7/12/2019 Disclosures PUTTING IT ALL TOGETHER: CASE STUDIES I have nothing to disclose. Tiffany Kim, MD Assistant Professor of Medicine San Francisco VA Health Care System University of California, San Francisco Case 1 Medical History • Mr. F is a 82 yo man with a history of non small cell lung cancer s/p lobectomy, • Medical history • No known family history of fracture osteoporosis, T2DM, COPD who presents for osteoporosis management • Non small cell lung cancer s/p lobectomy • Osteoporosis • Treated with alendronate x 6 years • Health related behaviors • T2DM • Asking if he can stop taking alendronate • 60 pack year smoking history, stopped • COPD, no significant glucocorticoid use after lung cancer diagnosis • Rare alcohol use • Medications • Lives alone, performs ADLs • Budesonide/formoterol inhaler independently, likes to work in the • Cholecalciferol 800 IU daily garden • Metformin 1500 mg • Simvastatin 10 mg • Tiotropium inhaler 1
7/12/2019 Baseline Evaluation Interim Data: Part I • No prior fractures • Treated with alendronate for 6 years (2010-2016) • PE: 5’ 6”, 155 lb, BMI 25, poor dentition • No interval fractures • Hip x-ray for groin pain in 2010 concern for osteopenic/osteoporotic bones 2010 2016 • Baseline DXA (2010) +14.9% increase since 2010 L spine -3.2 -2.2 • L spine -3.2 Fem neck -3.2 -2.9 • Fem. neck -3.2 Total hip -1.8 -2.1 No sig. change since 2010 • Total hip -2.8 • 25(OH) vitamin D: 22 ng/ml repleted • Otherwise unremarkable Approach to Long Term Bisphosphonate Management Endocrine E-consult • “80 yo man with osteoporosis on alendronate for 6 years, patient wants to reduce pill burden… would appreciate guidance on recommendations for therapy” • Recommendation: Given high risk, consider continuing therapy High fracture risk: age >70-75, other strong risks for fracture, or FRAX score above country-specific threshold Adler, JBMR 2015 2
7/12/2019 Interim Data: Part II Unfortunately, patient sustained a left intertrochanteric hip fracture • Patient chose to stop alendronate • 2017: Worsening back pain, found to have acute L4 compression fracture, chronic compression fractures of T12 and L3 on MRI • Endocrine e-consult recommends IV zoledronic acid or denosumab • Patient declines • 2019: Right sided chest pain, no trauma, found to have subacute rib fractures • 2019: Endocrine clinic consult, recommend dental evaluation and then IV Conclusion: patient is scheduled for zoledronic acid (patient declined teriparatide) follow up, willing to re-initiate therapy Case 1 Summary Case 2 • Mr. C is a 61 yo man with a history of HIV, osteoporosis, hypogonadism, GERD • Certain patients may need >5 years of alendronate • Has been on alendronate from 2006 to 2018 (12 years) • High risk • 2 recent metatarsal fractures in his right foot • Hip BMD T-score ≤ -2.5 • End the drug holiday and re-initiate therapy if the patient develops fractures 3
7/12/2019 Medical History Baseline Evaluation • Medical history • No known family history of fracture • Fractures: broke a finger in his 20’s when playing baseball • HIV: diagnosed 1989, h/o tenofovir use • Osteoporosis • Health related behaviors: • PE: 5”10”, 160 lb, BMI 23 • Hypogonadism • Remote smoker for 5 years, occasional • GERD glass of wine • Cervical spinal stenosis • Walks 4x/week, no strenuous exercise • Baseline DXA (screening in 2006) • Medications • L spine -2.5 • Fem. neck -2.4 • Lamivudine, ritonavir, darunavir, dolutegravir • Total hip -2.4 • Testosterone 1.62% gel, 1 pump/day • Omeprazole 20 mg • 25(OH) vitamin D: 22 ng/ml repleted • Ca carbonate 500mg/Vit D 200 IU BID • Ibuprofen prn • Otherwise unremarkable Interim Data Why is he fracturing? • Interval fractures • Poor adherence? • 2011: left humerus s/p fall • Treatment failure? • 2016: right wrist s/p fall • High risk patient? • 2018: 2 right stress foot fractures (3 rd and 5 th metatarsals), minimal trauma How would you approach this? What would be your next steps? • 25(OH) vitamin D: 44 ng/ml • Otherwise unremarkable 4
