Osteoporosis

1. Osteoporosis Capital Conference 2007 Marc Childress, MD

2. Osteoporosis Epidemiology Risk Factors Prevention Screening Diagnosis Treatment Osteoporosis in Men Management Falls Acute Complications

3. Osteoporosis Average female bone mineral density peaks at age 35, slow decline thereafter Density loss is accelerated post-menopausally

4. Epidemiology 1.3 million osteoporotic fractures in U.S. every year 40% of women over 50 have osteopenia 7% of women over 50 have osteoporosis Presence of osteoporosis carries 4-fold increase in fracture rate (over 50 years old)

5. Epidemiology Among those who live to 90 years old, 1/3 of women and 1/6 of men will have sustained osteoporotic fracture Hip fracture mortality at 1 year is approaching 25%

6. Risk Factors Female Gender 3X more likely to have hip or vertebral fracture than men 6X more likely to have forearm fracture Caucasian Race Higher than African-American, Asian race Smoking Low Body Weight (less than 58 kilos)

7. Risk Factors (cont�d) Sedentary Lifestyle Excessive Alcohol Intake Ample suggestion that moderate alcohol intake may be protective No clear threshold Nursing Home Residents 10X more likely to experience hip fracture than age-matched non-residents

8. Predisposing Medical Conditions Estrogen Deficiency Inflammatory Bowel Disease Type 2 Diabetes Mellitus Celiac disease Cystic fibrosis Hyperthyroidism Hyperparathyroidism Hypogonadism Liver Disease Corticosteroid use Heparin use Cyclosporine use Depo-Provera use Vitamin A (systemic retinoid) use

9. Risk Factors (cont�d) No clear increase in risk with carbonated beverages Although unclear risk association with excessive caffeine

10. What they want you to know� Chronic excess thyroid hormone replacement over a number of years in post-menopausal women can lead to diffuse nontoxic goiter osteoarthritis osteoporosis hyperparathyroidism

11. What they want you to know� A 31-year-old white female presents with her third stress fracture of a lower extremity in the past 4 years. Her history and examination are otherwise unremarkable except for a controlled seizure disorder. The most likely cause of her bone problem is Addison�s disease Hypothyroidism Osteogenesis imperfecta Anticonvulsive medication

12. Prevention Adequate total dietary calcium 1500 mg/day for postmenopausal without HRT 1000-1200 mg/day premen, postmen with HRT Vitamin D 800 IU/day for postmenopausal 400 IU/day premen, postmen with HRT Regular weight-bearing exercise Additional protective factors: increased BMI, African-American ethnicity, moderate EtOH intake

13. What they want you to know� Which of the following antihypertensives agents may help preserve bone mineral density? Atenolol (Tenormin) Doxazosin (Cardura) Enalapril (Vasotec) Hydrochlorothiazide Nifedipine (Procardia, Adalat) Which one of the following is associated with a reduced risk of post-menopausal osteoporosis? Corticosteroid use Cigarette smoking Diuretic use Low BMI Asian Ethnicity

14. Screening USPTF/AAFP� �routine screening� above the age of 65, consider between 60-65 for increased risk National Osteoporosis Foundation�recommend screening above 65, or in younger with risk factors Difficulty with recommendations Cost issues Time interval of screening examination

15. Screening Options Single Photon absorptiometry -can only be used at radius or calcaneus (unclear attenuation source) Dual Photon absorptiometry -can be used at deeper sites (spine,hip)

16. Screening Options Dual X-ray absorptiometry (DEXA)�MOST POPULAR Pros: -precise measurements at clinically relevant sites (hip and spine) -minimal radiation Cons: -not portable -expensive

17. Screening Options Quantitative CT Pros: -similar accuracy to DEXA -may have slightly better predictive value in risk of vertebral fracture Cons: -more expensive (than DEXA) -less reproducible (bigger variance) -higher radiation

18. Screening Options Ultrasound Pros: -studies thus far have suggested similar predictive ability of fracture to DEXA -No radiation -Portable Cons: -unable to provide true Bone Density Measurements (less applicable to current diagnostic standards and treatment goals based on BMD) *current role in identifying high risk individuals, not in pervasive screening

19. Diagnosis 2 Methods 1) Radiographic determination of Bone Mineral Density to be -1 Standard Deviations below young adult reference mean-OSTEOPENIA -2.5 Standard Deviations below young adult reference mean-OSTEOPOROSIS 2) Presence of fragility fracture (no signif trauma hx, and absence of osteomalacia or bone tumor)

20. Treatment Bisphosphonates- most appropriate initial treatment for women with osteoporosis Alendronate (10 mg/day or 70 mg weekly), -best when taken on empty stomach with 8 oz. water, standing upright for 30 minutes, risk of esophagitis - contraindicated in patients with active upper GI disease Risedronate (5 mg/day or 35 mg weekly) -less apparent GI risk than alendronate

21. Treatment SERMS (Selective Estrogen Receptor Modulators)- Raloxifene-best data among 2 in class, approved for both prevention and treatment of osteoporosis Tamoxifen�not FDA approved, but some data to suggest bone benefit

22. Treatment PTH (Teriparatide)-daily injections. Currently limited to those at very high fracture risk or those unresponsive to bisphosponate therapy due to high cost ($20/day) and risk of osteosarcoma Calcitonin- nasal spray. Less effect on bone than bisphosphonates, risk of tachyphylaxis. Unique role in acute treatment of osteoporotic fracture�may be switched to alternate therapy once pain diminished.

