Planning Committee Cheryl Lambing, MD, Co-Chair UCLA / Ventura County Medical Center Marjorie...

Planning Committee

• Cheryl Lambing, MD, Co-ChairUCLA / Ventura County Medical Center

• Marjorie Luckey, MD, Co-ChairSaint Barnabas Medical Center

• Steven T. Harris, MDUniversity of California, San Francisco

• Pamela Kushner, MDUniversity of California, Irvine

• Diane L. Schneider, MD, MScUniversity of California, San Diego

Learning Objectives

• Identify patients at high risk for osteoporotic fracture

• Individualize risk assessment including use of the WHO FRAX® tool

• Discuss general measures to optimize calcium, vitamin D, and exercise

• Evaluate the different pharmacologic therapies to match the patient’s clinical situation

• Utilize different modalities to improve adherence and compliance with treatment plan

Osteoporosis

• Systemic skeletal disorder of compromised bone strength increased risk of fracture– 34 million Americans: low bone mass– 10 million Americans: osteoporosis

• 1 in 2 women and 1 in 4 men >age 50 will have an osteoporosis-related fracture in their lifetime

• By 2020, 1 in 2 Americans >age 50 will be at risk for fractures from osteoporosis or low bone mass

US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004. Available at: http://www.surgeongeneral.gov/library/reports/bonehealth/full_report.pdf. Accessed September 13, 2013.

• 2 million bone breaks a year (“2 million 2 many”)1

• Only 2 in 10 patients with osteoporosis get a follow-up test or treatment for osteoporosis1

• Fractures may have serious consequences2

–Hip fracture

• 10%-20% additional mortality per year

• 20% of hip fracture patients require long-term nursing home care

• Only 40% fully regain their pre-fracture level of independence1

Fracture Facts!

1. National Bone Health Alliance. 2 Million 2 Many. Available at: http://www.2million2many.org/. Accessed September 13, 2013. 2. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004. Available at: http://www.surgeongeneral.gov/library/reports/bonehealth/full_report.pdf. Accessed September 13, 2013.

Underdiagnosed and Undertreated

• Underdiagnosed: National Osteoporosis Risk Assessment (NORA) study (200,160 postmenopausal women)1 – 40% osteopenic– 7% osteoporotic– 11% ≥1 fracture after age 45 years

• Undertreated: women meeting criteria for treatment2

– 15.7% not taking calcium– 18.6% not taking vitamin D– 52.7% not exercising >2 hrs per week– 35.3% not receiving therapy

1. Siris ES, et al. JAMA. 2001;286:2815-2822. 2. Schnatz PF, et al. Menopause. 2011;18:1072-1078.

The Clinical Challenge

• Often asymptomatic1

– Until fracture occurs1

– Even after some fractures (eg, 2/3 of vertebral fractures are asymptomatic)2

• The challenge to clinicians1:

– Identify patients at high risk for fracture

– Prevent first fracture

1. South-Paul JE. Am Fam Physician. 2001;63:1121-1128. 2. Lenchnik L, et al. AJR. 2004;183:949-958.

Sharon

• 62-year-old White female• 5′4″; 150 lbs

• 10 years postmenopause

• DXA performed 4 years ago– Spine T-score: -2.1– Right hip T-score (of neck): -1.6

Personal History - Sharon

• Her mother suffered hip fracture in her 70s

• Performs weight-bearing exercise 3 times per week

• Nonsmoker

• Rarely drinks alcohol

• Takes 1 calcium supplement each day – unknown dose

• Consumes no dairy products and no vitamin D

Sharon

Worried because of family history —

What is the next step?

Optimizing Fracture Prevention in Primary Care

• Identifying patients at high risk

• Individualized risk assessment

• Management strategies

– Nonpharmacologic modalities

– Pharmacologic therapy

– Modalities to improve adherence and compliance

The Good News

• Excellent diagnostic tools– Bone densitometry with DXA –

noninvasive test

– FRAX® – new tool to help with management decisions in patients with reduced bone mineral density

• Effective and safe treatments

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide. Accessed September 13, 2013.

Strong Relationship BetweenBone Density and Bone Strength

• Bone density accounts for 60% to 80% of bone strength in untreated patients1

• Best early predictor of fracture risk2

• Permits diagnosis before fractures

T-score

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20

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1. Kushida K. Clin Calcium. 2004;14:11-17. 2. Fogelman J, Blake GM. J Nucl Med. 2000;41:2015-2025.

