Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
DON'T Break A Leg: Clinical Decision-Making in Osteoporosis
Ashlyn Smith, MMS PA-CEndocrinology Associates: Scottsdale, AZ
President, American Society of Endocrine Physician AssistantsAdjunct Assistant Professor, Midwestern University
ASAPA Fall 2019
Disclosures Speaker’s Bureau and Consultant for Abbott nutrition
1. Discuss the current state of osteoporosis impact, detection, and management
2. Review the current osteoporosis screening and monitoring recommendations
3. Examine non-pharmaceutical, lifestyle, and pharmaceutical interventions for low bone density and fracture prevention
4. Illustrate case-based clinical pearls in key problematic areas of osteoporosis management
Pretest Question 1What is the most appropriate treatment recommendation for a 56-year-
old female with a hx of GERD and frequent steroid treatment for migraine breakthroughs? T-score LS -1.9 (6% decline), FN -2.2 (4% decline) Calculated FRAX: 23%, 4%
A. Weight bearing exercises and OTC calcium supplementationB. Alendronate (Fosamax) or Risedronate (Actonel)C. Zoledronic acid (Reclast) or Denosumab (Prolia)D. Romosozumab (Evenity)E. Teriparatide (Forteo) or Abaloparatide (Tymlos)F. HRT or Raloxifene (Evista)
Pretest Question 2 If a 62-year-old African American female with a 7-year hx of
osteoporosis started Alendronate (Fosamax) 5 years ago had declining T-scores, which treatment option is most appropriate?
A. Drug holiday for 1 yearB. Continue Alendronate (Fosamax) C. Drug holiday utilizing Zoledronic acid (Reclast)D. Drug holiday utilizing Denosumab (Prolia) or anabolic agentE. Add an anabolic agent to the current regimen
Pretest Question 3Which treatment option would bring the most benefit to a 64-year-old
female with osteoporosis and a hx of a vertebral compression fracture 3 years ago, after which she started Zoledronic acid (Reclast)? T-score LS -2.1 (stable), FN -3.4 (8% decline)
A. Drug holiday for 1 yearB. Transition to Alendronate (Fosamax) or Risedronate (Actonel)C. Continue Zoledronic acid (Reclast)D. Add Denosumab (Prolia) to the current regimenE. Transition to an anabolic agent
Pretest Question 4 Should a 59-year-old Caucasian male with a five-year hx of COPD and
former smoker frequently on inhaled and PO steroid tx for exacerbations be screened for low BMD?
A. Yes, all men >50 years old should be screenedB. Yes, based on his age >50 and risk factors of history of smoking and steroid useC. No, he does not currently smoke or use steroid treatmentsD. No, he is <70 years old
Impact of Osteoporosis and Fractures
1 in 2 women and 1 in 4 men >50 years old will have a fracture related to osteoporosis >2 million fragility fractures/year in people ≥65 years ~80% of people with a fragility fracture are not screened, identified,
or treated afterward Fragility fractures are associated with decreased bone loss, but the
majority of fractures occur in those with moderate bone loss
International Osteoporosis Foundation. “Facts and Statistics.” https://www.iofbonehealth.org/facts-statistics#category-14
International Osteoporosis Foundation. “Facts and Statistics.” https://www.iofbonehealth.org/facts-statistics#category-14
Osteoporosis-Related Fx
-Hospitalization-Significant cost
-Impaired mobility -Depression
>25% risk of mortality
>60% risk of loss of
independence
86%increased risk of a
second fx
Prevention is key!
