1. Review: Osteoporosis Dr Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD
Pharmacist, Bruyere Academic FHT
Assistant Professor, Dept Family Medicine, UOttawa
July, 2015

2. Objectives 8.3 Osteoporosis
Define osteoporosis and list risk factors for osteoporotic fracture
Screen for osteoporosis or reduced bone density appropriately according to age, sex and risk factors.
Manage osteoporosis and osteopenia effectively and according to guidelines including lifestyle advice (including exercise and diet), and medications where appropriate.

3. Resources 2010 Osteoporosis Clinical Guidelines - Osteoporosis Canada
2013 Appraisal of the 2010 Clinical Practice Guideline for the Diagnosis and Management of Osteoporosis in Canada;
Canadian Task Force on Preventive Health Care (CTFPHC)
2014 Clinician’s guide to prevention and treatment of osteoporosis;
National Osteoporosis Foundation Issue, Version 1;

4. Osteoporosis
Goals of Therapy
Prevention
Detection
Treatment

5. Osteoporosis The most common bone disease in humans Characterized by:
Low bone mass
Deterioration of bone tissue
Disruption of bone architecture
Compromised bone strength
Increase fracture risk

6. Osteoporosis WHO diagnostic classification:
BMD T score < 2.5 at the hip or lumbar spine
(T-score = standard deviations below the mean BMD of a young-adult reference population)
(Z-score = standard deviations below the mean BMD of an age-, sex- and ethnicity-matched reference population)
The risk of fractures is highest in those with the lowest BMD; BUT:
…the majority of fractures occur in patients with “low bone mass” rather than “osteoporosis”, due to the large number of patients in this range
Lifetime osteoporosis-related fracture risk:
Caucasian women: 1 in 2
N.B. Among women the annual incidence of osteoporotic fracture is more than twice that of heart attack, stroke and breast cancer combined
Men: 1 in 5
Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville
(MD): Office of the Surgeon General (US); Available from:

7. Osteoporosis Burden of disease
Fragility fractures are responsible for excess mortality, morbidity, chronic pain, admission to institutions and economic costs.
Causes 80% of all fractures in menopausal women >50 y.o.
Increased morbidity & mortality post-fracture
Hip fractures: 8.4% to 36% excess mortality within 1 year
Hip fractures: 2.5x increased risk of future fractures
Vertebral fractures: 5x increase in 2nd vertebral fracture
Vertebral fractures: 2x-3x increase in fracture at other sites
N.B. Osteoporosis is less frequent in African Americans, but those with osteoporosis have the same elevated fracture risk as Caucasians

8. Osteoporosis Burden of disease
Post-fracture mortality and institutionalization rates:
Higher for men than women.
~ 20% of hip fracture patients require long-term nursing home care
Only 40% fully regain their pre-fracture level of independence
Majority of vertebral fractures are initially clinically silent
Often associated with symptoms of pain, disability, deformity and mortality.
Postural changes associated with kyphosis may limit activity, result in restrictive lung disease and lumbar fractures may alter abdominal anatomy, leading to constipation, abdominal pain, distention, reduced appetite and premature satiety

9. Osteoporosis Pathophysiology

10. Osteoporosis Pathophysiology
Bones are not static! They are dynamic – always remodeling
Bone remodeling by osteoblasts and osteoclasts
(Blasts build; Clasts chew)
Bone loss occurs when bone removal > bone growth
Menopause
Remodeling accelerates, enhancing the effect of bone loss
Advancing age
Sex steroid deficiency
Glucocorticoid use
Effect:
disordered skeletal architecture
increased fracture risk

11. Osteoporosis Risk of Fracture

12. Osteoporosis Risk of Fracture

13. Skeletal Fragility
2014 Clinician’s guide to prevention and treatment of osteoporosis; National Osteoporosis Foundation Issue, Version 1; Release Date: April 1,

14. Skeletal Fragility
(for all)
(steroid use + immobility + dz effects)

15. Skeletal Fragility (↓Ca2+) (↓Ca2+)
(via changes in bone metabolism and/or falls risk)
(↓Ca2+)
(↓Ca2+)

16. Osteoporosis Risk of Fracture

17. Osteoporosis Risk of Fracture

18. Falls Risk
2014 Clinician’s guide to prevention and treatment of osteoporosis; National Osteoporosis Foundation Issue, Version 1; Release Date: April 1,

19. Osteoporosis Evaluation / Detection
Who should I assess for osteoporosis and fracture risk?
Patients > 50y.o.
Assess risk factors for osteoporosis and fracture to identify those at high risk.
(see previous slides on skeletal fragility and falls risk)
Patients > 50y.o. + Hx of fragility fracture should be assessed [grade A].

20. Osteoporosis Evaluation / Detection
Assessment:
Detailed history
Focused physical exam
Measure height annually, and assess for the presence of vertebral fractures [grade A].
If > 2 cm height loss – get imaging
Assess history of falls in the past year. If there has been such a fall, a multifactorial risk assessment should be conducted, including the ability to get out of a chair without using arms [grade A].

21. BMD measurement

22. 10 Year Fracture Risk
William D. Leslie, MD MSc FRCPC, Umanitoba. Module 5 - Speaking of Bones Osteoporosis For Health Professionals: Fracture Risk Assessment .

23. CAROC Risk Score
CAROC scoring tool:
The T-score for the femoral neck is derived from the National Health and Nutrition Education Survey III (NHANES III) reference database for white women.

