OSTEOPOROSIS

1. OSTEOPOROSIS Dr. K KSawlani Department of Medicine KGMU, Lucknow 30.07.14

2. OSTEOPOROSIS • A disease characterized by low bone mass (reduced bone density) and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. • Most common bone disease • Affects million of people worldwide

3. Development of osteoporotic bone Rizzoli R ed In Atlas of Postmenopausal Osteoporosis (1st edition) Science Press, 2004

4. OSTEOPOROSIS • Fractures related to osteoporosis affect around 30 % of women and 12 % of men in developed countries. • Major public health problem • Osteoporotic fractures can affect any bone • The most common sites are • Spine (vertebral fracture) • Forearm (Colles fracture) • Hip

5. Vertebral Fracture

6. Hip Fracture

7. Wrist Fracture (Colles fracture)

8. OSTEOPOROSIS • Hip fractures are the most serious • Immediate mortality is about 12 % • Continued increase in mortality of about 20 % when compared with age matched controls. • Account for the majority of health care cost associated with osteoporosis.

9. OSTEOPOROSIS • The prevalence increases with age reflecting that bone density decreases with age especially in women • Accompanied by increased risk of fractures • Fall in bone density • Increased risk of falling

10. Pathopysiology • Occurs because of defect in attaining peak bone mass and/or because of accelerated bone loss. • In normal individuals bone mass increases to reach a peak between the age of 20 and 40 years but falls thereafter.

11. Age-related changes in bone mass Attainment of peak bone mass Consolidation Age-related bone loss Menopause Bone mass Men Fracture threshold Women 0 10 20 30 40 50 60 Age (years) Compston JE. Clin Endocrinol 1990; 33: 653–682.

12. Pathopysiology • Peak bone mass and bone loss are regulated by both genetic and environmental factors. • Polymorphisms have been identified in several genes that contribute to pathogenesis. • Many of these are in the RANK and Wnt signaling pathways which play critical role in regulating bone turnover.

13. Major risk factors • Non modifiable • Age • Race • Female gender • Early menopause • Slender build • Positive family history • Modifiable • Low calcium intake • Low vitamin D intake • Estrogen deficiency • Sedentary lifestyle • Cigarette smoking • Alcohol excess (> 2 drinks/day) • Caffeine excess (> 2 servings / day)

14. Post menopausal osteoporosis • Most common cause • Accelerated phase of bone loss after menopause due to estrogen deficiency. • Causes uncoupling of bone resorption and bone formation • Amount of bone reduced by osteoclasts exceeds the rate of new bone formation by osteoblasts • Early menopause ( before the age of 45 years ) is important risk factor

15. Male osteoporosis • Less common in men • Secondary cause can be identified in 50% of cases • The most common causes are • Hypogonadism • Corticosteroid use • Alcoholism • Testosterone deficiency results in increase in bone turnover and uncoupling of bone resorption and bone formation. • Genetic factors important in the cases with no identifiable cause.

16. Corticosteroid induced osteoporosis • Risk increases with prednisolone use 5-7.5 mg daily for more than 3 months. • Reduced bone formation due to • Inhibitory effect on osteoblast function • Osteoblast and osteocyte apoptosis • Also reduce serum calcium • Inhibit intestinal calcium absorption • Renal leak of calcium • Secondary hyperparathyroidism with increased bone resorption • Hypogonadism may also occur with high doses.

17. Secondary causes of osteoporosis • Endocrine disease • Hypogonadism • Hyperthyroidism • Hyperparathyroidism • Cushing,s disease • Inflammatory disease • Inflammotory bowel disease • Ankylosingspondylitis • RA • Gastrointestinal • Malabsorption • Chronic liver disease • Lung disease • COPD • Cystic fibrosis • Drugs • Miscellaneous

18. Secondary causes of osteoporosis • Drugs • Corticosteroids • Thyroxine over-replacement • Anticonvulsants • GnRH agonists • Thiazolidinediones- pioglitazone • Alcohol intake • Heparin

19. Secondary causes of osteoporosis • Miscellaneous • Myeloma • HIV infection • Systemic masotcytosis • Renal failure • BMI < 18 • Anorexia nervosa • Heavy smokers

20. Clinical Features • Asymptomatic until a fracture occurs • Incidental osteopenia on X-ray performed for other reasons. • Spine fracture • Acute back pain ( 1/3 cases) • gradual loss of height , kyphosis and chronic pain • Peripheral fracture • Local pain, tenderness and deformity • Often with an episode of minimal trauma

21. Investigations • Measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA). • BMD can also be measured by computed tomography (CT) and ultrasound. • Central (spine and hip) are best predictors of fracture risk. • Peripheral( radius, heel and hands) are less expensive and widely available.

23. Investigations • T-Score: The number of SDs the patient value is below or above the mean value for young normal subjects. • Good predictor of fracture risk • Z-score: The number of SDs the patient value is below or above the mean value for age matched normal controls. • Whether or not the BMD is appropriate for age. • Absolute BMD: expressed in g/cm2 • Used to calculate changes in BMD during follow up.