ScreeningAmerican Association of Clinical EndocrinologistsNational Osteoporosis FoundationAmerican College of Physicians
Dual Energy X-ray Absorptiometry
(DXA)
Gold standard for evaluating and monitoring of bone mineral density (BMD)A marker for fracture risk
Measures lumbar spine and total hip/femoral neckAdd forearm in parathyroid
dysfunction1
1. AACE/AAES Task Force on Primary Hyperparathyroidism. “The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons Position Statement on the Diagnosis and Management of Primary Hyperparathyroidism. ENDOCRINE PRACTICE Vol 11 No. 1 January/February 2005
T-score: standard deviations from the average young, healthy populationNormal ≥ -1.0Osteopenia: T-score between -1.0 and
-2.5Osteoporosis: T-score ≤ -2.5
14
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2 3. Qaseem, Amir MD, PhD, MHA; et al. “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.” Ann Intern Med. 2017;166(11):818-839. DOI: 10.7326/M15-1361
American Association of
Clinical Endocrinologists
All postmenopausal
women ≥50 years
National Osteoporosis Foundation
All women ≥ 65 years and men ≥
70 years
Based on risk factors:
postmenopausal women and men
50–69 years
American College of Physicians
Women ≥ 65 years
Postmenopausal women < 65
years at increased risk of
osteoporosis
Include fracture risk assessment with clinical risk assessment tool such as the Fracture Risk Assessment Tool (FRAX) 10-year probability of osteoporotic fracture1, 3
Risk factors Low trauma fracture during adulthood2
Recent or ongoing long-term glucocorticoid treatment2
Loss of height of ≥ 1.5 in.(4 cm) from peak height at age 20 years to current2
Loss of height of ≥ 0.8 in.(2 cm) from a previous height measurement to current2
Hip fracture, smoking, excessive alcohol consumption, low body weight, postmenopausal3
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2 3. Qaseem, Amir MD, PhD, MHA; et al. “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.” Ann Intern Med. 2017;166(11):818-839. DOI: 10.7326/M15-1361
DiagnosisAmerican Association of Clinical EndocrinologistsNational Osteoporosis FoundationAmerican College of Physicians
American Association of Clinical Endocrinologists (AACE)
Fragility fracture: Low trauma spine/hip fx
T-score -2.5 • Lumbar spine• Femoral neck• Total hip• Distal third of
radius
Osteopenia with high FRAX • Major osteoporotic
fracture risk ≥20% • Hip fx risk ≥3%• OR Proximal
humerus, pelvis, distal forearm fx
Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf
National Osteoporosis Foundation (NOF)
Hip or Vertebral fracture
T-score -2.5 Lumbar spine Femoral neck Total hip
Osteopenia with high FRAX Major osteoporotic
fracture risk ≥20% Hip fx risk ≥3%
Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2
American College of Physicians (ACP)
Fragility fracture
T-score -2.5 • Lumbar spine• Femoral neck
• Total hip• Distal third of radius
Qaseem, Amir MD, PhD, MHA; et al. “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.” Ann Intern Med. 2017;166(11):818-839. DOI: 10.7326/M15-1361
Evaluate for secondary causes1,2
CMP, CBC Phosphorus, magnesium Intact parathyroid hormone (iPTH), Vitamin D Thyroid stimulating hormone (TSH) 24hour urine calcium
Monitor with DXA scan every 1-2 years while on tx Consider less frequent once stable1
Exception: ACP advocates for tx for 5 years without monitoring3
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2 3. Qaseem, Amir MD, PhD, MHA; et al. “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.” Ann Intern Med. 2017;166(11):818-839. DOI: 10.7326/M15-1361
Treatment OptionsLifestyle + OTCPharmaceutical
Calcium intakeSmoking cessationDecrease alcohol usePhysical activityHormone replacement therapy (HRT)
Dietary + supplemental calcium1,2
1,200mg QD for women ≥ 50 and men ≥ 71 1,000 mg QD for men 50–70Divide dose with ≤ 600mg per dose
15% reduction in fracture risk1,2
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2
Calcium carbonate Less expensive, fewer
tabletsTake with foodConstipation
Calcium citrateLower elemental calcium,
more tabletsFewer GI effects
Limit alcoholSmoking cessationWeight bearing exercises, balance, resistance trainingConsider PT
Fall precautions
Monitor anti-hypertensives, diureticsConsider imbalance,
neurological disorders, movement disordersVisual acuityAvoid CNS depressantsNocturia
