Lesson 9: Ch. 7: Bone (Osseous) Tissue

ossification or osteogenesis

the formation of bone

calcification

process of depositing calcium salts during bone ossification and in other tissues (ex: cartilage)

bone develops by two methods, both beginning with embryonic mesenchyme

1. intramembranous ossification

2. endochondral ossification

intramembranous ossification (dermal ossification)

• occurs in the dermis

• important in the lifelong thickening and remodeling of long bone

• produces the flat bones of the skull, most of the clavicle, and part of the mandible

intramembranous ossification summary of stages

1. deposition of osteoid tissue into embryonic mesenchyme

2. calcification of osteoid tissue and entrapment of osteoblasts, causing them to become osteocytes

3. honeycomb of spongy bone forms with the periosteum developing on the outside

4. osteoblasts under the periosteum fill in between the trabeculae, forming compact bone and leaving spongy bone underneath

endochondral ossification

bone develops from hyaline cartilage model; produces most bones of body (bones of limbs, vertebrae, ribs, sternum, scapula, pelvic girdle)

endochondral ossification summary stages (using the metacarpal as an example) (very simplified)

1. mesenchyme forms early hyaline cartilage model

2. formation of primary ossification center

3. formation of primary marrow cavity & formation of secondary ossification center

4. at birth: secondary marrow cavity & secondary ossification center

5. during infancy and childhood: epiphyseal plate

6. adult: epiphyseal line

primary marrow cavity

osteoblasts enter and line the cavity, formation of secondary ossification center (at an epiphysis)

epiphyseal plate

• cartilage

• serves as growth zone

metaphysis

the transitional zone on each side of the epiphyseal plate, where cartilage is replaced by bone

zone of reserve cartilage

composed of resting chondrocytes

zones of cell proliferation

multiplying chondrocytes forming lacunae

zones of cell hypertrophy

chondrocytes enlarge - no mitosis

zone of calcification

temporary mineral deposition between lacunae

zone of bone deposition

chondrocytes die, osteoblasts enter and deposit matrix to form concentric lamellae

bone elongation

• epiphyseal plate

• metaphysis

• zones of…

Zones of the metaphysis

1. reserve cartilage

2. cell proliferation

3. cell hypertrophy

4. calcification

5. bone deposition

zone of reserve cartilage

typical histology of resting hyaline cartilage

zone of cell proliferation

chondrocytes multiplying and lining up in rows of small flattened lacunae

zones of cell hypertrophy

cessation of mitosis

enlargement of chondrocytes and thinning of lacunae walls

zone of calcification

temporary calcification of cartilage matrix between columns of lacunae

zone of bone deposition

breakdown of lacuna walls, leaving open channels

death of chondrocytes

bone deposition by osteoblasts, forming trabeculae of spongy bone

interstitial growth

cartilage growth from within

achondroplastic dwarfism

long bones stop growing in childhood

results in normal torso length but shortened limbs

pituitary dwarfism

• lack of growth hormone from the anterior lobe of the pituitary gland

• normal proportions with short stature

achondroplastic dwarfism cause

• genetic cause: mutation in the FGFR3 gene

• spontaneous mutation produces mutant dominant allele

• causes failure of cartilage growth in metaphysis

FGFR3 gene

important in bone development and maintenance

appositional growth

deposition of new tissue at the bone surface

appositional growth occurs by intramembranous ossification at bone surface

• osteoblasts of inner layer of periosteum deposit osteoid tissue, become trapped as tissue calcifies

• the osteoblasts lay down matrix in layers parallel to the bone surface, forming circumferential lamellae

• as bone increases in diameter, the marrow cavity widens as osteoclasts of endosteum enlarge marrow cavity by dissolving inner surface bone tissue

bone remodeling

• bones continually remodeled (absorption and deposition) throughout life, replacing 10% of skeleton per year

• repairs microfractures, releases minerals into blood, reshapes bones in response to use and disuse

• wolff’s law of bone

wolff’s law of bone

• architecture of bone determined by mechanical stresses placed on it

• remodeling is a collaborative and precise action of osteoblasts and osteoclasts

• bony processes grow larger in response to mechanical stress

mineral deposition (mineralization)

• crystallization process in which calcium, phosphate, and other ions are taken from blood and deposited in bone

• osteoblasts produce collagen fibers that spiral the length of the osteon; fibers become encrusted with minerals

