1. Osteoporosis Educational Series: Treatment and Prevention Nahid Rianon, M.D., Dr.P.H. The University of Texas Health Science Center at Houston (UTHealth) Module 3 of 3

2. LEARNING OBJECTIVES: At the end of this presentation, attendees will be able to  Characterize the pathophysiology of osteoporosis  Identify the clinical diagnosis of osteoporosis  Summarize treatment and prevention options Objectives

3. Pre Quiz Question 1 of 5 Who needs to be treated for osteoporosis? (Choose one) T-score between -1.00 to -2.5 at femoral neck, total hip or spine AND a FRAX score showing 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 20% (FRAX) a) 10-yr probability of hip fracture ≥ 2% or any major osteoporosis-related fracture ≥ 20% b) 10-yr probability of hip fracture ≥ 2% or any major osteoporosis-related fracture ≥ 10% c) 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 20% d) 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 30%

4. Pre Quiz Question 2 of 5 Which of the following may be interpreted as improved state of bone turnover after treatment for osteoporosis? (Choose one) a)A T-score of -1.5 in the spine b)Suppression of urine NTX c)Improved DXA acquired BMD in both spine and femoral neck regions d)Suppressed levels of bone formation and resorption markers

5. Pre Quiz Question 3 of 5 Which of the following would indicate treatment failure, or need to consider alternate treatment for osteoporosis? a)BMD improved 1% since last DXA done 2 years ago b)Fracture of femoral shaft while being treated with bisphosphonate for 5 years c)Increased levels of bone markers since last measure a year ago d)Femoral neck BMD did not change since last DXA 2 years ago

6. Pre Quiz Question 4 of 5 An 80 year old Caucasian woman with dementia, falls and right hip fracture (1 year ago) while being on bisphosphonate, was referred for evaluation and treatment of osteoporosis. She had a mastectomy, followed by chemotherapy for breast cancer at age 66 and has been cancer free since then. Which of the following would be the best treatment option for her at this time? (Choose one) a) Ibandronate b) Calcitonin c) Teriparatide d) Denosumab

7. Pre Quiz Question 5 of 5 Selective Estrogen Receptor Modulator (SERM) is one of the first options for osteoporosis treatment. a)True b)False

8. Today’s Outline  Pathophysiology  Diagnosis  Treatment  Prevention

9. Normal Bone Remodeling Sequence Resorption = Formation No change in bone mass Pathogenesis of Osteoporosis LEGEND: LC = Lining Cells CL = Cement Line OS = Osteoid BRU = Bone Remodeling Unit Osteoclast Precursor Osteoclast Osteoblast Precursors Osteoblast Mononuclear Cells

10. Net bone loss Unbalanced Remodeling and Osteoporosis Resorption > Formation Influencers: Inadequate calcium or vitamin D Menopause Aging Medications or diseases

11. High Bone Turnover State Unbalanced Remodeling Osteoporosis Basic Pathology Normal Bone Structure Osteoporotic Bone Structure

12. Left hip A T- score of <-2.5 for BMD - considered osteoporosis Lumber spine Clinical Diagnosis of Osteoporosis

13. FormationResorption  Serum osteocalcin  Serum bone specific alkaline phosphatase (BAP)  Serum pro-collagen type 1 amino-terminal propeptide (P1NP)  Serum C-terminal cross- linking telopeptide of type I collages (CTX)  Urine N-terminal cross- linking telopeptide of type I collagen (NTX)  2 nd void sample in the AM Bone Markers

14. DXA Acquired BMD  Stable or improved BMD  Loss of BMD <%CV showing no significant change over mechanical drift from QA report for DXA machine Monitoring Treatment Success Bone Markers  Suppression of Bone markers  Both formation and resorption markers

15.  Hx of hip fracture  Other prior fractures and T-score between -1.0 to -2.5 at femoral neck, total hip or spine  T-score ≤-2.5 at femoral neck, total hip or spine  T-score between -1.0 to -2.5 at femoral neck, total hip or spine AND secondary cause ↑ risk of fracture  Steroid use, total immobilization  T-score between -1.0 to -2.5 at femoral neck, total hip or spine AND 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 20% (FRAX) Who Needs to be Treated?