Securing rugs Lighted walkwaysCaution with small pets Location of walker/caneAssistive devices on stairs,
bathroom
Anti-resorptive Bisphosphonates: Alendronate (Fosamax), Risedronate (Actonel),
Ibandronate (Boniva), Zoledronic acid (Reclast) Monoclonal antibody: Denosumab (Prolia) Calcitonin (Miacalcin)
Anabolic PTH Analogs: Teriparatide (Forteo) and Abaloparatide (Tymlos) Monoclonal antibody: Romosozumab (Evenity)
Hormonal tx HRT Selective Estrogen Receptor Modulators (SERM): Raloxifene (Evista)
Strongly recommend tx for diagnosed OP1,2
Alendronate (Fosamax) Risedronate (Actonel) Zoledronic acid (Reclast) Denosumab (Prolia)
Consider location of fx/low BMD Spine-specific: Ibandronate (Boniva), Raloxifene (Evista)
Approved agents for men Alendronate (Fosamax), Risedronate (Actonel), Zoledronic acid (Reclast),
Denosumab (Prolia), Teriparatide (Forteo)
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal-guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2
1 year: Risedronate (Actonel), Zoledronic acid (Reclast) Tx >5 years: increased risk of ONJ and atypical fxs
Romosozumab (Evenity)18 months: Teriparatide (Forteo), Abaloparatide (Tymlos)3 years: Denosumab (Prolia), other bisphosphonates
Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2
Bisphosphonates
Reduce fx risk by ~50% over 3 years Spine-specific: Ibandronate
(Boniva)
Oral preparations: gastric refluxContraindicated in eGFR <30ml/minBisphosphonate therapy >5 years
associated with increased risk of osteonecrosis of the jaw (ONJ) and atypical fxs
Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2
Monoclonal Ab Denosumab (Prolia)
Over 3 years, reduces2
Vertebral fractures by 68%Hip fractures by 40%Nonvertebral fractures by 20%
After 2 years off tx, BMD returned to baselineDrug holiday is not
recommended1
Less risk of ONJ and atypical fx vs bisphosphonates
1. Camacho, Pauline MD; et al. “The American Association of Clinical Endocrinologists and the American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis‐2016.” ENDOCRINE PRACTICE Vol 22 (Suppl 4) September 2016. https://www.aace.com/files/postmenopausal‐guidelines.pdf. 2. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198‐014‐2794‐2
Anabolic Agents: PTH Analogs Teriparatide (Forteo), Abaloparatide (Tymlos)
50-65% reduction in fx risk after 18 months of therapy
Osteosarcoma risk2 years of tx in a lifetime Do not have to be sequential
Follow up with antiresorptive after d/c anabolic agent Bone loss can be rapid after
discontinuation
Anabolic Agent: Monoclonal Ab Romosozumab (Evenity)
73% relative risk reduction at 1 year50% reduced fracture risk
vs alendronate at 1 year
Black Box WarningContraindicated if MI or
CVA within the last yearLimited to 1 year duration
of tx Efficacy, not safety
Calcitonin (Miacalcin)
30% reduction in vertebral fxoccurrence if prior vertebral fx1
No evidence of reduction of non-vertebral fracturesPossible link to malignancy2
1. Cosman, F., de Beur, S.J., LeBoff, M.S. et al. Osteoporos Int (2014) 25: 2359. https://doi.org/10.1007/s00198-014-2794-2 2. Wells, G; et al. “Does salmon calcitonin cause cancer? A review and meta-analysis .” Osteoporos Int. 2016; 27: 13–19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715844/
Hormonal
Spine-specificNo evidence of reduction in
non-vertebral fx
Prevention of OP 5 years of tx ~ 20-35%
reduction in fractures
Not recommended for osteoporosis tx: side effect profile vs efficacy
Qaseem, Amir MD, PhD, MHA; et al. “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.” Ann Intern Med. 2017;166(11):818-839. DOI: 10.7326/M15-1361
Osteoporosis in the WildCase 1
Case Study #1:
56-year-old Hispanic female with a 4-year hx of osteopenia Treatment-naiveHx of frequent steroid treatment for migraine breakthroughsHx of GERDCurrent DXA scan: T-score LS -1.9 (6% decline), FN -2.2 (4% decline) Calculated FRAX: 23%, 4%
Secondary work up is negative, vitamin D is optimal
Question 1What is the most appropriate treatment recommendation for a 56-year-
old female with a hx of GERD and frequent steroid treatment for migraine breakthroughs? T-score LS -1.9 (6% decline), FN -2.2 (4% decline) Calculated FRAX: 23%, 4%
A. Weight bearing exercises and OTC calcium supplementationB. Alendronate (Fosamax) or Risedronate (Actonel)C. Zoledronic acid (Reclast) or Denosumab (Prolia)D. Romosozumab (Evenity)E. Teriparatide (Forteo) or Abaloparatide (Tymlos)F. HRT or Raloxifene (Evista)
