OSTEOPOROSIS

INTRODUCTION

• DEFINITION : BONE DISORDER THAT INCREASES A PERSON’S RISK OF

FRACTURE DUE TO LOW BONE MINERAL DENSITY (BMD),
IMPAIRED BONE MICROARCHITECTURE OR MINERALIZATION, AND/OR
DECREASED BONE STRENGTH

• THIS ASYMPTOMATIC CONDITION OFTEN REMAINS

UNDIAGNOSED UNTIL IT MANIFESTS AS A LOW-TRAUMA FRACTURE OF
THE HIP, SPINE, PROXIMAL HUMERUS, PELVIS, AND/OR WRIST, WHICH
FREQUENTLY LEADS TO HOSPITALIZATION
 BURDEN OF OSTEOPOROTIC BONE

• The prevalence of osteoporosis is projected to rise in

the United States from approximately 10 million
people to more than 14 million people by 2020
• One in five of Americans who have osteoporosis or
low BMD
• In 2015, direct medical costs totaled $637.5 million
for fatal fall injuries and $31.3 billion for nonfatal
fall injuries. During the same year, hospitalizations
cost an average of $30,550 per fall admission,
totaling $17.8 billion
 OSTEOPOROTIC FRACTURE

Spine fracture

Hip fracture

Wrist fracture

Dennison E, Cole Z, Cooper C. Diagnosis and epidemiology of

osteoporosis. Curr Opinion Rheumatol 2005;17:456-61.
 BIOCHEMICAL MARKERS
OF BONE TURNOVER
Bone Formation Bone Resorption
Tartrate-resistant acid
Alkaline phosphatase
phosphatase
Osteocalcin (bone Gla-
Hydroxyproline
protein)
Procollagen type 1 Hydroxylysine
Α2 HS glycoprotein Pyridinoline
Deoxypyridinoline (collagen
cross-links)
N-telopeptide type I collagen
(NTX)
 BONE MASS DURING LIFE

Progressive decline of bone mass during the 5th decade in women

PATOPHYSIOLOGY
• IMBALANCE IN REMODELING ACTIVITY
 RESORPTION EXCEEDS FORMATION
 OSTEOPOROSIS
• ESTROGEN AND TESTOSTERONE ON
BONE REMODELING  INHIBITING BONE
BREAKDOWN
• CYTOKINES IN BONE REMODELING 
RECEPTOR ACTIVATOR OF THE
NUCLEAR FACTOR KAPPA-B LIGAND
(RANKL)
• RANKL  PRODUCED BY
OSTEOBLASTS; BIND TO RANK
RECEPTORS ON OSTEOCLASTS 
ACTIVATION AND MATURATION OF
OSTEOCLASTS AND CULMINATING IN
BONE RESORPTION
• RECENT ADVANCES IN MOLECULAR
BONE BIOLOGY HAVE IDENTIFIED A
POTENT PROTEASE NAMED
CATHEPSIN K (CATK)
• CATK  SECRETED BY ACTIVATED
OSTEOCLAST DURING BONE
RESORPTION  DEGRADATION OF
BONE MATRIX AND BREAKDOWN OF
MINERAL COMPONENTS OF BONE
TISSUE
• PARATHYROID HORMONE (PTH)
PLAYS AN IMPORTANT ROLE IN
BONE FORMATION BY INDIRECTLY
INCREASING THE PROLIFERATION
OF OSTEOBLASTS THROUGH
REGULATION OF CALCIUM
HOMEOSTASIS
Rigg and Nelson divided into :

A/. Primary osteoporosis

1. Post menopause osteoporosis
2. Senile osteoporosis
B/. Secondary osteoporosis
Osteoporosis due to other condition
of disease such as metabolic,
endocrine or malignancy, etc
 PRIMARY OSTEOPOROSIS

