
Barbiturates Lithium Thyroid hormones (in excess)
Cancer chemotherapeutic drugs Methotrexate Parenteral nutrition
1. Sweet MG, et al. Am Fam Physician. 2009;79(3):
2. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Accessed February 2013.

16. Most Women With Hip Fractures Do Not Have a T score ≤ -2.5
BMD measurements to predict future fracture risk
has a high specificity but a low sensitivity
Most Women With Hip Fractures Do Not Have a T score ≤ -2.5
Most women with hip fractures do not have a T score < -2.5
Wainwright et al JCEM 2005;90:2787

17. BMD and fracture risk
BMD provides the cornerstone for the diagnosis of osteoporosis the use of BMD alone is less than optimal as an intervernation
The fracture risk varies markedly in different countries ,but T-score varies by a small amount
Any given T-score to fracture risk in women from any one country
Depends on age
Fracture risk depends of clinical risk factors
Where as BMD provides the cornerstone for the diagnosis of osteoporosis the use of bmd alone is less than optimal as an intervernation
For any BMD, fracture risk higher
in the elderly than in the young
10 –year probability of hip fracture in women according to age and T-score for femoral neck BMD
Osteoporosis int 2013,24:23-57

18. Clinical Risk Factors that Affect Fracture Risk
A large number of risk factors have been ıdentified. For purposes of improving risk assesment,interest lies in those factors that contribute significantly to fracture risk over and above that provided by bmd measurement or age
The use of BMD measurements to predict future fracture risk has a high specificity but a low sensitivity, and most postmenopausal women presenting
with a fragility fracture have a BMD T-score higher than –51 Recently, the importance of clinical risk factors that affect fracture risk independently of BMD has been recognized

19. Fractures and Weight Fractures and weight
Compston JE et al. Am J Med 2011;124:1043

20. Fracture risk assessment: risk engines
guidelines have traditionally been based on BMD, the limitations
stimulated the development of risk engines that integrate clinical risk factors for fracture
Relative fracture risk BMD
10-year absolute fracture risk Risk Engines
Garvan fracture risk calculator
Q fracture
FRAX
Whereas assessment guidelines have traditionally been based on BMD, the limitations above have stimulated the development of risk engines that integrate several risk factors for fracture
Previous OSC guidelines advised intervention based on WHO category as a marker of relative fracture risk.
Now propose that an individual’s 10-year absolute fracture risk, rather than BMD alone, be used for fracture risk categorization

21. FRAX Computer-based algorithm (http://www.shef.ac.uk/FRAX)
Objective: To estimate fracture risk in order to help with treatment decisions
Rationale: BMD+CRFs predict fracture risk better than either alone
Calculates the 10 year probability of a major fracture (hip, clinical spine,humerus,wrist) and 10-year probability of hip fracture
designed only for postmenopausal women and men over the age of 40 who have not previously received bone-protective therapy

22. Fracture risk is calculated from age bmı, parantal history of hip fracture, current tovacco smoking, ever used long term oral GC,RA,other causes secondary osteoporosis
Femoral bmd can be optional input to enhance fracture risk prediction
These
are shown in Table 1 and are used in the World
Health Organization (WHO)-supported FRAX risk
algorithm, with or without femoral neck BMD.52,53
FRAX expresses fracture risk as the 10-year probability
of hip fracture and of major osteoporotic
fracture (hip, wrist, spine, or humerus), from which
intervention thresholds can be derived. Countryspecific
versions of FRAX are available for several
countries.
It should be noted that FRAX is designed only for
postmenopausal women and men over the age of
40 who have not previously received bone-protective
therapy

23. frax is calibrated to those countries where the epidemiology of fracture and death is known
Fracture probability differs markedly in different regions of the world.
İn this slide heterogenity in europe is shown . For this reason frax is calibrated to those countries where the epidemiology of fracture and death is known
Curently 45 countries

24. Absolute fracture risk in 10 years: low: <10% moderate: 10-20%
Categorization Based on 10-year Fracture Risk
Absolute fracture risk in 10 years:
low: <10%
moderate: %
high: >20%
The fracture risk category (low, moderate, high) is determined from the previous tables of corresponding T score and age. There are 3 categories for absolute risk: low (less than 10%, moderate (between 10-20%), and high (over 20%).
Similar risk categories have been used for cardiovascular risk assessment.
Similar risk categories have been used for cardiovascular risk assessment

25. Limitations of FRAX™ WHO Fracture Probability Tool
Not valid in patients on treatment
Only hip BMD is considered
Risk is “yes/no” – there is no consideration of “dose” (e.g., fractures, glucocorticoids, smoking, alcohol)
Not all risk factors are included (e.g., falls)
“Major osteoporotic fracture” is not the same as all osteoporotic fractures
Clinical judgment is required
Watts NB, et al. J Bone Miner Res 2009;24:

26. At present there is no universally accepted policy for population screening to identify ptients with osteoporosis or those at high risk of fracture
Patients are identifed opportunistically useing a case finding strategy on the finding of a previous fracture or the presence of significant risk factors
A general approach to risk assesment is shown here
Process begins with the asessment of racture probability and categorisation of fracture risk

27. Conclusion
At Present there is no universally accepted policy for population screening to identify patients with osteoporosis or those at high risk of fracture
Patients are identifed opportunistically useing a case finding strated
Clinical evaluation and judement is essential for assessment of fracture risk and treatment disicion
Osteoporosis is a disease that has a huge effect on public health. The imp
act of osteoporotic
fracture is far-reaching not only for the individuals themselves, but for the
health service, economy, and population as a whole. Osteoporotic fractures are
expected to rise in future generations. Recently several of the risk factors for this
disease have been elucidated, and models are currently being developed to allow
a more accurate assessment of fracture risk in patients to enable appropriate implementation
of preventative and therapeutic measures

28. Thank you