Osteoporosis

Question 1

What is osteoporosis?

Answer 1

A 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

Question 2

What does bone strength depend on?

Answer 2

Bone mass and bone microacrchitecture

Question 3

What do osteoclasts and osteoblasts do?

Answer 3

Osteoclasts excavate areas of damaged or weakened bone.

Osteoblasts then fill in the areas to form bone

Question 4

What causes bone reabsorption to become greater than formation?

Answer 4

Menopause (accelerates bone loss), aging (begins after mid 30s), disease and drugs

Question 5

Why is osteoporosis known as the silent thief?

Answer 5

Because it slowly steals bone density over many years without signs or symptoms until a bone breaks or fractures
Extreme curvature can form over time (kyphosis)

Question 6

What is a compression fracture?

Answer 6

A loss of >25% of vertebral height with end plate disruption

Can cause 6-9 inches loss in height.

Question 7

How do fragility fractures occur?

Answer 7

Spontaneously or from minor traumas like falling from sitting or standing height, at walking speed or climbing 3 stairs or coughing, hugging, sneezing.

Question 8

What are some common sites for a fragility fracture?

Answer 8

Hip, spine and wrist

Not feet, ankle, hands, craniofacial

Question 9

How is bone mineral density (BMD) assessed?

Answer 9

Using a Dual X-ray Absorptiometry (DXA) at the hip and spine

OP classification is a T-score less than -2.5

Question 10

What else is used to determine risk of fragility fractures?

Answer 10

BMD, age, height, weight, risk factors

Question 11

Who is eligible for BMD testing?

Answer 11

Fragility fracture, prolonged glucocorticoid use, >65 years use of high risk medications
Those >50 with RA, current smoking, high alcohol intake or low body weight
Those

Question 12

What are some disorders strongly associated with osteoporosis?

Answer 12

Primary hyperparathyroidism, diabetes, hypogadism, chronic liver disease, Cushing disease, COPD, chronic inflammatory conditions

Question 13

What will automatically increase a patient to the next fracture risk assessment category?

Answer 13

Fragility fracture after age 40, prolonged corticosteroid therapy (7.5 mg prednisone daily in previous year is equivalent to 3 months of it)

Question 14

What confers high risk in the 10-year fracture risk assessment tool?

Answer 14

Hip/vertebral fracture, >1 non-vertebral non-hip fragility fracture

Question 15

Who is a candidate for osteoporosis therapy?

Answer 15

Based on 10-year fracture risk calculation and fracture history
High risk should receive treatment, moderate may, low does not need

Question 16

What are some high risk fracture history scenarios?

Answer 16

Fragility fracture of the hip or spine, 2 or more non-hip, non-spine fragility fractures or 1 non-spine, non-hip fragility fracture after age 40 and prolonged glucocorticoid use in the previous year

Question 17

How should all patients maintain basic bone health?

Answer 17

Strength training twice a week, balance training or tai chi daily, 30 minutes aerobic physical activity daily, home safety and med assessment, calcium, vitamin D, smoking cessation, limit alcohol (2 per day), good nutrition (adequate protein, low sodium)
All very important adjunct to OP meds

Question 18

Which medications put patients at risk for falls?

Answer 18

Medications taken for sleep, mood, anxiety, depression, hypertension, allergies, pain and muscle spasms. They may impair balance, coordination, vision, dizziness, drowsiness, confusion

Question 19

How much calcium is needed daily?

Answer 19

1200 mg for those 50 years and older
1000 mg for those 19-50
Cannot get all from supplements (usually get ~300 mg from diet)

Question 20

How much vitamin D is needed daily?

Answer 20

400-1000 IU daily for adults 50

Question 21

What are some supplements of calcium available?

Answer 21

Calcium carbonate-Tums (must be taken with meals, GI complaints)
Calcium citrate (can be taken with or without food, good for patients who can't tolerate CaCO3 or are on PPI or H2 blocker)

Question 22

What are some side effects of over supplementation of calcium?

Answer 22

Kidney stones, increased risk of MI (without vitamin D)

Question 23

What does vitamin D do?

Answer 23

Helps the body absorb and use calcium/phosphorous to build/maintain strong bones and teeth
Low levels results in increased bone reabsorption
Excess levels results in hypercalcemia and calcification of organs

Question 24

What are the different types of vitamin D?

