Lecture 14 - Osteoporosis Flashcards
(95 cards)
1
Q
Define osteoporosis
A
“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
2
Q
What 2 things does bone strength depend on?
A
1) bone mass (a quantity indicator measured as BMD)
2) bone microarchitecture (measure of quality)
3
Q
What factors increase bone resorption > formation?
A
menopause
aging
disease
drugs
4
Q
peak bone mass occurs when?
A
mid 30’s
5
Q
bone loss accelerates at ____
A
menopause
6
Q
OP is known as the ____ ____
A
silent thief
7
Q
OP: describe it
A
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)
8
Q
What is a compression fracture?
A
loss of > 25% vertebral height with end plate disruption
*compression fractures in the spine can cause losses of 6-9 inches in height
9
Q
List some consequences of fractures
A
- 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)
10
Q
What is the most serious consequence of OP?
A
fragility fractures (diagnosed by x-rays)
11
Q
Fragility fractures occur ____ or from ____ _____
A
spontaneously or from minor traumas
12
Q
What are the common sites for fracture
A
hip, spine, wrist
13
Q
Describe the OP assessment:
A
- 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
14
Q
see slide 8 and 9
A
ok
15
Q
Can BMD (bone mineral density) alone determine fracture risk?
A
no - Bad result needs to be incorporated into a fracture risk calculator
16
Q
Candidates for Osteoporosis Therapy:
Decision to treat is independent of ______ result based on _____ _____
A
BMD
fracture history
17
Q
Candidates for Osteoporosis Therapy:
Based on fracture history
A
- 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
18
Q
Who else is a candidate for Osteoporosis Therapy:
A
- 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
19
Q
Exercise and fall prevention
A
- 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
20
Q
Recommended calcium for > 50 yrs old
A
1200 mg daily
21
Q
Recommended calcium for 19-50 yrs old
A
1000 mg daily
22
Q
Vitamin D recommended for adults under age 50 without OP or conditions affecting absorption ?
A
400 to 1000 IU daily
23
Q
Vitamin D recommended for adults over 50 ?
A
800 to 2000 IU daily
*if they require > 2000 IU daily, monitor serum 25-OH D levels
24
Q
List some other recommendations for basic bone health
A
- Quit smoking
- Limit alcohol to < 2 beverages per day
- Follow Canada’s food guide: adequate protein intake, keep sodium intake < 2300 mg/day
25
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
26
What regulates serum calcium levels?
calcitonin and parathyroid hormone (PTH)
(Calcitonin decreases and PTH increases serum Ca concentration)
#tb to mechem
27
300 mg Ca in ??
250 mL milk
| 3/4 cup of plain yogurt
28
245 mg Ca in ??
3 cm cube cheese
29
Calcium supplements:
| Less than or equal to ____mg Ca per dose maximizes absorption
500
30
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
31
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
32
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
33
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
34
Vitamin __ (ergocalciferol) is found in wild mushrooms, fungi and yeasts
D2
35
Vitamin D2 and D3 must be converted to the active form in the ____ and ______
liver and kidneys
36
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
37
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
38
Sources of Vitamin D?
fatty fish, egg yolks, milk/fortified food and beverages
39
How much Vitamin D in 2 large egg yolks?
80 IU
40
How much Vitamin D in 250 mL milk?
100 IU
41
How much Vitamin D in 3 oz sockeye salmon, cooked?
447 IU
42
How much Vitamin D in tuna, canned in water, drained?
154 IU
43
What is the optimal serum levels of Vitamin D?
