1. Conquering Challenges in Osteoporosis
Management & Treatment
Dr Larry Dian
Division Of Geriatric
Medicine, U.B.C.
1

2. Faculty/Presenter Disclosure
» Faculty: DR Larry Dian
» Relationships with commercial interests:
– Grants/Research Support: Amgen, Lilly
– Speakers Bureau/Honoraria: Novartis, Pfizer, Merck, Warner
Chilcott
– Consulting Fees: Merck.
3

3. 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 Larry Dian has received an honoraria funding from Amgen 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)
4

4. 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
5

5. 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
6

6. 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
7

7. 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
8

8. 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
9

9. Burden of Osteoporosis
10

10. Prevalence of Fractures in Canada
» Fractures from osteoporosis in Canadian women are more
common than heart attack, stroke and breast cancer combined1
Annual incidence of
common diseases
200,000
153,400
150,000
80,000
40,000
41,500
Other
38,900
Vertebral
32,700
Wrist
49,220
29,874
30,000
Hip*
0
22,700
10,300
Pelvis
Osteoporotic Heart
fractures1,2 Attack3
Stroke3
Breast
Cancer4
*Canadian
†Other
hip fractures from (1); Non-hip fracture data extrapolated from (2).
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.
11

11. Why is this Important to Family Physicians?
Osteoporosis is managed primarily
by Family Practice in Canada
• Based on Canadian prescriptions of osteoporosis therapies
Source: IMSB, Compuscript (Aug’11)
12

12. Only 15% of Patients are Treated After an
Osteoporotic Fracture
Percentage of patients (%)
A fracture is to osteoporosis what a
heart attack is to cardiovascular disease
100%
How do we
shift this
paradigm?
80%
60%
80%
40%
20%
15%
0%
Osteoporosis Treatment
Post Fracture1
Beta Blockers
Post Heart Attack2
A history of fracture is the strongest predictor of new fractures,
yet post-fracture treatment rates remain low
1. Bessette L, et al. Osteoporos Int. 2008;19:79-86.
2. Austin PC, et al. CMAJ. 2008;179:895-900.
13

13. What are the Consequences of Underdiagnosing
and Undertreating Osteoporosis?
In women with hip fracture:
Fracture begets
future fracture
Deteriorated
quality of life
40% had
40% need
prior fracture1 assistance walking2
Long-term care
admission
18% enter
LTC3
Mortality
23% die
within 1 year4
• Lifetime risk of hip fracture in women >50 is 12.1%5
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 2012 On-line September 2012.
4. Ioannidis G, et al. CMAJ 2009;181: 265-271. 5. Hopkins et al – Osteo Intl 2012; 23:921-927
14

14. Identifying Patients at
High Risk for Fracture
15

15. Learning Objective
 Effectively identify patients at high risk for
fracture.
16

16. Audience Question
» Is a BMD T-score of -2.5 sufficient to diagnose osteoporosis?
A. Yes
B. No
C. Maybe
17

17. Understanding Fragility Fracture: Key to
Appropriate Patient Management
BMD vs. Osteoporotic Fracture Rates/Number
Fracture Rate
Fracture rate per 1000 person-years
400
No of Fractures
50
450
350
300
40
30
60% of women with fragility fractures have
non-osteoporotic bone mineral density
(T-score >-2.5)
250
200
150
20
No of Fractures
BMD distribution
60
100
10
50
0
>1.0
0.5 to 0.0
1.0 to 0.5
–0.5 to –1.0
0.0 to –0.5
–1.5 to –2.0
–1.0 to –1.5
–2.5 to –3.0
–2.0 to –2.5
< –3.5
0
–3.0 to –3.5
BMD T-scores
Adapted from Siris ES, et al: JAMA 2001; 286:2815-22.
18

18. When Screening Remember...
What is the Call to Action?
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
19

19. Screening for osteoporosis: When to do a BMD1
Aged ≥ 65 years
Everyone
Aged 50-64 years
Aged <50 years
One or more risk factors for 2°causes of osteoporosis
(i.e. malabsorption)
fracture:
o
o
o
o
o
o
Fragility fracture after 40
Parental hip fx
Medication with high risk of
bone loss (i.e. steroids)
Smoking, alcohol (≥3/d)
Disorders associated with
osteoporosis (i.e. RA)
Low weight or major weight
loss
Prior fragility fracture
Medication with high risk of
bone loss
Clinical Note:
If you are ordering unrelated imaging (e.g. chest x-ray) for your
patient, consider adding “rule out vertebral fracture” on the order.
1. Papaioannou A, et al CMAJ 2010.
20

