Lecture 14 - Osteoporosis Flashcards
Define osteoporosis
“porous bone” - chronic skeletal disorder of compromised bone strength associated with low bone density (quantity) and deterioration of bone microarchitecture (quality) which often results in fragility fractures
What 2 things does bone strength depend on?
1) bone mass (a quantity indicator measured as BMD)
2) bone microarchitecture (measure of quality)
What factors increase bone resorption > formation?
menopause
aging
disease
drugs
peak bone mass occurs when?
mid 30’s
bone loss accelerates at ____
menopause
OP is known as the ____ ____
silent thief
OP: describe it
slowly steals bone density over many years without signs of symptoms until a bone breaks or fractures
(1/3 women and 1/5 men over 50 will suffer an OP fragility fracture)
What is a compression fracture?
loss of > 25% vertebral height with end plate disruption
*compression fractures in the spine can cause losses of 6-9 inches in height
List some consequences of fractures
- increased incidence of additional fractures
- chronic pain
- immobility
- decreased quality of life
- loss of independence
- institutionalization
- cost to healthcare
- death (esp after hip or spine fracture)
What is the most serious consequence of OP?
fragility fractures (diagnosed by x-rays)
Fragility fractures occur ____ or from ____ _____
spontaneously or from minor traumas
What are the common sites for fracture
hip, spine, wrist
Describe the OP assessment:
- Assess for fractures (diagnosed by x-rays)
- Bone Mineral Density (BMD) is assessed by DXA (dual x-ray absorptiometry) at the hip and spine
- WHO classification of OP based on BMD is a T-score < -2.5
- BMD correlates with fracture risk but is only ONE component
see slide 8 and 9
ok
Can BMD (bone mineral density) alone determine fracture risk?
no - Bad result needs to be incorporated into a fracture risk calculator
Candidates for Osteoporosis Therapy:
Decision to treat is independent of ______ result based on _____ _____
BMD
fracture history
Candidates for Osteoporosis Therapy:
Based on fracture history
- If had fragility fracture of the hip
- If had fragility fracture of the spine (66% are asymptomatic)
- If had > 2 non-spine, non-hip fragility fractures
- If had 1 non-spine, non-hip fragility fracture after age 40 AND prolonged glucocorticoid use in the previous year
Who else is a candidate for Osteoporosis Therapy:
- all men or women at high fracture risk should receive treatment
- those at moderate risk may need treatment (depends on presence of other risk factors)
- those who are deemed low risk do not treat treatment with OP medication
Exercise and fall prevention
- strength training 2x/week
- balance training or tai chi daily
- > 30 min aerobic physical activity daily
- walking is NOT enough without strength or balancing training
- encourage attention to posture and exercises for back extensor muscles daily
- hip protectors, home safety assessment, reassess meds
Recommended calcium for > 50 yrs old
1200 mg daily
Recommended calcium for 19-50 yrs old
1000 mg daily
Vitamin D recommended for adults under age 50 without OP or conditions affecting absorption ?
400 to 1000 IU daily
Vitamin D recommended for adults over 50 ?
800 to 2000 IU daily
*if they require > 2000 IU daily, monitor serum 25-OH D levels
List some other recommendations for basic bone health
- Quit smoking
- Limit alcohol to < 2 beverages per day
- Follow Canada’s food guide: adequate protein intake, keep sodium intake < 2300 mg/day
What types of medications can increase the risk of falls?
Meds taken for:
- Sleep
- Mood/behaviour
- Anxiety
- Depression
- Hypertension
- Allergies
- Pain
- Muscle spasms
*these meds may impair balance, co-ordination, vision, may cause drowsiness, dizziness, hypotension, may increase confusion and forgetfulness
What regulates serum calcium levels?
tb to mechem
calcitonin and parathyroid hormone (PTH)
(Calcitonin decreases and PTH increases serum Ca concentration)
300 mg Ca in ??
250 mL milk
3/4 cup of plain yogurt
245 mg Ca in ??
3 cm cube cheese
Calcium supplements:
Less than or equal to ____mg Ca per dose maximizes absorption
500
Calcium supplements:
List some things about Calcium carbonate
widely available, cheap, must be taken with a meal for optimal absorption, may be associated with more GI complaints
Calcium supplements:
List some things about Calcium citrate
can be taken with or without meals, recommended if patient on PPI or H2 blocker, may be option for those unable to tolerate CaCO3
Why is Vitamin D important?
