1

Dr. Kerstin Gustafson, MDM, FRCSC, NCMP

Conquering Challenges in Osteoporosis Management & Treatment

3

Faculty/Presenter Disclosure

» Faculty: Dr. Kerstin Gustafson, MDM, FRCSC, NCMP

» Relationships with commercial interests:» Speaker fees:

– Amgen– Bayer– Merck– Novartis– Novo-Nordisk– Warner-Chilcott

» Advisory Boards– Lilly– Amgen– Novartis

4

Disclosure of Commercial Support

» This program has received financial support from Amgen Canada in the form of an educational grant

» This program has received in-kind support from Amgen Canada in the form of material production and logistical support

» Potential for conflict(s) of interest:– Dr. K. Gustafson has received an honoraria funding from Amgen AND/OR

Merck, Warner Chilcott, Eli Lilly, Novartis, whose product(s) are being discussed in this program]

– Amgen developed and distributes denosumab ® a product that will be discussed in this program: denosumab (Prolia)

5

Mitigating Potential Bias

» Bias has be mitigated by the following:– All program content was developed and peer-reviewed by an

independent physicians steering group– All clinical recommendations are based on clinical guidelines and

peer-reviewed evidence– The program has been to developed to improve PMO patient

outcomes by increased screening and appropriate monitoring of patients at risk for fracture based on national needs assessment criteria

– Industry has not been involved in the development of the program

6

Audience Question

» Do you feel confident assessing fracture risk in women with post-menopausal osteoporosis (PMO)?

A. Very confident

B. Confident

C. Somewhat Confident

D. Not Confident

7

Learning Objectives

Upon completion of this session, participants will be able to implement strategies and action steps to:

Effectively identify patients at high risk for fracture

Implement PMO management plans

Use evidenced based medicine to optimize treatment for patients with PMO

Overcome challenges in PMO management

8

Agenda

Burden of Osteoporosis 5 minutes

Identifying Patients at High Risk for Fracture 10 minutes

Optimizing Treatment for PMO Patients 20 minutes

Challenges in Managing Patients on Treatment 15 minutes

Clinical Pearls & Question & Answer 10 minutes

9

Audience Question

» Which of the following is most common in women over 50 years of age in Canada?

A. Heart Attack

B. Breast Cancer

C. Stroke

D. Osteoporotic Fracture

10

Burden of Osteoporosis

11

Prevalence of Fractures in Canada

» Fractures from osteoporosis in Canadian women are more common than heart attack, stroke and breast cancer combined1

An

nu

al in

cid

ence

of

co

mm

on

dis

ease

s

Osteoporoticfractures1,2

80,000

150,000

0

40,000

200,000

49,220

Heart Attack3

Stroke3 Breast Cancer4

22,700

41,500Other

38,900Vertebral

32,700Wrist

10,300 Pelvis

30,000Hip*

153,400

*Canadian hip fractures from (1); Non-hip fracture data extrapolated from (2).†Other represents non-osteoporotic fractures sites (humerus, clavicle, hands/fingers, patella, tibia, fibula).2

1. Leslie WD, et al. Osteoporos Int . 2010; 21:1317‐1322; 2. Burge J, et al. J Bone Miner Res. 2007;22:465-475; 3. Canadian Institute for Health Information (2009) Health Indicators. ; 4. Canadian Cancer Society. 2009.

29,874

12

Why is this Important to Family Physicians?

Source: IMSB, Compuscript (Aug’11)

• Based on Canadian prescriptions of osteoporosis therapies

Osteoporosis is managed primarily by Family Practice in Canada

13

A history of fracture is the strongest predictor of new fractures, yet post-fracture treatment rates remain low

Only 15% of Patients are Treated After an Osteoporotic Fracture

Per

cen

tag

e o

f p

atie

nts

(%

)

1. Bessette L, et al. Osteoporos Int. 2008;19:79-86. 2. Austin PC, et al. CMAJ. 2008;179:895-900.

15%

80%

0%

20%

40%

60%

80%

100%

How do we shift this

paradigm?

A fracture is to osteoporosis what a heart attack is to cardiovascular disease

Osteoporosis Treatment Post Fracture1

Beta Blockers Post Heart Attack2

14

What are the Consequences of Underdiagnosing and Undertreating Osteoporosis?