20. There are Two Tools Available for Fracture Risk
Assessment
These tools incorporate other risk factors for fracture
in addition to BMD
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
21

21. Calculating 10-Year Absolute Fracture Risk for
Postmenopausal Women: CAROC
10-year absolute fracture risk in treatment naïve
women combining femoral neck T-score and age1
Increases to the
next risk category
0.0
Prior fragility fracture
after age 40
Prolonged
corticosteroid therapy*
Femoral Neck T-score
-0.5
-1.0
Low Risk
-1.5
< 10%
-2.0
-2.5
Moderate Risk
-3.0
10%–20%
-3.5
Prior hip or vertebral
fracture, or >1 nonvertebral fragility fracture
High Risk
>20%
-4.0
50
55
60
65
70
75
80
85
Age (years)
Lumbar spine or total hip T-score ≤ -2.5:
consider the individual to be at least at moderate risk
Calibrated using Canadian fracture data and have been directly validated in Canadians 2
*At least three months cumulative use during the preceding year at a prednisone-equivalent dose ≥ 7.5 mg daily
1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873. 2. Leslie WD, et al. J Bone Miner Res. 2009;24:353-360.
22

22. Medications known to cause/accelerate bone loss
•
•
•
•
Anticonvulsants
Antipsychotic drugs
Aromatase inhibitors
Chemotherapeutic/transplant
drugs
• Furosemide
• Hormonal/endocrine therapies (GnRH, agonists, LHRH analogs)
• Proton Pump Inhibitors (PPI)
• Selective serotonin reuptake
inhibitors (SSRIs)
Conditions and medications that increase the
risk of falling, potentially fracturing
Benzodiazepines, narcotics, neuroleptics, any
anticholinergic
Cognitive impairment, confusion, sedation,
drowsiness
Anticonvulsants, antidepressants,
antihypertensives, benzodiazepines, narcotics
Dizziness, orthostatic hypotension
Antidepressants, metoclopramide, neuroleptics
Gait abnormalities,
Beta-blockers, nitrates, vasodilators
Syncope
Neuroleptics, anticholinergics
Visual Disturbances (blurring)
23

23. Optimizing Treatment for
PMO Patients
24

24. Learning Objectives
 Implement PMO management plans.
 Use evidenced based medicine to optimize treatment
for patients with PMO.
25

25. Treatment Guidelines: The Challenge of the
Moderate Risk Patient
Low risk (<10%)
Moderate risk
High risk (>20%)
Papaioannou A, et al. CMAJ. 2010;182:1864-1873.
Lifestyle
Modification
?
Lifestyle
Treat
Treat
26

26. 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 (by >2 T-scores)
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.
27

27. How to Communicate the Importance of Fracture
Prevention to Your Patients
» Moderate risk patients have a 10-20% chance of
having a fracture within the next 10 years1
» Vertebral fractures can cause severe, disabling
back pain, dowager’s hump2, and increase the
likelihood of death within 5 years (~4 times)3
1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873. 2. Watts NB. Neurosurg Focus. 2001;10(4):E12. 3. Ioannidis G, et al. CMAJ. 2009;181:265-71
28

28. How to Communicate the Importance of Fracture
Prevention to Your Patients
» 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 of
death by 3 fold3 and increases admissions to long
term care4
» Therapy could reduce the risk of this happening5
Explain to your What is the moderate risk of fracture could mean6
patients what a Call to Action?
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. Siris ES, et al. Mayo Clin Proc. 2006;81:1013-1022. 6. Steering Group
Communications. Feb 9th, 2012.
29

29. Audience Question:
» When presenting treatment options to patients what is the most
important thing to consider and discuss?:
A.
B.
C.
D.
E.
Reducing fracture risk
Maintaining or increasing BMD
Safety profile and side-effects
Adherence to medication & patient preference
All of the above
30

