OSTEOPOROSIS. QunFang Ding Associate Professor of Geriatric dept.

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1 OSTEOPOROSIS QunFang Ding Associate Professor of Geriatric dept.

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3 A Common Problem in the General Population 200 million people at risk worldwide million people with osteoporosis 1.5 million women with spine fracture One in 2 women and One in 8 men over 50 will have an osteoporosis related fracture

4 Epidemiology Woman s risk of fracture is equal to her combined risk of breast, uterine and ovarian cancer 24% of hip fracture patients age 50 and older die in one year following fx Only 1/3 fully regain their prefracture level of independence Cost > $20 billion/yr

5 What is Osteoporosis?

6 Clinical Definition A systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.

7 Classification Primary Postmenopausal Decreased estrogen results in increased osteoclastic activity without increased osteoblastic activity Bone loss 2-3% per year of total bone mass Most common fx: vertebral, distal forearm Age related 3 rd decade of life starts slow decline in bone mass at rate of 0.5-1% per year Most common types of fx: hip and radius F>M Secondary

8 Secondary Osteoporosis Disease states Acromegaly Addison s 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

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

10 Pathology of osteoporosis

11 Osteoporosis Microscopic Anatomy

12 Scanning electron micrograph of slice of osteoporotic cancellous bone from the fourth lumbar vertebra of an elderly woman.

13 Normal Bone and Osteoporotic Bone Loss of trabecular plates (right) results in weakened bone structure significantly increasing risk of fractures.

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15 Common Locations of Osteoporotic Fractures in General Population Thoracic (vertebral) compression fractures Hip fractures Wrist/extremity fractures

16 Consequence of Osteoporosis: Fragility fractures Most common osteoporotic fracture = Vertebral Compression Fracture (VCF)

17 Vertebral fractures: Three forms

18 Hip fractures

19 Humerus fractures Osteoporotic fracture Osteoporotic bone

20 Survival Mortality rates after vertebral, hip, and distal forearm fracture 60% survival 5 years after vertebral fracture and 50% survival 5 years after hip fracture. Mortality due to any cause.

21 Why do people suffer OP?

22 The Components of Bone Tissue Mineral Calcium phosphorous Bone cells OsteoBlasts Build Bone. OsteoClasts Create Cavities in bone

23 Bone remodeling is the form of bone metabolism in adults

24 Bone Remodeling Process 1. Resting Phase Bone lining cells Bone surface covered by protective layer of bone cells - bone lining cells Bone

25 Bone Remodeling Process Bone lining cells 2. Resorption Osteoclasts invade the bone surface, erode it, thus dissolving mineral and matrix Osteoclasts Bone

26 Bone Remodeling Process Bone lining cells 3. Resorption Complete Small cavity created in bone surface - resorption is complete Cavity made by osteoclasts Bone

27 Bone Remodeling Process 4. Formation - Repair Bone forming cells (osetoblasts) begin filling in cavities with new bone Bone lining cells Osteoblasts New bone (includes collagen and minerals) Bone

28 Bone Remodeling Process 5. Repair Complete Bone lining cells Bone surface completely restored Bone

29 Bone Remodeling Unit Osteoblasts build bone Osteoclasts eat away the bone

30 Changes of bone mass in a person s life 1st stage: Increasing stage year of age Peak 2nd stage: Metabolic balance Female: year of age Male: year of age 3rd stage: Decreasing stage

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32 Etiology

33 Heredity Positive family history of OS is a risk factor. ER gene (estrogen receptor gene) VDRgene (vitd receptor gene) Gene of Type I collegen Gene of Calcitonin receptor Gene of Transfer Growth Factor Gene of IL-6 and its receptor

34 Reasons of negative balance of calcium in the elderly 1. Levels of estrogen 2.VitD intake; 3.Sunlight; 4. Resistance to 1,25-(OH)2-D3

35 VitD insufficiency Insufficient vitd intake Outdoor activity Decreased renal function Insufficient resorting of calcium in intestinal mucosa and renal tubules

36 Parathyroid Hormone Insufficient Calcium Secondary increase of PTH secretion Osteoblast activity Plasma PTH level increases with aging, about 50% of elderly beyond 70 reach 2-3 times higher of normal adults, 6%of them even reach 4 times.

37 Calcitonin When CT receptors in osteoclast combine with CT, activity of fibroblast will be inhibited, the transformation of mononeucleocytes to osteoclast will also be inhibited. CT levels decrease with aging after menopause.

38 Aging Aging number of osteoblast

39 Decreased Physical Activity

40 Insufficient Sex Hormone

41 What are typical Clinical manifestations?

42 Clinical Manifestation Chronic Pain Loss of body height Bone Fracture The onset of osteoporosis is chronic and obscure. No sever uncomfortable could be noticed until the bone loss reach to a fairly severe level.

