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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
alciumalciumCCCC
DDDDVitaminVitamin
xercisexerciseEEEE
FFFFPreventPrevent allsalls
ain weightain weightGGGGStopStop mokingmokingSSSS
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