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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

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

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

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

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

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

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

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

PREVENTION

LIFE STYLE• DIET

• Dairy Products

• SPORT• Walking

• Aerobic

• WRONG HABITS• Smoking

• Alcohol

• Excess Coffee

• Excess Protein

DIET

CALCIUM• Need

– 1000 mg Men, Women before Menopause

– 1500 mg Women after Menopause

CALCIUM• Need

– 1000 mg Men, Women before Menopause

– 1500 mg Women after Menopause

• Source

– Dairy Products Milk, Yoghourt, Cheese

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

CALCIUM• Need

– 1000 mg Men, Women before Menopause

– 1500 mg Women after Menopause

• Source

– Dairy Products Milk, Yoghourt, Cheese

– Vegetables Broccoli

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)

VITAMIN D

• Need

– 50 to 70 years 400 units

– > 70 years 600 units

TREATMENT

TREATMENT

WHO?

WHO?

• History of hip or vertebral fracture

• T-score ≤-2.5

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

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

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

Menopause Prevention

• HRT if no contraindication (WHI)

Menopause Prevention

• HRT if no contraindication (WHI)

• Anti-Resorptive Agents

• Alendronate 70 1 /week

Menopause Prevention

• HRT if no contraindication (WHI)

• Anti-Resorptive Agents

• Alendronate 70 1 /week

• Calcium + Vitamin D

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