10-Y

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Age Is a Major Risk Factorfor Fracture

With kind permission from Springer Science+Business Media: Kanis JA ,et al. Ten year probabilities of osteoporoticfractures according to BMD and diagnostic thresholds. Osteoporos Int.2001;12:989-995. Adapted from Fig. 3. © 2001 International Osteoporosis Foundation and National Osteoporosis Foundation.

80

70

60

50

AGE

Age 70T-score -2.524% Fx Risk

-3 -2 -1

2010 Guidelines for Bone Density Testing

1. Adapted from National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide. Accessed September 13, 2013.

2. US Preventive Services Task Force. Ann Intern Med. 2002;137:526-528.

• Screening– All women age 65 and older1,2

– All men age 70 and older1

• Test postmenopausal women and men >50 if1:– Fracture after age 50– Clinical risk factors for osteoporosis– Conditions/medications associated with bone loss

o COPD, RA, hyperparathyroidism, celiac disease, IBDo Oral glucocorticoids, anticonvulsants, proton pump

inhibitors, SSRIs, aromatase inhibitors

Majority of Fractures Occur in Patients With Osteopenia, Not Osteoporosis!

Why?

• Osteopenia patients outnumber those with osteoporosis 3:1

• Fracture risk—determined by more than just BMD

• Clinical factors such as age, lifestyle, and family and personal medical history also play a role

Implications

• Appropriate treatment depends on being able to accurately determine the risk of future fractures

Davey DA. S Afr Med J. 2012;102:285-288.

10-year risk of fractures:

≥3% for hip fracture or

≥20% for a major osteoporotic fracture

T-scores between -1.0 and -2.5 and

NOF Guidelines 2010:Whom to Treat

After exclusion of secondary causes, treat postmenopausal women and men

age 50 and older who have…

Osteoporosis

Clinical diagnosis:Hip or spine fracture

DXA diagnosis: T-score -2.5 or below

in the spine or hip


FRAX®

• Statistically robust fracture risk prediction tool developed by the WHO for world-wide use

• Combines BMD + clinical risk factors to predict fracture risk better than either alone

• Predicts the 10-year probability of major osteoporotic fracture

– Hip, spine, wrist, or humerus

• Use when the decision to treat is uncertain

WHO FRAX® Tool. http://www.shef.ac.uk/FRAX/. Accessed September 13, 2013.

Answering Risk Factor Questions in FRAX®

1. 1. National Osteoporosis Foundation. FRAX® Implementation Guide. Available at: http://www.iscd.org/wp-content/uploads/2012/10/FRAXImplementationGuide_000.pdf . Accessed September 13, 2013.

2. 2. Kanis J, et al. Osteoporosis Int. 2005;16:581-589.

Prior fractureDenotes a previous adult fracture after age 40 occurring with little or no trauma – fractures of face, fingers, toes excluded1

Systemic corticosteroids

Best applies to current or long-term past use of oral steroids (≥5 mg/day prednisone equivalent for ≥3 months)1,2

Select DXA manufacturer and enter BMD (g/cm2)

Use Femoral Neck Bone Mineral Density (BMD) only

FRAX® Caveats:Entering Bone Density Data

NOF Guidelines:≥20% major fx

≥3% hip fx

Benefits of FRAX®

• Treatment decisions in osteopenic patients clearer

– Decision is based on the risk of fracture, not T-score alone

• Identifies patients at high-risk for fractures to ensure that they are offered treatment to lower their risk

• Helps avoid giving medication to those who are at low risk and have little to gain from treatment


“Specific treatment decisions must be individualized”

When Clinical JudgmentIs Needed

FRAX® may underestimate fracture risk:• Some risk factors (glucocorticoids, smoking, alcohol,

fractures) are dose dependent, but FRAX® can’t consider dose

• Some risk factors that increase the risk of fractures independently of their effect on BMD are not included in FRAX®: – Falls

– Frailty

– Some diseases and medications (immobilization, diabetes, anticonvulsants, SSRIs, PPIs, TZDs)

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide . Accessed September 13, 2013; Gnudi S, et al. J Bone Miner Res. 2001;16:1130-1135; Nguyen TV, et al. J Bone Miner Res. 2005;20:1195-1201; Sornay-Rendu E, et al. J Bone Miner Res. 2005;20:1929-1935.