• ASSOCIATED WITH AGE AND SEX HORMONE DEFICIENCY

• AGE-RELATED OSTEOPOROSIS RESULTS FROM THE
CONTINUOUS DETERIORATION OF THE TRABECULAE IN BONE
• THE REDUCTION OF ESTROGEN PRODUCTION IN
POSTMENOPAUSAL WOMEN CAUSES A SIGNIFICANT INCREASE
IN BONE LOSS
• IN MEN, SEX-HORMONE–BINDING GLOBULIN INACTIVATES
TESTOSTERONE AND ESTROGEN AS AGING OCCURS, WHICH
MAY CONTRIBUTE TO THE DECREASE IN BMD WITH TIME
 SECONDARY OSTEOPOROSIS
• CAUSED BY SEVERAL COMORBID DISEASES AND/OR MEDICATIONS
• INVOLVE MECHANISMS RELATED TO THE IMBALANCE OF CALCIUM,
VITAMIN D, AND SEX HORMONES.
• CUSHING’S SYNDROME ACCELERATE BONE LOSS THROUGH EXCESS
GLUCOCORTICOID PRODUCTION
• RHEUMATOID ARTHRITIS  LONG-TERM GLUCOCORTICOID 
CONSIDERED THE MOST COMMON MEDICATIONS LINKED TO DRUG-
INDUCED OSTEOPOROSIS
• FOR MEN, EXCESSIVE ALCOHOL USE, AND HYPOGONADISM ARE MORE
COMMONLY ASSOCIATED WITH OSTEOPOROSIS
• MEN RECEIVING ANDROGEN-DEPRIVATION THERAPY (ADT) FOR
PROSTATE CANCER ARE AT INCREASED RISK OF OSTEOPOROSIS
• TANNENBAUM ET AL. FOUND THAT OSTEOPOROSIS IN 32.4% OF WOMEN
WAS ATTRIBUTED TO SECONDARY CAUSES, MOST OFTEN
HYPERCALCIURIA, MALABSORPTION OF CALCIUM,
HYPERPARATHYROIDISM, VITAMIN D DEFICIENCY, HYPERTHYROIDISM,
CUSHING’S DISEASE, AND HYPOCALCIURIC HYPERCALCEMIA
 DIAGNOSIS OF OSTEOPOROSIS

Calcaneal Ultrasound DXA

Dual energy X-ray absorptiometry (DXA) is standard

method for diagnosis of osteoporosis
 BMD CLASSIFICATION

Normal T-score > -1 SD

T-score < -1
Osteopenia
and > -2.5

Osteoporosis T-score < -2.5

T-score < -2.5 with fragility

Severe osteoporosis fracture

World Health Organization (WHO),1994

 FRAX SCORE

• TO PREDICT THE 10-YEAR PROBABILITY OF HIP FRACTURE AND

OTHER MAJOR OSTEOPOROTIC FRACTURE
• ACCOUNTS RISK FACTORS SUCH AS AGE, RACE, ALCOHOL USE,
GENDER, BODY MASS INDEX, SMOKING HISTORY, PRIOR
PERSONAL OR PARENTAL HISTORY OF FRACTURE, USE OF
GLUCOCORTICOIDS, SECONDARY OSTEOPOROSIS, RHEUMATOID
ARTHRITIS, AND FEMORAL NECK BMD MEASUREMENTS
• CAN BE USED IN CONJUNCTION WITH OTHER DIAGNOSTIC
TOOLS, SUCH AS THE DXA SCAN, TO DETERMINE APPROPRIATE
PATIENTS FOR TREATMENT
 MANAGEMENT
NONPHARMACOLOGY

• ADEQUATE CALCIUM AND VITAMIN D INTAKE

• WEIGHT-BEARING EXERCISE
• SMOKING CESSATION
• LIMITATION OF ALCOHOL/CAFFEINE
CONSUMPTION
• FALL-PREVENTION TECHNIQUES
 MANAGEMENT
NONPHARMACOLOGY

• VITAMIN D IS A KEY COMPONENT IN CALCIUM

ABSORPTION AND BONE HEALTH.
• THE IOM RECOMMENDS
• 600 IU PER DAY FOR MEN AND WOMEN 51 TO 70
YEARS OF AGE
• 800 IU PER DAY FOR MEN AND WOMEN OLDER
THAN 70 YEARS
 MANAGEMENT
PHARMACOLOGY
• THE GOAL OF PHARMACOLOGICAL THERAPY IS TO
REDUCE THE RISK OF FRACTURES

• ANTIRESORPTIVE
• DECREASE THE RATE OF BONE RESORPTION
• I.E., BISPHOSPHONATES, ESTROGEN AGONIST/ ANTAGONISTS
[EAAS], ESTROGENS, CALCITONIN, AND DENOSUMAB)

• ANABOLIC
• INCREASE BONE FORMATION MORE THAN BONE RESORPTION
• I.E., TERIPARATIDE
 MANAGEMENT
PHARMACOLOGY

• HORMONAL THERAPIES
• ESTROGEN AGONIST/ANTAGONIST 
RALOXIFENE, CONJUGATED ESTROGEN
(BAZEDOXIFEN)
• ESTROGEN-PROGESTIN THERAPY
• TESTOSTERONE THERAPY
• CALCITONIN
• PTH ANALOGUES  TERIPARATIDE,
ABALOPARATIDE
 MANAGEMENT
PHARMACOLOGY

• EMERGING THERAPIES
• ROMOSOZUMAB
• ODANACATIB
• LASOFOXIFENE