ASAPA Fall 2019 DON'T Break A Leg: Clinical Decision-Making in Osteoporosis · 2019. 10....

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

ashlyns9@endoassocaz.net

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

Questions?ashlyns9@endoassocaz.net