Be on the Lookout for Silent Fractures

• 65-year-old, T-score -1.6

• Height measurement: 2.5″ loss from her young adult height; lateral spine x-ray ordered

Vertebral Fractures: • 2/3 unrecognized by patients/clinicians

• Indicate very high risk for future spine and hip fractures

• Are a major indication for pharmacotherapy

• Consider Vertebral Fracture Assessment (VFA) if vertebral fracture is suspected clinically

Xu WW, et al. Bone. 2011;2:307-311. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide . Accessed September 13, 2013.

Identifying High-risk Patients in Clinical Practice – Summary

• Primary goal: fracture prevention-therefore, select patients based on risk of fracture

• Pharmacologic Therapy– Patients with osteoporosis by DXA OR

– With a history of hip or spine fractures

• FRAX® – Quantitative risk assessment

– Helps communicate risk to patients– May increase treatment of high-risk patients and decrease

treatment of low-risk patients

Osteoporosis Management

• Nonpharmacologic

• Pharmacologic

Challenges With Current Treatment Approaches

• Bone loss per se asymptomatic

• Patients may not appreciate fracture prevention

• No treatment agent meets the ideal profile—inexpensive, easy to take, uniformly effective, entirely free of risk

• Perceived risk of therapy may outweigh perceived benefit

• Patient motivation to “adhere” and “persist” with therapy may vary

Calcium Intake Recommendations From the IOM

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D: Report Brief. Washington, DC: IOM ; 2010. Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed September 13, 2013.

Life Stage GroupEstimated

Requirement (mg/day)Recommended Dietary

Allowance (mg/day)Upper Level Intake

(mg/day)

Infants 0 to 6 months * * 1,000


1–3 years old 500 700 2,500

4–8 years old 800 1,000 2,500

9–13 years old 1,100 1,300 3,000

14–18 years old 1,100 1,300 3,000

19–30 years old 800 1,000 2,500

31–50 years old 800 1,000 2,500

51–70 year-old male 800 1,000 2,000

51–70 year-old female 1,000 1,200 2,000

>70 years old 1,000 1,200 2,000

* For infants, adequate intake is 200 mg/day for 0 to 6 months of age and 260 mg/day for 6 to 12 months of age.

Vitamin D Intake Recommendations From the IOM

Life Stage Group

Estimated AvgRequirement

(IU/day)

RecommendedDietary Allowance

(IU/day)

Upper Level Intake (IU/day)

Infants 0 to 6 months * * 1.000


1–3 years old 400 600 2,500

4–8 years old 400 600 3,000

9–13 years old 400 600 4,000

14–18 years old 400 600 4,000

19–30 years old 400 600 4,000

31–50 years old 400 600 4,000

51–70-year-old male 400 600 4,000

51–70-year-old female 400 600 4,000

>70 years old 400 600 4,000

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D: Report Brief. Washington, DC: IOM; 2010. Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed September 13, 2013.

* For infants, adequate intake is 400 IU/day for 0 to 6 months of age and 400 IU/day for 6 to 12 months of age.

Benefits of Exercise

What type?– Weight-bearing– Muscle-strengthening

Expected benefits?– Small (1% to 2%) effect on adult BMD– Reduces the loss of muscle mass– May reduce risk of falls by improving strength and balance – Regular walking decreases risk of hip fractures

Centers for Disease Control and Prevention. Injury Center. www.cdc.gov/injury.

Exercise – Some Caveats

– Patients may have nonskeletal factors that increase the risk of falls and fractures

• Visual contrast sensitivity and depth perception1

• Women with wrist fractures—increased risk of future fractures1

– Forward flexion of spine and lifting can be problematic2,3

• Low BMD in spine• History of vertebral fractures

1. Edwards BJ, et al. Age Ageing. 2006;35:438-441. 2. Sinaki M. Pain Pract. 2013;13(1):68-75. 3. Myers ER, Wilson SE. Spine. 1997;22(24 Suppl):25S-31S.