- Helps body absorb & use calcium/phosphorus to build/maintain strong bones & teeth; can help protect older adults against OP; improves immune function
- Vitamin D supplementation has been shown to reduce falls in elderly
Vitamin ___ (cholecalciferol) is synthesized in skin on exposure to UVB light from sun and is found in fish, meat, egg, fortified food and milk products and several plant species
D3
Vitamin __ (ergocalciferol) is found in wild mushrooms, fungi and yeasts
D2
Vitamin D2 and D3 must be converted to the active form in the ____ and ______
liver and kidneys
What does low serum vitamin D result in? (<30 nmol/L)
- increased calcium resorption from bones
- associated with balance problems, high fall rates, low Bad and muscle weakness
What does excess vitamin D result in? (>250 nmol/L)
-hypercalcemia and increased calcium depositions in body and cause calcification of kidney, heart, lungs and blood vessels
Sources of Vitamin D?
fatty fish, egg yolks, milk/fortified food and beverages
How much Vitamin D in 2 large egg yolks?
80 IU
How much Vitamin D in 250 mL milk?
100 IU
How much Vitamin D in 3 oz sockeye salmon, cooked?
447 IU
How much Vitamin D in tuna, canned in water, drained?
154 IU
What is the optimal serum levels of Vitamin D?
> 75 nmol/L
> _____ IU daily should be followed by serum monitoring
2000
Vitamin D is a ___-soluble vitamin
fat
Anti-resorptive agents do what?
inhibit bone loss
List some anti-resorptive agents (inhibit bone loss)
Bisphosphonates (alendronate, risedronate, zoledronic acid)
Monoclonal Antibody (denosumab)
SERM (raloxifine)
Hormone Therapy (estrogen)
What do anabolic agents do?
bone forming
List an anabolic agent
PTH analogue (Teriparatide)
What are some benefits of OP Meds?
- Fracture risk reduction by approximately 50%
- Bone density is stabilized or improved slightly
- HIGH risk patient benefit the most
What are some risks of OP Meds?
- Side effects (as w all meds)
- Safety based on benefits outweighing risks
*Benefits > risks for all patients at high risk of fracture and possibly for those at medium risk
MOA of Teriparatide
PTH Analog
*remember PTH is released when Ca levels are too low
MOA of Bisphosphonates
bind to bone, inhibit osteoclasts
*remember osteoclasts break down bone
MOA of Raloxifene and Estrogen
reduce RANK ligand
RANK ligand works to differentiate and active osteoclasts to break down bone
MOA of Denosumab
RANK Ligand Inhibitor
RANK ligand works to differentiate and active osteoclasts to break down bone
see chart on slide 21
alllllllllrighttyyyy then
________: considered 1st line therapy for prevention and treatment of OP
Bisphosphonates
MOA of 1st gen BP (bisphosphonates)
- Bind directly to bone hydroxyapatite crystals (crystalline form of calcium & phosphate), are taken up by osteoclasts during remodelling and are incorporated in ATP (a source of energy in the cell)
- These ATP analogues accumulate in osteoclasts & induce cell death through inhibition of ATP-utilizing enzymes
- Much less effective than 2nd and 3rd gen BP’s
MOA of Nitrogen-containing BPs (N-BP’s)
alendronate, risedronate, zoledronic acid
- Bind directly to bone hydroxyapatite crystals, are taken up by osteoclasts during remodelling and act by inhibiting enzymes in the mevalonate pathway
- These enzymes are required for modification of proteins (GTPases) that are essential for osteoclast function and can also lead to osteoclast death
- Indicated as 1st line therapy in OP in both males and females
Bisphosphonates:
Must be taken when and how?
First thing in the AM with full class of water only on empty stomach
*beverages (esp milk, coffee, orange juice, mineral water) and food reduce absorption by up to 60%
Have to remain upright and refrain from taking other meds, food or beverages (except water) for at least 30 mins after dose
*Dairy rich foods, antacids, calcium and other divalent cations should ideally be taken 2-3 hours after BP
Bisphosphonates:
Metabolism?