• first few crystals act as seed crystals that attract more calcium and phosphate from solution

ectopic ossification

abnormal calcification of tissues, such as a lung, brain, eye, muscle, tendon, or artery (arteriosclerosis)

produces heterotopic bones

calculus

a calcified mass in an otherwise soft organ

heterotropic bones

• bones formed in non-skeletal tissue

• all forms of this type of disorders are characterized by pain and a decrease in the range of motion (ROM)

three main types of heterotopic bones

1. myositis ossificans

2. traumatic myositis

3. neurogenic heterotopic ossification

myositis ossificans

rare genetic form causes muscles to ossify

traumatic myositis

repeated trauma or single hard hit to soft tissue triggers ossification of tissue there (may also occur as a result of hip surgery)

neurogenic heterotopic ossification

frequent complication to spinal cord injury

fibrodysplasia ossificans progressiva (FOP)

• rare genetic heterotopic ossification disorder causes progressive muscle and connective tissue conversion to bone tissue

• treatment problematic since surgical removal of the heterotopic bones can trigger more ossification

• gene therapy may be a possible treatment

mineral resorption definition

process of dissolving bone; releases minerals into blood

mineral resorption

• performed by osteoclasts

• hydrogen pumps on the plasma membranes secrete hydrogen into space between osteoclast and bone surface

• chloride ions follow by electrical attraction

• hydrochloric acid (pH 4) dissolves bon minerals

• acid-tolerant protease enzyme digests collagen

calcium is needed for bone structure, neuron communication, muscle contraction, blood clotting, and exocytosis

• minerals deposited in the skeleton and withdrawn when they are needed for these other purposes

• about 18% of skeletal calcium is exchanged with blood each year

• normal calcium concentration in blood plasma is 9.2 - 10.4 mg/dl

hypocalcemia

• calcium deficiency

• causes excitability of nervous system and muscles

hypercalcemia

• calcium excess

• causes nerve and muscle cells to be less excitable than normal

• rare but results from variety of causes (low vitamin D, diarrhea, thyroid tumors, underactive parathyroid glands)

calcium homeostasis depends on a balance between dietary intake, urinary and fecal losses, and exchanges between osseous tissue and is regulated by three hormones:

1. calcitriol

2. calcitonin

3. parathyroid hormone

calcitriol

form of vitamin D produced by sequential actions of skin, liver, and kidneys

calcitriol process

1. epidermal keratinocytes use UV radiation to convert 7-dehydrocholesterol to previtamin D3; warm sun on skin converts this to vitamin D3 (cholecalciferol)

2. liver adds hydroxyl group converting that to calcidiol

3. kidney adds hydroxyl group converting that to calcitriol

calcitriol acts to raise blood calcium in three ways

1. increase calcium absorption by small intestine

2. increase calcium resorption from skeleton (stimulate formation of new osteoclasts)

3. weakly promotes reabsorption of calcium from the kidneys

Which hormone is necessary for bone deposition and why

calcitriol because it helps provide adequate calcium and phosphate

What does inadequate calcitriol result in

abnormal softness of bones in children (rickets) and in adults/elderly (osteomalacia)

calcitonin

• produces by parafollicular (clear, C) cells of thyroid gland

• secreted when blood calcium levels are too high

Calcitonin lowers blood calcium concentration in two ways

1. osteoclast inhibition, thereby reducing bone resorption

2. osteoblast stimulation, to deposit calcium into bone

Why is calcitonin important in children but has a weak effect in adults

• osteoclasts are more active in children due to faster remodeling

• may inhibit bone loss in pregnant and lactating women

Parathyroid hormone (PTH)

secreted by parathyroid glands on posterior surface of thyroid, in response to low calcium in blood

PTH raises calcium blood level by four mechanisms

1. binds to receptors on osteoblasts, which then stimulate osteoclasts to resorb bone

2. promotes calcium reabsorption by kidneys, so less lost in urine

3. promotes the final step of calcitriol synthesis in the kidneys, enhancing calcium-raising effect of calcitriol

4. inhibits collagen synthesis by osteoblasts, inhibiting bone deposition

phosphate levels are not regulated as tightly as calcium levels

• calcitriol raises phosphate levels by promoting its absorption by small intestine