PharmacologicOptions

Prevention Treatment

FDA-Approved Therapeutic Options

Estrogen

AlendronateRisedronateIbandronate

Zoledronic acidRaloxifene

Calcitonin

PTH (teriparatide)Denosumab

• Antiresorptive

• Decrease bone resorption

• Most treatment agents

• Examples: Bisphosphonates, SERMs, calcitonin, estrogen, denosumab

• Anabolic

• Stimulate bone formation

• Example: teriparatide

Antiresorptive and Anabolic Therapies

Estrogen Treatment (ET)

• Several approved oral and transdermal preparations

• Treats symptoms of estrogen deficiency

• Skeletal effects:– Decrease in biochemical markers of 50% to 60%

– 2-year BMD increase of 4% to 6% at hip and spine

– Decreased incidence of vertebral and hip fractures (34%) after 5 years in the Women’s Health Initiative (WHI)

– Effects in women with osteoporosis have not been evaluated in randomized controlled trials

• Concern about adverse effects

• Long-term use not recommended

Rossouw JE, et al. Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288:321-333.

The Concept of a SERMSelective Estrogen Receptor Modulator

(EAAs: Estrogen Agonist/Antagonists)

• Binds to the estrogen receptors

• Produces an estrogen agonist effect in some tissues

• Produces an estrogen antagonist effect in others

Raloxifene

• Raloxifene (60 mg daily)

• Skeletal effects:– Decrease in biochemical markers of 30%

– 3-year BMD increases of 2% to 3% at hip and spine

– Decreased incidence of vertebral fractures (30% to 50%) in women with pre-existing vertebral fractures or low bone density. No effect on nonvertebral or hip fractures has been observed

• Extra-skeletal effects: reduction in invasive breast cancer

Ettinger B, et al. JAMA. 1999;282:637-645.

Raloxifene

• Adverse effects

– Hot flashes

– 2- to 3-fold increased risk of venous thromboembolic events

– No increased risk of stroke, but Black Box Warning for increased risk of death following stroke

– Leg cramps

Sontag A, Wan X, Krege JH. Curr Med Res Opin. 2010;26:71-76.

Calcitonin

• Calcitonin (200 units daily by nasal spray)

• Skeletal effects:– Decrease in biochemical markers of 20%

– Small effect (1% to 2%) on bone density in spine

– Reduced incidence of vertebral fractures (36%) in women with pre-existing vertebral fractures

– No effect on nonvertebral or hip fractures has been observed

• Adverse effects– Nasal stuffiness

– Possible increased cancer risk

Chesnut CH 3d, et al. Am J Med. 2000;109:267-276. http://effectivehealthcare.ahrq.gov/slides/?pageaction=displaySlides&tk=49&dpg=9&scroll=314. Accessed: September 13, 2013. European Medicines Agency. Press release. July 20, 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2012/07/WC500130122.pdf. Accessed: September 13, 2013.

BisphosphonatesAlendronate, Risedronate, Ibandronate, and Zoledronic Acid

• Alendronate: 10 mg daily (tablet) or 70 mg weekly (tablet or liquid) for treatment, 5 mg daily or 35 mg weekly for prevention

• Risedronate: 5 mg daily or 35 mg weekly (tablet); 150 mg monthly (tablet)

• Ibandronate: 150 mg monthly by tablet; 3 mg intravenously over 15 to 30 seconds every 3 months

• Zoledronic acid: 5 mg by intravenous infusion over a minimum of 15 minutes once every year for treatment—and every other year for prevention

*2012 Jun 25;172(12):930-6


Bisphosphonates: Indications

• Treatment and prevention of postmenopausal osteoporosis

– Alendronate, risedronate, ibandronate, zoledronic acid

• Prevention and/or treatment of glucocorticoid-induced osteoporosis

– Risedronate, zoledronic acid, alendronate

• Treatment of men with low bone density

– Alendronate, risedronate, zoledronic acid

• Increased bone density in the spine by 5% to 8% and at the hip by 3% to 6% after 3 years

• Reduced incidence of vertebral fractures by 40% to 70%

• Alendronate, risedronate and zoledronic acid reduced non-vertebral fractures (25% to 40%), including hip fractures (40% to 60%), in women with osteoporosis

• Ibandronate: Overall, no effect observed on non-vertebral or hip fractures. In a post-hoc analysis, non-vertebral fracture reduction was seen in a high-risk subgroup with a baseline femoral neck T-score less than -3.0

Bisphosphonates: Effects Alendronate, Risedronate, Ibandronate and Zoledronic Acid

