RRRRCC

OSTEOPOROSISOSTEOPOROSIS

Rheumatology Research Center

INTERNAL MEDICINE CONGRESS 1382INTERNAL MEDICINE CONGRESS 1382INTERNAL MEDICINE CONGRESS 1382INTERNAL MEDICINE CONGRESS 1382

RRRRCCRRRRCC

RRRRCC

DEFINITIONDEFINITION

• Systemic Skeletal Disease • Low Bone Mass • Micro Architectural Deterioration

– Increase in Bone Fragility– Susceptibility to Fracture Am J Med 1993;94:644-650

• Bone Densitometry– t score: –2.5SD

WHO 1990

• Systemic Skeletal Disease • Low Bone Mass • Micro Architectural Deterioration

– Increase in Bone Fragility– Susceptibility to Fracture Am J Med 1993;94:644-650

• Bone Densitometry– t score: –2.5SD

WHO 1990

RRRRCC

EPIDEMIOLOGYEPIDEMIOLOGY

RRRRCC

EPIDEMIOLOGYEPIDEMIOLOGY

• USA (NHANESS III 1997)

– Women 13 - 18%

– Men 1 - 4%

• IRAN 4,575,000 - 7,150,000

• USA (NHANESS III 1997)

– Women 13 - 18%

– Men 1 - 4%

• IRAN 4,575,000 - 7,150,000

RRRRCC

FRACTURE RISK50 YEARS AND OVER

FRACTURE RISK50 YEARS AND OVER

WOMEN MEN

• Femur 17.5% 6.0%

• Spine 15.6 5.0

• Wrist 16,0 2.5

• Any Fracture 39.7 13.1

WOMEN MEN

• Femur 17.5% 6.0%

• Spine 15.6 5.0

• Wrist 16,0 2.5

• Any Fracture 39.7 13.1

RRRRCC

BONE PHYSIOLOGY

BONE PHYSIOLOGY

RRRRCC

BONE PHYSIOLOGYBONE PHYSIOLOGY

• Bone Resorption

– Osteoclast

• Bone Formation

– Osteoblast

• Bone Remodeling

Unit

– Positive < age 30

– Negative > age 30

• Bone Resorption

– Osteoclast

• Bone Formation

– Osteoblast

• Bone Remodeling

Unit

– Positive < age 30

– Negative > age 30

00.10.20.30.40.50.60.70.80.9

1

10 15 20 25 30 35 40 45 50 55 60 65 70 75

RRRRCC

OSTEOBLASTOSTEOBLAST

• Origin: Mesenchymal Cell

• Activation: PTH, Vitamin D

• Function

– Matrix Formation

– Bone Mineralization

– Matrix Degradation RANK L

• Origin: Mesenchymal Cell

• Activation: PTH, Vitamin D

• Function

– Matrix Formation

– Bone Mineralization

– Matrix Degradation RANK L

RRRRCC OSTEOCLASTOSTEOCLAST

• Origin– Blood Mononuclear Cells

• Differentiation

– CSF-1

– RANK L• Lymphocyte

• Osteoblast

• Action– Acidification

– Protein Degradation

• Origin– Blood Mononuclear Cells

• Differentiation

– CSF-1

– RANK L• Lymphocyte

• Osteoblast

• Action– Acidification

– Protein Degradation

H2O + CO2

HCO3

H+

Cl

RRRRCC

BONE REMODELING UNITBONE REMODELING UNIT

. . . ... . . .. . . .

. . . . . .