None
Bisphosphonates:
Half-life elimination?
Varies from months to years; slowly released with process of bone turnover
Bisphosphonates:
Excretion
Urine (up to 85%)
Feces (as unabsorbed drug)
Bisphosphonates:
When are they CI?
CrCl < 35 mL/min
Bisphosphonates:
Oral Adverse effects
may cause GI related problems such as abdominal pain, acid reflux, nausea, esophagitis, esophageal ulcers, erosions, gastric ulcers
Bisphosphonates:
Oral and IV adverse effects
can contribute to bone, joint & or muscle pain; ocular disorders
Bisphosphonates:
IV adverse effects
Acute-phase reaction with predominantly IV route; flu-like symptoms such as fatigue, fever, chills, myalgia and arthralgia; usually occurs 3-7 days following the infusion; generally mild-moderate but can last up to 2 weeks; reaction tends to lessen with subsequent infusions
Bisphosphonates:
What are some rare adverse effects with long term use?
Osteonecrosis of the jaw (ONJ)
Atypical femur fractures (AFF)
Bisphosphonates:
When are drug holidays recommended?
should be considered after 5 years of BP therapy in moderate-risk patients
Bisphosphonates:
Who are not candidates for drug holidays?
Patients at high risk of fracture
Denosumab is a ?
a fully human monoclonal antibody that targets RANKL in bloodstream
MOA of Denosumab
- Prevents RANKL from binding to RANK receptor on osteoclasts in the circulation
- Inhibits development, activation and survival of osteoclasts
AE of Denosumab?
- rare incidence of ONJ & atypical fragility fractures similar to bisphosphonates
- hypocalcemia
- severe infection (cellulitis, endocarditis, infections of abdomen, urinary tract, and ear)
- dermatitis, eczema, rashes
- musculoskeletal pain
- hypersensitivity rxns
What is the proposed mechanism for increased risk of infections when taking Denosumab?
activated T and B lymphocytes and lymph nodes express RANKL and denosumab inhibits RANKL
Dose of Denosumab?
60 mg SC every 6 months
Teriparatide is a ??
parathyroid hormone analogue
Describe the anabolic action of teriparatide?
-stimulates osteoblast activity
(osteoblasts build bone)
-increased GI calcium absorption
-increased renal reabsorption of calcium
**NOTE: intermittent PTH promotes bone formation and prolonged high PTH causes bone resorption
Results of Teriparatide?
increased BMD, bone mass, and strength and decreased OP-related fragility fractures in postmenopausal women
Teriparatide:
Who is it indicated for?
for severe OP (< -2.5 and fragility fractures) in men, postmenopausal women and glucocorticoid induced OP
Teriparatide:
Dose?
20 mcg SC once daily for 24 months (lifetime maximum) followed by anti-resorptive therapy to maintain bone gain
Teriparatide:
Adverse reactions?
- transient hypercalcemia 4-6 hours post-dose
- orthostatic hypotension
- dizziness, headache, nausea, arthralgia
Teriparatide:
Very ____
costly
see slide 29
cool
Who is estrogen indicated for?
postmenopausal OP with concomitant vasomotor symptoms
Estrogen:
MOA
- decreases bone resorption
- reduces RANKL
Estrogen:
Must be prescribed with progestin if ??
uterus intact
Estrogen:
AE?
- Increased risk of breast cancer with long term therapy
- Increased risk of stroke, DVT in older postmenopausal women
SERM (raloxifine):
Indicated for ?
OP in postmenopausal women
SERM (raloxifine):
MOA
- Decreases bone resorption
- Reduces RANKL
- Increases BMD
- Reduces fragility fracture incidence in at spine
SERM (raloxifine):
Agonist on ______
bone
SERM (raloxifine):
Antagonist at ??
breast and endometrium (no hyperplasia)
SERM (raloxifine):
Associated with invasive _____ cancer risk reduction in post menopausal women
breast
SERM (raloxifine):
May increase risk of ??
DVT or PE, risk higher during first 4 months of treatment
PE = ??
SERM (raloxifine):
Other adverse effects?
hot flashes
leg cramps/muscle spasms
see chart on slide 31
okay
