Chapter 73 RAT Material

Question 1

Define osteoporosis

Answer 1

Disease characterized by low bone density, impaired tone architecture, and weakened bone strength

Question 2

Explain the pathophysiology of osteoporosis

Answer 2

It depends on sex,age, diet, genetics, and presence of secondary causes. (endocrine, GI, Inflammatory, chronic illness, immobility/disuse, genetic)

Female (Postmenopausal) - estrogen deficiency results in increased osteoclast activity

Male - decreased testosterone causes bone loss

Age - accelerated bone turnover rate and reduced osteoblasts

Question 3

Identify risk factors associated with osteoporosis

Answer 3

Female
Advanced Age
Race/ethnicity

Smoking
Alcohol (3 more drinks a day)

Low bone density
Low calcium intake
Low vitamin D
Low body weight or BMI

Recent falls
Cognitive impairment
Impaired vision

History of fragility fracture
Past or present systemic oral glucorticoid use

Question 4

What are the tools to assess patients for osteoporosis

Answer 4

WHO fracture risk assessment (FRAX)
Peripheral Dual-Energy X-ray Absorptiometry (pDXA)
Central Dual-Energy X-ray Absorptiometry (DXA)
Vertebral Fracture Assessment (VFA)

Question 5

What is FRAX and when can it be used? When should it not be used?

Answer 5

It is using risk factors to predict the percent probability of a person fracturing in the next 10 years. Can be used when patients do not have access to DXA

It should not be used for patients ALREADY on therapy for osteoporosis

Question 6

What is pDXA? cDXA? Which one is more popular and why? When should pDXA not be used? When should cDXA not be used?

Answer 6

pDXA measures small bones such as fingers and hands to assess for any fractures and predict risk. cDXA measures the hip and spine for fractures.

pDXA is more common because it is cheap, easy to use, portable, and fast. Used in health fairs and community pharmacies

pDXA should not be used in patients that are already at high risk. Should be referred for cDXA

cDXA should not be used in the absence of suspected risk factors of osteoporosis in children, postmenopausal women, and men younger than 50.

Question 7

When using cDXA, what parameters are provided in a BMD report? What are they and what are they useful for?

Answer 7

Actual bone density - serial monitoring of therapy response

T-score - number of standard deviations from the mean of the reference population regarding BMD (healthy, young 20-29 YO, SEX-MATCHED, WHITE)

Z-score - same as T-score except race is considered

Question 8

What is VFA?

Answer 8

It is a measure of vertebral fractures. Recommended for males >70 and females >80

Question 9

What are the recommendations for calcium and vitamin D supplementation

Answer 9

???

Question 10

What are some non-pharmacological options to prevent and treat osteoporosis?

Answer 10

Good Diet:

• calcium
• vitamin D
• vitamin K
• low caffeine and alcohol

Other

• no smoking
• exercise
• fall prevention (hip protectors)

Question 11

What are some pharmacological options to prevent and treat osteoporosis?

Answer 11

Nutritional Supplements - Vitamin D and Calcium

Bisphosphonates

• Risendronate
• Alendronate
• Ibandronate
• Zoledronic acid

RANK ligand inhibitor
- Denosumab

Estrogen agonist antagonist
- Raloxifene

Recombinant human parathyroidhormone(PTH 1–34 units)
- Teriparatide

Calcitonin
- Calcitonin

Question 12

When would you consider pharmacological options? What are first line agents for these situations? Alternative? Last line?

Answer 12

If the patient presents with a low trauma fracture (in the hip or vertebrae

-OR-

cDXA reveals patient has osteoporosis or has a high risk score (Tscore <-2.5) or can be considered when score is -1.1 to -2.5

First Line: Alendronate, risendronate, zoledronic acid, and denosumab

Alternative: Ibandronate, teriparatide, and raloxifene

Last Line: intranasal calcitonin

Question 13

What is the overall mechanism that these drugs try to achieve?

Answer 13

Antiresorption (reduce breakdown of bone)

Question 14

Calcium

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 14

Calcium

Mechanism - increases BMD but less than Rx drugs

Benefit - prevents osteoporosis

Adverse events - CONSTIPATION, KIDNEY STONES (R)

CI/DDI - PPIs (lansoprazole, etc.)

Monitoring - dietary intake, constipation

Question 15

Vitamin D

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 15

Vitamin D

Mechanism - increase Ca++ concentration

Benefit - increases intestinal Ca++ absorption

Adverse events - Hypercalcemia (weakness, cardiac rhythm disturbance, headache, etc.), hypercalciuria

CI/DDI - Rifampin, anticonvulsants, BARs

Monitoring - serum 25(OH) vitamin D concentration

Question 16

Bisphosphonates

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 16

Bisphosphonates

Mechanism - mimics pyrophosphate and decreases osteoclast activity

Benefit - fracture risk reductions (usually seen first to 6-12 months during therapy)

Adverse events - musculoskeletal pain, nausea, dyspepsia, GI perforation (R), severe pain (R)

CI/DDI - dont take at same time with other drugs at same time (poor bioavailability) –> must taken 30min after 6 oz of water and normal Ca++ levels

–CRCL <30mL/min or hypocalcemia

Monitoring - bone density, fractures, serum calcium

Question 17

Denosumab

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 17

Denosumab

Mechanism - RANK ligand inhibitor -> less osteoclast formation

Benefit - Good for men having androgen-deprivation therapy for prostate cancer or women having aromatase inhibitor therapy for breast cancer.

Adverse events - Flatulence, eczema, cellulitis, infection

CI/DDI - PREGNANCY X

Monitoring - bone density, fractures, serum calcium

Question 18

Raloxifene

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 18

Raloxifene

Mechanism - estrogen agonists actions in bone and antagonist actions on breast and uterine tissue

Benefit - Good for PM osteoporosis prevention and treatment and good for reduction of risk in invasive breast cancer (also effects mostly the vertebrae)

Adverse events - Hot flushes (common), leg pain (common), spasms, venous thromboembolism

CI/DDI - Highly protein bound drugs like WARFARIN, and BARs decrease serum conc., PREGNANCY X and VTE history or active X

Monitoring - blood clots, hot flush, bone density, fractures

Question 19

Calcitonin

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 19

Calcitonin

Mechanism - endogenous hormone that decreases Ca++ when too high

Benefit - good for osteoporosis women that are at least 5 years past menopause

Adverse events - rhinitis, epistaxis

CI/DDI - Lithium

Monitoring - Bone density, fractures

Question 20

Teriparatide

Mechanism -

Benefit -

Adverse events -

CI/DDI -

Monitoring -

Answer 20

Teriparatide

Mechanism - Has 34 AA structure of PTH ==> increases bone formation, bone remodeling rate, and osteoblast number and activity

Benefit - reduces non + verterbral fractures in postmenopausal women, no data for men or glucocorticoid users doe

Adverse events - nausea, headache, orthostasis with first few injections

CI/DDI - avoid in patients with osteosarcoma

Monitoring - Ca++ trough conc. after 1 month therapy