24. CAROC: 10 Year Fracture Risk  Canadian Association of Radiologists & Osteoporosis Canada 
CAROC risk score increased by one category if:
(i.e. Low to Moderate or Moderate to High)
Fragility fracture after age 40
Recent prolonged systemic glucocorticoid use
For eg.
60y.o. woman; femoral neck T-score = -2.8
Hx of fragility #
CAROC scoring tool:

25. FRAX http://www.shef.ac.uk/FRAX/

26. FRAX http://www.shef.ac.uk/FRAX/

28. 2010 Guidelines HOW DO I ASSESS 10-YEAR FRACTURE RISK?
1. Absolute fracture risk based on age, BMD, prior fragility fractures and glucocorticoid use [Grade A].
2. Calculate risk using the 2010 CAROC tool and/or Canadian FRAX tool, because they have been validated in the Canadian population [Grade A].
3. For purposes of reporting BMD, the 2010 CAROC tool is the preferred national risk assessment system [Grade D].
4. Only the T-score for the femoral neck (derived from the reference range for white women of the NHANES III) should be used to calculate risk of future osteoporotic fractures under either system [Grade D].
5. Individuals with a T-score for the lumbar spine or total hip ≤ –2.5 should be considered to have at least moderate risk [Grade D].
6. Multiple fractures confer greater risk than a single fracture. In addition, prior fractures of the hip and vertebra carry greater risk than fractures at other sites [Grade B].

29. Osteoporosis Therapeutic Options
A) Exercise and Falls Prevention
1. Resistance training and/or weight bearing aerobic exercises [grade B].
2. Core stability exercises to compensate for weakness or postural abnormalities for patients with vertebral fractures [grade B].
3. Balancing exercises (eg. tai chi), or gait training if at risk of falls [grade A].
4. Consider hip protectors in long-term care facilities at high risk for fracture [grade B].

30. Osteoporosis Therapeutic Options
B) Calcium and Vitamin D
Vit D3 (cholecalciferol): iu daily
Enhances calcium absorption
Very safe in higher doses
Can administer all once weekly if desired
Elemental Calcium – 1200mg daily by diet first and supplements if needed
Any calcium salt will do
Doses > 1500mg/day may increase risk of CV disease, CVA, kidney stones
See: Calculate-My-Calcium online calculator

31. Osteoporosis Therapeutic Options
C) Pharmacological Therapy
Low risk (Major fracture CAROC or FRAX score = 0-10%)
No drug treatment
Moderate risk (10-20%)
Consider treatment – discuss with patient
High risk (>20%)
High risk: FRAX hip fracture score >3%
High risk: > 50y.o. + Hx of hip or spine fragility fracture
High risk: > 50y.o. + Hx of multiple fractures
Treat

32. Pharmacological Therapy 1st Line Therapy w/ Evidence for Fracture Prevention in Postmenopausal Women How to Choose?
William D. Leslie, MD MSc FRCPC, Umanitoba. Module 5 - Speaking of Bones Osteoporosis For Health Professionals: Fracture Risk Assessment .

33. Pharmacological Therapy 1st Line Therapy w/ Evidence for Fracture Prevention in Postmenopausal Women How to Choose?
William D. Leslie, MD MSc FRCPC, Umanitoba. Module 5 - Speaking of Bones Osteoporosis For Health Professionals: Fracture Risk Assessment .

34. Rational Prescribing 1. Efficacy 2. Toxicity
Prioritize:
Type of harm
Quantity of harm
Quality of evidence
Time to harm
Prioritize:
Type of benefit
Quantity of benefit
Quality of evidence
Time to benefit
1. Efficacy
2. Toxicity
3. & 4. Cost & Convenience

35. 1st Line Therapy w/ Evidence for Fracture Prevention in Postmenopausal Women How to Choose?
William D. Leslie, MD MSc FRCPC, Umanitoba. Module 5 - Speaking of Bones Osteoporosis For Health Professionals: Fracture Risk Assessment .

36. Agent Toxicity Cost / Convenience
Alendronate
(Fosamax®)
(Fosavance®)
Esophagitis
Adynamic bone disease
Osteonecrosis of the jaw
Hypocalcemia
10mg po daily
or 70mg po weekly
70mg+(2800iu or 5600iu Vit D) po weekly
ODB covered
Fasting, ++ H2O admin; upright
t1/2 ~ > 10 years!
Risedronate
(Actonel®)
(Actonel DR®)
~ same
5mg po QD / 35mg po qWk / 150mg po qMo
[Fasting, ++ H2O admin; upright]
35mg DR formulation – w/ food $$
ODB covered; t1/2 ~ 3 weeks
Zoledronate
(Aclasta®)
~ same (newer, less known)
(minus esophagitis)
(plus ?AFib)
infusion reactions, myalgias
5mg IV once yearly $$
Denosumab (Prolia®)
Unknown - too new
?malignancy, ?infection
?CV or ?ocular effects
Derm events
ONJ
60mg sc q6months
ODB covered with LU code 428 or 429
$$$

37. Duration of Therapy Usually sequential, not combination
Very rarely combo therapy for short term if very high risk
Benefits disappear rapidly after discontinuation
Benefits beyond 5 years not well described
Rare safety concerns more common after 5 years
Little guidance on when to stop or restart
Reassess after 5 – 7 years and ?D/C
Alendronate – t ½ 10 years: yr off then R/A
Risedronate – t ½ 3 weeks: 6 – 12 mo off then R/A
Denosumab – t ½ 4 weeks: 6 – 12 mo off then R/A

38. Unknowns in the Literature
When to D/C
When to restart
Ideal duration of therapy
Long-term safety data of newer agents
Clinical judgment required

39. Cases
Slide #40 onwards

40. Questions?