Bone and Parathyroid

Bones serve as a depot for

#NAME?

Osteoblasts

Bone forming cells

Osteoblasts line the bone surfaces and synthesize and secrete:

#NAME?

Full mineralization of an area of newly secreted matrix may take _________ to complete.

3-4 months

Osteoblasts differentiate from...

multipotential mesenchymal stem cells residing in the marrow.

Osteoblasts differentiates in response to...

local grow factors (morphogenic growth factors and FGFs)

Osteocytes

Mature bone cells

Mature osteoblasts that have completed matrix protein secretion and are now embedded in the matrix surrounded by cortical bone are known as...

osteocytes.

Osteocytes can be stimulated to resorb bone from the surrounding _______ that encase them.

canalicular walls

Osteocyte Function:

#NAME?

Osteoclasts

Bone resorption cells

Large, multinucleated cells on trabecular surfaces that are responsible for bone resorption:

Osteoclasts

Osteoclasts terminally differentiate under the stimulation of:

-Monocyte colony-stimulating factor (MCSF)
-Expression of the RANK surface receptor to bind the osteoblast-generated RANKL and downstream mediators of RANKL.
-Specific integrin receptors (?v?3) bind the osteoclasts to the underlying mineralized bone

Bone Formation: Active _______ synthesize and extrude collagen

osteoblasts

Bone Formation: Collagen fibrils form arrays of an organic matrix
called the...

osteoid.

Bone Formation:Calcium phosphate is deposited in the osteoid and
becomes...

mineralized.

Bone formation is dependent on:

#NAME?

Steps of Bone Formation:

#NAME?

______ in bone provide structural integrity of the bone and skeleton.

Calcium salts

Bone serves as a "buffer" to prevent...

sudden changes in blood Ca2+ levels.

Calcium is tightly co-regulated with
______ in the body.

phosphorous

Ca++ plasma levels

8.5-10 mg/dL

Only _____ Ca2+ is biologically active.

free, ionized

Phosphorous is an essential mineral necessary for:

#NAME?

PO4 plasma levels

3-4.5 mg/dL

Falling blood Ca2+ levels signal...

the parathyroid glands to release PTH.

Signals osteoclasts to
degrade bone matrix and
release Ca2+ into the blood:

PTH

Rising blood Ca2+ levels trigger the...

thyroid to release calcitonin.

Stimulates calcium salt deposit in bone:

Calcitonin

Chief cells of parathyroid release...

PTH

Oxyphil cells of parathyroid functions are unclear but...

#NAME?

PTH is stimulated by...

low blow Ca++

PTH increases plasma...

Ca

PTH decreases plasma

PO4

PTH effects on bone:

Increases osteoclast number & activity to increase resorption of bone.

PTH effects on kidney:

#NAME?

PTH effects on liver:

Stimulate synthesis
of 1, 25-(OH)2-vitamin D

_____ levels tend to move in
the opposite direction from blood
calcium levels.

Phosphate

PTH effects on intestine:

Decreases reabsorption of phosphate
from the gut

Despite close connection between Ca2+ and PO4, no direct control of PTH appears to be exerted by...

plasma phosphate levels.

Calcitonin acts to _______ plasma calcium.

decrease

Calcitonin is synthesized and
secreted by...

parafollicular cells (C cells) of thyroid gland

Calcitonin inhibits osteoclast...

motility and activity via increases in cAMP

The major effect of calcitonin administration is a fall in Ca2+
plasma levels due to...

inhibition of bone resorption.

The main function of 1,25(OH)2 vitamin D is to...

support circulating calcium concentrations.

Vitamin D stimulates calcium absorption from the gut lumen by:

#NAME?

Vitamin D increases bone resorption by stimulating osteoblastic production of..

RANKL.

Vitamin D increases the uptake of calcium in the gut by upregulating...

calbindin and TRPV6.

RANKL activates...

osteoclasts.

Vitamin D deficiency causes:

#NAME?

______ is the active and most potent metabolite of Vitamin D

1,25-dihydroxycholecalciferol (Calcitriol)

______ stimulates the hydroxylation to 1,25-dihydroxycholecalciferol
(Calcitriol)

PTH

Hypocalcemia is most often due to:

#NAME?

Hypocalcemia Symptoms:

#NAME?

Hypercalcemia is due to:

#NAME?

Hypercalcemia Symptoms:

#NAME?

Paget's Disease:

#NAME?

Paget's Disease Treatment:

#NAME?

Possible secondary causes of osteoporosis include:

-Glucocorticoid Use
-Cushing's Disease
-Kidney failure
-Thyrotoxicosis

Osteoporosis BMD

> 2.5 SD

Normal BMD

1 SD

Vitamin D RDA:

400-800 IU/day

Over age 50 Ca++ RDA

1200 mg/day

Bisphosphonates MOA

#NAME?

Biphosphanates is _______ on trabecular bone than it is cortical bone.

greater

Bisphosphonates include:

#NAME?

IV Bisphosphonates

#NAME?

Not approved (but used for osteoporosis)

#NAME?

Biphosphonates should never be administered with...

food.

Biphosphonates Side Effects:

Gastric and esophageal irritation

Biphosphonates Contraidications:

#NAME?

Substitution of carbon for
oxygen on pyrophosphate compound leads to:

#NAME?

Nitrogen-containing side
chain (R2) on pyrophosphate compound leads to:

#NAME?

Annual infusion for prevention and treatment of osteoporosis:

Zoledronate (Reclast)

Biphosphonate with less inhibition of bone mineralization and is suitable for long-term administration:

Alendronate (Fosamax)

FDA approved for Paget's disease
(Not approved for osteoporosis):

Etidronate (Didronel)

Risk of _____ with Etidronate (Didronel) in prolonged therapy

osteomalacia

Unlike other bisphosphonates, etidronate (Didronel) prevents...

bone calcification.

Approved for treatment of hypercalcemia of malignancy and bone cancer and also used for Paget's disease:

Pamidronate (Aredia)

Potency of bisophosphonates:

#NAME?

Bisphosphonate Side Effects:

#NAME?

SERMs definition:

Selective Estrogen Receptor Modulators

SERM agent:

Raloxifene (Evista)

Raloxifene (Evista) reduces risk of ________ fractures by 30-50%

vertebral

Raloxifene (Evista) should be used in conjunction with

#NAME?

Raloxifene (Evista) adverse reactions:

#NAME?

Raloxifene (Evista) is contraindicated in:

#NAME?

Teriparatide (Forteo) is a

recombinant human Parathyroid hormone
(PTH).

Teriparatide (Forteo) adverse reactions:

Nausea

Teriparatide (Forteo) Contraindications:

#NAME?

Calcitonin MOA

Decreases osteoclastic activity and tubular
reabsorption of calcium.

Denosumab (Prolia) MOA

Antibody against RANK Ligand which disrupts osteoclast differentiation and function,