30. Evaluating Treatment Recommendations
Goal of Osteoporosis Treatment:
To reduce fractures through risk reduction, early diagnosis &
appropriate treatment.1
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
31

31. Mechanism of Action of Available Osteoporosis
Therapies
Osteoclast
Precursors
Estrogen therapy
Selective estrogen
receptor modulators
Hormones
RANKL
RANK
Multinucleated
Osteoclast
Bisphosphonates
Binds to bone;
inhibits osteoclasts
Teriparatide
Denosumab
PTH analog
RANK Ligand inhibitor
Osteoblast
Adapted from: Boyle WJ et al. Nature 2003; 423:337-342.
Osteoclast
32

32. Anti-fracture Efficacy of Current Therapies
Therapeutic Options for Fracture Prevention in PMO Women1*†
Bone
Formation
Therapy
Antiresorptive Therapy
Type of
Fracture
Bisphosphonates
Alendronate
Risedronate
Zoledronic
Acid
Denosumab
Raloxifene
Estrogen *
(Hormone
Therapy)
Vertebral







Hip




-

-
Nonvertebral†




-


Teriparatide
* 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.
33

33. BMD Efficacy of Long-term Treatment*
In long term trials, BMD continues to increase or remains stable
Pivotal Study
Extended
Treatment
Duration
(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)
6
2343
15.2
7.5
Medication
* 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.
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. Brown JP, et al. 2011 ACR Annual Meeting. Presentation L8
34

34. What is the safety of long-term treatment?
Placebo
(Years 13)
(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%
Zoledronic Acid
(HORIZON ext)2,3
– 6 years
Risedronate
(VERT MN ext)1
–
5 years
RIS
(n = 135)
Placebo
(n = 130)
Any serious AE
24.4%
30.0%
Alendronate (FLEX ext)4,5 – Years 8-10
Incidence of AEs, %
Denosumab (FREEDOM Ext)6 Exposure-adjusted subject
incidences of AEs (Rates per 100 subject-years)
Discontinuatio
n
(n=83)
21.7
20.9
Placebo
ALN (10 mg)
(n=86)
Serious Aes
Denosumab
Years 1-3
(n = 3883)
Serious AEs
Infections**
Years 1-3
(n = 3879)
Years 4-6
(n = 2343)
10.4
10.6
10.6
1.3
1.5
1.3
• ONJ and atypical femoral fractures have been reported
• **Incidence of celllulitis/erysipelas similar in extension to that seen in placebo group of pivotal
trial
* p<0.05 compared to placebo
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.
35

35. Safety and Tolerability of Available Treatments
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)
* 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
36
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.

36. Preference and Adherence
» Decision to treat should be based on patient benefit/risk profile
» However, also consider:
–
–
–
–
patient preference
commitment to therapy
fit of therapy with lifestyle
other medical considerations
1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.
37

37. Challenges in Managing
Patients on Treatment
38

38. Learning Objective
 Overcome challenges in PMO management.
39

39. Audience Question:
» If your currently treated patient is not responding to treatment
(decrease in BMD) on an oral bisphosphonate, what would you
recommend?
A. Offer her a different oral bisphosphonate
(alendronate/risedronate)
B. Offer her a medication with a different mechanism of action (i.e.
denosumab, raloxifene)
C. Offer her a medication with a different route of administration
(i.e. denosumab, zoledronic acid)
D. Keep her on her current therapy and continue to monitor her
E. Let her stop therapy
40

40. 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.
41

41. 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
42

42. 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
43

43. Consider Drug Tolerance
» Generic agents may not be as well tolerated as the branded
version1
» Risedronate DR – may ease administration burden, however, in
clinical trial the GI events were similar to those seen with
Actonel weekly2
– Calcium supplements must be given separately 3
» GI intolerant patients who are taking a PPI may have decreased
efficacy of the BP and fracture risk4
1. Papaioannou A, et al. J Clin Densitometry 2008;11:458-459. Abstract 152. 2. McClung MR et al. Osteoporos Int as DOI 10.1007/s00198-0111791-y 3. Actonel Product Monograph, Warner-Chilcoott. 4.Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of
osteoporosis-related fractures. CMAJ 2008;179:319-26.
44

