Bone Lecture 2 Flashcards
Intramembranous Ossification is responsible for formation of bone for:
Bone healing
Growth of flat bones (i.e. skull, carpals, tarsals)
Thickening of long bones
Intramembranous Ossification
Osteoblasts secrete organic matrix (osteoid)
Osteoblasts then directly mineralize the matrix with hydroxyapatite crystals
Once surrounded by calcified matrix, osteoblasts become osteocytes
Osteoblasts are formed by differentiation of cells of the periosteum and endosteum or bone marrow stem cells (mesenchyme)
Osteoblasts secrete an organic bone matrix and then calcify the matrix
Endochondral Ossification
Chondrocytes produce cartilage matrix and calcify the matrix
Osteoblasts enter the area and deposit bone matrix (osteoid) over the calcified cartilage matrix
Osteoblasts/osteocytes – remove remnants of cartilage matrix resulting in typical bone matrix
Process of endochondral ossification is responsible for:
Growth of long bones (epiphyseal plate)
Bone healing
Epiphyseal Plate: Resting Zone
Resting zone
area of normal hyaline cartilage and chondrocytes
Epiphyseal Plate: Proliferative zone
Proliferative zone
area of intense mitosis (proliferation) of chondrocytes
Epiphyseal Plate: Hypertrophic zone
Hypertrophic zone
area of chondrocyte hypertrophy due to glycogen uptake
Cartilage ECM is partially resorbed
Remnants appear as septa of matrix material between hypertrophic chondrocytes
Epiphyseal Plate: Calcified cartilage zone
Calcified cartilage zone
Thin septa of cartilage matrix become calcified
Chondrocytes in this zone die after matrix calcification
Epiphyseal Plate: Ossification zone
Osteoprogenitor cells from the bone marrow are delivered to the calcified cartilage
Osteoprogenitor cells differentiate into osteoblasts
Osteoblasts deposit bone matrix over the calcified cartilage matrix = ossification
Endochondral ossification during fetal development is a similar process:
Osteoid deposition over cartilage matrix
Basics of Bone remodeling
Bone undergoes constant remodeling throughout life
Bone remodeling is dependent on stresses (forces) placed on bones
Bone matrix is deposited and resorbed in accordance with the stresses placed upon it
Wolff’s Law
Every change in form and function of bone, or in its function alone, is followed by certain, definite changes in its internal architecture and external form
Bone models and remodels [its internal architecture] in response to the mechanical stresses it experiences, so as to produce a minimal-weight structure that is ‘adapted’ to its applied stresses
Bones response to fx
Bone matrix/cells are destroyed
Damaged blood vessels produce a localized clot
Clot material is later removed by macrophages
Periosteum and endosteum respond with intense proliferation of cells
Bone response to fx and repair
Periosteal/endosteal fibroblasts differentiate into chondroblasts and form hyaline cartilage model = soft callus
Mesenchyme cells differentiate into osteoblasts and form osteoid
Endochondral and intramembranous ossification occur to form primary (woven) bone = hard callus Hard callus (woven bone) is replaced by lamellar bone
Healing time table
Soft Callus – 2wks
Hard Callus – 4wks
Lamellar Bone – 6wks
Healing bone is influenced by stresses placed upon it during healing
Effects on bone with inactivity
Inactivity or decreased loading of bone results in reduced osteoblast activity
Inactivity/decreased loading do not affect osteoclast activity
Osteoclast activity remains at/near normal levels
The overall result of inactivity is increased degradation of bone matrix and increase in serum Ca++ levels
(urine calcium levels increase since calcium is excreted by kidneys)
Exercise training: effects on bone
Increased loading (mechanical stress) results in improved bone qualities:
Hypertrophy of bone
↑ bone mass/density
↑ load to failure (strength)
Exercise training: effects on bone
Increased loading (mechanical stress) results in improved bone qualities:
Hypertrophy of bone
↑ bone mass/density
↑ load to failure (strength)
Flow for Effects on bone and exercise
Mechanical Stress–>Microscopic deformities
–>↑ blood flow & ↑ bioelectric potentials =
(Piezoelectric effect)
—>Increased osteoblast and osteoclast activity
Flow for Effects on bone and exercise
Mechanical Stress–>Microscopic deformities
–>↑ blood flow & ↑ bioelectric potentials =
(Piezoelectric effect)
—>Increased osteoblast and osteoclast activity
Stress Fx
Repetitive loading on bone creates microscopic deformities
Deformities are healed and bone repaired with rest
Stress fractures result when loading outpaces bone repair/remodeling
Stress Fx
Repetitive loading on bone creates microscopic deformities
Deformities are healed and bone repaired with rest
Stress fractures result when loading outpaces bone repair/remodeling
Osteopenia
reduction in bone mineral density below normal levels, results in decreased bone strength
Osteopenia is often a precursor to the development of osteoporosis
Osteopenia
reduction in bone mineral density below normal levels, results in decreased bone strength
Osteopenia is often a precursor to the development of osteoporosis
Osteopenia occurs as a result of
inactivity, aging, low intake of vitamin D and calcium, smoking
Osteopenia occurs as a result of
inactivity, aging, low intake of vitamin D and calcium, smoking
Osteoporosis
defined as ↓ bone density and ↓ in overall volume of bone
With osteoporosis, bone resorption > bone formation
Osteoporosis often results in pathologic fractures
Failure of bone in response to normal physiologic stress
Bones serves as what reservoir
Ca++ reservoir
99% of total body calcium is in the skeleton
Ca++ levels are tightly controlled by the endocrine system
Key regulators of calcium metabolism
Parathyroid hormone (parathyroid glands) Calcitonin (thyroid gland) Vitamin D (absorbed thru intestines)
Calcium levels in Blood
Hypercalcemia (↑ Ca++ level in serum) > 10.5 mg/dL of blood
Typical symptoms = mild to severe proximal weakness of the extremities
Hypocalcemica (↓ Ca++ level in serum ) < 8.5 mg/dL of blood
Typical symptoms = neuromuscular excitability and muscular tetany (especially UE flexion)
Parathyroid Hormone (PTH)
Secreted from the parathyroid gland in response to low Ca++ levels in the plasma
PTH promotes osteoclast resorption of bone matrix and subsequent liberation of Ca++ into the blood
PTH binds to osteoblasts and stimulates osteoblasts to:
Stop producing bone
Secrete an osteoclast-stimulating factor
PTH also:
Enhances calcium absorption from intestines
Decreases calcium excretion by kidneys
Calcitonin
Synthesized by the thyroid gland in response to elevated blood (plasma) Ca++ levels
Calcitonin
Inhibits matrix resorption by osteoclasts
Inhibits new osteoclast formation
Calcitonin has no effect on osteoblast activity, thus osteoblasts continue to produce bone matrix (and deposit excess the serum calcium onto new bone)
Vitamin D metabolism
Vitamin D is necessary for intestinal absorption of Ca++ and PO4- from the small intestine
Vitamin D is necessary for active reabsorption of Ca++ and PO4- from the kidney
Vitamin D formation is stimulated by UV light; initial molecule is inactive
VItamin D synthesis
Inactive Vit. D is “processed” in the liver and fully activated by the kidneys (hydroxylation)
Activated vitamin D enters the blood stream to assist with calcium absorption from the GI tract
A slight decrease in serum calcium below normal stimulates activation of “inactive” vitamin D
