Bone Homesostasis Flashcards
Calcium has this effect on blood coagulation
Promotes it
3 organ systems involved in calcium balance
Bone, kidney, intestine
3 hormones involved in calcium balance
PTH, Vitamin D, Calcitonin
This is the primary mineral form in bone
Hydroxyapatite (Ca10(PO4)6(OH)2)
Osteoid is the protein matrix of bone, and the majority of it is made up of this
Type I collagen oriented in a tight triple helical structure
This provides site of nucleation of hydroxyapatite crystals with alignment along collagen fibers for tensile strength
Type 1 collagen oriented in tight triple helical structure in osteoid (bone matrix)
Type 1 collagen oriented in a tight triple helical structure within osteoid provides site of nucleation of this, with alignment along collagen fibers for tensile strength
Hydroxyapatite crystals
Cells the promote bone formation
Osteoblasts
Cells that promote bone resoprtion
Osteoclasts
Osteoblasts that localize to the bone during during mineralization and remain there
Osteocytes
Cells that sense mechanical stress on bone and secrete factors to stimulate osteoblasts
Osteocytes
Osteocytes are this type of cell that localize to the bone matrix during mineralization and remain there
Osteoblasts
Flat quinescent cells with barrier function
Bone lining cells
Mononuclear cells that seem to prepare areas for new bone deposition
“Reversal” cells
Osteoprogenitor cells arise from this
Mesenchymal stem cells
When these cells are stimulated by growth factors, daughter cells differentiate into osteoblasts
Osteoprogenitor cells
When osteoprogenitor cells are stimulated by growth factors, daughter cells differentiate into these
Osteoblasts
Osteoblasts are activated by this signaling
Wnt/beta-catenin
The Wnt/beta-catenin signaling pathway governs this
Differentiation of osteoprogenitor cells into osteoblasts
Cells that produce and deposit organic components to form matrix, and initiate the mineralization process
Osteoblasts
Osteoblasts remaining on bone surface transforming to these
Bone lining cells
Osteoblasts surrounded by new matrix differentiate to these
Osteocytes
Osteocytes communicate via this
Canaliculi
Regulators of bone remodeling that communicate via canaliculi
Osteocytes
Osteocytes secrete this which decreases bone formation
Wnt inhibitor sclerostin
What is sclerostin?
Wnt inhibitor secreted by osteocytes that decreases bone formation
Cells that secrete Wnt inhibitor sclerostin that decreases bone formation
Osteocytes
Mechanical forces induce signaling of these cells, leading to expression of growth factors that stimulate osteoblasts and bone formation
Osteocytes
What effect does osteocyte death have on bone?
Triggers remodeling
(apoptosis recruits osteoclasts, initiates resorption; lack of mechanical stimulation increases apoptosis, also aging and glucocorticoids)
What effect does mechanical force/stimulation have on bone?
Induces osteocyte signaling, leading to formation of growth factors that stimulate osteoblasts and bone formation
Lack of mechanical stimulation increases osteocyte apoptosis, triggering remodeling
Osteoclasts originate from these
Myeloid precursors that arise from hematopoietic stem cells
Macrophage colony stimulating factor (M-CSF/CSF1), IL-2, and TNF regulate these cells
Osteoclasts
Osteoclasts are regulated by cytokines and growth factors, including these 3
Macrophage colony stimulating factor (M-CSF/CSF1), IL-2, and TNF
Cells that originate from myeloid precursors that arise from hematopoietic stem cells
Osteoclast
Mature multinucleated osteoclasts (a fusion of 6-12 precursors) survive about this long
2 weeks
Cells that promote bone resorption
Osteoclasts
Osteoclasts promote this
Bone resorption
Cells that bind tightly to bone surface via integrins attachment to vitronectin
Osteoclasts
Osteoclasts bind tightly to bone surface via this attachment
Integrins attachment to vitronectin
Osteoclasts bind tightly to bone surface via integrins attachment to this
Vitronectin
Cells that dissolve minerals by acid (uses proton pump system) and organic elements by proteases
Osteoclasts
Osteoclasts dissolve minerals by this
Acid (proton pump system)
Osteoclasts dissolve organic elements by this
Proteases
Cells that when mature, are multinucleated due to fusion of 6-12 precursors
Osteoclasts
Paracrine factor expressed by osteoblasts that induces osteoclast precursor differentiation
CSF1
CSF1 induces differentiation of this
Osteoclast precursors
Paracrine factor expressed by osteoblasts that promotes differentiation of preosteoclasts to osteoclasts
RANKL
RANKL promotes differentiation of this
Preosteoclasts to osteoclasts
Paracrine factor expressed by osteoblasts that inhibits differentiation of osteoclast precursors by competing with RANKL for receptor binding (a decoy)
Osteoprotegrin (OPG)
Osteoprotegerin (OPG) inhibits differentiation of this
Osteoclast precursors
(competes with RANKL for receptor binding)
What effect does RANKL have on bone?
Promotes osteoclasts, which promote bone resorption
What effect does Osteoprotegerin (OPG) have on bone?