Contraindications/Warnings/Precautions– Hypocalcemia

– Creatinine clearance <30 cc/min (<35 cc/min for zoledronic acid)

– For oral dosing: Esophageal stricture or impaired esophageal motility (alendronate);

inability to stand or sit for at least 30 minutes (alendronate/risedronate) or 60

minutes (ibandronate)

Notes: UGI symptoms per se are not a contraindication to oral dosing.Use in pregnancy: Class C

Oral dosing requirements– Tablets (with exception of delayed release risedronate) taken on an empty stomach

after overnight fast with 6 to 8 oz of plain water while in an upright position

– Patients should not eat or lie down for at least 30 minutes (alendronate

and risedronate) or 60 minutes (ibandronate)

– Calcium and vitamin D supplements, if needed, should be taken at a different time

of day than the oral bisphosphonate

Bisphosphonates

National Osteoporosis Foundation. Med Lett. 2011;53(1360):24.

• “Class warning” regarding UGI symptoms (no increase in UGI complaints in randomized controlled trials)

• Influenza-like symptoms may occur after first monthly oral dose of IV bisphosphonate

• “Class warning” regarding infrequent bone, joint, and/or muscle pain

• “Class warning” regarding jaw osteonecrosis

• “Class warning” about atypical fractures following long-term therapy

Bisphosphonates: Side Effects

“Osteonecrosis” of the Jaw (ONJ)

• An area of exposed alveolar or palatal bone that typically shows poor healing over several months

– 95% of cases have been reported with high-dose, chronic IV bisphosphonate treatment of myeloma and cancer metastatic to bone1

– Can occur with denosumab2

– Pain in 2/3 cases: infection may or may not be present

– Known risk factors: invasive dental procedures, oral trauma, periodontitis, poor oral hygiene, radiotherapy to the jaw, chemotherapy, corticosteroids, infection

– Pathogenesis is not known3

1. Woo SB, et al. Ann Intern Med. 2006;144:753-761. 2. Sutton EE, Riche DM. Ann Pharmacother. 2012;46:1000-1009.3. Khosla S, et al. J Bone Miner Res. 2007;22:1479-1491.

Atypical Fractures of Femur in PatientsTaking Anti-Resorptive Agents Long Term

Park-Wyllie LY, et al. JAMA. 2011;305:783-789. Shane E, et al. J Bone Miner Res. 2013 May 28. [Epub ahead of print]. Watts NB, Diab DL. J Clin Endocrinol Metab. 2010;95:1555-1565. Meier RP. Arch Intern Med. 2012;172:930-936.

• May begin with stress reaction or stress fracture of lateral femoral cortex (A)

• Transverse fractures of femoral diaphysis or in subtrochanteric region (B)

• Often bilateral

• Prodromal pain in thigh or groin in 70%

• Occurs in untreated patients, but increased incidence with long-term antiresorptive therapy, particularly bisphosphonates and denosumab

FDA Safety Update

• Be aware of the possibility of atypical fractures in patients taking bisphosphonates

• Evaluate any patient who presents with new groin or thigh pain to rule out fracture of the femoral shaft

• Discontinue potent antiresorptive medication in patients with atypical fractures

• Periodic reevaluation of need to continue bisphosphonate therapy, particularly in patients treated > 5 years

FDA. MedWatch Online Voluntary Reporting Form. https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm. Accessed: September 13, 2013. Whitaker M, et al. N Engl J Med. 2012;366(22):2048-2051.

Bisphosphonate Therapy: “Long-Term” Treatment

• Stopping treatment in high-risk patients

– After 5 years of alendronate-decline in BMD, rise in biochemical markers, no increased fracture risk except clinical vertebral fractures1

– After 3 years of risedronate, spine BMD rose, vertebral facture risk was still reduced compared with control patients2

– After 3 years of zoledronic acid, slight increase in morphometric fractures vs clinical vertebral fractures3

• Long-term treatment has not clearly been associated with safety issues or loss of efficacy

• Cessation of treatment after 2 to 5 years is associated with some persisting effect on biochemical markers, as well as BMD; this has been best characterized for alendronate and zoledronic acid

1. Black DM, et al. JAMA. 2006;296:2927-2938. 2. Watts NB, et al. Osteoporosis Int. 2008;19:365-372. 3. Black DM, et al. J Bone Miner Res. 2012;27:243-254.