Resorption Formation Completion

RRRRCC

STIMULATION

IL-1TNF-IL-6IL-11

PTHVit D

RANK

BONE RESORPTIONBONE RESORPTIONM-CSF

IL-1TNF-IL-6IL-11

PTHVit D

RANKSTIMULATION

RRRRCC

STIMULATION

PROGESTERONE

ANDROGEN

ILGF PTHVit D

ESTROGEN

ESTROGEN

STIMULATION

CALCITONIN

INHIBITION

COUPLING FACTOR

IL-1TNF-IL-6IL-11

INHIBITION

PTHVit D

RANK

BONE FORMATIONBONE FORMATION

RRRRCC

CLINICAL MANIFESTATIONS

CLINICAL MANIFESTATIONS

RRRRCC

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

• Symptoms Non

• Complications Fractures

– Macroscopic

• Vertebra

• Femoral Neck

• Wrist

• Others

– Microscopic

• Vertebrae: Mechanical Pain, Spine Deformity

• Symptoms Non

• Complications Fractures

– Macroscopic

• Vertebra

• Femoral Neck

• Wrist

• Others

– Microscopic

• Vertebrae: Mechanical Pain, Spine Deformity

RRRRCC

DIAGNOSISDIAGNOSIS

RRRRCC

OLD DAYSOLD DAYS

RRRRCC

20th CENTURY20th CENTURY

• X-RAY

• BONE BIOPSY

• X-RAY

• BONE BIOPSY

RRC

RRRRCC

NOWADAYSNOWADAYS

BONE DENSITOMETRYBONE DENSITOMETRY

RRRRCC Dual Energy X-ray Absorptiometry

(Gold Standard)

Dual Energy X-ray Absorptiometry

(Gold Standard)

