WHO Osteoporosis Definition (1996) “A systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, with a consequent increase in bone fragility with susceptibility to fracture.”* Bone density T-score  2.5 SD below young normal mean† *Consensus Development Conference: Diagnosis, prophylaxis, and treatment of osteoporosis, Am J Med 1993;94:646. † Kanis JA et al, J Bone Miner Res 1994;9:1137.

Who Is At Risk? Early menopause, surgical menopause Low body weight compared to height Diet - low intake of milk products and lack of vitamin D Life-style factors: cigarette smoking, caffeine, alcohol abuse, lack of exercise Drugs and diseases, corticoseroid treatment, hyperthyroidism, anorexia nervosa, amenorrhoea, arthritis Genetic factors (family history, race)

Bone turnover Trabecular bone Cortical bone 20% of the skeletal mass 80% of bone turnover Cortical bone 80% of the skeletal mass 20% of bone turnover

Bone Loss or Low Peak Bone Mass 100 80 60 Normal (% ideal peak bone mass) Relative Bone Mass Low Peak 40 Fast Loss 20 20 30 40 50 60 70 80 Age (years)

Osteoporosis Age (years)

INDICATIONS FOR BONE MINERAL DENSITY (BMD) TESTING Women aged 65 and older Postmenopausal women under age 65 with risk factors Men aged 70 and older Adults with a fragility fracture Adults with a disease or condition associated with low bone mass or bone loss Adults taking medications associated with low bone mass or bone loss Anyone being considered for pharmacologic therapy Anyone being treated, to monitor treatment effect Anyone not receiving therapy in whom evidence of bone loss would lead to treatment Women discontinuing estrogen INTERNATIONAL SOCIETY FOR CLINICAL DENSITOMETRY, Official position 2005

Bone Densitometry

Bone Densitometry Non-invasive test for measurement of BMD Major technologies Dual-energy X-ray Absorptiometry (DXA) Quantitative Ultrasound (QUS) Quantitative Computerized Tomography (QCT) Many manufacturers Numerous devices Different skeletal sites

Dual energy X Ray absorptiometry

DXA Technology Detector (detects 2 tissue types - bone and soft tissue) Very low radiation to patient. Very little scatter radiation to technologist Patient Collimator (pinhole for pencil beam, slit for fan beam) Photons X-ray Source (produces 2 photon energies with different attenuation profiles)

DXA “Gold-standard” for BMD measurement Measures “central” or “axial” skeletal sites: spine and hip May measure other sites: total body and forearm Extensive epidemiologic data Correlation with bone strength in-vitro Validated in many clinical trials Available

Dual-energy X-ray absorptiometry (DXA) What is measured? BMC: Bone Mineral Content (g) BMD: Bone Mineral Density (g/cm²) T-score: BMD compared to young normal Z-score: BMD compared to same age

What DXA Really Measures “Areal” BMD is calculated in g/cm2 “T-score” compares the patient’s BMD with the young-normal mean BMD and expresses the difference as a standard deviation (SD) score

DXA T=-3,1 Z=-0,4 T-score and Z-score Peak Bone Mass = 1.047 BMD = 0.700 AGE = 80 T-score and Z-score

Patient’s BMD – Young-Adult Mean BMD 1 SD of Young-Adult Mean BMD T-score Patient’s BMD – Young-Adult Mean BMD 1 SD of Young-Adult Mean BMD Example: T-score = 0.7 g/cm2 - 1.0 g/cm2 0.1 g/cm2 = - 3.0

Z-score Patient’s BMD – Age-Matched Mean BMD 1 SD of Age-Matched Mean BMD in g/cm2 Low Z-score (less than -2.0) may suggest increased likelihood of secondary osteoporosis, however . . . This is not validated in clinical trials High index of suspicion for secondary causes of osteoporosis is suggested in all patients

DXA WHO definition of diagnostic categories Normal: T > -1 Osteopenia: -1 > T > -2,5 Osteoporosis: - 2,5 > T Severe osteoporosis: plus fracture Which Skeletal Sites Should Be Measured? Spine L1-L4 Hip (Total Proximal Femur, Femoral Neck) Use lowest T-score of these sites

AP Spine

AP Femur

Diagnosis Caveats T-score -2.5 or less does not always mean osteoporosis (osteomalacia) Clinical diagnosis of osteoporosis may be made with T-score greater than -2.5 Example: atraumatic vertebral fracture with T-score equals -1.9 Low T-score does not identify the cause Medical evaluation should be considered Example: celiac disease with malabsorption

Diagnosis Caveats BMD measurements are not accurate in patients with degenerative disease compression fractures Soft tissue calcifications Metallic hardware

Why T-score And Not Z-score? T-score is related to bone strength T-score is related to fracture risk Using Z-scores would result in many “normal” patients having fragility fractures, and suggest that osteoporosis does not increase with age

T-score Discordance Different skeletal sites have different peak bone mass at different times and lose bone at different rates Different machines Different ROIs Different reference databases have different means and SD (the hip is the only skeletal site with a standardized reference database used by all manufacturers – National Health and Nutrition Examination Survey III)

Kanis JA et al. J Bone Miner Res. 1994;9:1137. Why -2.5? “Such a cutoff value identifies approximately 30% of postmenopausal women as having osteoporosis using measurements made at the spine, hip or forearm. This is approximately equivalent to the lifetime risk of fracture at these sites.” Kanis JA et al. J Bone Miner Res. 1994;9:1137.