16. Treatment Options  Bisphosphonates  Oral  Alendronate 10 mg daily or 70 mg weekly  Risedronate 5 mg daily or 35 mg weekly or 150 mg/mo  Ibandronate 150 mg/mo  Intravenous  Zoledronic acid 5 mg/yr  Calcitonin  Short-term for pain after vertebral fracture  Teriparatide  20 mcg sq daily  Recombinant human PTH (not >2 yrs)  Contra-indicated in cancer patients  Denosumab  60 mcg sc/q 6  Humanized monoclonal antibody  Usually as a 2 nd agent  Calcium (1200-1500 mg) + vitamin D (800-1000 IU daily)

17.  Adverse events ( mainly Bisphosphonates)  Atypical fracture  Jaw necrosis  Severe GERD/gastritis or GI bleed  Unimproved BMD despite treatment (reassess risk and check bone markers)  Fracture while being on tx  Intervention  Drug holiday  Monitor with DXA/2 yrs  Monitor bone markers/yr  Alternate options  Switch to other agents  ACEI/ARB* showed promise in observations studies – research continues Adverse Effects or Treatment Failure and Alternate Tx Options

18. Testosterone  If hypogonadism is the cause of osteoporosis Hormones as Treatment Options SERM  Raloxifene – not commonly used because it increases risk of DVT Estrogen/Progestin  Not encouraged due to increased risk of breast cancer, stroke, DVT and coronary diseases

19. Weight bearing exercise  Stimulates bone formation  2.5 to 4 hours/week of moderate to severe intensity physical activity* Calcium and Vitamin D  Regular supplemental required dose Non-skeletal Environmental/Behavioral  Fall prevention  Improve balance and gait- PT/OT  Smoking cessation  Avoid risk level alcohol use  Avoid flexion in patients with risk of or hx of vertebral fracture FLS (Fracture Liaison Services) network within the clinic, or group of providers Prevention

20.  Osteoporosis is a progressive metabolic bone disease that decreases bone density with deterioration of bone structure  Diagnosis = T- score of <-2.5 for BMD  Prevention and treatment should take comprehensive approach Take Home Message

21. Post Quiz Question 1 of 5 Who needs to be treated for osteoporosis? (Choose one) T-score between -1.00 to -2.5 at femoral neck, total hip or spine AND a FRAX score showing 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 20% (FRAX) a) 10-yr probability of hip fracture ≥ 2% or any major osteoporosis-related fracture ≥ 20% b) 10-yr probability of hip fracture ≥ 2% or any major osteoporosis-related fracture ≥ 10% c) 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 20% d) 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related fracture ≥ 30%

22. Post Quiz Question 2 of 5 Which of the following may be interpreted as improved state of bone turnover after treatment for osteoporosis? (Choose one) a)A T-score of -1.5 in the spine b)Suppression of urine NTX c)Improved DXA acquired BMD in both spine and femoral neck regions d)Suppressed levels of bone formation and resorption markers

23. Post Quiz Question 3 of 5 Which of the following would indicate treatment failure, or need to consider alternate treatment for osteoporosis? a)BMD improved 1% since last DXA done 2 years ago b)Fracture of femoral shaft while being treated with bisphosphonate for 5 years c)Increased levels of bone markers since last measure a year ago d)Femoral neck BMD did not change since last DXA 2 years ago

24. Post Quiz Question 4 of 5 An 80 year old Caucasian woman with dementia, falls and right hip fracture (1 year ago) while being on bisphosphonate, was referred for evaluation and treatment of osteoporosis. She had a mastectomy, followed by chemotherapy for breast cancer at age 66 and has been cancer free since then. Which of the following would be the best treatment option for her at this time? (Choose one) a) Ibandronate b) Calcitonin c) Teriparatide d) Denosumab

25. Post Quiz Question 5 of 5 Selective Estrogen Receptor Modulator (SERM) is one of the first options for osteoporosis treatment. a)True b)False

26. Thank You Questions ?

27. References Chodzko-Zajko WJ et al., 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis http://www.nof.org/professionals/clinical-guidelines http://www.nof.org/professionals/clinical-guidelines Photographs used for the cover slide are allowed by the MorgueFile free photo agreement and the Royalty Free usage agreement at Stock.xchng. They appear on the cover slide in this order: Wallyir at morguefile.com/archive/display/221205 Mokra at www.sxc.hu/photo/572286 Clarita at morguefile.com/archive/display/33743

28. Brought to you by TEXAS. The Training Excellence in Aging Studies (TEXAS) program promotes geriatric training from medical school through the practicing physician level. This project is funded by the Donald W. Reynolds Foundation to the division of Geriatrics and Palliative Medicine within the department of Internal Medicine at The University of Texas Health Science Center at Houston (UTHealth). TEXAS would also like to recognize the following for contributions: Houston Geriatric Education Center Harris County Hospital District Memorial Hermann Foundation Huffington Lecture Series The TEXAS Advisory Board Othello "Bud" and Newlyn Hare UTHealth Medical School Office of the Dean UTHealth School of Nursing UTHealth Consortium on Aging UTHealth Multimedia Scriptorium (www.uth.tmc.edu/scriptorium) Copyrighted images cannot be used in whole or part without the explicit permission of the owner.