Download Free Medical Osteoporosis Update-Advances in Treatment PowerPoint Presentation

Osteoporosis Update-Advances in Treatment PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Orthopaedics, which is titled "Osteoporosis Update: Advances in Treatment", to know about Advances in Osteoporosis Treatment.

Tags : Orthopaedics, Osteoporosis, Advances, Treatment

Published on : Aug 18, 2021 | Views : 1339 | Downloads : 8

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Osteoporosis Update: Advances in Treatment Suzanne Jan de Beur, MD Johns Hopkins University School of Medicine 8/21/2021 1
Slide 2-

Incidentally Discovered Vertebral Fracture A 70 year old female smoker being evaluated for a cough presents for discussion of recently order chest xray. You explain that the CXR shows no infiltrates or masses in the lung tissue itself but there is an incidental vertebral compression fracture at T12 noted. 8/21/2021 2
Slide 3-

What do you ask next? 8/21/2021 3
Slide 4-

Delving Deeper Upon further discussion you ascertain: She remembers a 2 month history of significant back pain that spontaneously resolved after a fall from standing height while working in the yard 3 years ago shortly after she retired She is 2 inches shorter than her peak adult height No previous fractures 8/21/2021 4
Slide 5-

Delving Deeper: Secondary Causes No current or past history use of steroids Alcohol intake is one glass of wine daily 50 pack year history of smoking Menopause age 52 No weight gain or weight loss No diarrhea or malabsorption symptoms Physically active and rarely falls Normal renal function with no kidney stones 8/21/2021 5
Slide 6-

Medical History PMH: Hypertension Hyperlipidemia Medications: amlodipine 5 mg, simvastatin 20 mg, multiple vitamin for “seniors” SH: retired school teacher FH: no hip fractures in either parent, mother developed Dowager’s hump 8/21/2021 6
Slide 7-

Physical Exam P=75, BP=135/80, Wt: 150 lbs, Ht: 66 inches, BMI=24.2 No Cushing Features No kyphosis or pain on spinal palpation No goiter, tremor, thyroid eye finds 8/21/2021 7
Slide 8-

What next? 8/21/2021 8
Slide 9-

Laboratory and Imaging DXA Lumbar Spine Tscore -1.6 Femoral Neck T score -1.5 Total Hip Tscore -1.3 FRAX 10 year Probability MOF 16%, HF 3.7% Secondary Evaluation is normal CMP, phos, CBC, TSH, 24hr urine calcium/creatinine, 25D, PTH, SPEP/UPEP 8/21/2021 9
Slide 10-

What do you Advise? Counsel for smoking cessation Treat with appropriate calcium and vitamin D Counsel about Fall prevention A. Initiate treatment with pharmacotherapy OR B. Reassure the patient that no intervention is needed 8/21/2021 10
Slide 11-

Smoking Cessation Reduces Fracture Risk FRAX 10 year Probability MOF 16%, HF 3.7% No Smoking: FRAX 10 year Probability MOF 16%, HF 2.2% 8/21/2021 11
Slide 12-

Fracture is SKELETAL FAILURE 8/21/2021 12
Slide 13-

Fracture is a Powerful Risk Factor for Future Fracture Relative Risk Thinness 1.3 If BMI <21 Smoking 1.5 If current Family history 1.6 Sister of hip fracture 1.3 Mother Spine Non-Spine Fractures Non-spine 2.2 1.5 Spine 1 fracture 3.2 1.6 2 fractures 8.0 2.0
Slide 14-

Mortality Following Clinical Fractures Fracture Intervention Trial Cauley JA, et al. Osteoporos Int. 2000;11:556-561 *6459 postmenopausal women ages 55-81 years,followed for an average of 3.8 years Any Symptomatic Age-Adjusted Relative Risk (95% CI) 0.0 1.0 2.0 5.0 16.0 Non-spine Other Forearm Spine Hip 10.0 6.7 8.6
Slide 15-

