Alimohammad Fatemi Assistant Professor of Rheumatology 1.
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OSTEOPOROSIS MANAGEMENT
(DRUGS) Alimohammad Fatemi
Assistant Professor of Rheumatology
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OSTEOPOROSIS
• A skeletal Disorder:
– Compromised Bone Strength
– Increased Risk of Fracture
Adams, Nat Rev Endocrinol. 2013
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• Bone Quality
• Bone Mineral
• Bone Material
BONE STRENGTH
Adams, Nat Rev Endocrinol. 2013
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Vertebra Body
Normal Osteoporosis
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EPIDEMIOLOGY
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Epidemiology
• 200 million women worldwide
• 1/3 women aged 60-70
• 2/3 women aged >80
IOF, 2015 (http://www.iofbonehealth.org/osteoporosis)
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Epidemiology
IOF, 2015 (http://www.iofbonehealth.org/osteoporosis)
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DIAGNOSIS
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Diagnosis
Comparison to Young-Adult Mean BMD
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WHO CLASSIFICATIONSuperior to Normal
Normal
Osteopenia
Osteoporosis
T+1
0
-1
-2.5
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FRACTURE RISK
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FRACTURE RISK50 YEARS AND OVER
WOMEN
MEN
• Femur 22.9%
10.7%
• Spine 15.1 8.3
• Wrist 20.8 4.6
• Any Fracture 46.4 22.4Kanis JA et al, Osteoporos Int, 2000:11:669-674
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Vertebrae
Hip
Wrist
50 60 70 80
40
30
20
10
Age (Years)
Ann
ual i
ncid
ence
per
10
00 w
omen
Incidence of Osteoporotic Fractures in Women
Wasnich RD, Osteoporos Int 1997;7 Suppl 3:68-72
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Incidence of Osteoporotic Fractures in Men
Age (Years)
Vertebrae
Hip
Wrist
50 60 70 80
4000
2000
0
Ann
ual i
ncid
ence
pe
r 10
0,00
0 m
en
Wasnich RD, Osteoporos Int 1997;7 Suppl 3:68-72
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FRACTURE MORBIDITY
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Cooper C, Am J Med, 1997;103(2A):12S-17S
80%
One year after a hip fracture:
Pat
ien
ts (
%)
Unable to carry out at least one independent activity of daily living
All Fractures Are AssociatedWith Morbidity
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All Fractures Are AssociatedWith Morbidity
40%
Unable to walk independently
80%
One year after a hip fracture:
Pat
ien
ts (
%)
Unable to carry out at least one independent activity of daily living
Cooper C, Am J Med, 1997;103(2A):12S-17S
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All Fractures Are AssociatedWith Morbidity
40%
Unable to walk independently
30%
Permanentdisability
80%
One year after a hip fracture:
Pat
ien
ts (
%)
Unable to carry out at least one independent activity of daily living
Cooper C, Am J Med, 1997;103(2A):12S-17S
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All Fractures Are AssociatedWith Morbidity
40%
Unable to walk independently
30%
Permanentdisability
20%
Death within one year
80%
One year after a hip fracture:
Pat
ien
ts (
%)
Unable to carry out at least one independent activity of daily living
Cooper C, Am J Med, 1997;103(2A):12S-17S
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Survival After Hip Fracture
Trombetti A et al, Osteoporos Int, 2002;13:731-737
Hip fractured Women
Hip fractured Men
Women
Men
Expected Survival In The General Population
2 4 6 8 10
0.00
0.25
0.50
0.75
1.00
Sur
viva
l pro
babi
lity
Time after hip fracture (years)0
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PREVENTION
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LIFE STYLE• DIET
• Dairy Products
• SPORT• Walking
• Aerobic
• WRONG HABITS• Smoking
• Alcohol
• Excess Coffee
• Excess Protein
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DIET
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CALCIUM• Need
– 1000 mg Men, Women before Menopause
– 1500 mg Women after Menopause
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CALCIUM• Need
– 1000 mg Men, Women before Menopause
– 1500 mg Women after Menopause
• Source
– Dairy Products Milk, Yoghourt, Cheese
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CALCIUM• Need
– 1000 mg Men, Women before Menopause
– 1500 mg Women after Menopause
• Source
– Dairy Products Milk, Yoghourt, Cheese
Milk 300 mg/cup
Cheese 300 mg/Oz
Yogurt 300 mg/cup
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CALCIUM• Need
– 1000 mg Men, Women before Menopause
– 1500 mg Women after Menopause
• Source
– Dairy Products Milk, Yoghourt, Cheese
– Vegetables Broccoli
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CALCIUM• Need
– 1000 mg Men, Women before Menopause
– 1500 mg Women after Menopause
• Source
– Dairy Products Milk, Yoghourt, Cheese
– Vegetables Broccoli
– Tablets Calcium Carbonate, Citrate
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CALCIUM
• Are Calcium Tab safe?
