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Ossification or Osteogenesis
the formation of bone
What are the two methods for ossification?
intramembranous ossification and endochondral ossification
Intramembranous Ossification
- mesenchymal cells differentiate into osteoblasts, which secrete matrix (osteoid) that calcifies, trapping cells to become osteocytes
- produces flat bones of skull and clavicle
In endochondral ossification, when does the epiphyses fill with spongy bone
during infancy and childhood
In endochondral ossification, cartilage is limited to
articular cartilage, which covers each joint surface and to the epiphyseal plate (growth plate)
Epiphyseal Plate (Growth Plate)
- thin layer of cartilage separating the primary and secondary marrow cavities in childhood and adolescence
- growth for bone elongation
What bones form under endochondral ossification?
long bones (e.g., femur, humerus), vertebrae, ribs, pelvis, and the base of the skull
Appositional Growth
- bones increase in width throughout life
- deposition of new bone at the surface
Osteoblasts Role in Appositional Growth
lay down matrix in layers parallel to surface
Osteoclasts Role in Appositional Growth
enlarge marrow cavity by breaking down bone on the internal surface (endosteum), preventing the bone from becoming too heavy
Bone Remodeling
- occurs throughout life (10% per year)
- repairs micro-fractures, releases minerals into blood, reshapes bones in response to use and disuse
Wolff's Law
- bone density determined by mechanical stresses placed on it and bones adapt to withstand those stresses
- adaption to stress = remodeling to grow larger
- action of osteoblasts and osteoclasts
- bone
Mineral Deposition (Mineralization or Calcification)
- crystallization process
- osteoblasts produce collagen --> fibers become encrusted with minerals
- osteoblasts neutralize calcification inhibitors in bone matrix
- first few crystals attract more calcium and phosphate from solution
Abnormal Calcification (Ectopic Ossification)
- may occur in lungs, brain, eyes, muscles, tendons, or arteries (arteriosclerosis)
- calcified mass in an otherwise soft organ such as the lung (calculus)
Mineral Resorption
the process of dissolving bone and releasing minerals into the blood
Mineral Resorption Process
- performed by osteoclasts at the ruffled border
- hydrogen pumps secrete hydrogen into space between the osteoclast and bone surface
- chloride ions follow by electrical attraction
- hydrochloric acid dissolves bone minerals
- acid phosphate enzymes digests the collagen
Where in the body is phosphate needed?
as a component of DNA, RNA, ATP, phospholipids, and pH buffers
Where in the body is calcium needed?
neuron communication, muscle contraction, blood clotting, and exocytosis
How much calcium is in the adult body?
about 1,100 g (99% in the skeleton)
What is the normal calcium concentration in blood plasma?
9.2 to 10.4 mg/dL
What percentage of Ca2+ can diffuse across capillary walls and affect other tissues; rest in reserve, and bound to plasma membranes
45%
Calcium Homeostasis Depends On
a balance between dietary intake, urinary and fecal losses, and exchanges between osseous tissue
What three hormones regulate calcium homeostasis?
calcitriol, calcitonin, and parathyroid hormone
Hypocalcemia
low calcium levels in the blood
Hypocalcemia can be caused by
- vitamin d deficiency
- diarrhea
- under active parathyroids
- pregnancy and lactation
- accidental removal of parathyroid glands during thyroid surgery
First Step of Activating Vitamin D to Calcitriol
- UV light converts 7-dehydrocholesterol to Vitamin D3 (cholecalciferol) and is released into blood
- absorbed by small intestine from diet
Second Step of Activating Vitamin D to Calcitriol
- Vitamin D3 circulates throughout the body
- converted to calcidol by liver enzymes
- both steps 1 and 2 occur continuously with limited regulation
Third Step of Activating Vitamin D to Calcitriol
- Calcidol circulates in the blood
- converted to calcitirol by kidney enzymes
- parathyroid hormone increases rate, so more calcitriol is formed
Calcitriol
stimulates absorption of calcium ions from small intestine into the blood
Parathyroid Hormone
secreted and released by parathyroid glands in response to reduced blood calcium levels
How do PTH and Calcitriol interact in the bones?
act synergistically to increase release of calcium from the bone into the blood by increasing osteoclast activity
How do PTH and Calcitriol interact in the kidneys?
stimulate the kidneys to excrete less calcium in urine and increase calcium reabsorption into the blood
How do PTH and Calcitriol interact in the small intestine?
only calcitriol increases absorption of calcium from small intestine into the blood
Stimulus in Calcium Homestasis
low blood calcium levels
Receptor in Calcium Homestasis
parathyroid glands detect low blood calcium levels
Control center in Calcium Homestasis
parathyroid glands release parathyroid hormone
Rickets
soft bones due to deficiency of calcium salts
What Causes Rickets?
