Osteoporosis

1. Osteoporosis Emily Webb, M.D.

3. Overview • Pathophysiology • Prevention • Screening • Secondary causes • Medications

4. Bone Types • Cortical- outer shell of bones • Trabecular- spongy, internal support

5. Bone Strength • Density • Turnover • Size • Shape • Microarchitecture • Damage accumulation • Mineralization • Matrix quality

7. Remodeling Cycle • Resting • Resorption • Reversal • Formation

8. Calcium • 98% stored in bones • Regulated by intestinal, renal, and skeletal systems • If inadequate dietary supply of calcium, will reabsorb skeletal stores to maintain plasma levels.

9. Vitamin D • 95% of vitamin D is from sunlight • Vit D  25(OH)D  1,25(OH)2D • Increases GI calcium absorption • Measure 25(OH)D to determine deficiency

10. Vitamin D deficiency • Vit D deficiency  secondary hyperparathyroidism (SH)  mobilize bone calcium stores  normal serum calcium • SH  decreases phosphorus levels  inadequate to mineralize skeleton • Kids = rickets • Adults = osteomalacia

11. Parathyroid Hormone • Increases renal calcium reabsorption • Stimulates renal vitamin D production • Releases calcium from the bone

12. Osteoclast Activity • Vitamin D deficiency • Estrogen deficiency • Parathyroid hormone excess • Hyperthyroidism

13. Bone Loss • Bone mass peaks at age 30 • Then 0.4 % bone lost per year • First 5-8 years after menopause, women lose 2% of cortical and 5% of trabecular bone per year • Early menopause- increased osteoclasts • Later menopause- decreased osteoblasts

14. Modifiable Risk Factors • Smoking • Alcoholism • Inadequate physical activity • Long-term low calcium or vitamin D intake • Poor nutrition

15. Potentially Modifiable Risk Factors • Estrogen deficiency • Low weight/BMI (<127 pounds) • Recurrent falls • Chronic steroid use • Thyroid hormone • Anticonvulsants

16. Hx of fracture FHx- first degree relative Caucasian/Asian Dementia Age Fraility Impaired eyesight Non-Modifiable Risk Factors

17. Amyloidosis Ankylosing spondylitis COPD Congenital porphyria Cushing’s disease Eating disorders Female athlete triad Gastrectomy Gaucher’s disease Hemochromatosis Hemophilia HIV Hyperparathyroidism Hypogonadism Hypophosphatasia Idiopathic scoliosis Inflammatory bowel IDDM Lymphoma & leukemia Malabsorption syndromes Mastocytosis Multiple myeloma Multiple sclerosis Pernicious anemia Medical Conditions

18. Medical Conditions • Rheumatoid arthritis • Severe liver disease • Spinal cord transsection • Sprue • Stroke • Thalassemia • Thyrotoxicosis

19. Aluminum Anticonvulsants Cytotoxic drugs Glucocorticosteroids GnRH agonists Immunosuppressants Lithium Long-term heparin Progesterone, parenteral, long acting Supraphysiologic thyroxine doses Tamoxifen (premeno) TPN Drugs Associated with Osteoporosis

20. Prevention of Fractures • Weight bearing exercise • Prevent falls • Limit sedating medications • No smoking • Limit alcohol • Calcium (800 mg 4-8 yo, 1300 mg 9-18 yo) and vitamin D (400-800 IU daily) • Some sunlight

21. Daily Elemental Calcium • Premenopausal women 25-50 years old: 1,000 mg • Postmenopausal women less than 65 years old on estrogen: 1,000 mg • Postmenopausal women not on estrogen: 1,500 mg • All women older than 65 years: 1,500 mg

22. Institute of Medicine • Young adults: 1,000 mg daily • 50 years old and older: 1,200 mg daily

23. Dietary sources of calcium • Milk 8 ounces = 300 mg • Yogurt 8 ounces = 400 mg • Cheese 1 ounce = 200 mg • Fortified foods and juices

24. Vitamin D • Fish, egg yolks, fortified milk • <50 yo- 200 IU • 50-70 yo- 400 IU • >70 yo- 600 IU • If minimal sun exposure, 1000 IU

25. Screening • Women aged 65 and over • Men aged 70 and over • Every two years unless a new risk factor develops • Postmenopausal with 1+ risk factors • All postmenopausal women with a fracture • Chronic steroid use