> 75 nmol/L
44
> _____ IU daily should be followed by serum monitoring
2000
45
Vitamin D is a ___-soluble vitamin
fat
46
Anti-resorptive agents do what?
inhibit bone loss
47
List some anti-resorptive agents (inhibit bone loss)
Bisphosphonates (alendronate, risedronate, zoledronic acid)
Monoclonal Antibody (denosumab)
SERM (raloxifine)
Hormone Therapy (estrogen)
48
What do anabolic agents do?
bone forming
49
List an anabolic agent
PTH analogue (Teriparatide)
50
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
51
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
52
MOA of Teriparatide
PTH Analog
*remember PTH is released when Ca levels are too low
53
MOA of Bisphosphonates
bind to bone, inhibit osteoclasts
*remember osteoclasts break down bone
54
MOA of Raloxifene and Estrogen
reduce RANK ligand
| RANK ligand works to differentiate and active osteoclasts to break down bone
55
MOA of Denosumab
RANK Ligand Inhibitor
| RANK ligand works to differentiate and active osteoclasts to break down bone
56
see chart on slide 21
alllllllllrighttyyyy then
57
________: considered 1st line therapy for prevention and treatment of OP
Bisphosphonates
58
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
59
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
60
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
61
Bisphosphonates:
| Metabolism?
None
62
Bisphosphonates:
| Half-life elimination?
Varies from months to years; slowly released with process of bone turnover
63
Bisphosphonates:
| Excretion
Urine (up to 85%)
| Feces (as unabsorbed drug)
64
Bisphosphonates:
| When are they CI?
CrCl < 35 mL/min
65
Bisphosphonates:
| Oral Adverse effects
may cause GI related problems such as abdominal pain, acid reflux, nausea, esophagitis, esophageal ulcers, erosions, gastric ulcers
66
Bisphosphonates:
| Oral and IV adverse effects
can contribute to bone, joint & or muscle pain; ocular disorders
67
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
68
Bisphosphonates:
| What are some rare adverse effects with long term use?
Osteonecrosis of the jaw (ONJ)
| Atypical femur fractures (AFF)
69
Bisphosphonates:
| When are drug holidays recommended?
should be considered after 5 years of BP therapy in moderate-risk patients
70
Bisphosphonates:
| Who are not candidates for drug holidays?
Patients at high risk of fracture
71
Denosumab is a ?
a fully human monoclonal antibody that targets RANKL in bloodstream
72
MOA of Denosumab
- Prevents RANKL from binding to RANK receptor on osteoclasts in the circulation
- Inhibits development, activation and survival of osteoclasts
73
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
74
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
75
Dose of Denosumab?
60 mg SC every 6 months
76
Teriparatide is a ??
parathyroid hormone analogue
77
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
78
Results of Teriparatide?
increased BMD, bone mass, and strength and decreased OP-related fragility fractures in postmenopausal women
79
Teriparatide:
| Who is it indicated for?
for severe OP (< -2.5 and fragility fractures) in men, postmenopausal women and glucocorticoid induced OP
80
Teriparatide:
| Dose?
20 mcg SC once daily for 24 months (lifetime maximum) followed by anti-resorptive therapy to maintain bone gain
81
Teriparatide:
| Adverse reactions?
- transient hypercalcemia 4-6 hours post-dose
- orthostatic hypotension
- dizziness, headache, nausea, arthralgia
82
Teriparatide:
| Very ____
costly
83
see slide 29
cool
84
Who is estrogen indicated for?
postmenopausal OP with concomitant vasomotor symptoms
85
Estrogen:
| MOA
- decreases bone resorption
| - reduces RANKL
86
Estrogen:
| Must be prescribed with progestin if ??
uterus intact
87
Estrogen:
| AE?
- Increased risk of breast cancer with long term therapy
| - Increased risk of stroke, DVT in older postmenopausal women
88
SERM (raloxifine):
| Indicated for ?
OP in postmenopausal women
89
SERM (raloxifine):
| MOA
- Decreases bone resorption
- Reduces RANKL
- Increases BMD
- Reduces fragility fracture incidence in at spine
90
SERM (raloxifine):
| Agonist on ______
bone
91
SERM (raloxifine):
| Antagonist at ??
breast and endometrium (no hyperplasia)
92
SERM (raloxifine):
| Associated with invasive _____ cancer risk reduction in post menopausal women
breast
93
SERM (raloxifine):
| May increase risk of ??
DVT or PE, risk higher during first 4 months of treatment
PE = ??
94
SERM (raloxifine):
| Other adverse effects?
hot flashes
| leg cramps/muscle spasms
95
see chart on slide 31
okay