24. Diagnosis • Any patient who sustains a fragility fracture. • On the basis of BMD T-score ≥ -1 = normal Between -1 and -2.5 = Osteopenia ≤ -2.5 = Osteoporisis

25. Changes in BMD with age (T-score values) Souce- Davidsons textbook of Medicine 22nd edition

26. Diagnosis • History: early menopause, smoking, excessive alcohol intake, corticosteroid therapy • Examination: Signs of endocrine disease, neoplasia, and inflammatory diseases • A history of fall should be taken • Unstable gait and unsteadiness

27. Diagnosis - Investigations • Renal function • Alkaline phosphatase • Serum calcium, Vit D 25 (OH) • Parathyroid (PTH) • Thyroid function tests • Immunoglobulins and ESR • Celiac disease antibody testing • Testosterone (men) • 24 hour urine calcium, sodium and creatinine.

28. Management • The aim of treatment is to reduce the risk of fractures • Non-pharmacological • Pharmacological

29. Non Pharmacological Treatment • Smoking cessation • Moderation of alcohol intake • Adequate dietary calcium intake • Exercise • Vitamin D • Fall prevention • Good nutrition

30. Pharmacological Treatment • Several drugs have been shown to reduce the risk of osteoporotic fractures. • Effect on vertebral and non-vertebral fracture is variable. • Considered with • BMD T-score < 2.5 • BMD T-score < 1.5 in corticosteroid induced • Vertebral Fractures ,unless resulted from significant trauma

31. DXA Results

32. CURRENT THERAPIES • Anti-resorptive • Anabolic • Calcium, Vitamin D, lifestyle modification • Adjunct to other treatments • 1000-1200 mg/day of calcium • 800-1200 U/day of vitamin D

33. Treatment Options in Osteoporosis Antiresorptive drugs • Bisphosphonates Etidronate Alendronate Risedronate Ibandronate Zoledronate • Denosumab (monoclonal antibody against RANK-L) • SERMs Raloxifene • Calcitonin • HRT (estrogen) Anabolic drugs Teriparatide(PTH 1-34) Dual Action Bone Agents (DABAs) Strontium ranelate

35. Bisphosphonates • Inhibit bone resorption by binding to hydroxyapatite crystals on bone surface • Osteoclasts reabsorb bone-drug released within cell-inhibt key signaling pathways. • Increase in Spine BMD of 5-8% and Hip BMD 2-4%. • Should be taken on an empty stomach with plain water. • No food should be eaten 30-45 minutes after administration

36. Adverse effects of biphosphonates • Common • Upper GI intolerance (oral) • Acute phase response(intravenous) • Less Common • Atrial fibrillation (IV zoledronic acid) • Renal impairment (IV zoledronic acid) • Atypical subtrochanteric fractures • Rare • Uveitis • Osteonecrosis of the jaw

37. INDICATIONS FOR ANABOLISM • Pre-existing osteoporotic fractures • Very low BMD • Very high fracture risk • Unsatisfactory response to antiresorptive therapy • Intolerant to anti-resorptive therapy

38. TERIPARATIDE • Daily SC injection 20 mcg • Maximum 18-24 months • May be followed by anti-resorptive therapy • PTH is expensive and is reserved for severe osteoporosis, who fail to response to other therapies. • No advantage of combined anabolic and anti-resorptive therapy

39. Selective estrogen receptor modulator (SERM) Raloxifene • 60 mg daily orally • Partial agonist of estrogen receptor in bone & liver • Antagonist in breast & endometrium • SE: muscle cramps, hot flushes, increased risk of VTE. • Bazedoxifene is a related SREM

40. HRT • Cyclical HRT wirh estrogen and progestogen • Prevents post menopausal bone loss and reduces risk of fractures in post menopausal women • Primarily indicated for prevention of osteoporosis in women with early menopause • Women in early fifties with troublesome menopausal symptoms. • Increased risk of breast cancer and cardiovascular disease

41. Duration of therapy • Oral biphosphonates long term (5 YRS) • HRT, raloxifene continuously • Denosumab continuously • Strontium ranelate not established • Teriparatide 2 yrs fbantiresorptiveTt

42. Response to drug treatment • Repeat BMD measurements after 2-3 yrs. • Spine BMD best for monitoring • Biochemical markers ( N-telopeptide) respond more quickly; can be used to assess adherence.

43. Surgery • Reduce and stabilize osteoporotic fractures Painful vertebral compression fractures • Vertebroplasty ( Injection of MMA) • Kyphoplasty ( balloon inflation – MMA)

44. Response to Drugs Fracture risk reduction • 30-40% # risk reduction with antiresorptives • 60% # risk reduction with teriparatide BMD • 2-3% BMD increase with anti-resorptives • 4-6% BMD increase with teriparatide

45. Osteoporosis MCQ 1. Most common cause of osteoporosis • Hypogonadism • Malabsorption • Post menopausal • Hyperparathyroidism

46. Osteoporosis MCQ 2. Most common bone disease is a. Osteomalacia b. Osteoporosis c. Secondaries bone d. Osteopetrosis

47. Osteoporosis MCQ 3. Which of the following drug is most common cause of drug induced osteoporosis a. Thyroxine over-relacement b. Corticosteroids c. Pioglitazone d. Anticonvulsants

48. Osteoporosis MCQ 4. Osteopenia is defined as T- Score of a. < -1 b. < -1 to < -2.5 c. < -2.5 d. None of the above

49. Osteoporosis MCQ 5. Risk of fracture in osteoporosis is best predicted by a. T-score b. Z-score c. Absolute BMD d. Serum calcium levels

50. Osteoporosis MCQ 6. Risk factors for osteoporosis are all except a. BMI > 30 b. Smoking c. Low calcium intake d. Immobilization