- disease caused by vitamin d deficiency in childhood and low blood calcium
- characterized by deficient calcification of osteoid tissue
- disturbances in growth, hypocalcemia, and tetany (cramps and twitches), bowlegged appearance
Calcitonin
- aids in regulating blood calcium levels
- less significant role than PTH or calcitriol
- released from the thyroid gland in response to high blood calcium levels
- also secreted in response to exercise
Calcitonin Function
- inhibits osteoclast activity
- stimulates kidneys to increase loss of calcium in the urine, reducing blood calcium levels
- greatest effect during greatest bone turnover (remodeling)
How much phosphorus is in the average adult body?
500 - 800 g
What percent of phosphate is in the bones?
85% - 90%
What is the normal plasma concentration?
3.5-4.0 mg/dL
Phosphate Occurs in Two Principle Forms
monohydrogen and dihydrogen
Why are phosphate levels not as tightly regulated as calcium levels?
there are no functional disorders
How does calcitriol raise phosphate levels?
by promoting its absorption by small intestine
How does Parathyroid hormone lower phosphate levels?
by promoting its urinary excretion
Bone growth is rapid in
puberty and adolescence
Why is bone growth rapid in puberty and adolescence?
- surges of growth hormone, estrogen, and testosterone occur and promote ossification
- these hormones stimulate multiplication of osteogenic cells, matrix deposition by osteoblasts, and chondrocyte multiplication and hypertrophy in metaphyses
Why do girls grow faster than boys and reach full height earlier?
estrogen has a stronger effect than testosterone on bone growth
What can cause growth to stop?
- anabolic steroids
- epiphyseal plate "closes" prematurely
- results in abnormally short adult stature
Orthopedics
- treatment of skeletal deformities in children
- deals with the 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
Achondroplastic Dwarfism
- long bones stop growing in childhood (normal torso, short limbs)
- failure of cartilage growth in metaphysis
- spontaneous mutation produces mutant dominant allele
Pituitary Dwarfism
- lack of growth hormone
- normal proportions with short stature
Osteogenesis Imperfecta
excessively brittle bones due to lack of protein, collagen
Stress Fracture
break caused by abnormal trauma to a bone (falls, athletics, and military combat)
Simple Fracture
broken bone not penetrating the skin
Compound Fracture
one or both ends of the bone pierce overlying skin
Pathological Fracture
- break in a bone weakened by some other disease (bone cancer or osteoporosis)
- would not break a healthy bone
How are fractures classified?
- direction of fracture line
- break in the skin
- multiple pieces
Closed Reduction
procedure in which the bone fragments are manipulated into their normal positions without surgery
Open Reduction
involves surgical exposure of the bone and the use of plates, screws, or pins to realign the fragments
Cast
medical support, normally used to stabilize and immobilize healing bone
What are the 4 steps of fracture repair?
