More Ch. 66.5 – 6.10

Bone Growth, Composition

and Conditions

Ossification • Skeleton begins to form in embryo at 6 week• During all future development bone undergoes

increases in size and ossificationo Ossification = bone formation o Calcification = deposition of calciumo Endochondral ossification = bone replaces cartilage that was already

presesnto Intramembranous ossification = bone develops directly from connective

tissue• Bone growth continues through adolescence, and on

average until about age 25• Toes “done” by age 11; pelvis and wrists may still be

growing at 25. Lots of growth happens in relation to puberty hormones

Endochondryal Ossification

• Chondros = cartilage• Endo = inside• Most bones start as hyaline cartilage and are

“models of adult bone” size and shape• Cartilage gradually replaced by bone• Time line: “This is an essay; timeline and pictures that

follow”o 6 weeks proximal end of limb bone present but as hyaline cartilageo New cartilage on outer surfaceo Cells at center enlarge, blood vessels growo Primary ossification starts and spread toward endso Increases in length and in diametero Centers of epiphyses calcify and become spongy boneo Cap of cartilage remains at articulationo Region of cartilage between epiphysis and diaphysis = lengthening bone

Figure 6-10 Endochondral Ossification (Step 1-7)As the cartilageenlarges,chondrocytes nearthe center of the shaft increasegreatly in size. Thematrix is reduced to a series of smallstruts that soonbegin to calcify. Theenlargedchondrocytes thendie and disintegrate,leaving cavitieswithin the cartilage.

Blood vessels growaround the edges ofthe cartilage, andthe cells of theperichondriumconvert toosteoblasts. Theshaft of thecartilage thenbecomesensheathed in a superficial layer ofbone.

Blood vesselspenetrate the cartilageand invade the centralregion. Fibroblastsmigrating with theblood vesselsdifferentiate intoosteoblasts and beginproducing spongybone at a primaryossification center.Bone formation thenspreads along theshaft toward bothends.

Remodeling occursas growth continues,creating a medullarycavity. The osseoustissue of the shaftbecomes thicker,and the cartilagenear each epiphysisis replaced by shaftsof bone. Furthergrowth involvesincreases in lengthand diameter.

Medullarycavity

Metaphysis

Medullarycavity

Primaryossificationcenter

SuperficialboneSpongybone

Bloodvessel

Boneformation

Diaphysis

Epiphysis

Hyaline cartilage

Enlargingchondrocytes within

calcifying matrix

Capillaries andosteoblasts migrateinto the epiphyses,creating secondaryossification centers.

Soon the epiphyses arefilled with spongy bone.An articular cartilageremains exposed to thejoint cavity; over time itwill be reduced to a thinsuperficial layer. At eachmetaphysis, an epiphysealcartilage separates theepiphysis from thediaphysis.

This light micrograph shows the ossifyingsurface of an epiphyseal cartilage. The pinkmaterial is osteoid, deposited by osteoblasts inthe medullary cavity. On the shaft side of theepiphyseal cartilage, osteoblasts arecontinuously invading the cartilage and replacingit with bone. On the epiphyseal side, new cartilageis continuously being added. The osteoblasts aretherefore moving toward the epiphysis, which isbeing pushed away by the expansion of theepiphyseal cartilage. The osteoblasts won’t catchup to the epiphysis, as long as both theosteoblasts and the epiphysis “run away” fromthe primary ossification center at the same rate.Meanwhile, the bone grows longer and longer.

Hyaline cartilage

Epiphysis

Metaphysis

PeriosteumCompact

bone

Articular cartilage

Spongybone

Epiphysealcartilage

Diaphysis

Epiphysealcartilage matrix

Cartilage cells undergoingdivision and secreting

additional cartilage matrix

Medullary cavityOsteoblastsOsteoid

LM 250Secondaryossification

center

THIS IS AN ESSAY QUESTION

Figure 6-10 Endochondral Ossification (Step 1-4)

As the cartilageenlarges,chondrocytes nearthe center of the shaft increasegreatly in size. Thematrix is reduced to a series of smallstruts that soonbegin to calcify. Theenlargedchondrocytes thendie and disintegrate,leaving cavitieswithin the cartilage.

