Definition

A DISEASE CHARACTERIZED BY: LOW BONE MASS MICRO-ARCHITECTURAL DETERIORATION OF THE BONE TISSUE LEADING TO: ENHANCED BONE FRAGILITY INCREASE IN FRACTURE RISK

Normal Bone vs Osteoporotic Bone

Loss of trabecular plates ( right) results in weakened bone structure significantly increasing risk of fractures.

Epidemiology
Disorder of postmenopausal women of northern European descent Increase in the incidence related to decreasing physical activity Over 27 million or 1of 3 women are affected with osteoporosis Over 5 million or 1of 5 men are affected with osteoporosis.

Fractures
1.5 million fx/yr 300,000 hip

700,000 vertebral
250,000 wrist

300,000 at other sites

Vertebra Fractures

Hip Fractures

Impact
Chronic pain Height loss Kyphosis Decreased selfesteem Restrictive lung dx Constipation, abdominal pain Depression

Risk Factors
ACTIVE RISK FACTORS

(May be ongoing and lead to cumulative bone loss)

DRUGS MALABSORPTION - Any cause: Medical or Surgical ONGOING ALCOHOL ABUSE HYPOGONADISM CHRONIC IMMOBILITY CHRONIC DISEASE

Risk Factors
INACTIVE RISK FACTORS

(Historical and not likely to lead to further bone loss,

once excluded can be ignored thereafter) FAMILY HISTORY EARLY MENOPAUSE PREVIOUS AMENORRHOEA PREVIOUS THYROID DISEASE PREVIOUS ALCOHOL ABUSE

HYPOGONADISM IMMOBILITY DURING BONE

DEVELOPMENT

Classification
Primary
Postmenopausal osteoporosis (type I) Caused by lack of estrogen Causes PTH to over stimulate osteoclasts Excessive loss of trabecular bone Age-associated osteoporosis (type II) Bone loss due to increased bone turnover Malabsorption Mineral and vitamin deficiency Secondary

Secondary Osteoporosis
Disease states
Acromegaly Addisons disease Amyloidosis Anorexia COPD Hemochromatosis Hyperparathyroidism Lymphoma and leukemia Malabsorption states Multiple myeloma Multiple sclerosis Rheumatoid arthritis Sarcoidosis

Severe liver dz, esp. PBC

Thalessemia Thyrotoxicosis

Secondary Osteoporosis Drugs

Aluminum Anticonvulsants Excessive etoh Excessive thyroxine Depo Provera (decreased bone mass reversible after stopping medication)
Glucocorticoids
GnRH agonists Heparin

Lithium

World Health Organization (WHO) Definition Based on BMD testing

Normal: T score above 1 Osteopenia: T score between 1 and 2.5 Osteoporosis: T score at or below 2.5 Severe osteoporosis: T score 2.5 or lower in the presence of 1 or more fractures

T scores vs. Z scores

T score number of SDs a patients BMD deviates from a reference population of normal young adults Z score number of SDs a patients BMD deviates from a reference population of subjects of the same age and sex Z scores indicate whether the BMD result is expected for the patients age. If it is much less than expected, suspect a secondary cause of osteoporosis (use 2 as a cutoff)

Types of BMD testing

Dual energy x-ray absorptiometry (DXA or DEXA). Gold Standard Measures BMD in spine, hip, or wrist Completed in a few minutes Radiation exposure is less Ultrasound densitometry Measures BMD in heel, patella Cost-effective Poor correlation between US and DXA Inconsistent young normal reference populations may contribute Single-energy x-ray absorptiometry and peripheral dual x-ray Quantitative computed tomography (QCT) Radiographic absorptiometry

MEASUREMENT OF BONE MINERAL DENSITY

PLAIN X-RAY
SINGLE PHOTON ABSORPTIOMETRY DUAL PHOTON ABSORPTIOMETRY

DUAL X-RAY ABSORPTIOMETRY

QUANTITATIVE COMPUTED TOMOGRAPHY

ULTRASOUND

Problems with interpretation of BMD testing

Guidelines developed for Caucasian women but have been applied to all races Overestimation of BMD
Fracture site Pre-existing developmental bone abnormality osteophytes (common in spine, so hip may be more accurate in people >65) Stroke or trauma leading to limb inactivity

Underestimation of BMD

Need to establish standard for comparability of different devices and anatomic sites

When to Measure BMD in Postmenopausal Women

All women 65 years and older Postmenopausal women <65 years of age:
If result might influence decisions about intervention One or more risk factors History of fracture

When Measurement of BMD Is Not Appropriate

Healthy premenopausal women Healthy children and adolescents Women initiating ET/HT for menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)

Dual Energy X-ray Absorptiometry Results

Bone mineral density BMD Expressed in grammes per cm2 (g/cm2) Need to compare with established reference range for the appropriate population. Final result expressed as a standard deviation from the mean BMD of an age and sex matched reference set (z-score) And A standard deviation from the mean BMD of sex matched young adult (t-score)