In women with hip fracture:

1. Hajcsar EE, et al. CMAJ 2000, 163:819-822.; 2. Cooper C. Am J Med. 1997:103:12S-19S; 3. Jean et al . JBMR 2013; 28:360-71. 4. Ioannidis G, et al. CMAJ 2009;181: 265-271. 5. Hopkins et al .Osteo Intl 2012; 23:921-927

Deterioratedquality of life

40% need assistance walking2

Fracture begets future fracture

40% had prior fracture1

Long-term care admission

18% enter LTC3

• Lifetime risk of hip fracture in women >50 is 12.1%5

Mortality

23% die within 1 year4

15

Identifying Patients at

High Risk for Fracture

16

Learning Objective

Effectively identify patients at high risk for fracture.

17

Audience Question

» Is a BMD T-score of -2.5 alone sufficient to diagnose osteoporosis?A. Yes

B. No

» Is a BMD T-score of -2.5 alone sufficient to treat osteoporosis?A. Yes

B. No

18

Understanding Fragility Fracture: Key to Appropriate Patient Management

Adapted from Siris ES, et al: JAMA 2001; 286:2815-22.

Fracture Rate

No of Fractures

BMD T-scores

>1.0

1.0 to 0.5

0.5 to 0.0

0.0 to –0.5

–0.5 to –1.0

–1.0 to –1.5

–1.5 to –2.0

–2.0 to –2.5

–2.5 to –3.0

–3.0 to –3.5

< –3.5

Fra

ctu

re r

ate

per

100

0 p

erso

n-y

ears

60

50

40

30

20

10

0

No

of

Fra

ctu

res

450

350

300

250

200

100

0

150

50

400

BMD distribution

BMD vs. Osteoporotic Fracture Rates/Number

60% of women with fragility fractures have non-osteoporotic bone mineral density

(T-score >-2.5)

60% of women with fragility fractures have non-osteoporotic bone mineral density

(T-score >-2.5)

19

When Screening Remember...It's Less than 2 minutes that Pay Off!

Question : “Since the last visit..."– " Have you broken any bones? "– " Have you fallen? "– " Have you had prolonged and unusual back pain? "– " Have you received oral or intravenous

steroids (cortisone) "Look

- Is there kyphosis? - Ability to perform the “Get up and Go” Test

Measure the patient’s height

EMR reminder tools may help to prompt screening4

1. Siminoski K et al. Osteoporos Int. 2006;17:290-6. 2. Papaioannou A, et al CMAJ 2010. 3. Timed Up-and-go test. Available at: http://www.saskatoonhealthregion.ca/pdf/03_Timed%20Up%20and%20Go%20procedure.pdf. 4. Loo TS et al. Arch Intern Med 171:1552-1558.

20

Aged ≥ 65 years Aged 50-64 years Aged <50 years

Everyone One or more risk factors forfracture:o Fragility fracture after age 40o Parental hip fractureo Vertebral fracture or osteopenia

identified on radiographyo Medication with high risk of bone loss

(i.e. steroids)o Smoking, alcohol (≥3/d)o Disorders associated with osteoporosis

(i.e. RA)o Low weight or major weight loss

2°causes of osteoporosis(i.e. malabsorption)

Prior fragility fracture

Medication with high risk of

bone loss

1. Papaioannou A, et al CMAJ 2010;182:1864-1873. 2. Steering Group Communications Feb 9 th 2012.

Screening for Osteoporosis: When to do a BMD1

Clinical Note:If you are ordering unrelated imaging (e.g. chest x-ray) for your

patient, consider adding “rule out vertebral fracture” on the order2.

21

There are Two Tools Available for Fracture Risk Assessment

1. OC Guidelines tool available at: http://www.osteoporosis.ca/multimedia/FractureRiskTool/index.html#/Home 2. FRAX® tool available at: http://www.shef.ac.uk/FRAX/tool.jsp 3. National Osteoporosis Foundation guidelines: www.nof.org/professionals/NOF_Clinicians_Guide.pdf

These tools incorporate other clinical risk factors for fracture in addition to BMD

22

Calculating 10-Year Absolute Fracture Risk for Postmenopausal Women: CAROC

1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873. 2. Leslie WD, et al. J Bone Miner Res. 2009;24:353-360.