1. fracture hematoma forms
2. fibrocartilaginous (soft) callus forms
3. hard (bony) callus forms
4. bone is remodeled
Fracture Hematoma Forms
blood vessels torn within periosteum causing a hematoma to form
Fibrocartilaginous (Soft) Callus Forms
- fracture hematoma reorganized into a CT pro-callus
- fibroblasts produce collagen fibers
- condroblasts form dense regular CT
- pro-callus becomes fibrocartilaginous (soft) callus
Hard (Bony) Callus Forms
- osteoblasts adjacent to callus produce trabeculae
- replaces callus
- forms a hard (bony) callus
- continues to grow and thicken
Bone is Remodeled
- final phase of fracture repair
- osteoclasts remove excess bony material
- compact bone replaces primary bone
- usually leaves a slight thickening of bone
Osteoporosis
- the most common bone disease
- severe loss of bone density
- bones break down at a greater rate than absorption by age 40
- low estrogen levels
Osteoporosis Risk Factors
women, caucasian or asian, thin, family history, early menopause, smoking, diet low in calcium, excessive caffeine or alcohol consumption, sedentary lifestyle
Osteoporosis Treatments
- estrogen replacement therapy slows bone resorption, but increases risk of breast cancer, stroke and heart disease
- drugs: Fosamax, Actonel destorys osteoclasts
- PTH slows bone loss if given as daily injection (forteo)
- best treatment is prevention
First Way Aging Affects Bone
- decreased tensile strength
- reduced rate of protein synthesis by osteoblasts
- relative amount of inorganic material increases
- bones become brittle and susceptible to fracture
Second Way Aging Affects Bone
- bone loss of calcium and other minerals
- bones become thinner and weaker
Osteopenia
- occurs slightly in all people with age
- begins ages 35-40
- osteoblast activity declines, osteoclast activity at previous levels
- vertebrae, jaw bones, epiphyses lose large amounts of mass
- women lose more of their skeletal mass every decade than men
Appendicular Skeleton
bones of upper and lower limbs, girdles attaching limbs to axial skeleton, carry out movements
Red Bone Marrow
site of hematopoiesis - red blood cell formation, found in medullary cavity of diaphysis in all areas of spongy bone in newborns, in epiphyses of humerus and femur in diploe and some irregular bones (hip bones) in adults
Hematopoietic Tissue In Bones
red marrow is found within trabecular cavities of spongy bone and diploe of flat bones such as sternum
Osteogenic (osteoprogenitor) Cells
Found in periosteum and endosteum, Mitotically active, Differentiate into osteoblasts, OSTEOGENIC CELLS ARE UNDIFFERENTIATED CELLS (unlike stem cells they are already on trajectory to become bone cells, just not differentiated yet- stem cells not on any path-can become any # of different cells)
Osteoblasts
Mitotically active, Secrete bone matrix & enzymes for mineralization, Mature into osteocytes
Osteocytes
Mature osteoblasts-Not mitotically active-Do not secrete bone matrix but maintains bone matrix-Communicate with and control activity of osteoblasts and osteoclasts-FUNCTION: NOT SECRETING MATRIX BUT STILL VITAL IN MAINTAINING BONE MATRIX
Osteoclasts
Multi-nucleated cells-Differentiate from hematopoietic stem cells -Bone resorption - break down bone
Bone Resorption
the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood
Osteoid
IS ORGANIC PART OF THE MATRIX, Ground substance: largely consists of glycoproteins
Ossification (osteogenesis)
process of bone tissue formation
Endochondral Ossification
Bone forms by replacing hyaline cartilage, Bones are called cartilage (endochondral) bones, begins at primary ossification center in center of shaft, forms most bones in body
Intramembranous Ossification
bones are called membrane bones
Hypocalcemia
low levels of calcium cause hyperexcitability
Hypercalcemia
high levels of calcium cause non responsiveness, Sustained high blood calcium levels can lead to deposits of calcium salts in blood vessels or kidneys and formation of kidney stones
Osteomalacia
in adults; deficiency of vitamin D or Ca resulting in bone demineralization-Bones soften and weaken
Rickets
in children; deficiency of vitamin D or Ca, more severe in children because bones are still growing
Osteoporosis
more bone resorption than formation, Results in reduced bone mass Bones weaken & susceptible to fracture Occurs most often in older age Causal factors
Fibrous Joint
Dense (fibrous) connective tissue; no joint cavity
Cartilaginous Joint
Hyaline cartilage or fibrocartilage; no joint cavity
Synovial Joint
fluid filled joint cavity
Synarthroses
immovable
Amphiarthroses
slightly moveable
Diartroses
freely moveable
Sutures (fibrous joint)
Synarthrotic, no movement which serves to protect the brain, Ex: bones of skull, Made of short connective tissues that extend from periosteum -these ossify during middle age
Synovial Fluid
Reduce friction (as lubricant) between articular cartilages, when joint compressed
Nourishes Cartilage
Reinforcing ligaments - support and reinforce synovial joints
Fatty Pads (accessory of synovial joints)
Found in hip and knee joints, Between fibrous layer of articular capsule and synovial membrane