Vitamin D and Osteoporosis

1
Vitamin D and Osteoporosis

• Lindsey.elmore_at_ucsf.edu

2
Be able to describe the role of Vitamin D in
calcium homeostasis

• Ca is in active flux, and 98 of the Ca that is
  filtered at the kidney is resorbed. Ca is
  predominantly excreted in the feces.
• Vitamin D has many receptors throughout the body
  and many roles in differentiation and
  replication.

3
Be able to label a simple diagram of the
biosynthesis of Vitamin D
25 hydroxylase Not PTH dependent
Some bone activity, little intestine
Storage Form
a-1 hydroxylase PTH dependent
Most Active
24 hydroxylase
INACTIVE
4
Know the relative potencies of cholecaciferol, 25
OH D, and 1,25 OH2 D3 and what structural
differences between them account for these
differences.

• Cholecalciferol (D3) and ergocalciferol (D2) are
  used as supplementation and are too slow to be
  used for rescue therapy. These are equipotent and
  can be used to maintain Vitamin D levels for a
  very extended period of time.
• 25 OH D (calcifediol) has weak activity and must
  be converted to calcitriol under the influence of
  PTH. However can be used for a long time.
• Structurally, only the 1 OH makes a big
  difference, but the fact that forms other than
  calcitriol have to be processed makes a
  difference.

• 1,25 OH2 D3 is the most active form of Vit D
  (can cause hypercalcemia). Increases Vit D in a
  few days. Used to quickly boost serum D and Ca
  levels in rickets, hypoparathyroidism, ESRD.

5
What are the half-lives of the different forms of
vitamin D and how important in determining their
clinical uses.

• A)  Parent Compounds1)  Cholecalciferol (D3) 19
  to 48 hours
• Represents initial plasma half-life however,
  storage and slow release from tissues occurs, and
  the terminal half-life may exceed 3 weeks.
• 2)  Ergocalciferol (D2)
• 19 days
• B)  Metabolites1)  25-Hydroxycholecalciferol
  (Calcidiol)
• about 19 days
• 2) 1,25-Dihydroxycholecalciferol (Calcitriol)
• less than 24 hours

6
Know the differences of calcipotriol and
calcitriol.

• Calcipotriol is a Vit D antagonist that is used
  as a topical antipsoriatic. Recognizable because
  of cyclic propyl.
• Calcitriol is a Ca agonist that has strong
  binding in the gut that rapidly raises blood Ca.
  Hypercalcemia is the most common SE.

7
Useful agents to treat osteoporosis.

• Calcitriol and Ca supplements overall bone
  building.
• SERMs Raloxifene prevents bone loss
• Estrogen replacement therapy
• Calcitonin-salmon
• Bisphosphonates-sits on the surface of bone and
  prevents osteoclasts binding.
• PTH Recombinant Teriperitide-first 34 AAs of
  PTH mobilizes Ca from bone on a time course.
  When given constantly re-grows bone. Drug of
  last resort.

8
Fill in the box below with arrows to indicate the
effects of Vitamin D on various organ systems.
9
Label the diagram. Include the major sites where
metabolism takes place.
10
Name 7 drugs that are used to treat osteoporosis.

• Which ones are used for prevention? Which ones
  are used for treatment?
• What is the rationale for using these drugs?