1. Osteopenia and Osteoporosis Bradley K. Harrison, MD

2. Who should we screen? Women aged ≥ 65 Postmenopausal women with fragility fracture Women on or starting glucocorticoid therapy Younger postmenopausal women with risk factors YES Not addressedYES Not addressedYES At age 60 if: Weight < 154 lb Estrogen deficient No recommendations for or against bone density testing in women <60 year Weight < 127 lb Early menopause Smoking Family history of fracture Medical causes USPSTF*NOF*/AACE* *USPSTF: US Preventative Services Task Force *NOF: National Osteoporosis Foundation *AACE: American Association of Clinical Endocrinologists

3. Evaluating Patients for Screening  Low bone mass at any skeletal site is associated with a substantially increased risk of fracture Height loss: vertebral fractures are diagnostic of skeletal fragility  Advancing age  Low body weight  Maternal history of osteoporosis  Smoking  Early menopause  Corticosteroid usage  The presence of a previous fracture!

4. What is a DEXA?  Dual-energy x-ray absorptiometry Originally intended for use in epidemiologic and public health studies; only applicable to hip, spine, and forearm measurements Painless, quick, safe, accurate, precise, relatively inexpensive way to assess bone mineral density Hip and Spine: 2 most common sites of osteoporotic fractures The World Health Organization (WHO) has established diagnostic criteria for osteoporosis Absolute readings vary among different manufacturer’s DEXA scanners, the patient’s results are compared with the mean BMD of a normal population on the same equipment

5. What is a T-score?  T Score Number of standard deviations the bone-mineral-density (BMD) measurement is above or below the young-normal mean bone density  Diagnose osteoporosis and to estimate fracture risk  Z Score Used to compare the patient's BMD to a population of peers, is calculated by subtracting the mean BMD of an age-, ethnicity-, and sex-matched reference population from the patient's BMD and dividing by the SD of the reference population  Indicate if BMD is lower than expected for the patient at a given age; signals need for earlier intervention; unsuspected conditions

6. T-scores…  Spine: aggregate of all lumbar vertebrae (L1-L4) are used  Hip: 3 sites for diagnosis (femoral neck, trochanter, total hip)  The lowest T-score is used to establish the patient’s diagnosis  -2.5: the point at which the proportion of white women older than 50 years with osteoporosis diagnosed by bone density (30%) nearly matches the % of women older than 50 years who will experience a fracture (spine, hip, forearm) in their lifetime (40%)  Between -1.0 and -2.5 indicative of low bone density…osteopenia

7. The WHO Criteria ≥ -1.0Normal -2.5Osteopenia ≤ -2.5Osteoporosis ≤ -2.5 or lower + fracturesSevere Osteoporosis T-ScoresDiagnosis

8. The Clinical Problem  Osteoporosis Progressive disease of increased skeletal fragility accompanied by low bone mineral density and microarchitectural deterioration  Spectrum: asymptomatic bone loss to hip fracture ($40K) Defined: T score for bone mineral density below -2.5 1.5 million osteoporotic fractures per year, annual direct cost of $18B (373K stroke, 345K MI, 216K Breast CA) < 25% of women who sustain an osteoporotic fracture currently receive appropriate treatment

9. 10-Year Probability of any Fracture in Untreated Postmenopausal Women* 3.84.75.97.49.211.314.1 4.15.36.78.510.713.416.8 5.16.58.210.413.016.220.2 6.38.010.012.615.619.323.9 7.19.011.514.618.322.828.4 7.09.111.815.219.424.530.8 AGE T-Score 50 55 60 65 70 75 0-0.5 -1.0 -1.5 -2.0 -2.5 -3.0 National Osteoporosis Foundation *Note: other independent risk factors for fracture will increase fracture risk

10. Decision to treat?  At present, no national guidelines regarding the absolute threshold at which pharmacologic therapy should be instituted  Osteoporosis therapy can reduce the risk of fracture by as much as 50%, but some women have fractures despite treatment  Changes in lifestyle, compliance with medication regimen, as well as cost ($70/mo), are lifetime commitments  A substantial percentage of fractures occur in women who have osteopenia, not osteoporosis

11. Treatment Decisions  Everyone Maintain adequate calcium intake Adopt good general nutrition Ensure adequate vitamin D intake Engage in regular weight-bearing exercise Avoid use of tobacco  Nonpharmacologic options  Pharmacologic options Any postmenopausal woman with prior spine/hip fracture

12. Nonpharmacologic options  Calcium + Vitamin D Combined: slow bone loss, enhance the effect of pharmacologic therapy, reduce hip/nonvertebral fractures Additional Vitamin D: significantly increased muscle strength, reduced body sway, and resulted in fewer falls “Calcium has been singled out as a major public health concern today because it is critical to bone health and the average American consumes levels of calcium that are far below the amount recommended for optimal bone health” – HHS, OTSG, 2004  Calcium: 1200mg/day divided into 600mg doses  Vitamin D: 400 IU, although suggested higher intake (800-1200) General agreement that exercise important for bone health

13. Pharmacologic therapy  SERM (Raloxifene 60mg/d) Reduced vertebral fractures, no effect on hip  Calcitonin (Nasal Spray 200 IU/d) Reduced vertebral fractures, no effect on hip  Bisphosphonates (Alendronate 70mg/wk treatment or 35mg/wk prevention, Risedronate 35mg/wk, or Ibandronate 150mg/mo) Reduced hip and vertebral fractures, ibandronate not hip  Estrogen/Estrogen plus progestin Reduced vertebral, wrist, and hip fractures  Anabolic therapy (Teriparatide [PTH] 20mcg/d) Reduced vertebral and nonvertebral fractures

14. What Do You Do With Osteopenia? -2.5 or below or fracture STOP (red light) High Risk Treat -1.5 to -2.5Caution (yellow light) Consider therapy if other risk factors of fracture Above -1.5OK (green light) Low risk General preventation Summary of treatment decisions for postmenopausal women based on risk factors for osteoporotic fracture (American Association of Clinical Endocrinologists Guidelines)

15. Osteopenia anyone? Anyone?  Women with a T-score between -1.5 and -2.5 may be treated, depending on their calculated fracture risk based on age, BMD, and the presence of other independent risk factors (National Osteoporosis Foundation)  Everyone with osteopenia (-1.0 to -2.5) or osteoporosis gets the treatment dosage of bisphosphonates (personal communication with Dr. Wood, DDEAMC Endocrinologist)

16. 10-Year Probability 3.84.75.97.49.211.314.1 4.15.36.78.510.713.416.8 5.16.58.210.413.016.220.2 6.38.010.012.615.619.323.9 7.19.011.514.618.322.828.4 7.09.111.815.219.424.530.8 0-0.5 -1.0 -1.5 -2.0 -2.5 -3.0 AGE T-Score 50 55 60 65 70 75

17. BMD Test Reimbursement  The Bone Mass Measurement Act (Medicare) Estrogen-deficient women at risk for osteoporosis Vertebral anomalies Chronic glucocorticoid therapy* Primary hyperparathyroidism Assess response to, or efficacy of, FDA-approved osteoporosis drug  Covered by Medicare every 23 months*