Calibrated using Canadian fracture data and have been directly validated in Canadians2

*At least three months cumulative use during the preceding year at a prednisone-equivalent dose ≥ 7.5 mg daily

-4.0

-3.5

-1.5

-1.0

-0.5

0.0

Fe

mo

ral

Ne

ck

T-s

co

re

50 55 60 65 70 75 80 85

Age (years)

Low Risk < 10%

High Risk >20%

-3.0

-2.5

-2.0

Moderate Risk 10%–20%

10-year absolute fracture risk in treatment naïve women combining femoral neck T-score and age1

Lumbar spine or total hip T-score ≤ -2.5: consider the individual to be at least at moderate risk

Prolonged corticosteroid therapy*

Prior fragility fracture after age 40

Increases to the next risk category

Prior hip or vertebral fracture, or >1 non-vertebral fragility fracture

23

Understanding a Fragility Fracture is Critical

Definition of a fragility fracture*:

A fracture that occurs spontaneously or following a minor trauma such as:– Fall from a standing height (ie, on the ice)– Fall from a sitting position– Fall from a supine position

(bed or reclining deck chair < 1 meter high)– Fall after having missed 1 to 3 steps in a staircase– After a movement outside of the typical plane of motion

or coughing

1. Bessette L, et al. Contemp Clin Trials 2008; 29:194-210.2. Brown JP, et al. J Bone Miner Res 2007;23(suppl 1): M350.

* Fragility fracture includes all bones, except: skull and face, patella, hands and feet, cervical spine

24

Medications known to cause/accelerate bone loss

• Proton Pump Inhibitors (PPI)• Selective serotonin reuptake

inhibitors (SSRIs)• Aromatase inhibitors• Hormonal/endocrine

therapies - (GnRH, agonists, LHRH analogs)

Medications that increase fall risk and potential to fracture

» Benzodiazepines» Neuroleptics» Anticholinergics» Anticonvulsants» Antidepressants» Antihypertensives» Beta-blockers, nitrates,

vasodilators

* Note: not an exhaustive list

25

Optimizing Treatment for PMO Patients

26

Learning Objectives

Implement PMO management plans. Use evidenced based medicine to optimize treatment

for patients with PMO.

27

Treatment Guidelines: The Challenge of the Moderate Risk Patient

Low risk (<10%)

Moderate risk

High risk (>20%) Treat

Lifestyle Modification

Lifestyle

Treat

Papaioannou A, et al. CMAJ. 2010;182:1864-1873.

?

28

Top 5 Reasons to Consider Treatment in the Moderate Risk Patient:

1. Fracture: vertebral (on lateral spine X-ray) or wrist fracture (in patient >65 or BMD ≤ -2.5)

2. Lumbar spine T-score << femoral neck T-score

3. Concurrent high risk disorder or medications, including:• Hypogonadism or premature menopause (age <45 yr)• Primary hyperparathyroidism• Hyperthyroidism• Rheumatoid arthritis• Glucocorticoids (long-term or repeated use)• Aromatase inhibitor therapy

4. Falls (≥2 in the past year)

5. Patient preference to be treated

Steering Group Communications. Feb 9th, 2012.Based on Osteoporosis Canada Guidelines: Papaioannou A, et al. CMAJ. 2010;182:1864-1873.

29

Audience Question:

» Do your elderly patients perceive osteoporosis to be as severe as heart disease, breast or colon cancer?

» Is osteoporosis of major concern to them for their overall health?

30

Fracture Prevention: Importance to Your Patients

1. Barrett-Connor E et al. Osteoporos Int. 2008;19:607-613. 2. Melton LJ III et al. Osteoporos Int. 1999; 10:214-221. 3. Ioannidis G, et al. CMAJ. 2009;181:265-71. 4. Osteoporosis Long-term Care. http://osteoporosislongtermcare.ca/ Accessed Feb 2012. 5. Watts NB. Neurosurg Focus. 2001;10(4):E12. 6. Ioannidis G, et al. CMAJ. 2009;181:265-71. 7. Siris ES, et al. Mayo Clin Proc. 2006;81:1013-1022.