Bisphosphonate Holidays

• In patients at high risk for fractures, continued treatment seems reasonable. Consider a drug holiday of 1 to 2 years after 10 years of treatment

• For lower risk patients, consider a “drug holiday” after 4 to 5 years of stability

• Follow BMD and bone turnover markers during a drug holiday period, and reinitiate therapy if bone density declines or markers increase

Watts NB et al; AACE Osteoporosis Task Force. Endocr Pract. 2010;16(Suppl 3):1-37. Whitaker M, et al. N Engl J Med. 2012;366(22):2048-2051.

Denosumab• Monoclonal antibody to RANKL

• 60 mg subcutaneous injection every 6 months

• 9% increase in spinal BMD after 3 years in the pivotal FREEDOM trial; 4% to 5% increase in hip BMD

• Reduction in fracture risk after 3 years:– 68% decrease in new vertebral fractures

– 40% decrease in hip fractures

– 20% decrease in nonvertebral fractures

• 8-year data: continued increase BMD, reduced bone turnover, good safety

Cummings SR, et al. N Engl J Med. 2009;368:756-765Prolia (prescribing information). Thousand Oaks, CA: Amgen; June 2012. McClung MR, et al. Osteoporos Int. 2013;24(1):227-235.

Denosumab Adverse Events

Adverse events that occurred more commonly in denosumab group (as listed in the PI):

– Serious infections leading to hospitalization

– Dermatitis, eczema, rashes

– Back pain, pain in the extremity, musculoskeletal pain, hypercholesterolemia, cystitis

– Pancreatitis

– Osteonecrosis of the jaw

– Significant suppression of bone remodeling

Prolia (prescribing information). Thousand Oaks, CA: Amgen; June 2012.

Teriparatide: rhPTH [1-34]

• The only treatment agent that is anabolic—stimulates bone formation rather than inhibiting bone resorption

• 20 μg daily (subcutaneously) for no more than 2 years

• Indication: treatment of men and postmenopausal women with osteoporosis who are at high risk for fracture

• Effects:– Increased bone density in spine by 9% and hip by

3% vs placebo over 18 months– Reduced incidence of vertebral fractures (65%) and

nonvertebral fragility fractures (53%) in women with pre-existing vertebral fractures

– Studies too small to evaluate effect on hip fractures

• Adverse reactions: arthralgia, pain, nausea; warning about osteosarcoma risk in rats

Neer RM, et al. N Engl J Med. 2001;344:1434-1441. Forteo (prescribing information). Indianapolis, IN: Eli Lilly and Company; March 21, 2012.

BMD Doesn’t Fully Predict the Reduction in Fracture Risk

• Antiresorptive treatment decreases fracture risk more rapidly and to a larger extent than one would predict from the relatively small changes in BMD1

– Fracture protection can be observed in the absence of a significant change in BMD2

• Fracture protection persists even when the BMD reaches a plateau

– BMD stability does not mean “nonresponse”

1. Harrington JT, et al. Calcif Tissue Int. 2004;74:129-135. 2. Wasnich RD, Miller PD. J Clin Endocrinol Metab. 2000;85:231-236.

Safe and effective therapies are available

Antiresorptive agents• Prevent bone loss and preserve architecture• Improve quality of bone• Reduce the risk of vertebral fractures (all agents)• Alendronate, risedronate, zoledronic acid, and denosumab

proved to reduce the risk of nonvertebral and hip fractures

Anabolic agent: rhPTH [1-34] (teriparatide) • Increases bone density and size• Improves quality of bone• Reduces the risk of vertebral and nonvertebral fractures;

no hip fracture data

Patient factors determine the most appropriate drug to use

Treatment: Summary

The right medication for the right patient at the right time

• Susceptibility to side effects

– Past history of DVT – no estrogen or raloxifene

– Esophageal stricture – use of IV bisphosphonates or denosumab

• Dosing/convenience

• Adherence

Treatment Considerations

• This winter, Sharon slipped on wet leaves and fell on the grass, fracturing her wrist

• How does the current fracture impact on clinical decision-making?

• Should Sharon have an updated DXA?

• Should any laboratory tests be requested?

Sharon – Updated Medical History

62

DXA at age 58

Evaluation of the Patient With Osteoporosis

Tannenbaum C, et al. J Clin Endocrinol Metab. 2002;87:4431-4437.

