Review: Osteoporosis
Dr Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD
Pharmacist, Bruyere Academic FHT
Assistant Professor, Dept Family Medicine, UOttawa
Twitter: @RolandHalil
July, 2015
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.
Resources
• 2010 Osteoporosis Clinical Guidelines - Osteoporosis Canada
– http://www.osteoporosis.ca/health-care-professionals/guidelines/
– http://www.cmaj.ca/content/early/2010/10/12/cmaj.100771.full.pdf+html
• 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)
– http://canadiantaskforce.ca/appraised-guidelines/2013-osteoporosis/
• 2014 Clinician’s guide to prevention and treatment of
osteoporosis;
– National Osteoporosis Foundation. 2014 Issue, Version 1;
– http://nof.org/files/nof/public/content/file/2791/upload/919.pdf
Osteoporosis
• Goals of Therapy
– Prevention
– Detection
– Treatment
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
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); 2004. Available from: http://www.ncbi.nlm.nih.gov/books/NBK45513/
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
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
Osteoporosis
Pathophysiology
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
Osteoporosis
Risk of Fracture
Osteoporosis
Risk of Fracture
Skeletal Fragility
2014 Clinician’s guide to prevention and treatment of osteoporosis; National Osteoporosis Foundation. 2014 Issue, Version 1; Release Date: April 1, 2014
http://nof.org/files/nof/public/content/file/2791/upload/919.pdf
Skeletal Fragility
(for all)
(steroid use + immobility + dz effects)
Skeletal Fragility
(via changes in bone metabolism and/or falls risk)
(↓Ca2+)
(↓Ca2+)
Osteoporosis
Risk of Fracture
Osteoporosis
Risk of Fracture
2014 Clinician’s guide to prevention and treatment of osteoporosis; National Osteoporosis Foundation. 2014 Issue, Version 1; Release
Date: April 1, 2014 http://nof.org/files/nof/public/content/file/2791/upload/919.pdf
Falls Risk
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].
Osteoporosis
Evaluation / Detection
– Assessment:
• Detailed history
• Focused physical exam
1. Measure height annually, and assess for the
presence of vertebral fractures [grade A].
•
If > 2 cm height loss – get imaging
2. 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].
BMD measurement
William D. Leslie, MD MSc FRCPC, Umanitoba. Module 5 - Speaking of Bones Osteoporosis For Health Professionals: Fracture
Risk Assessment . http://www.osteoporosis.ca/wp-content/uploads/Module-5-Fracture-Risk-Assessment-ppt.pdf
10 Year Fracture Risk
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.
CAROC scoring tool: http://www.osteoporosis.ca/multimedia/pdf/CAROC.pdf
CAROC Risk Score
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)
1. Fragility fracture after
age 40
2. Recent prolonged
systemic glucocorticoid
use
•
For eg.
–
–
60y.o. woman; femoral
neck T-score = -2.8
Hx of fragility #
CAROC scoring tool: http://www.osteoporosis.ca/multimedia/pdf/CAROC.pdf
FRAX
http://www.shef.ac.uk/FRAX/
FRAX
http://www.shef.ac.uk/FRAX/
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].
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].
Osteoporosis
Therapeutic Options
• B) Calcium and Vitamin D
– Vit D3 (cholecalciferol): 1000-2000 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
• http://www.osteoporosis.ca/osteoporosis-and-you/nutrition/calculate-my-calcium/
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
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 . http://www.osteoporosis.ca/wp-content/uploads/Module-5-Fracture-Risk-Assessment-ppt.pdf
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 . http://www.osteoporosis.ca/wp-content/uploads/Module-5-Fracture-Risk-Assessment-ppt.pdf
Rational Prescribing
Prioritize:
1. Type of harm
2. Quantity of harm
3. Quality of evidence
4. Time to harm
Prioritize:
1. Type of benefit
2. Quantity of benefit
3. Quality of evidence
4. Time to benefit
1. Efficacy
2. Toxicity
3. & 4. Cost & Convenience
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 . http://www.osteoporosis.ca/wp-content/uploads/Module-5-Fracture-Risk-Assessment-ppt.pdf
Agent
Alendronate
(Fosamax®)
(Fosavance®)
Toxicity
Cost / Convenience
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!
~ same
5mg po QD / 35mg po qWk / 150mg po qMo
[Fasting, ++ H2O admin; upright]
35mg DR formulation – w/ food $$
ODB covered; t1/2 ~ 3 weeks
Risedronate
(Actonel®)
(Actonel DR®)
Zoledronate
(Aclasta®)
Denosumab
(Prolia®)
~ same (newer, less known)
(minus esophagitis)
(plus ?AFib)
infusion reactions, myalgias
Unknown - too new
?malignancy, ?infection
?CV or ?ocular effects
Derm events
ONJ
Hypocalcemia
5mg IV once yearly
ODB covered
$$
60mg sc q6months
ODB covered with LU code 428 or 429
$$$
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: 1 - 2 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
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
Cases
• http://www.osteoporosis.ca/wpcontent/uploads/Module-5-Fracture-RiskAssessment-ppt.pdf
• Slide #40 onwards
Questions?