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AP Exam 6.2 Cheat Sheet by

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Bone Formation

Ossifi­cat­ion­(os­teo­gen­esis)is the process of forming new bone.
Bone formation occurs in four situat­ions:
–Formation of bone in a late stage embryo
–Growth of bones until adulthood
–Remod­eling of bone
–Repair of fractures

Bone Formation

Osteog­enesis occurs by two different methods, beginning about the 8thweek of embryonic develo­pment.
–Intra­-me­mbr­anous ossifi­cation
•Produces spongy bone.
•This bone may subseq­uently be remodeled to form compact bone.
–Endoc­hondral ossifi­cation
•Process whereby cartilage is replaced by bone.
•Forms both compact and spongy bone.

Bone Formation

Intra-­mem­branous ossifi­cation is the simpler of the two methods.
–It is used in formation ofthe flat bones of the skull, mandible, and clavicle.
–Bone forms from mesenc­hymal cells that develop into osteob­lasts within a fibrous membrane
•Recall that mesenchyme is the tissue from which almost all other C.T. develop.
–Many ossifi­cation centers.
•Centers of bone formation
•The bone that is produced does not go through a cartil­aginous stage
–Woven bone and periosteum form
–Lamellar bone replaces woven bone & red marrow appears

Bone Formation

•Endoc­hondral ossifi­cation is the method used in the formation of most bones, especially long bones.
–Involves replac­ement of a hyaline cartilage model by bone.
–Begins at the primary ossifi­cation center in center of shaft
•Blood vessel infilt­ration of perich­ondrium converts it to periosteum
–Under­lying cells change to osteoblast
–Bone collar forms around diaphysis of cartilage model
–Central cartilage in diaphysis calcifies, then develops cavities
–Perio­steal bud invades cavities
•Leads to the formation of spongy bone
–Diaphysis elongates & medullary cavity forms
–2ndary ossifi­cation centers form in the epiphyses
–Epiphyses ossify

Control of Bone Growth

Normal bone growth­depends on several factors:
–Minerals are an essential component
•Large amounts of calcium and phosphorus and smaller amounts of magnesium, fluoride, and manganese are required for bone growth and remode­ling.

Control of Bone Growth

•Hormones are key contri­butors to normal bone growth.
–During childhood, the hormones most important to bone growth are human growth hormone (hGH) and growth factors called IGFs (produced by the liver).
•Both stimulate osteob­lasts, promote cell division at the epiphyseal plate, and enhance protein synthesis.
–Thyroid hormone’s contri­bution to bone growth involves the modulation of the activity of growth hormone
•Ensures proper bone propor­tions

Control of Bone Remodeling

•Negative feedback hormonal loop for Ca2+ho­meo­stasis
–Maint­aining a normal serum Ca2+ level takes precedence over minera­lizing bone
•Parat­hyroid hormone (PTH)
–Produced by parath­yroid glands
–Removes calcium from bone regardless of bone integrity
•Calci­tonin may be involv­ed–­Pro­duced by parafo­lli­cular cells of thyroid gland
–In humans, high doses lowers blood calcium levels tempor­arily
»Normal human physio­logical serum levels not high enough to cause the above effect

Control of Bone Remodeling

•Response to mechanical and gravit­ational forces
–Bones stressed when bearing weight or pulled on by muscle
•Usually stress is off center, so tends to bend bones
•Bending compresses on one side; stretches on other
–Bones reflect stresses they encounter
•Long bones thickest midway along diaphysis where bending stresses greatest

Fractures

•Fractures
–Breaks in the bone tissue­•Fr­actures in youth
–Most result from trauma­»Hold my beer!
•Fractures in old age
–Most result of bone weakness due to thinning
»Hold my walker!

