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Planning Committee

Cheryl Lambing, MD, Co-Chair


UCLA / Ventura County Medical Center

Marjorie Luckey, MD, Co-Chair


Saint Barnabas Medical Center

Steven T. Harris, MD
University of California, San Francisco

Pamela Kushner, MD
University of California, Irvine

Diane L. Schneider, MD, MSc


University 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 patients 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.

Fracture Facts!
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 consequences 2
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
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 treatment 2

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
54; 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. Clinicians 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.

Relative Risk
of Hip Fracture

Strong Relationship Between


Bone Density and Bone Strength
30
20
10
0
-5

-4

-3

-2

-1

T-score

Bone density accounts for 60% to 80%


of bone strength in untreated patients1
Best early predictor of fracture risk2
Permits diagnosis before fractures
1.
2.

Kushida K. Clin Calcium. 2004;14:11-17.


Fogelman J, Blake GM. J Nucl Med. 2000;41:2015-2025.

Age Is a Major Risk Factor


for Fracture
10-Year Probability of
Symptomatic Fracture (%)

AGE
80
70
Age 70
T-score -2.5
24% Fx Risk

60
50

-3

-2

-1

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

2010 Guidelines for Bone Density Testing


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
o

COPD, RA, hyperparathyroidism, celiac disease, IBD


Oral glucocorticoids, anticonvulsants, proton pump
inhibitors, SSRIs, aromatase inhibitors

1. Adapted from National Osteoporosis Foundation. Clinicians 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.

Majority of Fractures Occur in Patients


With Osteopenia, Not Osteoporosis!
Why?
Osteopenia patients outnumber those with osteoporosis 3:1
Fracture riskdetermined 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.

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

T-scores between
-1.0 and -2.5 and

10-year risk of fractures:


3% for hip fracture
or
20% for a major osteoporotic fracture

National Osteoporosis Foundation. Clinicians 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.

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
Prior fracture
Denotes 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
1.
2.

1. National Osteoporosis Foundation. FRAX Implementation Guide. Available at: http://www.iscd.org/wpcontent/uploads/2012/10/FRAXImplementationGuide_000.pdf . Accessed September 13, 2013.
2. Kanis J, et al. Osteoporosis Int. 2005;16:581-589.

FRAX Caveats:
Entering Bone Density Data
Use Femoral Neck Bone
Mineral Density (BMD) only
Select DXA manufacturer and enter BMD (g/cm 2)

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
National Osteoporosis Foundation. Clinicians 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.

When Clinical Judgment


Is Needed

FRAX may underestimate fracture risk:


Some risk factors (glucocorticoids, smoking, alcohol,
fractures) are dose dependent, but FRAX cant 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. Clinicians 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. Clinicians 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
Estimated
Requirement (mg/day)

Recommended Dietary
Allowance (mg/day)

Infants 0 to 6 months

1,000

Infants 6 to 12 months

1,500

13 years old

500

700

2,500

48 years old

800

1,000

2,500

913 years old

1,100

1,300

3,000

1418 years old

1,100

1,300

3,000

1930 years old

800

1,000

2,500

3150 years old

800

1,000

2,500

5170 year-old male

800

1,000

2,000

5170 year-old female

1,000

1,200

2,000

>70 years old

1,000

1,200

2,000

Life Stage Group

Upper Level Intake


(mg/day)

* 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.
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.

Vitamin D Intake Recommendations


From the IOM
Estimated Avg
Requirement
(IU/day)

Recommended
Dietary Allowance
(IU/day)

Upper Level Intake


(IU/day)

Infants 0 to 6 months

1.000

Infants 6 to 12 months

1,500

13 years old

400

600

2,500

48 years old

400

600

3,000

913 years old

400

600

4,000

1418 years old

400

600

4,000

1930 years old

400

600

4,000

3150 years old

400

600

4,000

5170-year-old male

400

600

4,000

5170-year-old female

400

600

4,000

>70 years old

400

600

4,000

Life Stage Group

* 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.
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.

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 fracturesincreased risk of future fractures 1

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.

Pharmacologic
Options

FDA-Approved Therapeutic Options


Prevention

Treatment

Estrogen

Calcitonin

Alendronate
Risedronate
Ibandronate
Zoledronic acid
Raloxifene
PTH (teriparatide)
Denosumab

Antiresorptive and Anabolic


Therapies
Antiresorptive
Decrease bone resorption
Most treatment agents
Examples: Bisphosphonates, SERMs, calcitonin,
estrogen, denosumab

Anabolic
Stimulate bone formation
Example: teriparatide

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 Womens 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 Womens Health Initiative Investigators. JAMA. 2002;288:321-333.

The Concept of a SERM


Selective 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 preexisting 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.

Bisphosphonates
Alendronate, 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 treatmentand every other
year for prevention
National Osteoporosis Foundation. Clinicians 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.

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 glucocorticoidinduced osteoporosis


Risedronate, zoledronic acid, alendronate

Treatment of men with low bone density


Alendronate, risedronate, zoledronic acid

Bisphosphonates: Effects
Alendronate, Risedronate, Ibandronate and 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
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

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

Bisphosphonates: Side Effects


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

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 Patients


Taking Anti-Resorptive Agents Long Term
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

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.

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;368:756-765
Prolia (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 anabolicstimulates bone


formation rather than inhibiting bone resorption
20 g 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 Doesnt 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 BMD 1

Fracture protection can be observed in the absence


of a significant change in BMD2

Fracture protection persists even when the BMD reaches


a plateau

1.
2.

BMD stability does not mean nonresponse

Harrington JT, et al. Calcif Tissue Int. 2004;74:129-135.


Wasnich RD, Miller PD. J Clin Endocrinol Metab. 2000;85:231-236.

Treatment: Summary
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 Considerations
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

Sharon
Updated Medical History
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?

DXA at age 58
62

Evaluation of the Patient


With Osteoporosis
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
o
o
o
o

Chemistry (Ca, P, Alk Phos, Cr, LFTs)


CBC
24-hour urine calcium
25 OH vitamin D
TSH if taking thyroid hormone or symptoms

Sensitivity: 92%
Tannenbaum C, et al. J Clin Endocrinol Metab. 2002;87:4431-4437.

Sharon
Sharons laboratory tests are normal
She considers her individualized risk,
and chooses an antiresorptive agent
Sharon does fairly well with her onceagent for the first 3 months

weekly

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

Percent Adherent on Weekly


Bisphosphonate

Most Patients Discontinue Oral


Bisphosphonates
Soon After Treatment Initiation
100

Rapid drop in persistence


due to nonacceptance

80
Further decrease in persistence due to
multiplicity of factors

60
40
20
0
0

6
9
12
Months Following Therapy Initiation

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
In Canadian study of postmenopausal osteoporotic
patients said their doctors
Did not always give them adequate information
about their medications
Did not communicate this information in a format
that was easy to comprehend
Lack of communication with the HCP was perceived
to be a major factor affecting adherence

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

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
IMPROVED
OUTCOMES
Practice
Organization

Around osteo
management

Quality
Measures

Health IT

Pt reminders
Pt support, tx

Patient
Experience

Optimizing FX Support
prevention
Adherence

Family Medicine

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