Fitzpatrick - Osteoporosis

Question 1

Define T-score

Answer 1

Expression of Bone mass density (BMD) determined by a radiographic procedure (DEXA) is essential for surveillance & diagnosis of osteoporosis.

Question 2

T-Score and % for BMD of women 30-40 years old:

• Osteoporosis
• Osteopenia
• Normal

Answer 2

• Osteoporosis = Less than -2.5; 0-6%
• Osteopenia = -1 to -2.5; 6-15%
• Normal = 4 to -1; 15-100%

Question 3

What does T-score compare and equation.

Answer 3

“T-score” compares the patient’s BMD with young-normal mean BMD and expresses the difference as a standard deviation (SD) score:
(Patient’s BMD – Young-Adult Mean BMD) / (1 SD of Young-Adult Mean BMD)

Question 4

T-Score Significance:
Every 1 SD less than normal =
\_\_\_% drop in BMD =
\_\_\_ risk of vertebral
fracture

Answer 4

Every 1 SD = 10-20% drop in BMD = 2x risk of vertebral fracture

Question 5

Calcium carbonate

1. What % Ca2+?
2. What does it need to dissolve?
3. Take it when?
4. Potential disadvantage with increasing age of person.

Answer 5

1. 40%
2. Needs ACID to dissolve.
3. Take “at” or “after” meals
4. Less stomach acid with aging.

Question 6

Calcium citrate

1. What % Ca2+?
2. What does it need to dissolve?
3. Take it when?
4. Potential problem disadvantage.

Answer 6

1. 20% Calcium
2. No need for stomach acid for absorption
3. May be taken between meals
4. Higher cost

Question 7

The “sufficient” % of Dietary Calcium absorbed - and what Vitamin promotes intestinal absorption?

Answer 7

• 30-40%

- 1,25 (OH)3 Vitamin D3 promotes intestinal Ca2+ absorption.

Question 8

Normal Vitamin D requirement.

Answer 8

400-800 IU/day

Question 9

Vitamin D requirement exceeds 800IU/day in persons… (four)

Answer 9

• With GI malabsorption disorders
• Receiving corticosteroids, certain anticonvulsants, loop diuretics, heparin
• Who are elderly or who have
-less exposure/response to sunlight
-less hydroxylation in liver & kidney

Question 10

Name the 6 drugs that lower serum Ca (2dary causes of osteoporosis).

Answer 10

• GC: Prednisone, methylprednisolone; inhaled Budesonide
• Anticonvulsants: Carbamazepine; phenytoin
• Loops: Furosemide

Question 11

Use and adverse effect of (GC) Prednisone and methylprednisolone

Answer 11

• Use: Severe inflammation asthma, COPD, bronchitis, ulcerative colitis, etc
• AE: Impairs vitamin D absorption & impairs metabolic activation in liver & kidney

Question 12

Use and adverse effect of (GC) inhaled Budensonide

Answer 12

• Use: Asthma, COPD

- AE: Impairs vitamin D absorption & impairs metabolic activation in liver & kidney

Question 13

Use and adverse effect of (anticonvulsants) Carbamazepine and phenytoin

Answer 13

• Use: epileptic seizures

- AE: Induction fo cytochrome p450 hepatic INACTIVATION of vit D

Question 14

Use and adverse effect of Furosemide

Answer 14

• Use: HTN, HF

- AE: Calcium wasting

Question 15

Indication for bone density testing

Answer 15

• To diagnose osteoporosis
• To predict fracture risk
• To monitor therapy like before initiation of systemic GC therapy –> induces bone loss w/in 6mo)

Question 16

Name the MOA of SERMs, Bis-Posphonates, Antibodies, and Biologicals (Calcitonin)

Answer 16

Anti-Resorptive Therapy - These drugs inhibit osteoclasts, cells in bone responsible for resorption of bone matrix ….cells that eat hydroxyapatite (Ca2+)

Question 17

Name the MOA of the biologicals (Teraparatide)

Answer 17

Anabolic Therapy - Activate osteoblasts, cells in bone that deposit hydroxyapatite (Ca 2+)

Question 18

Name the drugs in Selective Estrogen-Receptor Modulators class/SERMs (two)

Answer 18

Raloxifene, Tamoxifen

Question 19

Name the drugs in Bis-Phosphonate class (five)

Answer 19

Alendronate, Ibandronate, Pamidronate, Risedronate, Zolendronate

Question 20

Name the drugs in Biologicals class (two)

Answer 20

Teraparatide, Calcitonin

Question 21

Name the drug in the Antibody class (one)

Answer 21

Denosumab

Question 22

Peak bone mass in women.

Answer 22

30 to 50(ish) years old.

Question 23

Estrogen deficit at menopause does what to bone resorption and formation?