Outcomes of Hip Fractures 300,000 hip fractures annually1 24% excess mortality in 12 months2 50% do not recover baseline function3 25% require long-term nursing home care4 1 U.S. Congress, OTA,. Hip Fracture Outcomes. OTA-BP-H-120, 1994. 2 Ray, N.F. et al. J. Bone Mineral Res. 1997;12:24-35 3 Consensus Develop. Conf., Am. J. Med. 1993;94:646-650 4 Riggs, B.J. and Melton, L.J. Bone 1995;17:505S-511S
Slide 16-

Guidelines for Osteoporosis Screening 8/21/2021 16
Slide 17-

Indication for Pharmacologic Treatment Initiate pharmacologic treatment in: Those with clinical or asymptomatic hip or vertebral fracture Those with a T score <-2.5 at the hip, spine or femoral neck Those with osteopenia and a FRAX 10 yr probability >20% of major osteoporotic fracture or >3% of hip fracture 8/21/2021 17
Slide 18-

Take Home Points A fragility fracture is skeletal failure Initiate pharmacologic treatment in: Those with clinical or asymptomatic hip or vertebral fracture regardless of T score Those with a T score <-2.5 at the hip, spine or femoral neck Those with osteopenia and a FRAX 10 yr probability >20% of major osteoporotic fracture or >3% of hip fracture 8/21/2021 18
Slide 19-

Advances in Treatment 8/21/2021 19
Slide 20-

Outline New long term data for Denosumab New data about treatment of Osteopenia New treatments: Abaloparatide New treatments: Romosozumab 8/21/2021 20
Slide 21-

2–4 weeks 3–4 months Resting stage Reversal phase Formation Remodeling completed Activation Resorption Lining cells Osteoclast precursors Osteoclasts Osteoblasts Bone remodeling unit Lining cells Normal Bone Remodeling
Slide 22-

FDA-Approved Osteoporosis Medications Antiresorptives Estrogen/HRT* Bisphosphonates Alendronate (Fosamax)* Risedronate (Actonel)* Ibandronate (Boniva) Zoledronic Acid (Reclast)* SERMS: Raloxifene (Evista) Bazedoxifene (Duavee) Calcitonin (Miacalcin) Denosumab(Prolia)* Anabolics Parathyroid Hormone (Teriparatide, Forteo) PTHrP Analogue (Abalopartide, Tymlos)* Romosozumab(Evenity) *reduces non vertebral fracture
Slide 23-

ppt slide no 23 content not found
Slide 24-

Denosumab New Long Term Data 8/21/2021 24
Slide 25-

Denosumab Mechanism 8/21/2021 25
Slide 26-

FREEDOM Extension 8/21/2021 26
Slide 27-

FREEDOM EXTENSION: 10 yr Data 8/21/2021 27 HM Bone, Lancet Diab Endo, 2017
Slide 28-

Incidence of New Fractures in Long Term Group 8/21/2021 HM Bone, Lancet Diab Endo, 2017 28
Slide 29-

FREEDOM EXTENTION 10 year data The FREEDOM trial open-label extension 4,450 women on denosumab for either 7 or 10 years 10 yrs of DMAb was associated with: sustained low fracture rates steadily increasing bone mineral density persistent reduction of bone turnover no increase in adverse events over time 8/21/2021 29
Slide 30-

Bone Markers Rebound within 3 months of Stopping Dmab 8/21/2021 Tsourdis, BONE, 2017 30
Slide 31-

Bone Density Drops within 6 months of Stopping Dmab 8/21/2021 Tsourdis, BONE, 2017 31
Slide 32-

Vertebral Fractures Increase when Dmab is Stopped 8/21/2021 32 ALL With Prevalent Vertebral Fracture Cummings, JBMR, 2018
Slide 33-