» Women with a wrist fracture have double the risk of any future osteoporotic fracture1

» Vertebral fracture predicts future hip fracture2

» A hip fracture increases the likelihood ofdeath by 3 fold3 and increases admissions to long term care4

» Vertebral fractures can cause severe, disabling back pain, dowager’s hump5, and increase the likelihood of death within 5 years (~4 times)6

» Therapy could reduce the risk of this happening7

31

Audience Question:

» When selecting a treatment option for your patient what is of most importance to you? – Safety?– Efficacy?– Adherence?

» What is of most importance to your patients?– Safety?– Efficacy?– Preference?– Cost/coverage ?

32

Evaluating Treatment Recommendations

Considerations:» Mechanism of action» Efficacy» Risk/benefit ratio – safety & tolerability » Generic vs. branded medication» Patient preference and adherence» Drug cost and coverage

1. Osteoporosis Canada 2008 National Report Card

Goal of Osteoporosis Treatment:

To reduce fractures through risk reduction, early diagnosis & appropriate treatment.1

33

Mechanism of Action of Available Osteoporosis Therapies

Osteoclast Osteoblast

MultinucleatedOsteoclast

OsteoclastPrecursors

RANKL

RANK

TeriparatidePTH analog

Estrogen therapy

Selective estrogenreceptor modulators

Hormones

Bisphosphonates Binds to bone;

inhibits osteoclasts

Denosumab RANK Ligand inhibitor

Adapted from: Boyle WJ et al. Nature 2003; 423:337-342.

34

Anti-fracture Efficacy of Current Therapies: Osteoporosis Canada Guidelines1

Therapeutic Options for Fracture Prevention in PMO Women1*†

Type of Fracture

Antiresorptive TherapyBone

Formation Therapy

BisphosphonatesDenosuma

bRaloxifene

Estrogen‡

(Hormone Therapy)

TeriparatideAlendronate Risedronate

Zoledronic Acid

Vertebral

Hip - -Non-vertebral∆ -

* Based on GRADE A evidence as assessed in the Osteoporosis Canada 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada† For postmenopausal women, indicates first line therapies and Grade A recommendation. ‡ Hormone therapy (estrogen) can be used as first-line therapy in women with menopausal symptoms. ∆ In Clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle.

1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.

35

BMD Efficacy of Long-term Treatment*

Medication Pivotal Study Extended

TreatmentDuration

(yrs)

# of Participants

% Change Lumbar

Spine BMD Ŧ

% Change Total Hip

BMDŦ

Risedronate1 VERT-MN 7 68 11.5 3.9

Alendronate¥2 FLEX 10 86 13.7 6.7

Zoledronic Acid3

HORIZON(interim analysis of 9 year study)

6 616 12.1 4.3

Denosumab4

FREEDOM(interim analysis of 10 year study)

8 2343 18.4 8.3

1. Mellstrom D et al. Calcif Tissue Int 2004;75:462–468 2. Bone HG et al. N Engl J Med 2004;350:1189-99. 3. Black DM, et al. J Bone Miner Res. 2012; 27(2):243-254. 4. Papapoulos, S. ASBMR 2013, Abstract LB-MO26

* Not head to head analyses: Results cannot be compared due to differing study populations and methodologies. Ŧ Represents % change from BL of Pivotal Trial. ¥Represents 10 mg dose only.

In long term trials, BMD continues to increase or remains stable

36

What is the safety of long-term treatment?

1. Sorensen OH, et al. Bone 2003;32:120-126. 2. Black D, et al. N Eng J Med. 2007; 356 : 1809-1822. 3. Black DM, et al. J Bone Miner Res. 2012; 27(2):243-254. 4. Black DM JAMA. 2006; 296: 2927-38. 5. Bone HG et al. N Engl J Med 2004;350:1189-99. 6. Papapoulos S et al. J Bone Miner Res. 2012;27:694-701. 7. Papapoulos, S. ASBMR 2013, Abstract LB-MO26

Risedronate (VERT MN ext)1 – 5 years

RIS(n = 135)

Placebo(n = 130)

