A Review of the 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada

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

hip spine

What is Osteoporosis?Bone density

strong dense bone

fragile osteoporotic

bone

What is Osteoporosis?Deterioration of bone micro-architecture

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.

• 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

What is Osteoporosis?Costs

Brown JP, Josse RG. CMAJ 2002;167(10 suppl):S1-S34.

Osteoporosis - DiagnosisMajor 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 - DiagnosisMinor 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

Osteoporosis - DiagnosisIndications for measuring bone mineral density

Papaioannou A, et al. CMAJ 2010;182:1864-73

Osteoporosis - DiagnosisBMD 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 - DiagnosisRecommended 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

Brown JP, Josse RG. CMAJ 2002;167(10 suppl):S1-S34.

Long-term glucocorticoid

therapy

Long-term glucocorticoid

therapy

Start bisphosphonate

therapy

Start bisphosphonate

therapy

Obtain DXA BMD

for follow-up

Obtain DXA BMD

for follow-up

Personal historyof fragility fracture

after age 40

Personal historyof fragility fracture

after age 40

Low DXA BMD

(T-score ≤−2.5)

Low DXA BMD

(T-score ≤−2.5)

Clinical risk factors

(1 major or 2 minor)

Clinical risk factors

(1 major or 2 minor)

Non-traumaticvertebral

compressiondeformities

Non-traumaticvertebral

compressiondeformities

AND

Low DXA BMD (T-score <−1.5)

AND

Low DXA BMD (T-score <−1.5)

Consider therapy

Consider therapy

Repeat DXA BMDafter 1 or 2 years

Repeat DXA BMDafter 1 or 2 years

Osteoporosis - DiagnosisWho should be treated?

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

OsteoporosisCalcium – regulation in the body

Age Daily calcium requirement

4 to 8 800 mg

9 to 18 1300 mg

19 to 50 1000 mg

50+ 1500 mg

pregnant or lactating women 18+           

1000 mg

OsteoporosisCalcium – requirements

• 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

                      

   

OsteoporosisCalcium – maximizing intake through diet

• 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

OsteoporosisCalcium – minimizing food that cause calcium loss

OsteoporosisCalcium – 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

OsteoporosisCalcium – 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%

OsteoporosisCalcium – 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

OsteoporosisCalcium – supplements• can be difficult to swallow.• can cause:

– stomach upset, constipation, nausea

• many different types– different salts– price– purity– quality

• 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)

OsteoporosisVitamin D

• 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.

OsteoporosisVitamin D - sources

• 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

OsteoporosisPhysical activity

• 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

OsteoporosisSmoking cessation

Strong association between falls and fractures• a safe environment is important to reduce risk of falls

– 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

OsteoporosisFalls prevention

• reduction of fractures• prevention of osteoporosis in

those who are at high risk of developing the disease.– prevent further bone density loss

OsteoporosisPharmacologic therapy - goals

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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

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

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic therapy – bisphosphonates

OsteoporosisPharmacologic 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).

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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.

OsteoporosisPharmacologic 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)

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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)

OsteoporosisPharmacologic 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

OsteoporosisPharmacologic 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

OsteoporosisClinical Practice Guidelines

CMAJ 2010;182:1864-73

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