Osteoporosis

an underestimated disease

Definition of osteoporosis

World Health Organization (WHO). Technical Report Series 843, Geneva 1994Update TRS 921, 2003

…a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk.

normal osteoporotic

Osteoporosis diagnosis

Spine/hip dual energy X-ray absorptiometry measurement (DEXA) is the diagnostic standard

Areal bone mineral density is a important predictor of fracture risk.

WHO. Technical Report Series 921, Geneva 2003

Dual Energy X-ray Absorptiometry or DEXA

Measures X-ray absorption Bone mass per projected area (g/cm2) BMD correlates with whole bone strength

Bouxsein ML, et al. Bone 1999; 25(1):49-54.

BMD T-score = number of SD vs. mean BMD of healthy young female population (at peak bone mass)

WHO, 1994 – update 2003

DEXA as BMD-measurement method

T-score0 –1 –2 –2.5

Peak Bone Mass

OsteopeniaNormal

Osteoporosis

DEXA = Dual-Energy X-ray Absorptiometry

WHO criteria for osteoporosis in women

T-ScoreNormal -1 and above

Osteopenia -1 to -2.5

Osteoporosis -2.5

‘Severe’ osteoporosis

-2.5 and one or more fragility fractures

‘Established osteoporosis’

World Health Organization (WHO). Technical Report Series 843, Geneva 1994Update TRS 921, 2003

Diagnosis of Osteoporosis

BMD T-score -2.5 DEXA

and / or

presence (history)

of osteoporotic fracture RX

Post-menopausal Osteoporosis

Osteoblast

Osteoclast

imbalance of

bone-remodeling

Age 40Age 40 Age 60Age 60 Age 70Age 70

Progression of vertebralProgression of vertebralfractures in osteoporosisfractures in osteoporosis

1959 19891996

Inger Lundegaardh, Sweden

IOF: international osteoporosis foundation, http://www.osteofound.org

Pathophysiology of osteoporosis:bone remodelling

Newly laid osteoid mineralises overNewly laid osteoid mineralises overseveral monthsseveral months

BoneBone

Lining cells cover Lining cells cover resting boneresting bone

Activation resorption Activation resorption phase phase ~20 days~20 days

BoneBone

Osteoclasts Osteoclasts resorb boneresorb bone

Reversal formation Reversal formation phase phase ~160 days~160 days

Osteoblasts lay Osteoblasts lay new osteoidnew osteoid

BoneBone BoneBone

IndirectIndirecteffectseffects

Postmenopausal bone loss: role of estrogen deficiency

Directly increasesDirectly increasesosteoclast numberosteoclast number

and longevityand longevity

DietaryDietarycalciumcalcium

(decreased absorption(decreased absorptiondue to Vit. D deficiency)due to Vit. D deficiency)

SecondarySecondaryhyperparathyroidismhyperparathyroidism

Increased boneIncreased boneresorptionresorption

BoneBoneLossLoss

DecreasedDecreasedbonebone

formationformation

Remodelling Remodelling imbalanceimbalance

??

Adapted from Riggs BL, et al. J Bone Miner Res 1998; 13(5):763-773.

EstrogenEstrogendeficiencydeficiency

Age-related bone lossoccurs in men and women

0 20 40 60 80 100Age (years)

Bo

ne m

ass

I

III

Men

WomenI

II

III

I Peak bone massII Rapid bone loss (menopause)III Age-related bone loss

Bone Remodelling throughout Life

Bone turnover = a coupled process

always : bone resorption → bone formation

Childhood & adolescence: resorption < formation

As from the age of 40: resorption > formation

– always negative balance per bone remodelling cycle– slow bone loss

Postmenopausal period: accelerated bone loss

– estrogens inhibit bone turnover– E-deficiency → higher bone turnover rate

Pathogenesis of Osteoporosis

High TURNOVER = high BONE LOSS

Low TURNOVER = low BONE LOSS

> 40 y negative net balance per bone remodelling

cycle

Ultimately leading to loss of CONNECTIVITY

Bone Turnover

Trabecular Bone Cortical Bone

% of bone mass 20% 80%

% of bone turnover 80% 20%

mostly present in Epiphysis of long bones

+ Vertebral Bodies

Diaphysis of long bones

Distribution of trabecular and cortical bone throughout the skeletal system

adapted from

http://www.merckmedicus.com

Vertebrae66% trabecular34% cortical

Forearm(distal radius)20% trabecular80% cortical

Trochanteric region50% trabecular50% cortical

Femoral neck25% trabecular75% cortical

Consequences of

Postmenopausal Osteoporosis

Incidence of osteoporotic fractures in women

50 60 70 80

Vertebrae

Hip

Wrist

Age (years)