Any serious AE 24.4% 30.0%

Zoledronic Acid (HORIZON ext)2,3 – 6 years

Placebo(Years 1-

3)(n =

3861)

Zoledronic Acid

(Years 1-3)(n = 3875)

Zoledronic Acid

(Years 3-6)(n =613)

Serious AEs 30.1% 29.2% 31.2%

Increase in serum creatine >0.5 mg/dL

0.4% 1.2%* 2.9%*

Atrial Fibrillation (Serious AE)

0.5% 1.3%* 2.0%

* p<0.05 compared to placebo

Alendronate (FLEX ext)4,5 – Years 8-10Incidence of AEs, %

Discontinuation

(n=83)

ALN (10 mg)(n=86)

Serious AEs 21.7 20.9

Denosumab (FREEDOM Ext)6,7 Exposure-adjusted subject incidences of AEs (Rates per 100 subject-years)

Placebo Denosumab

Years 1-3(n = 3883)

Years 1-3(n = 3879)

Years 4-8(n = 2343)

Serious AEs 10.4 10.6 10.7

Infections** 1.3 1.5 1.4

• ONJ and atypical femoral fractures have been reported• **Incidence of celllulitis/erysipelas similar in extension to that seen in placebo group of pivotal trial

37

Safety and Tolerability of Available Treatments

* Correct with adequate calcium & Vitamin D intake prior to initiating therapy. † Rarely, oral bisphosphonates have been associated with severe esophageal events. ‡ Uncommon; mostly with cancer patients and/or dental procedures. ¶ Consider risk/benefit balance for women with a history of stroke or risk factors for stroke or venous thromoboembolism.§Urinary calcium monitoring should be considered for patients with active urolithiasis and hypercalciuria. ** Recommended that all patients have their renal function assessed prior to treatment. Refer to respective Product Monographs for full Prescribing Information.

Bisphosphonates Denosumab Raloxifene Teriparatide

Hypocalcemia* Hypocalcemia* Vasodilation Transient orthostatic hypotension

GI symptoms† Infections (serious events 4.1% vs. 3.4% placebo)

Venous thromboembolism (↑ risk vs. placebo)

Osteosarcoma (only observed in animal trials, not clinical trials)

Postmarketing reports of musculoskeletal pain

Dermal events (10.8% vs. 8.2% placebo)

Lipid and triglyceride monitoring

Urolithiasis §

Osteonecrosis of jaw‡ Osteonecrosis of jaw‡ Stroke¶

Atypical Fracture (rare) Atypical Fracture (rare)

Renal impairment ** Suppression of bone turnover

Atrial fibrillation (2.5% vs. 1.9% placebo)

38

Is your patient afraid to take their medication?Help put patient concerns in perspective

Fatal motor vehicle accidents

8.4/100,000 person/year1

Murder 1.8/100,000 person/year2

ONJ* <1/100,000 pts/year3

Atypical fracture** 2/100,000 pts on 2 yrs BPs113.3/100,000 pts on 8 yrs BPs4

1. Transportation Canada. 2007 Casualty Rates. http://www.tc.gc.ca/eng/roadsafety/tp-tp3322-2007-1039.htm#t5. 2. Statistics Canada. 2009 Homicide Rate.http://www40.statcan.ca/l01/cst01/Legal12b-eng.htm. 3. Khan A, et al.J Rheumatol. 2011;38:1396-1402. 4. Dell R, et al. JBMR 2011. 27(12): 2544-2550. 5. Wang et al JBMR 2011; 26: 553-60.

6. Khosla S et al. JBMR 2007:22:1479-91. 7. Kim SY et al. JBMR . 26(5): 993–1001. 8. Amgen, data on file. 9. Shane E et al. JBMR 2010; 25:2267-2294.

For every 100 hip fractures prevented there is 1 atypical femur fracture5

**Reports of AFF have also been documented with other osteoporosis therapies7-8 and in patients who have never received BP therapy9

*The risk of ONJ is higher among cancer patients treated with high doses anti-resorptives6

39

How do I Approach Drug Holiday in Osteoporosis Management?