44. 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
ONJ*
1.8/100,000 person/year2
<1/100,000 pts/year3
Atypical fracture**
2/100,000 pts on 2 yrs BPs
113.3/100,000 pts on 8 yrs BPs4
For every 100 hip fractures prevented there is
1 atypical femur fracture5
*The risk of ONJ is higher among cancer patients treated with high doses anti-resorptives6
**Reports of AFF have also been documented with other osteoporosis therapies7-8 and in
patients who have never received BP therapy9
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-
45

45. 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
BP = bisphosphonate
1. Gold DT, et al. Gend Med. 2008;5:374-84. 2. Lo JC, et al. Osteoporos Int. 2006;17:922-928.
46

46. Would Switching Therapy Benefit Your Patient?
After switching from alendronate, denosumab increases BMD1 and
zoledronic acid maintains2 BMD at lumbar spine
Percent Change
in Lumbar Spine BMD (%)
Zoledronic acid 5 mg QY (n = 113)
Alendronate 70 mg QW (n = 241)
Alendronate 70 mg QW (n = 112)
3.03%
3
†
2
1.85%
1
P<0.0001
0
0
6
Study Month
12
Percentage Change
In Lumbar Spine BMD (%,)
Denosumab 60 mg Q6M (n = 246)
4
4
3
2
1
0.81%
NS
0.17%
0
0
12
Study Month
n = number of patients. NS = not statistically significant
» No increase in adverse events upon switching therapies1,2
Adapted from: 1. Kendler DL, et al. J Bone Miner Res. 2010;25:72-81. 2. McClung M, et al. Bone. 2007;41:122-128.
47

47. Would Switching Therapy Benefit Your Patient?
Greater increases in BMD at 12 months in patients who transitioned to
denosumab vs. patients who transitioned to risedronate1
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. Adapted from: Roux C, et al. Presented at: The American Society for Bone and Mineral Research Annual Scientific Meeting; October 12-15, 2012;
Minneapolis, MN.
48

48. When Selecting a Therapy Consider That
Adherence is Different Between Treatments
2 year, open-label, cross-over study of 250
postmenopausal women
• 92% Adherence to Denosumab
after 12 month Alendronate
Percent of Subjects
Adherent after 2 years
100
80
Denosumab (N = 106)
92.5%
60
Alendronate (N = 115)
63.5%
40
20
0
Adherence
Freemantle N, et al. Osteoporos Int. 2012; 23: 317-326
49

49. Patient Support Programs can Improve
Adherence
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
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. 50
Available at: http://www.healthandbone.ca/en/home. Accessed November 2010. 6. Drug Coverage.ca Available at: http://www.drugcoverage.ca Accessed October 2010.

50. How do I Approach Drug Holiday in Osteoporosis
Management?
Drug holiday: time off of bisphosphonate therapy,
assuming reinitiation in future. 1
RECOMMENDATIONS:
Patients at HIGH RISK for fracture should continue therapy2
After 3-5 years of therapy, re-assess your patient1,3-4:
BMD ≤ -2.5
or fracture
or ongoing glucocorticoid therapy
Evaluate Continued Therapy
BMD >-2.5 and no fracture
Consider A Drug Holiday
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 DOI 10.1002/jbmr.1854.
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51. Clinical Pearls
52

52. 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
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53. 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
» Patient at MODERATE RISK for fracture:
– Consider additional risk factors
– Discuss fracture risk and treatment options with
patient
54

54. Clinical Pearls for Patient Management
1.Have they broken any bones since their last visit?
2.Has their BMD decreased > 3% since their last
BMD?
3.Are they not taking their medication properly?
4.Is their BMD stable?
5.Are there new risk factors since their last visit?
–If yes – they may still be at increased risk for
fracture
–Add other multipliers
55

55. Clinical Pearls for Patient Management
1. Individuals at HIGH RISK for fracture should
continue osteoporosis therapy1
2. When monitoring patients on therapy, consider:
• Efficacy
• Tolerability/Side Effects
• Adherence
• Preference
1. Papaioannou A, et al. CMAJ. 2010;182:1864-1873.
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56. Final Clinical Pearl
• The goal of PMO treatment and management is
preventing a fracture.
Healthy bones are strong bones!
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57. Question and Answer
Session
58