Quiz 1 Flashcards by Melanie Stein

When is parathyroid hormone released?

Released due to low blood calcium

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What does parathyroid hormone indirectly stimulate?

Osteoclastic bone breakdown

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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

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What does activated vitamin D do?

increases intestinal absorption of calcium

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Which hormone activates Vitamin D ?

PTH

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Physiological increases of PTH have been shown to do what?

Increases calcium in adipocytes

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PTH excess may promote what? How? (review this article)

Weight gain

-by impeding catecholamine induced lipolysis

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What do Parafollicular cells release?

calcitonin

-(a peptide hormone)

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What stimulates calcitonin release?

Elevated blood calcium and gastrin

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What does Calcitonin do regarding osteoblasts?

Calcitonin binds to and inhibits osteoclasts thus increasing osteoblastic activity

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What two things does calcitonin increase?

Renal excretion of calcium

- Renal absorption of phosphate

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What two diseases is calcitonin used in?Why?

osteoporosis
Pagets
inhibits bone pain

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What peptide hormone may be used as a diagnostic marker in medullary thyroid cancer?

Calcitonin

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Bisphosphonates have been shown to what?

Increase bone mineral density in patients with osteoporosis and osteopenia

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What has been shown to reduce vertebral fracture rates with minimal change in bone density

Calcitonin

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What has been shown to reduce bone pain associated with fractures?

calcitonin

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How do androgens affect bone directly?

Via interactions with androgen receptors

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How do androgens affect bone indirectly?

Via binding to ERalpha and ER beta after aromatization

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What two things preserve trabecular bone?

How?

Androgens
Estrogens
By decreasing osteoclastogenesis after interacting with bone marrow osteoblast precursors and possibly osteoclasts

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What do androgens and estrogens prevent?

Prevent osteoblast apoptosis

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What do androgens and estrogens stimulate?

Osteoclast apoptosis

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How do androgens exert their major effect on trabecular bone?

Local aromatization to estrogens

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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?

1. ) Bone morphogenetic proteins (BMP) 2. ) Wnt proteins (mammalian homologue of winglessness in drosophila) 3. ) Insulin-like growth factor 1 (IGF-1) 4. )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?

1. ) TSHR acts via an alternative pathway or 2. ) 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