1. Watts NB & Diab DL. J Clin Endocrinol Met; 2010, 95 (4): 1555-1565 2. Papaioannou A, et al. CMAJ. 2010;182:1864-1873. 3. Black DM et al. NEJM 2012;366:2051-2053. 4. Cummings SR et al. JBMR 2013; 28: 439-441

RECOMMENDATIONS:

Patients at HIGH RISK for fracture should continue therapy2

After 3-5 years of therapy, re-assess your patient1,3-4:

Drug holiday: time off of bisphosphonate therapy, assuming reinitiation in future1.

BMD ≤ -2.5 or fracture or ongoing glucocorticoid therapy

Evaluate Continued Therapy

BMD >-2.5 and no fracture

Consider A Drug Holiday

40

Challenges in Managing Patients on Treatment

41

Learning Objective

Overcome challenges in PMO management.

42

Audience Question:

» If your currently treated patient is not responding to treatment (decrease in BMD) on an oral bisphosphonate, what would you recommend?

A. A different oral bisphosphonate (alendronate/risedronate)

B. A medication with a different mechanism of action (i.e. denosumab, raloxifene)

C. A medication with a different route of administration (i.e. denosumab, zoledronic acid)

D. Continue to monitor her (no change in therapy)

43

Ensure that a Loss in BMD is not due to Secondary Causes of Osteoporosis

What are the recommended Biochemical Tests?» Calcium, corrected for albumin » Complete blood count» Serum creatinine (eGFR) » Alkaline phosphatase» Thyroid stimulating hormone (TSH)» Serum protein electrophoresis for

patients with vertebral fractures» 25-hydroxy vitamin D (25-OH-D)*

* Should be measured after 3-4 months of adequate supplementation

and should not be repeated if an optimal level ≥75 nmol/L is achieved.

1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.

44

Is your patient failing on treatment?

Treatment failure can be considered after 1 year on therapy if1:- Patient has a decrease in BMD on treatment (4-5%)- Patient has 2 or more fragility fractures on treatment

» Are there any new risk multipliers in your patient’s profile that would increase bone loss?– Change in medications– Co-morbidities

» Consider that lack of adherence could also cause treatment failure

1. Diez-Perez A et al. Osteoporos Int 2012 23:2769-2774

45

Is your patient taking their oral BP properly?

Instructions for taking oral BPs:

In the morning, at least 1/2 hour before breakfast Should remain sitting upright for at least 1 hour Take only with water* Take alone, with no other medications Give only to residents who can swallow effectively Vitamin D and calcium supplements should be taken at a

different time

*Risedronate DR – needs to be taken with food

www.osteoporosislongtermcare.ca

46

Consider Drug Intolerance

» Generic agents may not be as well tolerated as the branded version1

» Risedronate DR – may ease administration burden, however, in the clinical trial the GI events were similar to those seen with Actonel weekly2

– Calcium supplements must be given separately 3

» For patients with osteoporosis using PPIs:– Ensure optimal calcium and vitamin D supplementation and instruct patient

to optimize food intake of calcium

– Prescribe the lowest effective PPI dose and review indication and alternatives periodically

– Consider alternate formulation of calcium (eg, calcium citrate) 1. Papaioannou A, et al. J Clin Densitometry 2008;11:458-459. Abstract 152. 2. McClung MR et al. Osteoporos Int 2012:; 23: 267-276 3. Actonel Product Monograph, Warner-Chilcoott.

47

Polypharmacy: An Adherence Issue in Osteoporosis Patients

» Patients on osteoporosis medication have a high likelihood of being on multiple medications for other chronic diseases– 40% of women on bisphosphonate therapy are

also on ≥4 other concomitant medications1

» Polypharmacy can decrease adherence rates – Women on several other medications were 21% more

likely to discontinue weekly BPs2

1. Gold DT, et al. Gend Med. 2008;5:374-84. 2. Lo JC, et al. Osteoporos Int. 2006;17:922-928.

BP = bisphosphonate

48Adapted from: 1. Kendler DL, et al. J Bone Miner Res. 2010;25:72-81. 2. McClung M, et al. Bone. 2007;41:122-128.

n = number of patients. NS = not statistically significant

Alendronate 70 mg QW (n = 241)

Denosumab 60 mg Q6M (n = 246)