Take Home Points Denosumab must be administered in a timely and continuous fashion No medication holiday with denosumab Best practice for transitioning off treatment is being studied 8/21/2021 33
Slide 34-

Treatment Efficacy in Osteopenia 8/21/2021 34
Slide 35-

Zoledronic Acid in Women with Osteopenia IR Reid, NEJM, 2018 6 year, double-blind, placebo controlled trial 2000 women, age 65+ Osteopenia (T score -1 to -2.5 in the total hip/femoral neck) Zoledronic acid 5 mg every 18 months (4 infusions) OR Placebo Vitamin D administered and 1 gram calcium intake encouraged Primary endpoint: time to first occurrence of a fracture 8/21/2021 35
Slide 36-

Study Design and Baseline Characteristics 8/21/2021 36
Slide 37-

Zoledronic Acid in Osteopenia: Fracture Outcomes 8/21/2021 37
Slide 38-

Zoledronic Acid in Osteopenia: Fracture Outcomes 8/21/2021 38
Slide 39-

Adverse Events 8/21/2021 39
Slide 40-

Bisphosphonates and Mortality RCT of ZA in men and women after hip fracture demonstrated a 28% decrease in mortality (Lyles K, NEJM, 2007) Meta-analysis of 8 osteoporosis trials with duration >12 months showed a 11% reduction in mortality (Bolland M, JCEM, 2010) Observational study of 209 post-hip fracture subjects reported a 63% reduction in mortality (Beaupre LA, Osteoporosis Int, 2010) Observational study of nursing home subjects showed 27% reduction on mortality in BP users (Sambrook PN, Osteo Int, 2010) Prospective, cohort study of 2043 men and women over 60 demonstrated a 69% reduction in mortality in women on BPs (Center J, JCEM 2011) 8/21/2021 40
Slide 41-

Take Home Points ZA is effective in reducing fracture in older osteopenic women 4 infusions over 6 years was sufficient Decreased mortality and decreased cancer incidence in ZA treated women 8/21/2021 41
Slide 42-

Abaloparatide
Slide 43-

2–4 weeks 3–4 months Resting stage Reversal phase Formation Remodeling completed Activation Resorption Lining cells Osteoclast precursors Osteoclasts Osteoblasts Bone remodeling unit Lining cells Bone Remodeling
Slide 44-

PTH and PTHrp Bind to PTHR1 8/21/2021 44
Slide 45-

Abaloparatide Synthetic peptide analog of human PTHrp Potent anabolic agent for the treatment of osteoporosis in PMO Daily subcutaneous injection 2 years of therapy Must be followed by antiresorptive therapy 8/21/2021 45
Slide 46-

Abaloparatide Comparator Trial in Vertebral End point (ACTIVE) Randomized controlled and comparator 80 mcg abaloparatide, 20 mcg TPTD, injected placebo 18 months 2463 post menopausal women (1901 completed) 8/21/2021 PD Miller, JAMA, 2016 46
Slide 47-

ACTIVE: Abaloparatide v. Teriparatide 8/21/2021 Miller PD, JAMA, 2016 47
Slide 48-

ACTIVE: Fracture 8/21/2021 PD Miller, JAMA, 2016 48
Slide 49-

Side Effects Black Box: Contraindicated h/o skeletal irradiation, Pagets, mets, open epiphysis Hypercalcemia Urolithiasis Increased Uric acid Palpitations Hypotension 8/21/2021 49
Slide 50-

Take Home Points Abaloparatide is a potent anabolic agent used for those at high risk of fracture or for those who fail antiresoptive therapy More effective than teriparatide in reducing fracture especially at hip Patch delivery in development 8/21/2021 50
Slide 51-

Anti-Sclerostin Antibodies 8/21/2021 51
Slide 52-

2–4 weeks 3–4 months Resting stage Reversal phase Formation Remodeling completed Activation Resorption Lining cells Osteoclast precursors Osteoclasts Osteoblasts Bone remodeling unit Lining cells Bone Remodeling
Slide 53-

