Prevention and Treatment of OSTEOPOROSIS 骨質疏鬆的預防與治療

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1 Prevention and Treatment of OSTEOPOROSIS 骨質疏鬆的預防與治療 Gwo Jaw Wang, M.D. 王國照教授 University of Virginia (U.S.A.) & National Cheng Kung University (Taiwan) Learning Objectives Pathophysiology of osteoporosis Diagnosis of osteoporosis Treatment of osteoporosis 2 Osteoporosis is the most common bone disease, characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to bone fragility and an increase in the risk of fracture. Why Osteoporosis Is an Important Medical Issue Increased aging population Substantial cost with treatment of complications Women s health issue Men s health issue 4 1

2 Word wide 200 million It is estimated 13 to 18% of postmenopausal white women in the U.S.( 4 to 6 million) have osteoporosis, and an additional 30 to 50% have low bone density at the hip. In Taiwan 18% Aging Women 12% Aging Men Sustained Vertebral Fracture from Osteoporosis 5 Approximately 33% of women 60~70 y/o 66% of women > 80 y/o 47% of women 22% of man Have Osteoporosis Older than 50% will sustained fracture 6 NOF (National Osteoporosis Foundation ) estimates 25 million are being treated for osteoporosis Male : Female = 1:4 Most Serious Outcome of Osteoporosis Is Hip Fractures >90% were hip fractures Approximately 30,000/year Up to 10 to 20% mortality 25% need long-term care 50% never regain prefracture status 7 2

3 Fractures per year 1.5 million 432,000 hospital admissions 2.5 million physician visits 180,000 nursing home admissions Direct medical expenditures at 13.8 billion Aging Menopause Medication * Glucocorticosteroid * Anticonvulsants * Cigarette smoking * Excessive alcohol * Tamoxifen Etiology 9 10 Etiology Malnutrition RSD Diseases * Addison s disease & Cushing s Syndrome * Chronic obstructive pulmonary disease * Gonadal insufficiency * Osteogenesis imperfecta * Severe liver diseases 11 Risk Factors for Osteoporotic Fractures Nonmodifiable * Personal history of fracture as an adult * History of fracture in first degree relative * Caucasian race * Advanced age * Female sex * Dementia * Poor health/ frailty 12 3

4 Risk Factors for Osteoporotic Fractures Potentially modifiable *Current cigarette smoking *Low body weight *Estrogen deficiency - Early menopause (< age 45) - Bilateral oophorectomy - Prolonged premenopausal amenorrhea (> 14 yrs) Diagnosis Be alert to secondary causes of osteoporosis, i.e. medicines, diseases Biochemical testing * Serum thyrotropin * Parathyroid hormone * Vitamin D level * Urine calcium or cortisol Clinical symptoms of pain or fracture * When a postmenopausal woman suffers a fracture, osteoporosis is a presumptive diagnosis * BMD serves to confirm the diagnosis and determine the severity of the disease * All patients should receive counseling about diet, exercise, and pharmacologic treatment 15 Radiological Signs of Osteoporosis (Patients With Osteoporosis, Osteomalacia or Hyperparathyroidism) Ill defined sharp trabeculae Loser s Zone Bowing Subperiosteal resorption Subligamentous resorption Thin cortex Focal deficiency Interrupted trabeculae 16 4

5 BMD Testing Techniques Quantitative Diagnosis of Osteoporosis DXA pqct QUS Radiographic absorbmetry 17 Fragility fracture Radiologic osteopenia Family history Early menopause Prolonged steroid use Transplant patients Indications for DEXA DEXA Measured at a site which is most predictable of fracture Spine, hip or wrist Can be completed in a few minutes with radiation exposure = 1/10 chest x-ray 18 Fracture risk doubles for each standard deviation of bone mineral density below the young adult means. Hip BMD is the best predictor of T-scores (young normal adults mean) Z-scores (age mean) Standard Deviation (1 SD equals a 12% difference in bone density) T- Score & Diagnosis T-Score > < -2.5 DX Normal Osteopenia Osteoporosis hip fractures. 20 5

6 Peripheral DXA Advantage Disadvantage DX Normal Osteopenia Treatment Prevention Prevention Follow-up Every 2-3 yrs Every 1-2 yrs Low Cost Least Space Easy to use as screening device Unable to detect early bone loss Site specific, i.e. calcaneus, esp. in older patients Serial scan required Osteoporosis RX Every Year 21 Quantitative Computed Tomography Most commonly used to measure trabecular bone density in the spine. May be used as an alternative to DXA Disadvantage : Radiation Quantitative Ultrasound Unable to define bone density & structure Can predict overall fracture risk Can t predict bone mineral density at other site? Monitor progression

7 Diagnosis of Insufficiency Fracture Radionuclide Bone Scan Sensitive Non specific Potential false negative MRI T 1 signal ( non specific) T 2 signal (non specific) Location (spatial resolution) Morphology ( linear incomplete) 25 Treatment of Osteoporosis Diet Exercise Fall prevention Medications Diet