Study Month

3.03%

1.85%

0

1

2

3

0 6 12

4

P<0.0001

†

Per

cen

t C

han

ge

in L

um

bar

Sp

ine

BM

D (

%)

Per

cen

tag

e C

han

ge

In L

um

bar

Sp

ine

BM

D (

%,)

Study Month

0 120

1

2

3

4

NS

0.81%

0.17%

After switching from alendronate, denosumab increases BMD1 and zoledronic acid maintains2 BMD at lumbar spine

» No increase in adverse events upon switching therapies1,2

Alendronate 70 mg QW (n = 112)

Zoledronic acid 5 mg QY (n = 113)

Would Switching Therapy Benefit Your Patient?

49

Patients were previously on alendronate but had stopped taking alendronate or had insufficient adherence.BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.*Data are least-squares means and 95% confidence intervals.†p < 0.0001 denosumab vs risedronate.

1. Roux C, et al. Bone 2014; 58: 48-54.

Greater increases in BMD at 12 months in patients who transitioned to denosumab vs. patients who transitioned to risedronate1

Would Switching Therapy Benefit Your Patient?

50

When Selecting a Therapy Consider That Adherence is Different Between Treatments

For each treatment group, time points with > 95% cumulated subjects were excluded

Freemantle N, et al. Osteoporos Int 2012;23(1):317-26.

Pro

po

rtio

n o

f S

ub

ject

s A

dh

erin

g

Year 1 Year 2

Alendronate (N = 115)Denosumab (N = 106)

Study Week

124 111 107 97 95126 124 124 118 118

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

ALNDMAb

Alendronate (N = 124)Denosumab (N = 126)

115 93 87 82 77106 106 106 104 104

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

ALNDMAb

Study Week

Treatment cross-over

Open-label, randomized, cross-over study of denosumab subcutaneous 60 mg Q6M and oral alendronate 70 mg QW

51

Patient Support Programs can Improve Adherence

1. For My Bones Program. Available at: https://www.formybones.ca/help_en.do. Accessed October 2010 report 2. Patient Direct, ProVital ™ Program. Available at: http://www.provital.ca. Accessed Nov 30, 2011. 3. Patient Direct, ProVital ™ Program, as at Nov 30, 2011 report. 4. Osteoporosis Canada. Available at: http://www.osteoporosis.ca. Accessed November 2010. 5. Health and Bone. Available at: http://www.healthandbone.ca/en/home. Accessed November 2010. 6. Drug Coverage.ca Available at: http://www.drugcoverage.ca Accessed October 2010.

Consider patient support programs offering services such as nurse support, reimbursement information, dose reminders, and education1,2

Adherence in these programs has been shown to be as high as 94%3

Reputable websites on osteoporosis and therapies may also provide patients with valuable information

• Osteoporosis Canada4:• Patient and physician resources• Links to scientific references

• HealthandBone.ca5:• Educational website for patients

• Drugcoverage.ca6:• Search tool• Overview of private insurance plans and government drug benefit programs

52

Clinical Pearls

53

Clinical Pearls for Patient Assessment:

1.Have they fallen?

2.Has their BMD decreased (>3%) since their last BMD?

3.Have they lost height? (> 2cm height since last visit or >6 cm historically)

4.Have they broken any bones?

5.Are there any other risk factor multipliers to consider? – If yes: they are at increased fracture risk and should

be further assessed, possibly by a lateral x-ray

54

Clinical Pearls for Who to Treat

» Treat all patients at HIGH RISK for fracture: –Prior hip or vertebral fracture–Multiple fractures–10 yr absolute fracture risk >20%

» Patient at MODERATE RISK for fracture:– Consider additional risk factors– Discuss fracture risk and treatment options with

patient

55

Clinical Pearls for Patient Management

1. Individuals at HIGH RISK for fracture should continue osteoporosis therapy without a drug holiday1

2. Discuss benefit vs. risk of therapy with patients

3. When monitoring patients on therapy, consider:• Long-term efficacy• Safety & tolerability• Adherence• Patient preference

1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.

56

Final Clinical Pearl

• The goal of PMO treatment and management is preventing a fracture.

Healthy bones are strong bones!

57

Question and Answer Session