Question 1: Answer CWhat is the most appropriate treatment recommendation for a 56-year-old
female with a hx of GERD and frequent steroid treatment for migraine breakthroughs? T-score LS -1.9 (6% decline), FN -2.2 (4% decline) Calculated FRAX: 23%, 4%
C. Zoledronic acid (Reclast) or Denosumab (Prolia)
Rationale: Her current dx is osteoporosis, thus treatment with Alendronate (Fosamax), Risedronate (Actonel), Zoledronic acid (Reclast), or Denosumab (Prolia) recommended. Her hx of GERD precludes oral bisphosphonates. Anabolic agents are an option but not the most appropriate option for a treatment-naïve patient with moderate osteoporosis. HRT and Raloxifene (Evista) are not recommended due to efficacy versus the side effect profile.
Case Study #1:
Osteopenia + high FRAX scores = OsteoporosisDeclining T-scores
Hx of GERD precludes PO bisphosphonate therapyConsider Zoledronic acid (Reclast) which is IV or
Denosumab (Prolia) which is IM
Osteoporosis in the WildCase 2
Case Study #2:
62-year-old African American female with a 7-year hx of osteoporosisStarted Alendronate (Fosamax) 5 years ago and reports
adherence Current DXA scan: T-score LS -2.3 (stable), FN -2.6 (3% increase)
Question 2 If a 62-year-old African American female with a 7-year hx of
osteoporosis started Alendronate (Fosamax) 5 years ago had declining T-scores, which treatment option is most appropriate?
A. Drug holiday for 1 yearB. Continue Alendronate (Fosamax) C. Drug holiday utilizing Zoledronic acid (Reclast)D. Drug holiday utilizing Denosumab (Prolia) or anabolic agentE. Add an anabolic agent to the current regimen
Question 2: Answer D If a 62-year-old African American female with a 7-year hx of
osteoporosis started Alendronate (Fosamax) 5 years ago had decliningT-scores, which treatment option is most appropriate?
D. Drug holiday utilizing Denosumab (Prolia) or anabolic agent
Rationale: Due to the duration of therapy, a drug holiday off bisphosphonates is recommended due to the increased risk of ONJ and atypical fractures. Therefore continuing Alendronate (Fosamax) or transitioning to Zoledronic acid (Reclast) is not appropriate. Dual therapy is not currently recommended. With declining T-scores, using an alternative class of medication during the drug holiday should be considered.
Case Study #2:
Recommend drug holiday due to 5 sequential years on bisphosphonateMay resume bisphosphonate therapy after 1 year pending
stability of T-scoresWhat if: T-scores have been declining? Concomitant steroid tx? Severe osteoporosis?Consider alternative agent during drug holiday
Osteoporosis in the WildCase 3
Case Study #3:
64-year-old Caucasian female with a 3-year hx of osteoporosis dx after vertebral compression fractureHx of osteoarthritisStarted Zoledronic acid (Reclast) 3 years ago and tolerating wellCurrent DXA scan: T-score LS -2.1 (stable), FN -3.4 (8% decline)Secondary work up including serum calcium and iPTH is
negative, vitamin D is optimal
Question 3Which treatment option would bring the most benefit to a 64-year-old
female with osteoporosis and a hx of a vertebral compression fracture 3 years ago after which she started Zoledronic acid (Reclast)? T-score LS -2.1 (stable), FN -3.4 (8% decline)
A. Drug holiday for 1 yearB. Transition to Alendronate (Fosamax) or Risedronate (Actonel)C. Continue Zoledronic acid (Reclast)D. Add Denosumab (Prolia) to the current regimenE. Transition to an anabolic agent
Question 3: Answer EWhich treatment option would bring the most benefit to a 64-year-old
female with osteoporosis and a hx of a vertebral compression fracture 3 years ago after which she started Zoledronic acid (Reclast)? T-score LS -2.1 (stable), FN -3.4 (8% decline)
E. Transition to an anabolic agent
Rationale: Due to the current T-scores, treatment is indicated. Declining T-scores indicates treatment failure on bisphosphonate therapy, so changing to a new class of medication is recommended. Therefore, Alendronate (Fosamax) and Risedronate (Actonel) would be unlikely to change her response. Dual therapy is not currently recommended and adding a second agent while continuing Zoledronic acid (Reclast) increases the risk of side effects without known benefit. Transition to an alternative class of medication with an anabolic agent or Denosumab (Prolia) is most beneficial.
