Mineral Homeostasis and Bone Turnover Flashcards
What two specialized cells are responsible for skeleton remodeling?
Osteoblasts and osteoclasts
Bone remodeling usually occurs in response to what two factors?
Mechanical forces
Endocrine and paracrine factors
Bone is ___% organic component and ___% inorganic component
25%, 75%
What is the main inorganic compound of bone?
Hydroxyapatite
What are the main organic components of bone?
Cells and osteoid
What percent of body calcium is stored in the skeleton and in what form?
99%, hydroxyapatite
What vitamin helps enhance absorption of calcium in the body?
Vitamin D
Inherited deficiency of RANKL or RANK causes a form of what?
Osteopetrosis
Inherited deficiency of OPG causes increased bone resorption and what?
Osteoporosis
Osteoclasts are responsible for what process?
Bone resorption
Osteoblasts are responsible for what process?
Bone formation
What is the most numerous bone cell type?
Osteocytes
What is the function of sclerostin?
It is a protein that inhibits bone formation
Which three hormones mainly mediate calcium and phosphate homeostasis?
parathyroid hormone (PTH), vitamin D, and FGF-23
Vitamin D refers to which two compounds?
Cholecalciferol (D3) and ergocalciferol (D2)
True or false: Vitamin D3 is produced endogenously in the parathyroid gland
False. In the skin
Why is Vitamin D considered a hormone?
It travels from the skin where it is produced in the blood to effect responses in distant target tissues
Why or how is sunlight an important source of Vitamin D?
Vitamin D production in the skin is produced via exposure to sunlight
Antiresorptive agents MOA
Antiresorptive agents prevent or arrest bone loss by suppressing osteoclastic bone resorption
Hormone Replacement Therapy antiresorptive MOA
Estrogens reduce bone resorption by suppressing the transcription of genes coding for RANKL and cytokines such as IL-6
Adverse effects of Hormone Replacement Therapy
Vaginal bleeding
Breast tenderness
Increased risk of venous thromboembolism
Increased long-term risk of breast cancer
What are the different classes of antiresorptive agents?
Hormone Replacement Therapy Selective Estrogen Receptor Modulators Bisphosphonates RANKL Antagonists Calcitonin
What is the most commonly used class of antiresorptive drugs?
Bisphosphonates
Bisphosphonates are analogues of pyrophosphates in which the readily _____ P-O-P bond is replaces by a ______ P-C-P bond
hydrolysable, nonhydrolyzable
5 common examples of bisphosphonates
Alendronate Risedronate Ibandronate Pamidronate Zoledronate
What characteristic of bisphosphonates increases their antiresorptive activity?
Nitrogen-containing amino, pyridine, or imidazole moiety in the side chain
Bone anabolic agents MOA
Increase bone mass and bone strength, not just prevent its loss
What was the first bone anabolic agent?
Fluoride
Fluoride MOA
Converts hydroxyapatite to fluoroapatite, which is denser and more brittle
Native PTH contains how many amino acids?
84 AAs
Is PTH an antiresorptive agent or a bone anabolic agent?
Bone anabolic agent
What three classes of drugs are used to treat secondary hyperparathyroidism in CKD?
Oral phosphate binders
Calcitriol and its analogues
Calcimimetics
What are the three active vitamin D congeners approved for treatment of secondary hyperparathyroidism?
Calcitriol- dihydroxylated form of vitamin D3
Paricalcitol- synthetic analogue of vitamin D
Doxercalciferol- 1α-hydroxylated form of vitamin D2
Which was the first approved calcimimetic drug? What is its MOA?
Cinacalcet. Binds to the transmembrane region of the calcium-sensing receptor and thereby modulates receptor activity by increasing its sensitivity to calcium