Blood vessels growaround the edges ofthe cartilage, andthe cells of theperichondriumconvert toosteoblasts. Theshaft of thecartilage thenbecomesensheathed in a superficial layer ofbone.

Blood vesselspenetrate the cartilageand invade the centralregion. Fibroblastsmigrating with theblood vesselsdifferentiate intoosteoblasts and beginproducing spongybone at a primaryossification center.Bone formation thenspreads along theshaft toward bothends.

Remodeling occursas growth continues,creating a medullarycavity. The osseoustissue of the shaftbecomes thicker,and the cartilagenear each epiphysisis replaced by shaftsof bone. Furthergrowth involvesincreases in lengthand diameter.

Medullarycavity

Metaphysis

Medullarycavity

Primaryossificationcenter

SuperficialboneSpongybone

Bloodvessel

Boneformation

Diaphysis

Epiphysis

Hyaline cartilage

Enlargingchondrocytes within

calcifying matrix

Figure 6-10 Endochondral Ossification (Steps 5-7)

Capillaries andosteoblasts migrateinto the epiphyses,creating secondaryossification centers.

Soon the epiphyses arefilled with spongy bone.An articular cartilageremains exposed to thejoint cavity; over time itwill be reduced to a thinsuperficial layer. At eachmetaphysis, an epiphysealcartilage separates theepiphysis from thediaphysis.

This light micrograph shows the ossifyingsurface of an epiphyseal cartilage. The pinkmaterial is osteoid, deposited by osteoblasts inthe medullary cavity. On the shaft side of theepiphyseal cartilage, osteoblasts arecontinuously invading the cartilage and replacingit with bone. On the epiphyseal side, new cartilageis continuously being added. The osteoblasts aretherefore moving toward the epiphysis, which isbeing pushed away by the expansion of theepiphyseal cartilage. The osteoblasts won’t catchup to the epiphysis, as long as both theosteoblasts and the epiphysis “run away” fromthe primary ossification center at the same rate.Meanwhile, the bone grows longer and longer.

Hyaline cartilage

Epiphysis

Metaphysis

PeriosteumCompact

bone

Articular cartilage

Spongybone

Epiphysealcartilage

Diaphysis

Epiphysealcartilage matrix

Cartilage cells undergoingdivision and secreting

additional cartilage matrix

Medullary cavityOsteoblastsOsteoid

LM 250Secondaryossification

center

An x-ray of growing epiphysealcartilages (arrows)

Epiphyseal lines in anadult (arrows)

APPOSITIONAL GROWTH = Superficial layers of bone forms early in endochondral ossification New growth in the bones diameter results in layers – New lamella added in concentric rings around outside while inner layers are recycled

Intramembranous Ossification

• Osteoblasts differentiateo Fibrous connective tissue ( mesenchymal cells)o Matrix is createdo Crystallization of calcium saltso Very active process requiring lots of nutrientso Osteoblasts ossification spicules formo Initially only spongy boneo Remodeling can lead to compact bone

• Creates dermal boneso Flat bones of skull, mandible (lower jaw), and clavicle (collar bone)

Blood and nerve supply to bones

• Bone maintenance and grow require blood supply• Osseous tissue is highly vascular

o Nutrient artery and vein: supply diaphysis, usually only one of each ( femur has more)

o Enter through foramina – branch into smaller canalso Metaphyseal vessels – supply blood to cartilage that is or will be replaced

by boneo Periosteal vessels – blood to periosteum and superficial osteons – branch

during ossificationo All are very interconnected

• Lymph – connect blood and lymph through osteons• Nerves – travel along nutrient artery ( injuries to

bones are very painful)