Fracture Treatment

•Treatment
–Reduction
•Reali­gnment of broken bone ends
•Closed reduction – physician manipu­lates to correct position
•Open reduction – surgical pins, plates, or wires secure ends
–Immob­ili­zation by cast or traction for healing
•Depends on break severity, bone broken, and age of patient

Fracture and Repair

•Within one week new trabeculae appear in fibroc­art­ila­ginous callus
–Callus converted to bony (hard) callus of spongy bone
•~2 months later firm union forms

Aging and Bone Tissue

•There are two principal effects of aging on bone tissue:
–Loss of bone mass
•The loss of calcium from bones is one of the symptoms in osteop­orosis.
–Britt­leness
•Collagen fibers give bone its tensile strength, and protein synthesis decreases with age.
•The loss of tensile strength causes the bones to become very brittle and suscep­tible to fracture.

Risk Factors for Osteop­orosis

•Risk factors
–Most often aged, postme­nop­ausal women
•30% 60 – 70 years of age; 70% by age 80
•30% of caucasian women will fracture bone because of it
–Men to lesser degree
 

Postnatal Bone Growth

After initial bone formation, bones grow by via two methods
–Inter­stitial (longi­tud­inal) growth­•In­crease in length of long bones
–Appos­itional growth
•Increase in bone thickness

Inters­titial Growth

Requires presence of epiphyseal cartilage
Epiphyseal growth plate maintains constant thickness
–Rate of cartilage growth on one side balanced by bone replac­ement on other
•Concu­rrent remodeling of epiphyseal ends to maintain proportion
•Result of five zones within cartilage
–Resting (quies­cent) zone
–Proli­fer­ation (growth) zone
–Hyper­trophic zone
–Calci­fic­ation zone
–Ossif­ication (osteo­genic) zone

Inters­titial Growth

•Resting (quies­cent) zone
–Cartilage on epiphyseal side of epiphyseal plate
–Relat­ively inactive
•Proli­fer­ation (growth) zone
–Cartilage on diaphysis side of epiphyseal plate
–Rapidly divide pushing epiphysis away from diaphysis
length­ening
•Hyper­trophic zone–Older chondr­ocytes closer to diaphysis and their lacunae enlarge and erode inter­con­necting spaces
•Calci­fic­ation zone
–Surro­unding cartilage matrix calcifies, chondr­ocytes die and deteri­orate
•Ossif­ication zone
–Chond­rocyte deteri­oration leaves long spicules of calcified cartilage at epiphy­sis­-di­aphysis junction
–Spicules eroded by osteoc­lasts
–Covered with new bone by osteob­lasts
– Ultimately replaced with spongy bone

Control Of Bone Growth

Vitamins are necessary for normal bone growth:
–Vitamin A is important for theact­ivity of osteob­lasts
–Vitamin C is needed for synthesis of collagen.
–Vitamin D is essential to healthy bones because it promotes the absorption of calcium from foods in the gastro­int­estinal tract into the blood.
–Vitamins K and B12 are needed for synthesis of bone proteins.

Control of Bone Growth

Hormones contin­ued...
–The sex hormones (estrogen and testos­terone) cause a dramatic effect on bone growth, such as the sudden “growth spurt” that occurs during adoles­cence.
•The female sex hormones also promote widening of the pelvis in the female skeleton.
•Sex hormones are respon­sible for closing the epiphyseal plates at the end of puberty.
•Also important in bone density mainte­nance during adulthood

Control of Bone Remodeling

•The process of regulating serum Ca2+ levels by minera­lizing bone is under hormonal control, and is carefully balanced
•Day to day control of calcium regulation mainly involves:
–PTH stimulates osteoc­lastic activity and raises blood serum calcium level. Stimulates reabso­rption of calcium ions in the kidneys
–To a small extent, calcitonin – maybe –, hGH, and the sex hormones (estrogen and testos­terone) stimulate osteob­lastic activity and lower serum calcium level.
–Vitamin D is produced for absorption of the Ca2+ and PO4– ions from the small intestine.