– Risk of Cardiovascular event
BMJ 336, 262–266 (2008)JAMA Intern. Med. http://dx.doi.org/10.1001/jamainternmed.2013.3283
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Patients should be encouraged to obtain 500–
1,000 mg of calcium from their daily diet
CALCIUM
Nat. Rev. Endocrinol. 9, 255–256 (2013)
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VITAMIN D
• Need
– 50 to 70 years 400 units
– > 70 years 600 units
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TREATMENT
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TREATMENT
WHO?
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WHO?
• History of hip or vertebral fracture
• T-score ≤-2.5
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WHO?
• History of hip or vertebral fracture
• T-score ≤-2.5
• T-score between -1 and -2.5
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CLINICAL RISK FACTORSfor FRACTURE
• Age• Sex• Weight• Height• History of Fracture• Parental History of Fracture• Current Smoking• Steroid Use• Alcohol Use• RA• Secondary Osteoporosis
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FRAX
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WHO?
• History of hip or vertebral fracture
• T-score ≤-2.5
• T-score between -1 and -2.5 AND:
– 10-year probability of hip fracture ≥3 percent or
– 10-year probability of any major osteoporosis-related
fracture ≥20 percent
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DRUGS
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Drugs Used In Osteoporosis Treatment
• HRT
• SERM/Raloxifene
• Calcitonin
• Bisphosphonates
- Alendronate
- Zoledronate
- Ibandronate
· Parathyroid Hormone (PTH)
• Denosumab
• Strontium Ranelate
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ESRTROGEN
• Antiresorptive
• Fracture Risk
• Its effect lost 1 year after stop it
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SERM
• Raloxifene 60 mg
– Vertebral Fracture
– Breast Cancer
– DVT
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Calcitonin
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Calcitonin
• Nasal Spray (200 unit/day)
– Vertebral Fracture
– No effect on Hip fracture
– Minimal effect on Bone Density
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Calcitonin
• Safe?
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Calcitonin
• Safe?
– May Increase Skin Cancerhttp://www.ema.europa.eu
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BISPHOSPHONATES
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BISPHOSPHONATES
• Fracture Risk
– Vertebral– Non Vertebral
• Bone Density
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BISPHOSPHONATES
• Adverse Effects:
– Atypical fracture of Femur
– Osteonecrosis of Jaw
– Esophageal Cancer?
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PTHFORTEO
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PTH
• Anabolic Agent
• 20 μg Daily SC (18-24 months)
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• Indications:
– Vertebral Compression Fracture
– Other Osteoporotic-Fracture with Low BMD
– T-score < -3
PTH
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DENOSUMAB
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DENOSUMAB
• An antiresorptive
• Suppress Osteoclasts
• 60 mg every 6 months (SC)
• Injection site reaction
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StrontiumRanelate
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STRONTIUM RANLEATE
• Bone Formation
• Bone Resorption
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STRONTIUM RANLEATE
• Bone Formation
• Bone Resorption
• Powder 2g/ Day
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STRONTIUM RANLEATE
• Bone Formation
• Bone Resorption
• Powder 2g/ Day
• But, Increases DVT
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HOW TO TREATIN IRAN
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Menopause Prevention
• HRT if no contraindication (WHI)
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Menopause Prevention
• HRT if no contraindication (WHI)
• Anti-Resorptive Agents
• Alendronate 70 1 /week
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Menopause Prevention
• HRT if no contraindication (WHI)
• Anti-Resorptive Agents
• Alendronate 70 1 /week
• Calcium + Vitamin D
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FOLLOW-UP• Every 6 Months
• Ca, P, Alkaline Phosphatase, 24h Calciuria
• Every 1.5 to 3 Years
• BMD
• Change of Treatment Strategy
• Side Effects
• Non-Responsive
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THANKS FOR
YOUR ATTENTION