7/12/2019 Treatment Failure Considerations (IOF) Treatment Failure – International Osteoporosis Foundation (IOF) • Fractures of the hand, skull, digits, feet and ankle: not fragility fractures • Review adherence • Significant BMD decline: • Search for occult secondary causes of osteoporosis • >5% at the lumbar spine • >4% at the proximal femur • Consider treatment change if: • Two or more incident fragility fractures • Significant bone turnover response: • One incident fracture AND significant BMD decline OR no bone turnover marker response • Significant BMD decline + no bone turnover markers response • >25% decline for anti-resorptive treatments • If baseline levels unknown: level below the average value of young healthy adults • Falls are an important driver of fracture Diez-Perez, Osteoporos Int 2012 Diez-Perez, Osteoporos Int 2012 A closer look at the fractures Case 2 • Interval fractures • Review adherence intermittently took ALN from 2006-2011 • 2011: left humerus s/p fall • Search for occult secondary causes of osteoporosis none identified • Patient not adherent during this time? • 2016: right wrist s/p fall • Consider treatment change if: • Fragility fracture • 2018: 2 right stress foot fractures (3 rd metatarsal, 5 th metatarsal), minimal trauma • Two or more incident fragility fractures • Foot fractures may not be fragility fractures • One incident fracture AND significant BMD decline OR no bone turnover marker response • Significant BMD decline + no bone turnover markers response 5
7/12/2019 Spontaneous fracture and suppression of bone turnover No decline in BMD, bone turnover markers suppressed related to long term alendronate use? 2006 2010 2012 2014 2016 2018 L spine -2.5 -2.0 -1.5 -0.9 -0.9 -1.1 Fem neck -2.4 -2.4 -2.2 -2.1 -2.0 -2.0 Total hip -2.4 -2.3 -2.2 -1.9 -2.0 -1.9 • CT BMD Lumbar Spine: 104.1 mg/cc osteopenia • CTX (bone resorption marker): 73 L (87 – 345 mcg/l) • PINP (bone formation marker): 10 L (30 – 110 pg/ml) Odvina, JCEM 2005 Should this patient go on a drug holiday? Case 2 • Review adherence Intermittently took ALN from 2006-2011 ? • Search for occult secondary causes of osteoporosis None identified • Consider treatment change if: • Two or more incident fragility fractures Maybe not • One incident fracture AND significant BMD decline OR no bone turnover marker response No • Significant BMD decline + no bone turnover markers response No Conclusion: Decided to start drug holiday 6
7/12/2019 Case 2: Summary Case 3 • Ms. P is a 62 yo woman with h/o acute myeloid leukemia s/p chemotherapy, radiation and bone marrow transplant, abdominal desmoid tumor complicated • Considerations for treatment failure: by small bowel obstruction, osteoporosis, osteoarthritis • Assess adherence • Assess occult secondary causes of osteoporosis • Consider fractures, BMD response or bone turnover markers • Medical history • Remote acute myeloid leukemia s/p chemotherapy, radiation, and bone marrow transplant • Fractures on therapy may be due to poor adherence or over-suppression of • Menopause at age 47 due to chemotherapy bone turnover (uncommon) • Abdominal desmoid tumor complicated by small bowel obstruction and ileal resection • Osteoporosis • Osteoarthritis, h/o steroid injections into hands/shoulders for 3-4 years Medical History Initial Evaluation • Fracture history: Fractured ulna after falling from bike at age 28 • Medications • Family history: Mother had a hip fracture at age 60 • Calcium 500mg/Vitamin D 200 IU • PE: 5’5”, 145 lb, BMI 24 BID • Lidocaine patch • Health related behaviors: • Baseline DXA (2009, age 53) given chemical menopause and +family history • Meloxicam prn • Never smoker, 2 drinks/month • L spine: -1.8 • Some gardening and lifting • Fem neck: -2.7 • Total hip: -2.1 • 25(OH) vitamin D: 28 ng/ml 7
7/12/2019 Interim Data: Part I Case 3 • Treated with alendronate for 5 years (2009-2014) • Review adherence Only picked up 6 prescriptions in 5 years • 2014: Stubbed toe against furniture 3 rd proximal phalangeal fracture • Search for occult secondary causes of osteoporosis 2009 2014 • Consider treatment change if: L spine -1.8 -2.2 -4.9% decrease since 2009 • Two or more incident fragility fractures Fem neck -2.7 -3.0 • One incident fracture AND significant BMD decline OR no bone turnover marker response Total hip -2.1 -2.3 -3.9% decrease since 2009 • Significant BMD decline + no bone turnover markers response • Switched to IV zoledronic acid for improved compliance Interim Data: Part II Case 3 • Treated with IV zoledronic acid for 3 years (2015, 2016, 2017) • Review adherence Received yearly infusions • No interval fractures • Search for occult secondary causes of osteoporosis None identified 2009 2014 2018 L spine -1.8 -2.2 -1.7 +6% increase since 2014 • Consider treatment change if: Fem neck -2.7 -3.0 -3.1 • Two or more incident fragility fractures No Total hip -2.1 -2.3 -2.4 No sig. change since 2014 • One incident fracture AND significant BMD decline OR no bone turnover marker response No • Significant BMD decline + no bone turnover markers response No • CTX: 136 (40 – 465 pg/ml) Patient did not fail but did not get a good response, what would you do? • 25(OH) vitamin D: 28 ng/ml • 24 hour urine calcium: 174 mg/dl 8
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