• 37% to 63% of patients with osteoporosis and/or fractures have been found to have previously unrecognized underlying disorders affecting bone (eg, vitamin D deficiency, hypercalciuria, calcium malabsorption, hyperthyroidism, multiple myeloma, etc)

• All patients need evaluation prior to initiation of pharmacologic therapy:– Careful history and examination– Lab testing

o Chemistry (Ca, P, Alk Phos, Cr, LFT’s)o CBC o 24-hour urine calciumo 25 OH vitamin Do TSH if taking thyroid hormone or symptoms

Sensitivity: 92%

Sharon

• Sharon’s laboratory tests are normal

• She considers her individualized risk, and chooses an antiresorptive agent

• Sharon does fairly well with her once- weekly agent for the first 3 months

• She fails to refill her prescription for several weeks

• Over the next several months, she often misses her weekly dose

Adherence to Treatment in Osteoporosis Patients

Most Patients Discontinue Oral Bisphosphonates

Soon After Treatment Initiation

Months Following Therapy Initiation

100

80

60

40

20

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Rapid drop in persistencedue to nonacceptance

Further decrease in persistence due to multiplicity of factors

With permission from Springer Science+Business Media: Weycker D, et al. Compliance with drug therapy for

postmenopausal osteoporosis, Osteoporos Int, 2006;17:1645-1652. Figure 1. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006.

Adherence With Osteoporosis Therapies

• Clinical trials– Good adherence (usually >80%)– Significant reduction in risk of vertebral,

nonvertebral, and hip fractures1

• Real-world adherence is poor– Up to 83% of patients nonadherent with prescribed

osteoporosis Rx2-4

– Poor correlation was reported between patient and physician perceptions of compliance

• Consequences of poor adherence– Magnitude of risk reduction for hip and vertebral

fractures lower than expected4,5

1. Siris ES, et al. Am J Med. 2009;122(2 suppl):S3-S13. 2. Hamilton B, et al. Osteoporos Int. 2003;14:259-262.3. Yood RA, et al. Osteoporos Int. 2003;14:965-968. 4. Caro JJ, et al. Osteoporos Int. 2004;15:1003-1008. 5. Eastell R, et al. Calcif Tissue Int. 2003;72:408. Abstract P-297.

Why Do Patients Resist Change?

Historically, several notions have been proposed as to why patients struggle with adherence to treatment plans:

– Denial or lack of insight

– Lack of knowledge

– Lack of skills

– Lack of caring

Butterworth SW. J Manag Care Pharm. 2008;14(6 Suppl S-b):S21-S25.

Improving Adherence

• Assess patient beliefs/understanding

• Understand current medication use patterns

• Identify patients likely to be nonadherent

Impact of Lack of Patient Education

• Did not always give them adequate information about their medications

• Did not communicate this information in a format that was easy to comprehend

Lau E, et al. Can Fam Physician. 2008;54:394-402.

In Canadian study of postmenopausal osteoporotic patients said their doctors

Lack of communication with the HCP was perceived to be a major factor affecting adherence

Side Effects and Adherence

• Discuss side effects of the medicines

• Put into perspective of risk vs benefits

• Reiterate patient's high risk of fracture

• Address other information sources (media, Internet, friends)

– May deter from starting– Encourage to stop use

Motivational Interviewing

• Open-ended

• Express empathy

• Roll with resistance

• Support autonomy

• Explore ambivalence

• Create an action plan

Butterworth SW. J Manag Care Pharm. 2008;14(6 suppl S6):S21-24.Solomon DH, et al. Osteoporos Int. 2010;21:137-144.

Patient-Centered Medical Home (PCMH): Osteoporosis Management

PracticeOrganization • Around osteo

management

IMPROVEDOUTCOMES

Quality Measures• Optimizing FX

prevention

Health IT• Pt reminders• Pt support, tx

Family Medicine

Patient Experience• Support • Adherence

Summary of Optimal Osteoporosis Management

• Utilize tools to identify high-risk patients

• Target any patient with a fracture for evaluation

• Ensure adequate calcium and vitamin D

• Promote physical activity

• Discuss medicine options with high-risk patients

• Remove barriers to adherence

Introduction to

Osteoporosis PI

Activity

Questions

Planning Committee Cheryl Lambing, MD, Co-Chair UCLA / Ventura County Medical Center Marjorie...

Documents

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