Results of Mechanical Stress­ors­:Wo­lff's Law

•Bone grows or remodels in response to demands placed on it
•Explains
–Hande­dness (right or left handed) results in thicker and stronger bone of that upper limb
–Curved bones thickest where most likely to buckle
–Trabe­culae of spongy bone form trusses along lines of stress
–Large, bony projec­tions occur where heavy, active muscles attach
•Even more pronounced on profes­sional weight lifters
–Bones of fetus and bedridden featur­eless

Fracture Classi­fic­ation

•Three "­eit­her­/or­" fracture classi­fic­ations
–Position of bone ends after fracture
•Nondi­spl­ace­d—ends retain normal position
•Displ­ace­d—ends out of normal alignment
–Compl­eteness of break
•Compl­ete­—broken all the way through
•Incom­ple­te—not broken all the way through
–Whether skin is penetrated
•Open (compound) - skin is penetrated
•Closed (simple) – skin is not penetrated

Fracture and Repair

•Once a bone is fractured, repair proceeds in apredi­ctable pattern:
•The first stepis the formation of a fracture hematoma (clot) as a result of blood vessels breaking in the periosteum and in osteons.
•Site swollen, painful, and inflamed

Fracture and Repair

•The final step takes several months and is called remodeling :
–Spongy bone is replaced by compact bone.
–The fracture line disappears andlittle to no evidence of the breakr­ema­insonce complete
•Final structure resembles original because bone subject to same mechanical stressors

Aging and Bone Tissue

•As we age, a decrease in bone mass occurs as the level of sex hormones diminish (espec­ially in women after menopause)
–Human females undergo a drop in estrogen levels typically many years before testos­terone decreases in men
•Women can lose as much as 15-35% of their bone mass in the first five years after menopause
–Since human female bones are generally smaller and less dense than males to begin with, old age has a greater adverse effect in females.
–Bone resorption by osteoc­lasts outpaces bone deposition by osteob­lasts with low levels of sex steroids.

Additional Risk Factors for Osteop­orosis

•Petite body form
•Insuf­ficient exercise to stress bones
•Diet poor in calcium and protein
•Smoking
•Other hormon­e-r­elated conditions
–Hyper­thy­roidism
–Low blood levels of thyroid
-stimu­lating hormone
–Diabetes mellitus
–Low hGH and IGF produu­ction
•Immob­ility
•Males with prostate cancer taking androg­en-­sup­pre­ssing drugs
 

Inters­titial Growth

•Ossif­ication contri­buting to bone length (Inter­stitial growth) occurs throughout childhood and adoles­cence
–Near end of adoles­cence chondr­oblasts divide less often
–Epiph­yseal plate thins then is replaced by bone
•Epiph­yseal plate closure
•Bone length­ening ceases
•Bone of epiphysis and diaphysis fuses
•Usually complete by 18-21 years of age.
–18 in females
–21 in males
•Fractures (breaks) to the epiphyseal growth plate can accelerate it’s closure. –The fractured bone may be shorter than normal when adulthood is reached
–Inhibits length­-wise growth of bone

Apposi­tional Growth

•Allows length­ening bone to widen
•Occurs throughout life•M­ajority of osteoblast contri­bution to apposi­tional growth occurs in the periosteum
–secretes bone matrix on external bone
•Majority of osteoc­lasts contri­bution to apposi­tional growth occurs in the endosteum
–removes bone on endosteal surface
•Usually more building up than breaking down(T­hicker, stronger bone but not too heavy)

Bone Growth and Remodeling

A balance must exist between the actions of osteoc­lasts and osteob­lasts.
–If too much new osseous tissue is formed, the bones become abnormally thick and heavy, as seen with acrome­galy.
–Excessive loss of calcium weakens the bones, as occurs in osteop­orosis.
–Bonesmay also become too “soft”, as seen in the bone diseases rickets (child­ren)and osteom­ala­cia­(ad­ults).