When to initiate treatment

High Risk
T score <-2.0 ---------------- Treat

Moderate Risk
T score 1.5 to 2.0 -------Treat if other risk factors are present

Low Risk
T score above 1.5 --------Check again in 1-2 years

When to Retest
Repeat testing in 2 yrs additional bone loss response to treatment More frequent testing if: glucocorticoid therapy for more than 3 years evidence of a secondary cause of osteoporosis

Bone Markers
Serum osteocalcin, procollagen I carboxyterminal propeptide, procollagen type I Nterminal propeptide, N and C-telopeptides

Treatment
Preventive Measures
Prevention of Bone Loss

Calcium HRT SERMS Calcitonin Bisphosphonates

Calcium Requirements
NO FIRM CONCLUSIONS MALES 11 - 18 YEARS
FEMALES 11 1 8 YEARS ADULTS (MALE AND FEMALE) LACTATION OSTEOPOROSIS

U.K.

1000

800

700

1250 1000

Sources of Calcium
FOOD
MILK - WHOLE MILK - SEMISKIMMED MILK - SKIMMED YOGHURT CHEDDAR CHEESE COTTEGE CHEESE ICE-CREAM SARD DIINES (with bones) ORANGE WHITE BREAD BAKED BEANS

SERVING SIZE
1 GLASS (190ML) 1 GLASS (190ML) 1 GLASS (190ML) 1 POT (150g) S MALL PIECE (30g) 2 TABLESPOONS 2 SCOOPS 2 CAN NED 1 MEDIUM 2 SLICES 3 TABLESPOONS

CALCIUM(mg)
225 231 236 225 216 58 156 230 75 72 64

Indications for treatment of osteoporosis

Pharmacological treatments: modes of action

Treatment Estrogen Replacement Therapy (ERT)

Indication: Used to prevent and treat osteoporosis (FDA indication is for prevention)
Mechanism: Decreases osteoclast activity Dose: Estrogen: 0.625mg qd, 0.3mg offers bone protection as well; Progesterone 2.5mg qd (if uterus present)

ERT
Advantages Increases bone density (15%) and decreases risk of fracture (25%) Relief of hot flashes, vaginal dryness Decreases LDL, increases HDL Prevention of Alzheimers disease Relatively inexpensive

Disadvantages
Accelerated bone loss after stopping Increased risk of uterine ca (if unopposed) Increased risk of thromboembolic events Possible increased risk of breast cancer Side effects: breast tenderness, breakthrough bleeding Increased risk of coronary events in women with known CAD in first year of use (HERS trial)

Selective Estrogen Receptor Modulators (SERMs)

Indication: Treatment and prevention of osteoporosis
Mechanism: Decreases bone resorption Dose: Raloxifene (Evista) 60mg qd

SERMS
Advantages
Increases bone density (2%) and decreases fracture risk (30%) No stimulation of breast or endometrial tissue No need for progestin in women with uterus Decrease LDL

Disadvantages
Increased risk of thromboembolic events Doesnt treat postmenopausal sx May increase hot flashes No effect on HDL $60.90/30 day supply

Bisphosphonates
Approved agents Alendronate (Fosamax), Risedronate (Actonel)

Indication Approved for prevention and treatment of osteoporosis including steroid-induced osteoporosis
Mechanism Bind to hydroxappetite at sites of active bone resorption inhibiting osteoclast function Dose Prevention Alendronate 5mg qd or 35mg qweek Risedronate 5mg qd or 30mg qweek Treatment Alendronate 10mg qd or 70mg qweek Risedronate 5mg qd or 30mg qweeek

Bisphosphonates
Take first thing in am, no food or meds for 30 minutes Take with 8oz glass of water Dont lie down for at least 30 minutes Separate Ca, Al, and Mg containing meds by at least 4 hours

Bisphosphonates
Advantages
Increases BMD by 1-4%, decreases fracture risk by 41-44% No increased risk of breast, uterine ca or thromboembolic events Weekly dosing

Disadvantages
Risk of gastrointestinal sx Cost $61.20/30 day supply Complex dosing instructions Contraindicated in ESRD; need to adjust dose according to creatinine clearance

Calcitonin
Indication: Treatment only

Decreases bone resorption

Dose:
Nasal (Miacalcin) 200IU alternate nostrils qd SC, IM increased risk of anaphylaxis

Advantage May provide analgesic effect on bone pain associated with fractures Disadvantage Inconsistent effects on BMD and fracture risk

Parathyroid Hormone
Daily SC injections of 40mcg of PTH increased BMD by 9-13% and decreased risk of vertebral fractures by 65 to 69 % Side effects: Occasional headache and nausea Pending FDA approval

NEJM 2001;344:1434-41.