• NON INVASIVE

– Irradiation: 1/100 Chest X-ray

– 1 h. Sun Exposure

• SENSITIVITY 1.0%

• ACCURACY 2.8%

• REPEATABLE

• LONGITUDINAL STUDY

• NON INVASIVE

– Irradiation: 1/100 Chest X-ray

– 1 h. Sun Exposure

• SENSITIVITY 1.0%

• ACCURACY 2.8%

• REPEATABLE

• LONGITUDINAL STUDY

RRRRCC

BONE MINERAL DENSITYBONE MINERAL DENSITY

• SPINE

• FEMUR

• FOREARM

• OTHERS– Whole Body

– Heel

– hand

• SPINE

• FEMUR

• FOREARM

• OTHERS– Whole Body

– Heel

– hand

RRRRCC

RESULTRESULT

• BMD 0.857

• Comparison To Young Adult

– % 76%

– t Score -2.4

• Comparison To Same Age

– % 101%

– z Score+0.1

• BMD 0.857

• Comparison To Young Adult

– % 76%

– t Score -2.4

• Comparison To Same Age

– % 101%

– z Score+0.1

RRRRCC SPINESPINE

RRRRCC SPINESPINE

RRRRCC FEMURFEMUR

RRRRCC FEMURFEMUR

RRRRCC FOREARMFOREARM

RRRRCC FOREARMFOREARM

RRRRCC

DIFFERENT STANDARDSDIFFERENT STANDARDS

• COUNTRIES and ETHNICITIES

• MACHINES

– Hologic

– Lunar

– MediLink

– Norland

• COUNTRIES and ETHNICITIES

• MACHINES

– Hologic

– Lunar

– MediLink

– Norland

RRRRCC AMERICAN STANDARDAMERICAN STANDARD

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

Standardized BMD

PBM1124 mg

1006 mg

829 mg

Osteopenia

Osteoporosis

Female - SpineFemale - Spine

RRRRCC IRANIAN STANDARDIRANIAN STANDARD

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

Standardized BMD

PBM1097 mg Female - SpineFemale - Spine

RRRRCC COMPARISONCOMPARISON

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

400

500

600

700

800

900

1000

1100

1200

20 30 40 50 60 70

Standardized BMD

PBM diff2.5%

1006 mg

829 mg

Osteopenia

Osteoporosis

Female - SpineFemale - Spine

RRRRCC

DEFINITIONSDEFINITIONS

• NORMAL BONE

– 1.0 to -1.0 SD over/bellow PBM

• OSTEOPENIA

– -1.0 to -2.4 SD bellow PBM

• OSTEOPOROSIS

– -2.5 SD bellow PBM

• NORMAL BONE

– 1.0 to -1.0 SD over/bellow PBM

• OSTEOPENIA

– -1.0 to -2.4 SD bellow PBM

• OSTEOPOROSIS

– -2.5 SD bellow PBM

RRRRCC BMD REPORTBMD REPORT

• FRACTURE RISK Spine Neck

– t = -1 SD 2.2 2.6

– t = -2 SD 5.0 7.0

– t = -3 SD 11.0 18.0

• Comparison Iranian Standard

• Advice

– Evaluation

– Prevention/Treatment

• FRACTURE RISK Spine Neck

– t = -1 SD 2.2 2.6

– t = -2 SD 5.0 7.0

– t = -3 SD 11.0 18.0

• Comparison Iranian Standard

• Advice

– Evaluation

– Prevention/Treatment

RRRRCCPURPOSE and APPLICATIONPURPOSE and APPLICATION

• DIAGNOSIS

– Osteoporosis

– Osteopenia

– Normal Bone

• CALCULATION

– Time to Osteopenia

– Time to Osteoporosis

• DIAGNOSIS

– Osteoporosis

– Osteopenia

– Normal Bone

• CALCULATION

– Time to Osteopenia

– Time to Osteoporosis

RRRRCC BONE LOSSBONE LOSS

0.53

0.85

1.02 1.05

0.9

0.5

0

0.2

0.4

0.6

0.8

1

1.2

35-40 40-45 45-50 50-55 55-60 60-65

0.53

0.85

1.02 1.05

0.9

0.5

0

0.2

0.4

0.6

0.8

1

1.2

35-40 40-45 45-50 50-55 55-60 60-65

%

Age

22% Loss 35-65 Y

Spine – Iranian Women

RRRRCC INDICATION(People at Risk)

INDICATION(People at Risk)

• Menopause

• Inflammatory Diseases

• Endocrine Disorders

• Predisposing Drugs

• Familial History

• Fracture

• Menopause

• Inflammatory Diseases

• Endocrine Disorders

• Predisposing Drugs

• Familial History

• Fracture

RRRRCC

BONE TRABECULABONE TRABECULA

RRRRCC

BONE TRABECULABONE TRABECULA

RRRRCC

RRRRCC

BONE TRABECULABONE TRABECULA

RRRRCC

PREVENTIONPREVENTION

RRRRCC

PREDISPOSING FACTORSPREDISPOSING FACTORS• Genetic

– Stature

– Vitamin D Receptor: DD, Dd, dd

• Alimentation– Calcium, Protein

• Physical Activity• Habits

– Coffee, Alcohol, Smoking

• Disease– Endocrine, Inflammatory Diseases, Renal Disorders

• Drugs– Steroids, Cytotoxic, Anti-epileptic, Heparin, Thyroxine

• Genetic– Stature

– Vitamin D Receptor: DD, Dd, dd

• Alimentation– Calcium, Protein

• Physical Activity• Habits

– Coffee, Alcohol, Smoking

• Disease– Endocrine, Inflammatory Diseases, Renal Disorders

• Drugs– Steroids, Cytotoxic, Anti-epileptic, Heparin, Thyroxine

RRRRCC PREVENTION(Normal Person, Normal BMD)

PREVENTION(Normal Person, Normal BMD)

• Young– Alimentation

– Sport

• Mid Age (up to menopause)

– Habits

• Menopause– HRT (Allendronate?), Calcium, Exercises

• Senile– Exercises

• Young– Alimentation

– Sport

• Mid Age (up to menopause)

– Habits

• Menopause– HRT (Allendronate?), Calcium, Exercises

• Senile– Exercises

RRRRCC

PREVENTION(Disease or Medication, Normal BMD)

PREVENTION(Disease or Medication, Normal BMD)

• Same as for Normal Person

• Adequate Management of the Disease

– Minimum Required Dose of Predisposing Drug

• Medication

• Calcium

• Exercise

• Same as for Normal Person

• Adequate Management of the Disease

– Minimum Required Dose of Predisposing Drug

• Medication

• Calcium

• Exercise

RRRRCC

RRRRCCDRUGSDRUGS

• Bone Forming– Synthetic PTH

– Fluoride 20-40 mg/daily + Ca + Vit

D

– Progesterone

– Anabolic agents Nandrolone Decanoate

• Resorption Preventing– Estrogen & Analogs ERT, HRT, Ralloxiphen

– Calcitonin Injectable, Nasal Spray

– Bisphosphonate Etidronate, Allendronate

• Bone Forming– Synthetic PTH

– Fluoride 20-40 mg/daily + Ca + Vit

D

– Progesterone

– Anabolic agents Nandrolone Decanoate

• Resorption Preventing– Estrogen & Analogs ERT, HRT, Ralloxiphen

– Calcitonin Injectable, Nasal Spray

– Bisphosphonate Etidronate, Allendronate

RRRRCC

ALLENDRONATEALLENDRONATE

• Osteofos

• Prevention– 5 mg daily

• Treatment– 10 mg daily

• Precautions– 30 Minutes Before Breakfast

– Upright Position

• Side Effects

• Osteofos

• Prevention– 5 mg daily

• Treatment– 10 mg daily

• Precautions– 30 Minutes Before Breakfast

– Upright Position

• Side Effects

RRRRCC INTERNAL MEDICINE CONGRESS 1382

Rheumatology Research Center