Quiz 1 Flashcards
When is parathyroid hormone released?
Released due to low blood calcium
What does parathyroid hormone indirectly stimulate?
Osteoclastic bone breakdown
Parathyroid hormone increases what 4 things?
- Renal Calcium absorption in the DCT and CD
- Renal excretion of phosphate
- Intestinal absorption of phosphate
- Renal activation of Vitamin d to its active form
What does activated vitamin D do?
increases intestinal absorption of calcium
Which hormone activates Vitamin D ?
PTH
Physiological increases of PTH have been shown to do what?
Increases calcium in adipocytes
PTH excess may promote what? How? (review this article)
Weight gain
-by impeding catecholamine induced lipolysis
What do Parafollicular cells release?
calcitonin
-(a peptide hormone)
What stimulates calcitonin release?
Elevated blood calcium and gastrin
What does Calcitonin do regarding osteoblasts?
Calcitonin binds to and inhibits osteoclasts thus increasing osteoblastic activity
What two things does calcitonin increase?
- Renal excretion of calcium
- Renal absorption of phosphate
What two diseases is calcitonin used in?Why?
- osteoporosis
- Pagets
- inhibits bone pain
What peptide hormone may be used as a diagnostic marker in medullary thyroid cancer?
Calcitonin
Bisphosphonates have been shown to what?
Increase bone mineral density in patients with osteoporosis and osteopenia
What has been shown to reduce vertebral fracture rates with minimal change in bone density
Calcitonin
What has been shown to reduce bone pain associated with fractures?
calcitonin
How do androgens affect bone directly?
Via interactions with androgen receptors
How do androgens affect bone indirectly?
Via binding to ERalpha and ER beta after aromatization
What two things preserve trabecular bone?
How?
- Androgens
- Estrogens
- By decreasing osteoclastogenesis after interacting with bone marrow osteoblast precursors and possibly osteoclasts
What do androgens and estrogens prevent?
Prevent osteoblast apoptosis
What do androgens and estrogens stimulate?
Osteoclast apoptosis
How do androgens exert their major effect on trabecular bone?
Local aromatization to estrogens
What mediates androgens effects on growth plate closure?
aromatization to estrogens and binding to ERalpha
Androgens promote growth in what direction?
Radial
Estrogens promote growth in what direction?
Longitudinal
Why do female growth plates ossify more rapidly
Estrogen promoting longitudinal growth formation
New thoughts on progesterone?
it is likely working through bone formation pathways to play a role in maintaining women’s bone and in osteoporosis prevention
-progesterone as co-therapy with antiresorptive agents may have promise
Is glucocorticoid excess affect on bone good or bad?
Bad!
What can glucocorticoids do to bone in excess?
reduce bone formation and restoration
- causes a disorder of mesenchymal stroll cells
- induces osteoporosis
What are four factors that influence bone remodeling?
- ) Bone morphogenetic proteins (BMP)
- ) Wnt proteins (mammalian homologue of winglessness in drosophila)
- ) Insulin-like growth factor 1 (IGF-1)
- )Receptor activator of nuclear factor k-b(RANK) ligand
What are Bone Morphogenetic Proteins (BMP)
-what is their mechanism of action?
- BMP belong to family of transforming growth factor beta
- MOA: formation of new osteoblasts
What are WNT proteins and what is their MOA?
- Glycoproteins functioning through multiple pathways
- MOA:
1. ) specification of osteoblasts from chondrocytes
2. ) enhanced formation of osteoblasts
3. ) Enhanced survival of osteoblasts and osteocytes
What is insulin-like growth factor 1 (IGF-1) and what is its MOA?
- in charge of bone production stimulated by parathyroid hormone
- MOA: osteoblast differentiation and prevention of osteoblast apoptosis
What is Receptor activator of nuclear factor k-B (RANK) Ligand and what is its MOA?
- Protein produced by osteoblasts
- MOA: promotes osteoclast activation and favors bone reabsorption
Hypothyroidism can cause what on bones?
impaired bone formation and growth retardation
What does thyrotoxicosis (surpassed tsh) result in?
accelerated growth, advanced bone aage and decreased bone mass
-leads to increased risk of osteoporotic fracture
What does recent research show that TSH may be?
a negative regulator of bone turnover acting via the TSH receptor on both osteoblasts and osteoclasts
New research shows that TSH deficiency could be responsible for what?
skeletal loss seen in thyrotoxicosis
What is the only thing that responds to TSH regarding bone?
Osteoclasts
What does the lack of cAMP response to TSH or TSHrab in mature osteoclasts suggest?
- ) TSHR acts via an alternative pathway or
- ) TSH effects on osteoclast numbers and resorption pits reflect its early actions on progenitor cells to regulate osteoclast recruitment and differentiation
What does growth hormone do?
Stimulate growth of bone, cartilage and connective tissue
-increases the number of cells (ex.muscle and bones)
What does the family of polypeptide called somatomedin do?
mediates the effects of growth hormone on skeletal growth?
What is necessary for normal osteogenesis?
- Thyroid hormone
- Insulin
What does Insulin do in regards to osteogenesis?
Increases cytoplasmic growth
What does thyroid hormone required for?
Full effect oh growth hormone on DNA replication
Growth hormone stimulates what?
proliferation of human osteoblasts
What did studies show about IGF-1 and II?
they exerted proliferative effects on both Human osteoblast like cells (HOB) and human marrow stromal cells (HMS)
Studies showed that co-stimulation of IGF-I and II with GH exhibited what?
synergism in enhancing the proliferative response
What is the active form of vitamin D?
1,25(OH)2D3
What is vitamin D responsible for?
absorption of calcium from the gut
-acts indirectly by increasing serum calcium levels thus reducing effect of PTH on bone
Where is Vitamin D synthesized?
- Skin
- Liver
- Kidney
Vascular calcification, angiogenesis and vascular cell migration is regulated by what protein?
vitamin k dependent protein
What is Matrix Gal Protein (MGP)
Type of Vitamin K dependent protein that inhibits osteogenic factors thereby inhibiting vascular and soft tissue calcification
What are the Normal T Score Findings
What do they mean
T>-1.0
Low fracture risk
only give lifestyle advice
T= -1.0 to -2.5
Above Average
Possible osteopenia
HRT in women, possible vitamin D
T < -2.5
Osteoporosis
High fracture risk
give bisphononates
