Transcript Document

A Review of the 2010 Clinical
Practice Guidelines for the
Diagnosis and Management of
Osteoporosis in Canada
Luis Viana, R.Ph., B.Sc. Phm., M.Ed., CGP
What is Osteoporosis?
Definition
• a disease characterized by:
– low bone density
– decreased bone strength
– deterioration of bone micro-architecture
• leads to increased bone fragility and increased
risk of fracture
– especially of hip, spine and wrist
• “the silent thief”
– bone loss occurs without symptoms
What is Osteoporosis?
Bone density
hip
spine
What is Osteoporosis?
Deterioration of bone micro-architecture
strong dense
bone
fragile
osteoporotic
bone
What is Osteoporosis?
Prevalence
•
•
•
•
affects 1.4 million Canadians
women: 1 in 4 >50 years of age.
men: 1 in 8 >50 years of age.
can strike at any age.
What is Osteoporosis?
Costs
• Financial
– $1.3 billion in Canada
– long term, hospital and chronic care account for
majority of costs
• Human:
– reduced quality of life
•
•
•
•
disfigurement
lowered self-esteem
reduction or loss of mobility
decreased independence
Osteoporosis - Diagnosis
Major risk factors
• age>65 years
• vertebral compression
fracture
• fragility fracture
• family history (maternal)
• steroids > 3 months
•
•
•
•
•
malabsorption syndromes
primary hyperparathyroid
propensity to fall
hypogonadism
early menopause (<45 yrs)
Brown JP, Josse RG. CMAJ 2002;167(10 suppl):S1-S34.
Osteoporosis - Diagnosis
Minor risk factors
• rheumatoid arthritis
• past history of
hyperthyroidism
• low calcium
• smoker
• excessive alcohol
• excessive caffeine
• weight < 57kg
• weight loss >10% at age 25
• medications:
– chronic heparin therapy
– anticonvulsants
Brown JP, Josse RG. CMAJ 2002;167(10 suppl):S1-S34.
Osteoporosis - Diagnosis
Indications for measuring bone mineral density
Papaioannou A, et al. CMAJ 2010;182:1864-73
Osteoporosis - Diagnosis
BMD and T-scores
Bone Mineral Density
(BMD) results are
reported as a T-score
which compares the
reported BMD to optimal
or peak density of a
30 year old, healthy adult
and determines the
fracture risk
Osteoporosis - Diagnosis
Recommended blood tests
• calcium
– corrected for albumin
• complete blood count
• creatinine
• alkaline phosphatase
• thyroid stimulating hormone
• serum protein electrophoresis
– for patients with vertebral fractures
• 25-hydroxyvitamin D
– should be measured after
3-4 months of adequate
supplementation
– should not be repeated if an
optimal level (at least 75 nmol/L)
is achieved
Osteoporosis - Diagnosis
Who should be treated?
Long-term
glucocorticoid
therapy
Personal history
of fragility fracture
after age 40
Non-traumatic
vertebral
compression
deformities
Clinical risk
factors
(1 major or 2 minor)
Low
DXA BMD
(T-score ≤−2.5)
AND
Start
bisphosphonate
therapy
Low DXA BMD (T-score <−1.5)
Obtain
DXA BMD
for follow-up
Consider
therapy
Repeat DXA BMD
after 1 or 2 years
Brown JP, Josse RG. CMAJ 2002;167(10 suppl):S1-S34.
Osteoporosis
Calcium – regulation in the body
Body ensures that calcium is always available:
• absorbs calcium directly from food
• balance between:
– osteoclast activity – bone resorption
– osteoblast activity – bone formulation
• takes calcium from bones if not enough
is available (osteoclast activity)
– leaves bone less dense & more fragile
• maintain an adequate supply of calcium so that the body does not have
to take calcium from bones (osteoblast activity)
• slows down calcium excretion in urine by returning some to the blood
Osteoporosis
Calcium – requirements
Age
4 to 8
9 to 18
19 to 50
50+
pregnant or lactating women
18+
Daily calcium
requirement
800 mg
1300 mg
1000 mg
1500 mg
1000 mg
Osteoporosis
Calcium – maximizing intake through diet
• eat foods that contain calcium that is easily absorbed
–
–
–
–
milk, cheese and yogurt
calcium fortified soy beverages & orange juice
vegetables
fish products containing bones
• canned salmon and sardines
– meat alternatives
• lentils and beans
Osteoporosis
Calcium – minimizing food that cause calcium loss
• calcium loss through urine is increased by the
consumption of:
– excess salt
• keep salt intake and salty food to a minimum
– caffeine
• 2-3 cups of coffee, tea or cola a day is probably
not detrimental if calcium intake is adequate
• >4 cups/day, have at least one glass of milk
for every cup of caffeine containing beverage
Osteoporosis
Calcium – supplements
• preferred source of calcium is in the diet.