Remodeling• Bone matrix constantly being recycled and

renewed• Used for both maintenance and changes to bone

shape and structure• Youth – recycle about 1/5 of calcium salts per

year; more likely in areas of spongy bone• Heavy metals are dangerous because they can be

incorporated into bone – stay in circulatory system for many years. (Chernobyl Nuclear reactor leak; 1986 Ukraine, only other level 7 leak is Fukushuma Daiichi in 2011)

Impact of Exercise on bones

• “stresses” on mineral crystals cause bone growth • Increases in muscle mass increase both weight

and tension on bones = growth• Ridges and bumps on bone relate to pull of

tendons, diameter of bone relates to mass – • non-athletes have more fragile bones

(osteoporosis and arthritis)• A broken leg with no stress, can lose 1/3 mass

while using crutches• ? Bedridden and paralyzed

Impact of Hormones on bones

• Calcitrol: o made by kidneys o increases absorption of Ca and PO4 in digestive tract

• Growth hormoneo Made by pituitaryo Stimulates osteoblast and synthesis of matrix

• Thyroxineo Thyroido Also stimulates osteoblasts and synthesis of matrix

• Estrogen/ androgenso Ovaries and testeso Stimulates osteoblastso Estrogen closes epiphysis earlier than androgens

• Parathyroid hormoneo Parathyroid glandso Stimulates osteoclasts and osteoblastso Increases Ca level in body fluids

• Calcitonino Thyroid glando Inhibits osteoclastso Reduces Ca in body fluidso Triggers kidneys to lose calcium

NOT a memorize slide

Impact of Nutrition on bones

• Dietary sources of calcium and phosphate are required for healthy bone growth and maintenance

• Also required are: magnesium, fluoride, iron and manganese

• Vitamin C is needed for enzymatic reaction that makes cartilage

• Vitamin D is required for calcitrol to cause intestinal absorption of Ca and PO4

• Vitamins A, K and B12 are also needed for normal bone growth

Nutrition and Calcium• Bones are a mineral reservoir

o 1-2 Kg of calcium ( 2.2 – 4.4 lbs) in bodyo 99% is in the bones

• Calcium levels are important for many functions:o Permeability of plasma membraneso Firing of nerve impulseso Contraction of muscle fibers

o Widely varying ion concentrations can result in seizures or deatho “electrolytes”

Figure 6-16a Factors That Alter the Concentration of Calcium Ions in Body Fluids

Bone Response Intestinal Response Kidney Response

Parathyroid Gland Response

Factors That Increase Blood Calcium LevelsThese responses aretriggered when plasmacalcium ion concentrationsfall below 8.5 mg/dL.

Low Calcium Ion Levels in Plasma(below 8.5 mg/dL)

Low calcium plasma levels causethe parathyroid glands to secreteparathyroid hormone (PTH).

Osteoclasts stimulated torelease stored calcium ionsfrom bone

Osteoclast

Bone

Rate ofintestinalabsorptionincreases

Kidneys retaincalcium ions

PTH

more

calcitriol

Calcium released Calcium absorbed quickly Calcium conserved

Decreased calciumloss in urine↑Ca2+

levels inbloodstream

Figure 6-16b Factors That Alter the Concentration of Calcium Ions in Body Fluids

Bone Response Intestinal Response Kidney Response

Thyroid Gland Response

Factors That Decrease Blood Calcium Levels

These responses aretriggered when plasmacalcium ion concentrationsrise above 11 mg/dL.

HIgh Calcium Ion Levels in Plasma(above 11 mg/dL)

Parafollicular cells (C cells) in thethryoid gland secrete calcitonin.