8 Vitamin D Source Natural source Salmon (wild) (3.5oz) 600~1000 IU Vit D3 (farmed)(3.5oz) 100~250 IU Vit D3 Tuna 230 IU Vit D3 Shiitake mushrooms fresh (3.5oz) 100 IU Vit D3 sun dried (3.5oz) 1600 IU Vit D3 Exposure to sunlight 3000 IU Vit D Fortified food Fortified milk 100 IU Vit D3 Supplements Prescription Vit D IU/ cap Drisdol liquid 8000 IU/ ml Vitamin D deficiency 25-dihydroxyvitamin D level < 20ng/ml 1 billion people world wide 50% postmenopausal women children and young adult 52% of Hispanic and Black adolescents in Boston 48% of white preadolescents in Marie Over the counter Multivitamin 400 IU Vit D3 400, 800, 1000 or 2000 IU elderly French women Receive 1200mg of calcium 800 IU Vit D3 Risk of Hip Fracture 43% Risk of Vertebral Fracture 32% Daily for 3 yrs Chapuy et al.nejm Vitamin D deficiency Muscle weakness More than 200 gene are controlled directly or indirectly by 1-25 dihydroxyvitamin D Immunomodulator Increase production of 1-25 dihydroxyvitamin D cathelicidin destroy M. Tuberculosis 32 8

9 High Vitamin D may also lower risk of colorectal CA Breast & prostate CA Adequate intake of calcium and Vitamin D Dietary calcium at least 1200 mg/d Dietary Vitamin D 400 to 800 IU/d Controlled clinical trials have demonstrated that the combination of supplemental calcium and Vitamin D reduces the risks of fracture Regular Weight Bearing Exercise Weight bearing and muscle strengthening exercise can improve agility, strength and balance, thus reducing the risk of falls. Initiate therapy in women with BMD T-Score below -2 in the absence of risk factors and in women with T-Scores below 1.5 if other risk factors are present Women over age 70 with multiple risk factors should be treated without BMD testing Avoid tobacco smoking and keep alcohol intake moderate. 35 9

10 Step 1: Estimate calcium intake from dairy products* Product Milk(8oz) Yogurt(8oz) Cheese(1oz) No. of servings/day Calcium Content per Serving, mg x300 x400 x200 Calcium mg = = = Step 2: Dairy calcium +250mg for nondairy source = total dietary calcium * About 75% to 80% of the calcium consumed in American diets is from dairy products 37 Drugs for Osteoporosis Hormone Replacement Therapy Reduces 50 to 80% of vertebral fractures and reduces 25% of other fractures with 5 years of treatment 50 to 75 % decrease of all fractures with 10 years of treatment May also prevent cardiovascular disease Associated with modest increase in risk of breast cancer and DVT with long-term use 38 Alendronate Treatment reduces the incidence of fracture at the spine, hip and wrist by 50% May be used for those that failed with HRT treatment Alendronate must be taken on an empty stomach 30 minutes before eating-5 mg for prevention and 10 mg for treatment GI irritation is a side effect Mechanism of Action FOSAMAX inhibits the bone-dissolving activity of the osteoclast cells Osteoblast enter the shallower cavity to rebuild bone tissues When, on average, more bone is formed than is removed, bone mass increases toward normal 39 Bisphosphonate Decrease rate of bone turn over Increase bone mineral density Improve bone structure and material properties of bone tissue Reduce the risk of fracture 40 10

11 Concerns Income rigidity (2 to osteoclastic activity) Decrease toughness (2 to bone remodeling)? Brittle bone Calcitonin Hormone that inhibits bone resorption 200 units intranasal spray daily Decreases vertebral fractures by 40% May be an alternative for HRT or Alendronate IU calcitonin 1000mg Calcium BMD 6.8% at 6 months Daily for 1 year 11% after 12 months Kapetanos et al. Act. Ortho. Scan Suppt Bone strength depends on Stiffness (To resist bending) Toughness (Ability to absorb energy) (Flexibility) Require modeling and remodeling (Bone turnover) 44 11

12 Ideal treatment for osteoporosis Induce regular bone turnover to promote balance in remodeling process. PTH, SERM, Estrogen, etc. 45 Parathyroid Hormone PHT (1-34) An anabolic agent for bone formation induces bone formation by activating steoblasts and promoting differentiation of precursors into osteoblasts. Resulted in increases bone dimension and biomechanical competence. 46 Persistent high concentration of PTH Bone Resorption 1 hr/day exposure increase bone formation Ma Y. L. et. al. Endocrinology 2001, 142 PTH Bone Formation Callus Ultimate Load Fracture Healing Nakajima et al J. Bone & Min. Res

13 PTH(1-34) Reduction in non-spine fracture risk 53% Prevent new moderate/ severe vertebral fracture 86% Increase BMD Spine 9-13% Femoral neck 3-6% 49 Study of 1262 Women Treated with rhpth (1-34) for 50 months No difference between group Sustained effect of rhpth in reducing the risk of non vertebral fragility fractures up to 30 months after discontinuation of treatment Prince etal. J. of Bone and Mineral Research Vol 20 Bo Evaluating Fracture Risk Known Vertebral Fracture? Study of 801 patients (placebo 398 PTH treated 403) Teriparatide [rhpth(1-34)] 20ug daily Greatly reduces the increase of fracture burden and eliminated the risk for future fracture Genant et al Bone 37 (2005) YES NO Willing to consider treatment Rx HRT YES NO Alendronate Age Calcitonin Calcium <65 >65 Exercise Risk Factors Smoking Cessation NO YES Calcium Exercise Smoking Cessation BMO Optional Measure Hip BMP 51 See Treatment Guidelines 52 13

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