– total daily intake for people > 50 yrs old = 1200 mg
• calcium supplements come as many types of
calcium salts:
– carbonate, citrate, phosphate, gluconate, lactate
• elemental calcium is the most important
• different calcium salts have different percentages of
elemental calcium
Osteoporosis
Calcium – supplements
500 mg Elemental Calcium is equivalent to:
% Elemental Calcium
1250 mg calcium carbonate
40%
2350 mg calcium citrate
21%
1282 mg calcium phosphate
39%
3846 mg calcium lactate
13%
5556 mg calcium gluconate
10%
Osteoporosis
Calcium – supplements
• when to take:
– calcium carbonate
• with food or right after eating
– other calcium salts (citrate, lactate, gluconate)
• well absorbed any time
• how to take:
– take with plenty of water
– take no more than 500 mg per dose
Osteoporosis
Calcium – supplements
• can be difficult to swallow.
• can cause:
– stomach upset, constipation, nausea
• many different types
–
–
–
–
different salts
price
purity
quality
Osteoporosis
Vitamin D
• Vitamin D3 increases calcium absorption by as much as
30-80%.
• Requirements:
– healthy adults at low risk of vitamin D deficiency
• 400 – 1000 iu per day
– adults over 50 who are at moderate risk of vitamin D
deficiency
• 800-1000 iu per day (up to 2000 iu considered safe)
Osteoporosis
Vitamin D - sources
• milk – 100 IU per 250 mL glass.
• small amounts:
– margarine, eggs, chicken livers, salmon,
sardines, herring, mackerel, swordfish
and fish oils (halibut and cod liver).
• supplements
– most multivitamin preparations
contain 400 IU
• sunlight does not appear to be sufficient to replace
ingested forms of vitamin D.
Osteoporosis
Physical activity
• weight bearing exercise.
– walking, jogging, aerobics, dancing,
stair climbing, skating
• resistance exercise
– free weights.
• activities that improve:
– balance and coordination (Tai-chi)
– posture
• back extension, arm, shoulder and abdominal exercises
Osteoporosis
Smoking cessation
• smoking
– decreases estrogen levels in women
• protective effective on bone health
– reduces calcium absorption
– has a toxic effect on osteoblasts
• smoking cessation will help to optimize bone mass
• patients of all ages at risk for osteoporosis should
be counselled regarding smoking cessation
Osteoporosis
Falls prevention
Strong association between falls and fractures
• a safe environment is important to reduce risk of falls
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–
–
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improve lighting
remove throw rugs or use rugs with non-slip backing
remove loose electrical or telephone wires
raised toilet seats, grab bars in bathroom, seat in
bathtub or shower
– replace low furniture with higher furniture
• medication review to reduce or eliminate medications
that may contribute to falls
Osteoporosis
Pharmacologic therapy - goals
• reduction of fractures
• prevention of osteoporosis in
those who are at high risk of
developing the disease.
– prevent further bone density loss
Osteoporosis
Pharmacologic therapy – antiresorptive agents
Antiresorptive agents preserve bone by
inhibiting bone resorption
• patients with osteoporosis must be
receiving adequate calcium and Vitamin D
while on an antiresorptive therapy to
minimize risk of hypocalcemia
Osteoporosis
Pharmacologic therapy – bisphosphonates
alendronate, risedronate, zoledronic acid
• bind permanently to surfaces of bone and
slow down osteoclasts (bone-eroding cells)
– allows osteoblasts (bone-building cells) to
work more effectively
– can stay in bone up to 10 years
• prevention and treatment of osteoporosis
– vertebral, hip and non-vertebral fractures
• poor bioavailability – administer alendronate and
risedronate with water only
Osteoporosis
Pharmacologic therapy – bisphosphonates
Medication
Strength & Frequency
Time of day
Instructions
alendronate
Daily therapy – 10 mg
Monthly therapy – 70 mg
first thing in the
morning, ½ hour before
eating
•Take with glass of water.
•Don’t lie down for ½ hour.
•No calcium supplements or
vitamins for ½ hour.
alendronate +
vitamin D
Weekly therapy
-alendronate 70 mg + vitamin D 2800 iu
-alendronate 70 mg + vitamin D 5600 iu
first thing in the
morning, ½ hour before
eating
•Take with glass of water.
•Don’t lie down for ½ hour.
•No calcium supplements or
vitamins for ½ hour.
risedronate
Daily therapy – 5 mg
Weekly therapy – 35 mg
Monthly duet therapy – 75 mg
Monthly therapy – 150 mg
first thing in the
morning, ½ hour before
eating
•Take with glass of water.