Wnt Signaling in Bone Canalis, 2013
Slide 54-

Romosozumab Administered by a health care professional 2 subcutaneous injections once a months for 12 months Must be followed by an antiresorptive 8/21/2021 54
Slide 55-

Romosozumab Bone Mineral Density 8/21/2021 55 McClung, NEJM, 2014 412 postmenopausal women with osteoporosis
Slide 56-

Cosman F et al. N Engl J Med 2016;375:1532-1543 Romozosumab-Denosumab Treatment in Women with PMO
Slide 57-

Cosman F et al. N Engl J Med 2016;375:1532-1543 Romosozumab-Denosumab Bone Density and Bone Markers Cosman, NEJM, 2016
Slide 58-

Cosman F et al. N Engl J Med 2016;375:1532-1543 Incidence of New Vertebral, Clinical and Nonvertebral Fractures Cosman F et al. N Engl J Med 2016;375:1532-1543
Slide 59-

Romosozumab-Alendronate 8/21/2021 Saag, NEJM, 2017 59
Slide 60-

Romosozumab-Alendronate 8/21/2021 60 Saag, NEJM, 2017
Slide 61-

Romozosumab OFF and Alendronate Pretreatment 419 postmenopausal women(55-85 y) Tscore -2.5-3.5 at LS , TH, or FN Rxed with 210 mg Q M for 2 years After 2 yrs, randomized to placebo or Dmab 60 mg q6 m McClung, JBMR 2018
Slide 62-

Romosozumab Off Effect and Effect of Alendronate Lead In Effect of Romo plateaus after 12 months Romo needs to be followed by antiresporptive therapy to prevent bone loss Bisphosphonates before Romo blunt response 8/21/2021 62 McClung, JBMR 2018
Slide 63-

Romozosumab v. Teriparatide 8/21/2021 63 Langdahl, Lancet 2017
Slide 64-

Side effects Black Box: CV (contraindicated in those with MI or stroke within a year) Arthralgia/myalgia Hypocalcemia Atypical femoral fracture Osteonecrosis of the jaw 8/21/2021 64
Slide 65-

Take Home Points Romosozumab is a potent bone anabolic agent used in severe osteoporosis or those that fail other therapy Vertebral fracture reduction>non vertebral Romo followed by Dmab is best CV side effects seen in clinical trials 8/21/2021 65
Slide 66-

Change in BMD at 24 months in Spine and Total Hip with Various Regimens 8/21/2021 66 McClung Osteo Sarc 2018
Slide 67-

Summary Fragility fracture is skeletal failure and must prompt evaluation and treatment Denosumab use for up to 10 years is safe and effective New data suggest that a limited course of Zoledronic acid even in those with osteopenia reduces fracture There are a variety of new treatment options for osteoporosis that can allow tailoring therapy to the individual characteristics “Medication Holiday” applies only to Bisphosphonates other agents including denosumab must be continued or followed by other therapy 8/21/2021 67
Slide 68-

Johns Hopkins Hospital Baltimore, Maryland 8/21/2021 68
Slide 69-

NNT vs. RR Atypical Fracture 8/21/2021 Black and Rosen, NEJM 2016 69
Slide 70-

Vertebral Fracture Risk in RCTs of Osteoporosis Treatments .53 .59 .48 .35 .50 .67 .66 .30 .62 .32
Slide 71-

Nonvertebral Fracture Risk in RCTs of Osteoporosis Treatments .80 .6 .5 .9 .88 .76 .75 .7 .80
Slide 72-

ppt slide no 72 content not found
Slide 73-

WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998. T-Score World Health Organization (WHO) Osteoporosis Definition SD
Slide 74-

Previous Guidelines Initiate pharmacologic treatment in: Those with a T score <-2.5 at the hip, spine or femoral neck Those with osteopenia and a FRAX 10 yr probability >20% of major osteoporotic fracture or >3% of hip fracture 8/21/2021 74
Slide 75-

