骨質疏鬆病症機轉與檢驗方式之報告

1. An Overview of Osteoporosis
報告學生: M5 柯皓禎
指導老師: 吳仲鼎 醫師
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology

2. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Definition
Osteoporosis is a disease that is characterized by
Low bone mass
• Deterioration of bone tissue
• Disruption of bone
microarchitecture
Lead to:
1. Compromised bone strength
2. An increase in the risk of fractures
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3. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Definition
─ Cause
Osteoporosis can be classified into two main groups by
considering the factors affecting bone metabolism
Primary
Idiopathic Postmenopausal Senile
Secondary
Endocrine Disorders Gastrointestinal Drugs Miscellaneous
• Addison disease
• Diabetes, type 1
• Hyperparathyroidism
• Hyperthyroidism
• Hypothyroidism
• Pituitary tumors
• Neoplasia
• Carcinomatosis
• Multiple myeloma
• Hepatic insufficiency
• Malabsorption
• Malnutrition
• Vitamin C, D
deficiencies
• Alcohol
• Anticoagulants
• Anticonvulsants
• Chemotherapy
• Corticosteroids
• Anemia
• Homocystinuria
• Immobilization
• Osteogenesis
imperfecta
• Pulmonary disease
(Robbins, 9e)
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4. (Harrison, 19e)
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Definition
─ Cause
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5. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
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6. In osteoporosis, old bone is being reabsorbed faster than
new bone is being made
(Robbins, 9e)
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
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7. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
─ Signaling factors
Normal bone homeostasis is dependent on the balance
between the cytokine
Receptor activator of nuclear factor κβ ligand (RANKL)
• its receptor RANK
• its decoy receptor osteoprotegerin (OPG)
Regulation:
• IL-1, 4, 6, 7, 11, 17
• TNF-α
• TGF-β
• PGE2
• Hormones
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8. Skeletal system
Immune system
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
─ Signaling factors
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9. Skeletal system
Immune system
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
─ Signaling factors
• In bone, RANKL is expressed by both stromal cells and osteoblasts.
• RANKL stimulates the receptor RANK on osteoclast precursor cells
and mature osteoclasts, and activates intracellular signaling pathways
to promote osteoclast differentiation and activation that increases
resorption and bone loss.
• OPG, secreted by stromal cells and osteoblasts, acts as a “decoy”
receptor and blocks RANKL binding to and activation of RANK 10

10. Immune system
Skeletal system
• In the immune system, RANKL is expressed and secreted by T cells, and
T-cell–derived RANKL also can activate RANK on osteoclasts.
• Dendritic cells may regulate these processes by secreting OPG
• T cells, and dendritic cells (antigenpresenting cells), which enhances
bone loss that occurs in inflammatory bone diseases such as RA.
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
─ Signaling factors
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11. Vascular system
Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Bone remodeling
─ General mechanism
─ Signaling factors
• In the vascular system, endothelial cells express RANKL and the
RANK receptor.
• RANKL/RANK interactions contribute to endothelial and smooth
muscle cells and can block RANKL binding.
• The physiologic significance of the OPG/RANKL/RANK system in
endothelial and smooth muscle cells is being studied
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12. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Morphology
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13. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Morphology
─ Clinical features
Fracture Stooped posture
The disease begins to manifest itself in the later stages, as the bone thins
gradually, without causing the person discomfort or any pain. Some
people even in case of advanced osteoporosis do not feel its symptoms.
Femoral neck fracture: 48.4%
Intertrochanteric fracture: 51.6% 14

14. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
FRAX骨折風險評估
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15. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
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16. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
─ Bone mineral density
A bone mineral density test measures how much calcium and other types
of minerals are in an area of your bone.
QUS
These smaller machines measure the bone
density in your wrist, fingers, leg, or heel.
These machines are in health care offices,
pharmacies, and at health fairs.
DEXA
The scanner passes over lower spine and hip.
In most cases, patient do not need to undress.
This scan is the best test to predict risk of
fractures, especially of the hip.
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17. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
─ Bone mineral density
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18. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
─ Bone mineral density
─ Lab test
Blood and urine tests can be used to identify possible causes of bone
loss. Some of these tests include:
• Blood calcium levels
• 24-hour urine calcium measurement
• Thyroid function tests
• Parathyroid hormone levels
• Testosterone levels in men
• 25-hydroxyvitamin D test to determine whether
the body has enough vitamin D
• Biochemical marker tests, such as NTX and CTX
For identifying selected
secondary causes of
low bone mass
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19. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Criteria
─ Bone mineral density
─ Lab test
─ Other test
Test Purpose
X-Rays
Vertebral Fracture
Assessments (VFAs)
Show breaks in the spine.
Nuclear bone scans
CT Scans
MRIs
Show changes that may be caused by cancer, bone
lesions, inflammation, new broken bones or other
conditions.
They are often used to help find the cause of back pain
or to follow up on abnormalities seen on an x-ray.20

20. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
(X-ray)The thoracic vertebra
fractured due to osteoporosis
• Severe osteoporotic fracture of the
T12 vertebral body (open arrow)
• Mild osteoporotic fracture of the L1
vertebral body (arrow).
• Lumbar scoliosis with obliquity of
the lower three lumbar vertebrae (*).
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21. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
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22. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
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23. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
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24. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
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25. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
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26. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Algorithm
─ Medication
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27. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Prevalence
• 骨質疏鬆症已是全球第二大的重要流行病，僅次於心血管疾病
• 依據2005-2008年國民營養調查報告指出50歲以上男女骨鬆症盛行率分別
為23.9%及38.3%。依中央健康保險署住院資料，50歲以上的男性每年髖部
骨折個案，由1999年3551例逐年增加至2010年8616例；女性則由6096例
增加至13893例，平均每年增加9.3%
• 若依2006年台灣平均壽命女性為80.8歲及男性74.6歲推估而言，大約三分
之一的台灣婦女在一生中會發生一次脊椎體、髖部或腕部之骨折；男性也
約有五分之一的風險，即使校正因年齡分佈之差別，這樣的流行率，已與
美國白人相當，都屬於高流行率地區
• 對女性而言，這種風險高於乳癌、卵巢癌和子宮癌風險的總和。對於男性
而言，這種風險高於前列腺癌的風險
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28. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Prevalence
• 發生過一次骨質疏鬆骨折後，約50%患者將會再發生第二次骨折，每次骨
折之後，再出現新骨折的風險呈指數形式增高
• 依中央健康保險署紀錄，發生髖部骨折的老人，在2009年一年內死亡率，
女性為11.2%、男性為18%，但2010年時對照之標準死亡率已大幅下降，
女性只有2.8%、男性為3.6%，所以相差更大，表示到2010年髖部骨折對
死亡率之影響更放大了
• 死因則以長期臥床引發之感染為主
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29. Introduction │ Pathogenesis │ Symptom │ Diagnosis │ Treatment │ Epidemiology
─ Prevalence
─ Risk factor
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30. Reference
• 2015年台灣成人骨質疏鬆症防治之共識與指引
• British Columbia-Osteoporosis: Diagnosis, Treatment and
Fracture Prevention
• Pathophysiology-The Biologic Basis for Disease in Adults and
Children(7e)
• Robbins and Cotran Pathologic Basis of Disease(9e)
• Harrison's Principles of Internal Medicine(19e)
• US Pharmacist
• MedScape
• UpToDate
• UFHealth
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