文档介绍：Pathophysiology of Metastatic Bone Disease and the Role of Bisphosphonates
Prof. Robert Coleman, MD, FRCP
Cancer Research Centre
Weston Park Hospital
Sheffield, England
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Disease prevalence, Bone mets. Median . (in thousands) incidence (%) survival (mo)
Myeloma 75 - 100 70 - 95 24
Renal 198 20 - 25 12
Melanoma 467 14 - 45 6
Bladder 582 40 6 - 9
Thyroid 207 60 48
Lung 386 30 - 40 7
Breast 1,993 65 - 75 24
Prostate 984 65 - 75 36
Clinical Importance and Prognosis of Bone Metastases
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NCI, 1997; International Myeloma Foundation, 2001.
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plications in Metastatic Bone Disease Are Significant
% of patients affected in PLACEBO arms of:
Pamidronate trials ZOMETA® trials
Disease Breast Myeloma Prostate Others Observation time 12 months 9 months 15 months 9 months
Radiation to bone 33 22 29 32
Fractures 41 30 22 21
Hypercalcaemia of malignancy 9 6 1 3
Surgery to bone 8 5 3 4
Spinal cord compression 2 3 7 4
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Role of the osteoclast in bone pathology
Growth factors
Osteoclast activity
Osteolysis
Direct bone destruction
Bone
Bone secondaries
Primary
Local factors
Systemic factors
Tumour cells
plications
Pathophysiology of Bone Metastases
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Activated
osteoclast
4
Cancer and Bone Cell Interactions
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Osteolytic bone disease
Osteoblastic bone disease
Osteoclast
Osteoblast
Unknown
GFs
TGF-
5
Bone Remodelling Cancer Effects
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Coupled and balanced
Bone
Uncoupled but balanced
Bone
Coupled but imbalanced
Bone
Uncoupled and imbalanced
Bone
6
Lytic
Blastic
Mixed
X-ray pattern
Bone-specific alkaline phosphatase (ng/mL)
N-telopeptide (BCE/M Cr)
Bone Markers in Osteolytic and Osteosclerotic Metastatic Bone Disease
0
10
30
20
40
50
60
Lytic
Blastic
Mixed
X-ray pattern
0
100
300
200
400
500
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Lipton A. Semin Oncol. 2001;28:54-59.
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Increased
bone
resorption
Hypercalcaemia
Fracture
Bone pain
Consequences of Increased Bone Resorption
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Bone
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Treatment of Bone Metastases
Traditional treatments
Rad