What is FRAX®? The FRAX® tool has been developed by WHO to evaluate fracture risk of patients. It is based on individual patient models that integrate the risks associated with clinical risk factors as well as bone mineral density (BMD) at the femoral neck. The FRAX® models have been developed from studying population-based cohorts from Europe, North America, Asia and Australia. The FRAX® algorithms give the 10-year probability of fracture. The output is a 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture).
Slide 76-

http://www.shef.ac.uk/FRAX/
Slide 77-

ppt slide no 77 content not found
Slide 78-

ppt slide no 78 content not found
Slide 79-

ppt slide no 79 content not found
Slide 80-

Screening for Osteoporosis DXA as indicated previously AND screening for asymptomatic vertebral fracture 8/21/2021 80
Slide 81-

Screen for Asymptomatic Fracture Vertebral Fracture in: Women over 70 and men over 80 with T score <-1.0 at hip, FN or spine Women over 65 and men over 70 with T score <-1.5 at hip, FN or spine Postmenopausal women and men age 50+ with specific risk factors Low trauma fracture during adult hood (age 50+) Historical height loss of 1.5 inches or more Prospective height loss of 0.8 inches or more Recent or ongoing glucocorticoid treatment 81
Slide 82-

Methods of Screening for Vertebral Fracture: Thoracic and Lumbar Xray DXA with VFA 8/21/2021 82
Slide 83-

Repeat Vertebral Imaging Repeat vertebral imaging only indicated if: Prospective height loss of 0.8 inches New back pain New postural changes 8/21/2021 83
Slide 84-

8/21/2021 84
Slide 85-

Take Home Points A fragility fracture is skeletal failure Measure and follow for height loss Screen for asymptomatic vertebral fracture Women over 70 and men over 80 with T score <-1.0 at hip, FN or spine Women over 65 and men over 70 with T score <-1.5 at hip, FN or spine Postmenopausal women and men age 50+ with specific risk factors 85
Slide 86-

Who should we screen with DXA measurements? ALL women age >65 and ALL men >70 Post menopausal women and men 50-70 with risk factors Adults 50+ with Low trauma fracture Radiographic evidence of osteopenia Long term glucocorticoid therapy Hypogonadal men Patients with hyperparathyroidism Patients with height loss >1.5 inches
Slide 87-

Combination and Sequential Therapies 8/21/2021 87
Slide 88-

DATA Study Design Lancet 382:50-56, 2013 100 Postmenopausal women 45+ years Open label, randomized, controlled trial for 1 yr “High fracture” risk: T-2.5 or less at spine, hip, FN T-2.0 or less with 1 BMD independent RF T score -1.0 or less with fragility fracture 1:1:1 randomization to TPT, Dmab, or both Outcome: BMD and bone markers 8/21/2021 88
Slide 89-

DATA: Change in BMD 8/21/2021 89
Slide 90-

DATA Switch DMAb to PTH or PTH to DMAb in PMO: Design: after 2 years of treatment switched to alternate treatment at 1 year PTH (27 women)and PTH/Dmab (21 women) combo treated switched to Dmab alone Dmab (24 women) treated switched to PTH Outcome BMD at 6 and 12 months ASBMR 2014, #1150
Slide 91-

Transition from Dmab to PTH or PTH to Dmab in PMO: DATA Switch
Slide 92-

DATA & DATA Switch Conclusion Combined TPT/Dmab increased BMD more than either agent alone TPT followed by Dmab resulted in greater increase in BMD Dmab followed by TPTresults in loss of BMD Combo treatment may be useful for treatment in very high risk patients 8/21/2021 92
Slide 93-

Romo Retreatment 8/21/2021 93 Kendler, Osteo Int, 2019
Slide 94-

Romo Retreatment: BMD and Bone Markers 8/21/2021 94 Kendler, OI, 2019