Answer 23

IMBALANCES - excess bone resorption and less bone formation

Question 24

Five risks of HRT (estogens +/- medroxyprogesterone)

Answer 24

Increased risk of: Breast Cancer, Uterine Cancer, MI, stroke, thrombosis

Question 25

MOA of Estrogen HRT

Answer 25

Full agonists at estrogen receptors in ALL tissues.

Question 26

FDA Approved Options: | - Name the two classes of "prevention and treatment"

Answer 26

SERMs and Bisphosphonates

Question 27

FDA Approved Options: | - Name the three drugs for "Treatment only"

Answer 27

Calcitonin, Teriparatide, Denosumab

Question 28

MOA of SERMs at Estrogen Receptors in osteoclasts v. breast epithelium

Answer 28

Estrogens & SERMs are: | - AGONISTS at ERs in Osteoclasts - ANTAGONISTS in breast epithelium

Question 29

MOA of SERMs at Estrogen Receptors in osteoclasts

Answer 29

``` ER receptor  Occupied  Dimerized  Nuclear transport  Gene transcription ```

Question 30

What is the SERM of choice and why?

Answer 30

- Raloxifene (v. Tamoxifen) bc of its safety and efficacy. Usually chosen when there is an independent need for breast cancer prophylaxis. - Raloxifene is not associated with vaginal bleeding or an increased risk of endometrial hyperplasia or cancer

Question 31

Adverse effect of all HRT estrogens and SERMs

Answer 31

Increased risk of VENOUS thromboembolic events.

Question 32

Describe bisphosphonates - where do they accumulate?

Answer 32

Chemically related to Ca2+ phosphate(s); Analogs of pyrophosphate •Sequestered by bone NEAR REMODELING SITES • Accumulate into bone matrix/osteoCLASTS --> EATS THE BP AND BP then inhibits their fxn

Question 33

Key enzyme in osteoclast activation that Bisphosphonates inhibit

Answer 33

Farnesyl Pyrosphosphate Synthase (FPP) synthase

Question 34

- Contraindication of bisphosphonate. | - Half life of BP

Answer 34

- pre-existing hypocalcemia | - Half-Life = 12 years

Question 35

Bisphosphonate administration. If non-compliant, what adverse effect results?

Answer 35

 Take with a full glass of water in morning  Do NOT eat or drink anything for at least 30 minutes after taking (Ibandronate: 60 min)  Do NOT lie down for at least 30 minutes (Ibandronate: 60 min) ****Non-compliance = ESOPHAGITIS****

Question 36

What BP has the highest affinity for bone? Most potency for FPP-synthase inhibition?

Answer 36

Zoledronate

Question 37

A major adverse effect of BPs and the type of pt this AE occurs in (three).

Answer 37

Osteonecrosis of the Jaw  Receiving i.v. bisphosphonates, ~ 90%  Diagnosed with multiple myeloma, breast cancer, and prostate cancer, ~85%  Having tooth extractions, dental trauma ~60%

Question 38

FDA about BP

Answer 38

Bc they remain in bone for decades, consider periodic reevaluation of continued therapy in people treated for ***>5 years*** LONG TERM SAFETY

Question 39

MOA of denosumab

Answer 39

Inhibits osteoCLAST formation/lineage expansion. It is a humanized monoclonal antibody against RANKL (osteoclast RANK cannot bind to osteoBLAST RANKL)

Question 40

Use of calcitonin

Answer 40

Decreases pain with acute vertebral compression fracture. | -Inhibits osteoclast action (anti-resorptive)

Question 41

MOA of teriparatide (PTH fragment)

Answer 41

Intermittent administration that | Stimulates osteoblast activity (anabolic)

Question 42

Contrast teriparatide to BPs

Answer 42

* Very short t ½ | * No deposition in bone

Question 43

Teriparatide is reserved for what type of patients?

Answer 43

Treatment of: -postmenopausal F with osteoporosis at high risk for fracture -increase bone mass in M with primary or hypogonadal osteoporosis at high risk for fracture - Treatment of M/F with osteoporosis associated with sustained, systemic glucocorticoid therapy at high risk for fracture high cost and risk of osteosarcoma + injection daily

Question 44

MOA of cincalcet

Answer 44

- A calcimimetic agent; lowers PTH levels by | * **increasing the sensitivity of the Ca2+-sensing receptor to extracellular Ca2+***

Question 45

Use of cincalcet

Answer 45

- Treats overactive parathyroid gland in dialysis patients with CKD (secondary hyperparathyroidism). - Treat high blood Ca2+ levels in patients with parathyroid cancer.

Question 46

Use of denosumab

Answer 46

When adverse effects of BP (esophagitis) cannot be tolerated.