43 Fractures 1.5 million fx/yr 300,000 hip 700,000 vertebral 250,000 wrist 300,000 at other sites

44 Problems related to bone fracture in the Chronic pain Height loss Kyphosis Decreased self-esteem Restrictive lung dx Constipation, abdominal pain Depression elderly

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46 What are Risk Factors For Osteoporotic Fractures?

47 Personal history of fracture as an adult History of fracture in a first degree relative Caucasian Female Low body weight (<127 lbs) Estrogen deficiency Early menopause (<age 45) Bilateral oopherectomy Prolonged amenorrhea (>1 yr)

48 Hypogonadism in men Alcoholism Current cigarette smoking Low calcium intake (lifelong) Inadequate physical activity Dementia Recurrent Falls Poor health/frailty

49 How to define osteoporosis?

50 Testing: Bone Mineral Density Duel-energy X-ray absortiometry (DEXA) *Most precise and cost efficient Quantitative Ultrasonography of the Heel No radiation. Poor precision. Poor correlation with DEXA. Generally not recommended. Quantitative Computed Tomorgraphy (QCT) Generally used for research. Lower precision and higher radiation. Better at measuring trabecular bone. X-ray testing

51 DEXA 双能 X 线吸收仪 Typically measured at L1-L4, and at the hip the amount of x-ray that does not pass through the bone is a measure of the amount of bone mass Bone mineral density is then compared to reference data and expressed as T scores.

52 T score T score (same as standard deviation) Compares patient s bone mineral density with mean value in young adult.

53 How to do the examination?

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55 When to perform a bone density test National Osteoporosis Foundation (NOF) Guidelines All postmenopausal women under age 65 who have one or more additional risk factors for osteoporotic fx (besides menopause) All woman aged 65 and older regardless of additional risk factors Postmenopausal women who present with fractures If BMD would facilitate decision of whether or not to start treatment

56 Work-up BMD testing Screen for secondary causes Serum calcium, phosphorus, alk phos PTH if calcium is high (hyperparathyroidism) 25-hydroxyvitamin D if low ca, low phos and high alk. phos (osteomalacia) Thyroid function tests (thyrotoxicosis) SPEP, UPEP (multiple myeloma) 24-hour urinary calcium or urine ca/creat (hyper or hypo calciuria) Serum testosterone (hypogonadism)

57 When to initiate treatment High Risk T score < Treat Moderate Risk T score 1.5 to Treat if other risk factors are present Low Risk T score above Check again in 1-2 years

58 When to Retest Repeat testing in 2 yrs to determine if there is additional bone loss and to assess response to treatment Medicare will pay for more frequent testing if: Monitoring patients receiving glucocorticoid therapy for more than 3 years If there is clinical data to support sooner testing such as evidence of a secondary cause of osteoporosis

59 Bone Markers Because BMD monitoring requires 1-2 yrs to see change, biochemical markers used for research may become available for clinical use Serum osteocalcin, procollagen I carboxyterminal propeptide, procollagen type I N-terminal propeptide, N and C-telopeptides

60 Outline Epidemiology of osteoporosis Basic terminology Mechanism of Osteoporosis Bone density test Treatment of osteoporosis

61 Targets of treatment: 1.To maintain and increase bone mass, to improve the microstructural changes of bone. 2.To prevent bone fracture in patients with a negative history 3.To prevent new bone fracture in patients with positive history 4.To relieve symptoms associated with osteoporosis 5.To improve deformities and related dysfunctions

62 Calcium Treatment Preventive Measures Vitamin D ( IU) Regular weight bearing exercise Weight lifting, salsa dancing, walking, jogging, tennis Smoking cessation Minimize etoh Fall prevention

63 Calcium Requirements Recommended elemental calcium needs by age in mg/ca/day Children 800 Up to age Women Pregnant and breast feeding Women over 50 Taking ERT 1000 Not taking ERT 1500 Women over Men 25 to Men over

64 Sources of Calcium Dietary 8oz milk or yogurt = 300mg 2oz cheese = 400mg Calcium carbonate Ingest with meals Generic = mg Caltrate = 600mg TUMS Ultra = 400mg Calcium citrate Independent absorption; use of pt. is taking H2 blocker or proton pump inhibitor Citrical = 500mg Calcium gluconate Generic = 60mg * All above values represent mg of elemental calcium

65 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)

66 ERT Advantages Increases bone density (1-5%) and decreases risk of fracture (25%) Relief of hot flashes, vaginal dryness Decreases LDL, increases HDL?Prevention of Alzheimer s disease Relatively inexpensive ($30/30 day supply) 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)

67 Selective Estrogen Receptor Modulators (SERMs) Indication: Treatment and prevention of osteoporosis Mechanism: Decreases bone resorption Dose: Raloxifene (Evista) 60mg qd

68 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 Doesn t treat postmenopausal sx May increase hot flashes No effect on HDL $60.90/30 day supply

69 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

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

71 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

72 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

73 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.

74 Outline 大纲 Epidemiology of osteoporosis Basic terminology Mechanism of Osteoporosis Bone density test Treatment of osteoporosis

75 Thank you