26. DXA • Dual energy x-ray absorptiometry • Lumbar spine and hip • Use the same machine • T score- SD above/below the mean for young adults of the same sex • Z score- compared with reference population of the same age, race, sex • For every standard deviation decrease, risk of fracture doubles

27. Secondary Causes • Hypogonadism • Hyperparathyroidism • Rheumatologic disorders • Malignancy • GI disorders • Vitamin D deficiency • Chronic steroid use

28. Workup for Secondary Causes • First: serum calcium, serum chemistry, 24 hour urine calcium and creatinine, parathyroid hormone, TSH if taking thyroid hormone • Second: renal profile, vitamin D level, thyroid function, serum protein electrophoresis, maybe cortisol level if worried about Cushings

29. Cost Effective Work-Up • For $75 per patient (85%): 24 hour urine calcium, serum calcium, serum PTH • For $116 per patient (98%): add vitamin D

30. Diagnosis

31. When to Treat • T score –2 without risk factors • T score –1.5 with risk factors • Z score –1 (look for secondary causes)

32. Bisphosphanates • Alendronate (Fosamax) and risendronate (Actonel) • Inhibit osteoclasts • Decrease fractures (spine and nonvertebral) in osteoporosis • Prevention and treatment • Upper GI side effects • Poor absorption <1% • Take on an empty stomach with water, upright for 30 min without food or drink, weekly or daily

33. Bisphosphanates Studies • Fracture Intervention Trial • Vertebral Efficacy with Risendronate Therapy in North America • Fosamax Actonel Comparison Trial

34. SERMs • Estrogen like effects on the skeleton • Raloxifen • Tibolone • Tamoxifen

35. Raloxifen (SERM) • Binds to estrogen receptors on bone to decrease bone resorption and increase BMD • Prevention and treatment • Decreases vertebral fx in women with osteoporosis, but no reduction in hip fx • No endometrial stimulation • Possible decrease in breast cancer • Side effects- vasomotor, clots • Risks similar to estrogen

36. Tibolone • Androgen and progesterone effects • Prevention of bone loss • Still in trials

37. Tamoxifen • Chemoprevention for breast cancer • Slight decrease in bone fracture risks • Side effects- vasomotor, stimulates endometrium

38. Hormones • Inhibits osteoclasts • FDA approved for prevention of osteoporosis • Since WHI, not first line • Prempro • Menostar (estradiol transdermal)- weekly

39. Salmon Calcitonin • Nasal or subcutaneous • Treatment, not prevention • Inhibits osteoclasts • Approved for women who are 5 years postmenopause • Works for spine, but not hip fractures • Decreases bone pain from vertebral fx • Side effects- nausea, flushing

40. Teriparatide • Fragment of parathyroid hormone • Subcutaneous daily • Increases trabecular bone density and connectivity • Postmenopausal women • Treatment, not prevention • Use when other treatments fail • Expensive • Don’t use in combination with the bisphosphonates

41. Prevention • Bisphosphonates • Raloxifene • Estrogen

42. Treatment • Bisphosphonates • Raloxifene • Calcitonin • Parathyroid hormone

43. Repeat DXA • Every 3-5 years in untreated postmenopausal women (T > -1) • Every 2 years in treated women • Yearly if on steroids or elevated PTH • Every 1-2 years if osteopenia • Spine shows improvement earlier than hip

44. New Technology • MRI for microarchitecture and cross-section geometry • CT for cross-section geometry • Ultrasound of heel may predict hip fracture • Research only

45. Conclusion • Prevention • Screening • Treatment

46. References • Bilezikian, Holick, et al. “Osteoporosis: Diagnosis, Treatment, and Monitoring Considerations.” CME Forum. Vol. 3 Boston University School of Medicine. March 2004. • Mechcatie, E. “Secondary Causes of Bone Loss Often Missed.” Ob.Gyn. News. March 2003. • Osteoporosis Insight 2004. University of Texas Southwestern. Jersey City, NJ. Vol. 1. • “Osteoporosis.” ACOG Practice Bulletin. January 2004. Pg 203-216.

47. References • Sullivan, M. “Teens Lose Bone on DMPA, Recover It After Stopping Use.” Ob.Gyn. News. March 2003. • The 2004 Surgeon General's Report on Bone Health and Osteoporosis: What It Means To You