An

nu

al i

nci

den

ce

Adapted from Wasnich RD, Osteoporos Int 1997;7 Suppl 3:68-72and Sambrook P et al. Lancet 2006; 367(9527):2010-2018

Lifetime fracture risk of people at 50 years of age

Adapted from Melton LJ, III, et al. J Bone Miner Res 1992; 7(9):1005-1010. .

All fractures are associated with morbidity

40%

Unable to walk independently

30%

Discharged toNursing Home

≥20%

Death within one year

80%

One year after a hip fractureP

atie

nts

(%)

Unable to carry out at least one independent activity of daily living

Adapted from Cooper C. Am J Med 1997; 103(2A):12S-17S.

Morbidity after vertebral fractures

Back pain

Loss of height

Deformity (kyphosis, protuberant abdomen)

Reduced pulmonary function

Diminished quality of life: loss of self-esteem, distorted body image, dependence on narcotic analgesics, sleep disorder, depression, loss of autonomy, social dependence

Increased mortalityhttp://www.osteofound.org/

Mortality after major types of osteoporotic fracture in men and women

5 - Year Prospective Cohort Study

Age-Standardized Mortality Ratio

Fracture Women Men

Proximal femur 2.2 3.2Vertebral 1.7 2.4Other major 1.9 2.2Minor 0.8 1.5

Adapted from Center JR, et al. Lancet 1999; 353(9156):878-882..

Economic Impact

Number of bed days (men and women)in Switzerland in 1992:

701,000 for osteoporosis

889,000 for chronic obstructive pulmonary disease

533,000 for stroke

328,000 for myocardial infarction

201,000 for breast cancer

Osteoporosis # 1 when looking at

women only

Adapted from Lippuner K, et al. Osteoporos Int 1997; 7(5):414-425.

Risk factors for Osteoporosis

‘Case-finding’

Risk factors that provide indications for the diagnostic use of bone densitometry

1. Presence of strong risk factors

2. Previous fragility fracture

3. Radiographic evidence of osteopenia or vertebral deformity or both

4. Loss of height, thoracic kyphosis(after radiographic confirmation of vertebral deformities)

Kanis JA. Lancet 2002; 359(9321):1929-1936.

Risk Factors that identify people who should be assessed* for Osteoporosis

Major Risk Factors

• Age 65 years• Vertebral compression fracture• Fragility fracture after age 40• Family history of osteoporotic

fracture (esp. maternal hip fract.)• Systemic glucocorticoids (> 3 m)• Early menopause ( (before 45)• Malabsorption syndrome• Primary hyperparathyroidism• Propensity to fall• Osteopenia apparent on x-ray

film• Hypogonadism• High Bone Turnover• Major immobility

• Rheumatoid Arthritis• Hyperthyroidism • Anticonvulsant therapy• Chronic heparin therapy (UFH)• Calcium Intake < 500 mg/d• Smoking• Excessive alcohol intake• BMI < 19

Minor Risk Factor

.

Adapted from Brown JP, et al. CMAJ 2002; 167(10 Suppl):S1-34.

* BMD measurement is recommended for those with at least 1 major or 2 minor risk factors

Who to test (BMD-measurement) for Postmenopausal Osteoporosis ?

post-menopausal, 65 y

post-menopausal, < 65 y– with additional risk factors, or

– with fragility fracture, or

– with loss of height or deformity of the spine (kyphosis)

pre- or post-menopausal– with disease or receiving a treatment, known that they can

cause a ‘secondary’ form of osteoporosis

Adapted from Raisz LG. N Engl J Med 2005; 353(2):164-171.

Preventing osteoporosis

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TREATMENT of OSTEOPOROSIS

in order

to prevent (new) fractures

Drugs used in osteoporosis treatment

• HRT

• SERM/Raloxifene

• Calcitonin

• Bisphosphonates- Alendronate

- Risedronate

- Ibandronate

Parathyroid hormone

Inhibition of resorption Stimulation of formation

Strontium ranelate