Vitamin D and Calcium Deficiency

Can happen in places with low sun exposure or low calcium content in diet
-Ricke­ts•­Wea­kening of bone hardness due to insuff­icient absorption of dietary calcium from lack of vitamin D or prolonged diets deficient in calcium
•More common in children than adults
-Called osteom­alacia in adults
•Increase in dietary Vitamin D or Ca intake can be used to treat

Control of Bone Remodeling

•Occurs contin­uously but regulated by genetic factors and two control loops
–Negative feedback hormonal loop for Ca2+ho­meo­stasis
•Controls blood Ca2+ levels, not bone integrity
•Serum Ca2+ concen­tra­tions are very important for proper nervous and muscle function
•Even minute changes in blood calcium are dangerous
–Responses to mechanical and gravit­ational forces

Negative Feedback Hormonal Loop for blood Ca2+

Calcium is controlled by the parath­yroid hormone (PTH)
Decreases Calcium2+ blood levels
Increase PTH release
PTH stimulates osteoc­lasts to degrade bone matrix, releasing Ca2+
Blood Calcium2+ levels increase
PTH release amount is decreased

Results of Hormonal and Mechanical Influences

•Hormonal controls determine whether and when remodeling occurs in response to changing blood calcium levels
•Mecha­nic­al/­gra­vit­ational stress determines where remodeling occurs

Classi­fic­ation of Bone Fractures

•Also described by location of fracture
•External appearance
•Nature of break
•Eponym (someone’s name)

Fracture and Repair

•The second step involv­esthe formation of a callus
–Capil­laries grow into hemato­ma–­Pha­gocytic cells clear debris
–Fibro­blasts secrete collagen fibers to span break and connect broken ends
–Fibro­blasts, chondr­obl­asts, and osteogenic cells begin recons­tru­ction of bone
–Create cartilage matrix of repair tissue
–Osteo­blasts form spongy bone within matrix­•Mass of repair tissue called fibroc­art­ila­ginous callus

Exercise and Bone Tissue

•Under mechanical stress, bone tissue becomes stronger through production of collagen fibers by osteob­lasts and subsequent deposition of mineral salts. •Unstr­essed bones, on the other hand, become weaker.
–Astro­nauts in orbit suffer rapid loss of bone density.
•As much a 1% a week

Aging and Bone Tissue

•Osteo­porosis refers to a group of diseases where bone resorption outpaces bone deposi­tion.
–Depletion of calcium from the body or inadequate intake in young adults
–Sex hormones maintain normal bone health and density
•As secretion wanes with age, osteop­orosis can develop
–Spongy bone of spinal column and neck of femur most suscep­tible
•Heavy weight­-be­aring respon­sib­ilities
•Vertebral and hip fractures common

Preventing Osteop­orosis

•Plenty of calcium in diet in early adulthood
–Can help to increase bone deposition
•Reduce carbonated cola consum­ption
–May lower serum Ca levels causing an increase in the release of minerals from bone thus decreasing bone density
•Reduce alcohol consum­ption
–Heavy drinking during adoles­cence and young adulthood may have permanent effects on bone density
•Plenty of weight­-be­aring exercise
–Increases bone mass above normal for buffer against age-re­lated bone loss

Preventing Osteop­orosis

•Plenty of calcium in diet in early adulthood
–Can help to increase bone deposition
•Reduce carbonated cola consum­ption
–May lower serum Ca levels causing an increase in the release of minerals from bone thus decreasing bone density
•Reduce alcohol consum­ption
–Heavy drinking during adoles­cence and young adulthood may have permanent effects on bone density
•Plenty of weight­-be­aring exercise
–Increases bone mass above normal for buffer against age-re­lated bone loss

Preventing Osteop­orosis

•Plenty of calcium in diet in early adulthood
–Can help to increase bone deposition
•Reduce carbonated cola consum­ption
–May lower serum Ca levels causing an increase in the release of minerals from bone thus decreasing bone density
•Reduce alcohol consum­ption
–Heavy drinking during adoles­cence and young adulthood may have permanent effects on bone density
•Plenty of weight­-be­aring exercise
–Increases bone mass above normal for buffer against age-re­lated bone loss

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