• PTH lowers blood phosphate levels by promoting its urinary excretion

other factor affecting bone: vitamin C

required for collagen synthesis and stimulation of osteoblast differentiation

other factor affecting bone: vitamin A

stimulates osteoblast activity (important for normal bone growth in children)

other factor affecting bone: vitamin K and B12

help synthesize bone proteins

other factor affecting bone: grown hormone and throxine

stimulate bone growth

other factor affecting bone: estrogens and androgens

stimulate osteoblasts

other factor affecting bone: calcitonin and parathyroid hormone

regulate calcium and phosphate levels

growth hormone (GH)

hormone released by the pituitary gland that affects all cells in the body

growth hormone (GH) affects the skeletal system by

stimulating bone growth

Excessive GH release can cause

excessive bone growth and gigantism

when does acromegaly occur

when GH levels remain high after the epiphyseal plate calcifies into the epiphyseal line, causing bones to grow thicker but not longer

insufficient GH release by the pituitary gland…

stunts bone growth causing a form of pituitary dwarfism called proportionate dwarfism

orthopedics

• branch of medicine dealing with prevention and correction of injuries and disorders of bones, joints, and muscles

• includes the design of artificial joints and limbs and the treatment of athletic injuries

stress fracture

break caused by abnormal trauma to a bone (ex. in a fall)

pathological fracture

break in a bone weakened by disease (such as bone cancer or osteoporosis), usually caused by a stress that would not break a healthy bone

fractures also classified by structural characteristics

• direction of fracture line, such as nondisplaced, displaced

• cracked or in multiple pieces, such as comminuted, greenstick

major types of fractures

1. transverse

2. displaces

3. compression

4. spiral

5. compound

6. epiphyseal

7. comminuted

8. greenstick

9. colles

10. pott’s

transverse fractures

across the long axis

displaced fractures

produce new/abnormal bone arrangements

*nondisplaced fractures have bone/fragments in normal alignment

compression fractures

produced on vertebrae on hard falls to seat (often associated with osteoporosis)

spiral fractures

twisting stress on length of bone

compound fracture

bone fracture that breaks through the skin

epiphyseal fractures

usually occurs where bone matrix is undergoing calcification, can permanently stop longitudinal growth of that bone

comminuted fractures

shatters bone into multiple frgaments

greenstick fractures

only one side of bone is broken, other side is bent) generally occurs in children’s bones that have not fully ossified)

colles fractures

break in distal portion of radius (usually caused by reaching out to cushion fall)

pott’s fractures

occurs at ankle affecting tibia and fibula

uncomplicated vs complex fractures healing time

uncomplicated take around 8-12 weeks and complex take longer

stages of healing for a fracture

1. hematoma formation

2. soft callus formation

3. hard callus formation

4. bone remodeling

stages of healing for a fracture: hematoma formation

blood clot (fracture hematoma) converted to granulation tissue (from blood vessels, fibroblasts, macrophages, osteoclasts, osteogenic cells that invade area)

stages of healing for a fracture: soft callus formation

deposition of collagen and fibrocartilage converts granulation tissue to soft callus

stages of healing for a fracture: hard callus formation

osteoblasts deposit temporary bony collar to untie broken pieces while ossification occurs

stages of healing for a fracture: bone remodeling

• small bone fragments are removed by osteoclasts

• osteoblasts deposit spongy bone and convert it to compact bone

closed reduction

procedure in which bone fragments are manipulated into their normal positions without surgery (Ex. cast)

open reduction and internal fixation (ORIF)

involves surgical exposure of the bone and the use of plates, screws, or pins to realign the fragments

fractures taking more than 2 months to heal

• may be treated with electrical stimulation which suppresses effects of parathyroid hormone

  • PTH raises blood calcium levels by stimulating osteoclast break down of bone

Beginning around age 40, net loss of bone mass as resorption outpaces deposition, what are the contributing factors

• sex - females more affected than males

• build - small, light frames affected more than heavier people

• ancestry - white females of Asian and European origin especially vulnerable

• age - older individuals are more vulnerable

osteopenia

measurable decline in bone density; may advance to osteoporosis

osteoporosis

severe loss of bone density; bones easily fracture

osteoporosis

occurs in 29% of females over 45 years (18% in males of the same age)

estrogens and androgens

sex hormones that help maintain bone tissue

bone loss accelerates in females after menopause

• treatment: hormone replacement therapy (HRT)

• risks: increase risk of breast cancer, heart disease, stroke, blood blots

osteoclast-activating factor

stimulates osteoclasts to accelerate the break down of bone tissue (this causes severe osteoporosis)

severe osteoporosis can also be caused by cancerous tissue

tissue can release osteoclast-activating factor