Case Study #3:
Osteoarthritis: reliable LS T-score?Declining FN T-scoreAdherence is guaranteed Tx failure on bisphosphonate
High risk: Significant osteoporosis in FNHx of vertebral compression fxDeclining T-scores despite txAlternative treatment is recommended
Case Study #3:
Consider Denosumab (Prolia) Anti-resorptive Significant reduction in fx risk after 3 years
Anabolic agents: Teriparatide (Forteo), Abaloparatide (Tymlos) Significant reduction in fx risk after 18 months of therapy Risk of osteosarcoma Follow up with antiresorptive after d/c
Anabolic agent: Romosozumab (Evenity) Significant reduction in fx risk over 1 year of therapy Black Box Warning: contraindicated in MI or CVA within the last year Limited to 1 year duration of tx
Osteoporosis in the WildCase 4
Case Study #4:
59-year-old Caucasian male with a 5-year hx of COPD and former smoker Frequently on inhaled and PO steroid tx for exacerbations, most
recently within the last yearPresents with a low impact LS compression fractureCompletes first DXA scan: T-score LS -2.1, FN -2.3Calculated FRAX: 26%, 3%
Question 4 Should a 59-year-old Caucasian male with a 5-year hx of COPD and
former smoker frequently on inhaled and PO steroid tx for exacerbations be screened for low BMD?
A. Yes, all men >50 years old should be screenedB. Yes, based on his age >50 and risk factors of history of smoking and steroid useC. No, he does not currently smoke or use steroid treatmentsD. No, he is <70 years old
Question 4: Answer B Should a 59-year-old Caucasian male with a 5-year hx of COPD and
former smoker frequently on inhaled and PO steroid tx for exacerbations be screened for low BMD?
B. Yes, based on his age >50 and risk factors of history of smoking and steroid use
Rationale: Based on NOF criteria, men >50 years old with risk factors including a smoking history and steroid treatment should be screened for low bone density. His cumulative smoking history and recent steroid use are major risk factors and neither need to be current in order to screen him. Screening all men >50 or deferring all screening until men are >70 is inconsistent with the current guidelines.
Case Study #4:
Osteopenia + fragility fx + high FRAX = osteoporosisSecondary work up shows low vitamin D, otherwise WNLWould you treat Ron? With which agent?Approved agents for men: Alendronate (Fosamax), Risedronate
(Actonel), Zoledronic acid (Reclast), Denosumab (Prolia), Teriparatide (Forteo)
Summary
The Bottom Line Screen All women ≥ 65 years old Consider women and men >50 years old
Diagnose FRAX Score Any fragility fracture = osteoporosis!
Treat Consider lifestyle factors, including fall risks Prevention of the first fracture is key Pharmaceutical tx for osteoporosis is recommended Consider duration of therapy for efficacy and safety
Duration of Tx: Risedronate (Actonel)
Zoledronic acid (Reclast)Romozosumab (Evenity)
1 year
Teriparatide (Forteo)Abaloparatide (Tymlos)
18 months
Denosumab (Prolia)Other Bisphosphonates
3 years
Efficacy
Duration of Tx: Safety
Teriparatide (Forteo)Abaloparatide (Tymlos)
2 Years
Bisphosphonates 5 sequential
years