Osteoclasts inhibited whileosteoblasts continue to lockcalcium ions in bone matrix

Bone

Rate of intestinalabsorptiondecreases

Kidneys allowcalcium loss

Calcitonin

less

calcitriol

Calcium storedCalcium absorbed slowly Calcium excreted

Increased calciumloss in urine↓Ca2+

levels inbloodstream

Fractures• Crack or break in bone• Often from stress in unusual direction• Need blood supply and portions of endosteum

and periosteum in order to survive• Repair:

o Spongy bone formso External callus of cartilage stabilizes boneo Cartilage is replaced by boneo Remodeling removes dead bone or extra layers

• Fracture types: o Transverse, displaced, compression, spiral, epiphyseal, communicated

(shatter), greenstick

Figure 6-17 Types of Fractures and Steps in Repair

Fractures are named accordingto their external appearance,their location, and the nature ofthe crack or break in the bone.Important types of fractures areillustrated here by representative x-rays. The broadest general categories areclosed fractures and open fractures. Closed, or simple, fractures are completelyinternal. They can be seen onlyon x-rays, because they do notinvolve a break in the skin.Open, or compound, fracturesproject through the skin. Thesefractures, which are obvious oninspection, are more dangerousthan closed fractures, due to thepossibility of infection oruncontrolled bleeding. Manyfractures fall into more than onecategory, because the termsoverlap.

Transverse fractures,such as this fracture ofthe ulna, break a boneshaft across its longaxis.

Displaced fracturesproduce new andabnormal bonearrangements;nondisplaced fractures retain the normal alignment of the bones or fragments.

Compression fractures occur in vertebrae subjected to extreme stresses, such asthose produced by theforces that arise whenyou land on your seatin a fall.

Spiral fractures,such as this fractureof the tibia, areproduced by twistingstresses that spreadalong the length ofthe bone.

Immediately after the fracture, extensivebleeding occurs. Over aperiod of several hours, alarge blood clot, or fracturehematoma, develops.

An internal callus forms as a network of spongy boneunites the inner edges, and anexternal callus of cartilage and bonestabilizes the outer edges.

PeriosteumSpongy bone ofexternal callus

Fracturehematoma

Bonefragments

Deadbone

REPAIR OF A FRACTURE

TYPES OFFRACTURES

Tran

sver

se fr

actu

re

Dis

plac

ed fr

actu

re

Spi r

al fr

act u

re

Compressionfracture

Epiphyseal fracture

Comminuatedfracture

Gre

enst

ick

frac

ture

Col l

es fr

actu

r e

Pot t

’s f r

act u

r e

A Pott’s fractureoccurs at the ankleand affects bothbones of the leg.

A Colles fracture, abreak in the distalportion of the radius,is typically the resultof reaching out tocushion a fall.

In a greenstick fracture, such as this fracture of the radius, only one side of the shaft is broken, and the other is bent. This type of fracture generally occurs in children, whoseLong bones have yet to ossify fully.

Comminuted fractures, such as this fracture of the femur, shatter the affected area into a multitude of bonyfragments.

Epiphyseal fractures, such as thisfracture of the femur, tend tooccur where the bone matrix isundergoing calcification andchondrocytes are dying. A cleantransverse fracture along this linegenerally heals well. Unlesscarefully treated, fracturesbetween the epiphysis and theepiphyseal cartilage can perman-ently stop growth at this site.

The cartilage of the external callus has been replaced bybone, and struts of spongy bone nowunited the broken ends. Fragments ofdead bone and the areas of boneclosest to the break have beenremoved and replaced.

A swelling initially marks the location ofthe fracture. Over time, thisregion will be remodeled,and little evidence of the fracture will remain.

Externalcallus

Externalcallus

Internalcallus

Diseases and Disorders

• Osteopenia = inadequate ossificationo Aging ; begins between 30 and 40o Lose 3% per decadeo Vertebrae and jaw lose mass faster - spinal issues and loss of teeth

• Osteoporosis – enough bone is lost to compromise normal functiono Also related to decreasing estrogen and androgenso More of an issue in women because of menopause

• Cancers