Bone Mineral Homeostasis

Question 1

Hormonal Regulators : PTH, Vitamin D , and Calcitonin

1. What are their net effects and what are their bone effects?

Answer 1

PTH : Net = incr CA2+ IN PLASMA AND DECR PO4 IN PLASMA ; Bone = INCR bone resorption

Vit D : Net = INCR CA2+ and PO4 in plasma
; bone = incr bone mineralization

Calcitonin : Net N/A ; Bone = decreases bone resorption

Question 2

How does PTH work on your bone, kidney, and GI tract?

Answer 2

Bone : Bone resorption , more Ca and Phosphate in circulation

Kidney : Incr reabs of ca2+, decr reabs of po4 (more Po43- in urine), incr production of VitD metabolite

GI : Incr absorption of Ca2+ indirectly via VitD

Question 3

Action of PTH on Bone : Describe using PTH, Osteoblast, osteoclast, RANKL, OPG

Answer 3

PTH binds PTH-R (GPCR) on osteoblast, stimulate RANKL binding to Osteoclast . OPG is secreted from osteoblast it wants to bind RANKL! But RANKL>OPG

–> Resorption of Ca2+ and Po43-

Question 4

Sources of VitD? What is vitamin D3 name?
Whats the plant form?

How do you get activated Vitamin D (Calcitriol)?

Answer 4

Sources : Diet and Skin
Vitamin D3, cholecalciferol
Ergocalciferol Vitamin D2

Liver produces 25 hydroxylase –> Kidney 1 alpha hydroxylase –> active vitamin D

Question 5

VitaminD MAIN EFFECT/NET effect ?

Answer 5

Main –> increases absorption of Ca2+ and PO43- in GI tract to increase circulation –> net effect = incr ca and po43- in plasma

Side effect : Increases bone formation because of bone absorption of ca and po43-

Question 6

Calcitonin : Does what?

Answer 6

Blocks bone resorption , promotes bone formation
- inhibition of osteoclast activity

Question 7

Drugs that affect bone mineral Homeostasis : TERIPARATIDE, ABALOPARATIDE

1. what is it?
2. MOA?
3. In the concentration of the drug used clinically, what is made more than what?
4. Use is for?
5. AE’s? (3)
6. CI in ?
7. Admin?
8. Use for greater than ___ not recomended?

Answer 7

1. recombinant PTH
2. Binds to PTH-R
3. OPG»>RANKL . so OPG binds RANKL, no osteoclast involvement. Collagen –> mineralization –> Formation of Bone
4. Osteoporosis
5. Hypercalcemia, osteosarcoma, orthostatic hypotension on first dose
6. Osteosarcoma (BBW)
7. SC
8. 2 yrs

Question 8

Vitamin D
What’s the non rx, rx only , and activated form?

MOA?

use? (2)
AE? (rare)

take with ? (Name 2)

Calcium supplements usage?
Ae’s ?
DDI?

Answer 8

non rx = cholecalciferol = d3
rx = ergocalciferol = d2
activated = calcitriol

MOA : regulate gene transcription via vitamin D receptor

dietary supplement + osteoporosis (off label)

hypercalcemia

calcium supps (Calc carb which is insoluble so take with meal) or calcium citrate which is not affected by meal

osteoporosis prophylaxis with VitD

Constipation

Space drugs apart at least 2 hrs

Question 9

Calcitonin : From Where?

MOA? Agonist at, inhibits what?

Use? (3) state the admin routes as well

AE’s (5)

CI in ?

Answer 9

salmon

agonist at calcitonin-R (GPCR)
inhibits bone resorption by direct action on osteoclasts

Osteoporosis (Intranasal, IM , SC) , Hypercalcemia + Paget’s Disease (IM, SC)

rhinitis; allergic reactions, flushing of face and hands, malignancy (can incr risk of melanoma and breast cancer), HYPOcalcemia

Fish hypersensitivity

Question 10

SERMs (Selective estrogen receptor modulators) : Raloxifene

MOA? postive and neg effects on what?

Uses? (1)

AE’s (3)

CI (2)?

DDI? (2)

Answer 10

estrogen modulator. pos effects on bone and liver, neg effects on breast, uterus, and brain
–> INCR bone formation and decr bone resorption

Osteoporosis

Hot flashes, night sweats , incr risk of thromboembolism

Thromboembolic disease + Stroke (BBW)

levothyroxine (separate by 12 hrs) and warfarin (monitor INR)

Question 11

Non Hormonal : Biphosphonates + Denosumab

For the following Biphosph : State their dosing
1. alendronate
2. risedronate
3. Ibandronate
4. Zoledronic acid

Ibandronate is only ____ while all the other ones reduce?

Answer 11

1. once weekly , po
2. once weekly or once monthly, po
3. once monthly if PO, every 3 months if IV
4. Once yearly, IV

vertebral fracture reduction

vertebral fracture, hip fracture, and non vertebral fracture reduction

Question 12

MOA of biphosphonates?
(binds? inhibits? beneficial effect on?)
PK?
USEs (3)?

Answer 12

Binds hydroxyapatite in bone
inhibits osteoclastic bone resoprtion
beneficial effect on osteoBLASTS (prevents apoptosis)

poorly absrobed orally , give on empty stomach with water, ; wait 30 mins before ingesting food

Osteoporosis, hypercalcemia, paget disease

Question 13

AE’s of Biphosph? (3)

Other AE’s that are rare for oral and IV?

Answer 13

1. Upper GI side effects (reflux, esophagitis, ulcer) (oral drugs )
2. flu like symptoms (fever, myalgias, and arthalgias) (IV)
3. Musculoskeletal pain (IV)
4. HyPOcalcemia , osteonecrosis of jaw , atypical femur fractures

Question 14

CI of Biphosphonates ? (3)
DDI? (2)

Need to monitor?

keep patient on drug for how long? and then?

Answer 14

renal impairment, hypocalcemia, esophageal disorders

-take apart from drugs that contain cationic agents (antacids, mineral suppls)
-NSAIDS

Serum creatinine, serum calcium

3-5 yrs, then re-evaluate

Question 15

DENOSUMAB

1. MOA?
2. Uses? (2)
3. AE’s ? (3)
4. Admin?

Answer 15

1. fully humanized mAB to RANK-L
2. osteoporosis + hypercalcemia
3. Back pain, ONJ, Atypical femur fraction
4. SQ twice a year

Question 16

For Osteoporosis, state what the following are used for, prevention , tx, or both, and which fractures they help to reduce as a class?

1. Bisphosphonates
2. Denosumab
3. Raloxifene
4. Teriparatide

Answer 16

1. prevention + TX, ALL vertebral, hip, and non vertebral fractures . except ibandronate only vertebral
2. tx’s only. ALL
3. Prevention and TX . only vertebral
4. Treatment only . vertebral + non vertebral