•Don’t lie down for ½ hour.
•No calcium supplements or
vitamins for 2 hrs before or after.
zoledronic
acid
Once a year intravenous infusion
- 5 mg in 100 mL IV solution
Osteoporosis
Pharmacologic therapy – bisphosphonates
Adverse effects
• gastrointestinal effects
– diarrhea, constipation, nausea, abdominal pain, dyspepsia
– IV should be considered if unable to tolerate oral therapy
• arthralgia, back pain
• headache
• osteonecrosis of the jaw (rare)
– more commonly following dental work or mouth trauma
– to minimize risk
• complete any major dental work prior to initiating bisphosphonate therapy
• encourage routine dental care
Osteoporosis
Pharmacologic therapy – Raloxifene
• acts like estrogen in some parts of the body
(heart and bones)
– estrogen activity builds and maintains bone density
• blocks the effect of estrogen in uterus and breast
• for use in post-menopausal women.
– increases bone density
– evidence shows effective for prevention of vertebral fractures only
• dose = 60 mg by mouth once daily
• side effects:
– hot flashes
– increased risk of blood clots (similar to that for women using HRT).
Osteoporosis
Pharmacologic therapy – Hormone Replacement Therapy
• supplement levels of estrogen/progestin which
are lower following menopause
• provide hormone replacement therapy at the
lowest possible level to prevent bone loss
• significantly reduces vertebral, non-vertebral and hip fractures
• benefits must be balanced against the risk of coronary heart
disease, breast cancer, stroke, endometrial cancer, and
thromboembolic events
• not indicated first line as treatment for osteoporosis due to safety
concerns
– may be an additional beneficial effect when used for control of
menopausal symptoms
Osteoporosis
Pharmacologic therapy – Hormone Replacement Therapy
Premarin®, C.E.S.® (estrogen)
• 0.3 - 0.625 daily.
• side effects:
– depression, headaches, breast tenderness, PMS,
skin irritation, and weight gain.
– menstrual bleeding.
– increased risk of breast cancer, stroke and cardiovascular disease.
– increased risk of blood clots (similar to that for raloxifene).
– increased risk of endometrial cancer if estrogen is used without
progestin.
Osteoporosis
Pharmacologic therapy – teriparatide
Parathyroid hormone analogue (hPTH 1-34)
• bone formation therapy as opposed to
anti-resorptive therapy
• increases bone formation, remodeling, osteoblast
number and activity
• chronic exposure to PTH will deplete bone
– intermittent exposure through daily injections causes transient
increases in PTH levels and activates osteoblasts more than
osteoclasts
• bone mass and architecture are improved
• for vertebral and non-vertebral fractures (not hip)
Osteoporosis
Pharmacologic therapy – teriparatide
Parathyroid hormone analogue (hPTH 1-34)
• prior or concurrent use of bisphosphonates appears to decrease
the effect of teriparatide
– ideally used in high risk bisphosphonate naïve patients
• BMD gains are quickly lost once treatment when teriparatide is
discontinued
– important to initiate an antiresorptive therapy at the end of the 18
month course of therapy
• dose = 20 mcg by subcutaneous injection once daily
• adverse effects
– orthostatic hypotension, osteosarcoma
Osteoporosis
Pharmacologic therapy – denosumab
For:
• treatment of osteoporosis in postmenopausal
women
• prevention of androgen-induced bone loss in
men undergoing androgen-deprivation therapy
– eg. prostate cancer
• prevention of aromatase inhibitor induced bone loss in
breast cancer
Osteoporosis
Pharmacologic therapy – denosumab
Dose:
• 60 mg as a subcutaneous injection (single dose)
once every six months
Adverse effects:
• dermatologic
– dermatitis, eczema and rash
• hypocalcemia
– ensure adequate calcium and vitamin D intake
• skin, abdominal urinary or ear infections
Osteoporosis
Pharmacologic therapy – calcitonin
Mechanism of action:
• a natural hormone produced by the thyroid gland
that controls the activity of osteoclasts
(bone breakdown)
• slows down the work of osteoclasts
• allows osteoblasts to work more effectively (bone formation)
Osteoporosis
Pharmacologic therapy – calcitonin
Efficacy
• for use in treatment of osteoporosis in
pre and post menopausal women and men.
• not used for prevention of osteoporosis
• maintains or minimally increases bone density
• prevents vertebral fractures
• reduces pain associated with vertebral fractures
Osteoporosis
Pharmacologic therapy – calcitonin
• available as a nasal spray
• dose:
– one spray (200 iu) in one nostril,
in alternating nostrils, each day
• side effects:
– nasal dryness
– swelling of nasal membranes
Osteoporosis
Clinical Practice Guidelines
CMAJ 2010;182:1864-73
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