Inhibits differentiation of osteoclast precursors, preventing bone resorption
Cells that express CSF1, osteoprotegerin (OPG), and RANKL to control osteoclast differentiation
Osteoblasts
Osteoblasts express CSF1, osteoprotegerin (OPG) and RANKL to control differentiation of this cell type
Osteoclast
Osteoblasts secrete these 3 paracrine factors to control osteoclast differentiation
CSF1, osteoprotegerin (OPG), RANKL
Osteoclasts express this to induce osteoblast maturation
ephrinB4
Cells that express ephrinB4 to induce osteoblast maturation
Osteoclasts
Osteoclasts express ephrinB4 to induce maturation of this cell type
Osteoblast
What is ephrinB4?
Factor expressed by osteoclasts that induces osteoblast maturation
What effect do glucocorticoids have on bone?
Promote osteoblast cell death
PTH have this effect on calcium balance in the kidney
Promotes Ca reabsorption
PTH has this effect on phosphate balance in the kidney
Inhibits tubular phosphate reabsorption
Hormone that stimulates conversion of Vitamin D to 1,25-dihydroxyvitamin D (calcitriol) in the kidney
Parathyroid hormone
PTH in the kidney stimulates conversion of vitamin D to this
1,25-dihydroxyvitamin D (calcitriol)
Hormone that promotes calcium reabsorption in the kidney
PTH
Hormone that inhibits tubular phosphate reabsorption in the kidney
PTH
Hormone that stimulates conversion of Vitamin D to 1,25-dihydroxyvitamin D (calcitriol) in the kidney
PTH
Hormone that promotes bone homeostasis in the physiologic state
PTH
What effect does PTH have in bone in the physiologic state?
Promotes bone homeostasis
Hormone that stimulates bone resorption by osteoclasts during pathologic state
PTH
What effect does PTH have on bone in a pathologic state?
Stimulates bone resorption by osteoclasts
In the pathologic state, PTH inhibits synthesis of this by osteoblasts
Collagen
Hormone that stimulates calcium absorption by inducing expression of key proteins (calcium channels) and may also enhance diffusion by increasing overall permeability in the small intestine
Vitamin D
Hormone that stimulates phosphate absorption by increasing transporter protein levels in the small intestine
Vitamin D
What effect does Vitamin D have on phosphate balance in the small intestine?
Stimulates phosphate absorption by increasing transporter protein levels
Hormone that acts synergistically with parathyroid hormone to enhance calcium reabsorption in the kidney
Vitamin D
Vitamin D acts synergistically with this hormone to enhance calcium reabsorption in the kidney
PTH
What effect does Vitamin D have on calcium balance in the kidney?
Acts synergistically with parathyroid hormone to enhance calcium reabsorption
Hormone that directly mobilizes calcium out of bone
Vitamin D
Hormone that inhibits resorption activity when it binds to osteoclasts receptor to induce retraction
Calcitonin
What effect does calcitonin have on bone?
Binding inhibits resorptive activity of osteoclasts
In the kidney, this hormone promotes diuresis and excretion of phosphate, sodium and calcium in urine
Calcitonin
Does calcitonin secretion increase when calcium is high or low?
High
to inhibit osteoclast bone resorption and activate osteoblast bone formation
Does PTH secretion increase when calcium is high or low?
Low
to enhance Ca reabsorption in the kidney, stimulate conversion of vit D to calcitriol, and inhibit tubular reabsorption of P
Testosterone and estradiol have this effect on bone
Promote bone deposition
favors balance of bone formation over resorption
These enhance bone resorption by altering gene expression and cell survival
Glucocorticoids
promote death of osteoblasts and osteocytes
What effect do glucocorticoids have on bone?
Enhance bone resorption
Pyrophosphate analogs that chelate calcium, have strong affinity for bone and inhibit bone resorption
Bisphophonates
Bisphophonates are analogs of this
Pyrophosphate
Bisphophonates chelate this
Calcium
Bisphophonates have this effect on bone
Inhibit bone resorption
Which are more potent: nitrogenous bisphophonates or non-nitrogenous?
Nitrogenous
Heartburn and esophageal irritation are adverse effects of these
Bisphophonates
Very potent bisphophonate that may induce hypocalcemia and reduced renal function
Zoledronate
Zoledronate is this type of drug
Bisphophonate
Alendronate is this type of drug
Bisphophonates
Zoledronate is a Bisphophonate that may induce this
Hypocalcemia and reduced renal function
2 common adverse effects of Bisphophonates
Heartburn
Esophageal irritation
Monoclonal antibody targeting sclerostin
Romosozumab
Romosozumab targets this
Sclerostin
Anabolic drug with black box warning of increased risk of cardiovascular events
Romosozumab
Romosozumab have this black box warning
Increased risk of cardiovascular events
Anabolic drug that is a terminal fragment of PTH
Teriparatide
Anabolic drug that needs intermittent administration
Teriparatide
Anabolic drug with a black box warning of increased risk of osteosarcoma
Teriparatide
Teriparatide has a black box warning of this
Increased risk of osteosarcoma
Bisphophonate alternative that inhibits osteoclast formation by depleting RANKL, and can lead to bone gain
Denosumab
Bisphophonate alternative with a black box of severe hypocalcemia in patients with advanced kidney disease
Denosumab
Denosumab inhibits formation of these cells by depleting RANKL
Osteoclasts
Denosumab inhibits formation of these cells
Osteoclasts
Denosumab inhibits formation of osteoclasts by depleting this
RANKL
Denosumab has a black box of this in patients with advanced kidney disease
Severe hypocalcemia
What are SERMs?
Selective estrogen receptor modulators
Used as a Bisphophonate alternative
Ex: Raloxifene