23. Treatment Estrogen / Progestin therapy No longer first line, but still an option in women who may be contraindicated from or intolerant to bisphosponates or raloxifene. Combination therapy- there are demonstrable gains in using bisphosponates in combination with SERMs, and estrogen therapy if no contraindications and less than desired benefit on single osteoporosis therapy

24. What they want you to know� Raloxifene (Evista) : is used to manage hot flashes increases bone density stimulates breast tissue stimulates endometrial proliferation raises LDL and total cholesterol levels

25. Osteoporosis in Men --1.5 million men in U.S. with osteoporosis, 3.5 million at risk --1 in 6 men at 90 years of age will experience hip fracture. Mortality with hip fracture higher in men than in women. --Treatment includes testosterone therapy (unless contraindicated�see question) as first line, as well as bisphonate therapy (works equally well in men�see question). Likely role for recombinant PTH and possibly SERMs (raloxifene). --Must assure adequate calcium and vitamin D intake, although these are not sufficient for treatment of osteoporosis --Diagnosis best made with DEXA, still compared to standard of young woman

26. What they want you to know� A 79-year old white male with a previous history of prostate cancer has a lumbar spine film suggesting osteopenia. Subsequent bone density studies show a T score of -2.7. Which one of the following is appropriate first line therapy for this patient? A) Testosterone B) Calcitonin nasal spray (Micalcin) C) Raloxifene (Evista) D) Alendronate (Fosamax) Which one of the following is true regarding the use of Alendronate (Fosamax) for the treatment of osteoporosis in men? A) Its effectiveness is similar to that seen in women B) It is ineffective in patients with Paget�s disease C) It is contraindicated in patients taking NSAIDs D) It causes a decrease in height

27. Chronic Management --No advantage of remeasuring BMD within 1 year --Recommendations for remeasurement in 1 or 2 years once therapy has been started --If evaluated, and no change at one year, not indicative of eventual benefit. Recommend ensuring adequate calcium Vit D, and additional risk factor reduction (smoking cessation, deacreased EtOH, etc.)If significant worsening, likely unresponsive to therapy. If improvement, continue regimen and follow long term.

28. What they want you to know� A 70-year-old female had a lumbar vertebral fracture 3 years ago. At that time she had a dual-energy absorptiometry (DEXA) scan, with a T score of -2.6, and was placed on alendronate (Fosamax), calcium, and vitamin D. She recently quit smoking. Her BMI is 21. A DEXA scan today shows her bone mineral density to be -2.1. Which one of the following would be most appropriate in the management of this patient? Replace alendronate with raloxifene (Evista) Stop alendronate, but continue calcium and vitamin D Add raloxifene to her regimen Add teriparatide (Forteo) to her regimen Make no change to her regimen

29. Falls --Fracture risk is still significantly linked to risk of fall --Ability to safely transfer is independent risk factor --Vitamin D has been shown in numerous studies to decrease risk of falls independent of the structural bone benefit

30. What they want you to know� Which one of the following has been shown to reduce the risk of falls in the elderly? Vitamin D Amityriptyline (Elavil) Haloperidol (Haldol) Lorazepam (Ativan)

31. Acute Complications Remember that Calcitonin has additional benefit of pain reduction in acute course of compression fracture A 70-year-old white female with osteoporosis sees you for follow-up a few days after an emergency room visit for an acute T12 vertebral compression fracture. The fracture was suspected clinically and on plain films; the diagnosis was confirmed with a bone scan. The emergency department physician prescribed oxycontin and NSAIDs, but the patient is still experiencing considerable discomfort. In addition to increasing the dosage of oxycodone, which one of the following interventions would you suggest now to reduce the patient�s pain? Calcitonin (Miacalcin) Raloxifene (Evista) Alendronate (Fosamax) Physical therapy, including dexamethasone iontophoresis Vertebroplasty A 78-year-old white female presents with a 3-day history of lower thoracic back pain. She denies any antecedent fall or trauma, and first noted pain upon arising. Her description of the pain indicates that it is severe, bilateral, and without radiation to the arms or legs. Her past medical history is positive for hypertension and controlled diabetes milletus. Her meds include HCTZ, enalipril, metformin, and MVI. She is a previous smoker but does not drink alcohol. She underwent menopause at age 50 and took estrogen for a few months for hot flashes. Physical exam reveals her to be in moderate pain with a somewhat stooped posture and mild tenderness over T12-L1. She has negative straight leg raising and normal lower extremity sensation, strength, and reflexes. Which of the following is true regarding this patient�s likely condition? An MRI or nuclear medicine bone scan should be performed Prolonged (approximately 2 weeks) bed rest will increase the chance of complete recovery Investigation for an underlying malignancy is indicated Subcutaneous or intranasal calcitonin (Calcimar, Miacalcin) may be very helpful for pain relief

32. Questions?