Answer 24

Vitamin D3 is synthesized in skin on exposure UV and fortified food and milk
Vitamin D2 is found in wild mushrooms, fungi, yeasts
Both must be converted to active form in liver

Question 25

What are the optimal vitamin D serum levels?

Answer 25

>75 nmol/L >2000 IU daily should be followed by serum monitoring Check levels only after 3-4 months of supplementation/dose changes

Question 26

What are some examples of anti-resorptive agents (inhibits bone loss)?

Answer 26

``` Biphosphates (alendronate, risendronate, zoledronic acid-IV) Monoclonal antibody (denosumab), SERM (raloxifene) and estrogen ```

Question 27

What is an example of an anabolic agent?

Answer 27

PTH analogue (teriparatide)

Question 28

How does denosumab work?

Answer 28

It is a RANK ligand inhibitor to stop it from binding to the RANK receptors on osteoclasts in circulation so they can't work

Question 29

Which drugs reduce the RANK ligand?

Answer 29

Estrogen and raloxifene

Question 30

How does terparatide (rPTH) work?

Answer 30

A recombinant formulation of endogenous parathyroid hormone that stimulates osteoblast activity to form bone, increase GI and renal Ca reabsorption Anabolic action

Question 31

How do 1st generation biphosphates work?

Answer 31

Bind directly to bone hydroxyapatite crystals, are taken up by osteoclasts during remodeling and are incorporated into their ATP, accumulate and induce osteoclast cell death Etidronate

Question 32

Where does raloxifene work?

Answer 32

Spine | Agonist on bone, antagonist on breast and endometrium (no hyperplasia)

Question 33

Where does teriparatide work?

Answer 33

Spine and non-vertebral bones

Question 34

What is the first line therapy for patients with menopausal symptoms?

Answer 34

Estrogen

Question 35

What are the first line treatments in men?

Answer 35

Alendronate, risedronate and zoledronic acid

Question 36

How do 2nd and 3rd generation (nitrogen-containing biphosphonates) work?

Answer 36

Bind directly to hydroxyapatite crystals, taken up by osteoclasts during remodeling and act by inhibiting enzymes in the mevalonate pathway (needed for proteins required for osteoclast function), leading to death. 1st line therapy in males and females More effective than 1st gen

Question 37

How must biphosphonates be taken?

Answer 37

Take first thing in the morning with a full glass of water only on an empty stomach (food decrease absorption) and remain upright and avoid ingesting anything other than water for at least 30 minutes Dairy, antacids, calcium and other divalent cations should be taken 2-3 hours after

Question 38

What is the half-life elimination of biphosphonates?

Answer 38

Varies from months to years and is slowly released with the process of bone turnover

Question 39

What are the adverse effects of biphosphonates?

Answer 39

GI related problems (acid reflux, nausea, ulcers), bone, joint and/or muscle pain, ocular disorders, acute phase reaction (IV-flu-like symptoms) Rare: Osteonecrosis of jaw, atypical femur fractures

Question 40

When should drug holidays be considered in patients taking biphosphonates?

Answer 40

Should be considered after 5 years in moderate risk patients | High risk patients are not candidates for drug holidays

Question 41

What are the adverse effect of denosumab?

Answer 41

Increased risk of infection (activated T and B cells also express RANKL), dermatitis, eczema, rashes, musculoskeletal pain, hypersensitivity, rare incidence of ONJ

Question 42

When is teriparatide indicated?

Answer 42

For severe osteoporosis (BMD

Question 43

What are some adverse effects of teriparatide?

Answer 43

Transient hypocalcemia 4-6 hours post dose, orthostatic hypotension, dizziness, headache, nausea, arthralgia Very costly

Question 44

What must estrogen be prescribed with? When?

Answer 44

Progestin when the uterus is intact

Question 45

What are the adverse effects of estrogen?

Answer 45

Increased risk of breast cancer, stroke, DVT with long term therapy

Question 46

What are the adverse effects of raloxifene (SERM)?

Answer 46

Breast cancer risk reduction, increased risk of DVT or PE | Hot flashes, leg cramps/muscle spasms

Question 47

Which medications negatively affect bone metabolism?

Answer 47

Glucocorticoids (increase osteoclast proliferation, decrease calcium absorption), aromatase inhibitors (blocks estrogen synthesis) and androgen deprivation therapy (males-increases bone turnover)