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Bone tissueFunctions of the skeleton

SupportProtectionMovementElectrolyte balanceAcid-Base balanceBlood formationShapes of bones

Long bones longer than they are wide humerus, tibia, fibula, femur, radius, ulnaShort bones equal in length and width carpal and tarsal limited motion glide across one another Flat bones enclose and protect soft organsIrregular bones have elaborate shapes vertebra

General Features of bonesCompact (dense) boneMarrow cavitySpongy or cancellous boneDiaphysisEpiphysisArticular cartilageNutrient foraminaPeriosteum fibrous layer osteogenic layerPerforating fibersEpiphyseal plateDiploe

Bone CellsOsteogenic cells found in the endosteum, the inner layer of the periosteum, and in the central canals multiply and some become osteoblastsOsteoblasts cuboidal bone forming cells single layer on the bone surface under the endosteum and periosteum synthesize the soft organic matter of the bone matrix that hardens by mineral deposition stress and fractures stimulate osteogenic cells to multiply more rapidly osteoblasts are nonmitotic

Osteocytes former osteoblasts that have become trapped in the matrix that they deposited reside in lacunae connected by caniculi have cytoplasmic processes that communicate with other osteocytes and osteoblasts some resorb matrix and others deposit it strain sensorsOsteoclasts bone dissolving cells found on bone surface develop from bone marrow stem cells ruffled border reside in resorption bays

Bone Matrix organic matter synthesized by osteoblasts includes collagen, GAG, proteogycans and glycoproteins inorganic matter includes hydroxyapatite, calcium carbonate, magnesium, sodium, potassiumComposite ceramic and polymer in bone polymer is collagen and ceramic is hydroxyapatite

Compact bone concentric lamellae central canals lacunae osteon, perforating (Volkman) canals circumferential lamellae interstitial lamellaeSpongy bone trabeculae calcified and hard spaces filled with bone marrow matrix arranged in lamellae but no central canals (not needed) designed to impart strength to the bone while adding minimal weight trabeculae not randomly arranged but developed along lines of stressBone Marrow soft tissue that occupies marrow cavity of the long bones, spaces between the trabeculae of spongy bone, and the larger central canalsRed bone marrow in the child the marrow cavity of nearly every bone is filled with red bone marrow which is hemopoetic, produces blood cells looks like bloodYellow bone marrow In adults most of the red bone marrow turns yellow because of fat no longer produces blood but can transform back to red marrow in case of emergency red marrow in adults is limited to the skull, vertebrae, ribs, sterum, pelvic girdle and proximal heads of the humerus and femur

Bone Development formation of bone is osteogenesisIntramembranous ossification seen in flat bones, skull and most of the clavicle mesenchymal cells to osteogenic cells mesenchymal soft tissue to trabeculae osteogenic cells to osteoblasts to osteocytes creation of spongy bone bone deposition continues and spongy bone is converted to two layers of compact bone with spongy bone and marrow in the middle

Endochondral ossification

Primary ossification centerPrimary marrow cavityMetaphysisSecondary ossification centerSecondary marrow cavityEpiphyseal plate

Bone GrowthZone of reserve cartilageZone of cell proliferationZone of cell hypertrophyZone of calcificationZone of bone depositionInterstitial growthEpiphyseal lineBone widening and thickening apposition growth circumferential lamellaeAchondoplastic Dwarfism long bones of the limbs stop growing in childhood while growth of other bones is unaffected person has short stature but normal size head and trunk failure of the chondrocytes in zones 2 and 3 of the metaphysis to multiply and enlargePituitary dwarfism deficiency of growth hormone stunts the growth of all bonesIn Achondroplastic dwarfism the mutant allele is dominant

Bone Remodeling

Wolfs law of bone the architecture of a bone is determined by the mechanical stresses placed upon itBones are continually remodeled throughout life by the absorption of old bone and the deposition of new bone This process replaces about 10% of the skeletal tissue per year.This repairs microfractures, releases minerals into the blood and reshapes bones in response to use and disuse

Bone remodeling works through the collaboration of osteoblasts and osteoclastsIf a bone is little used osteoclasts remove matrixIf a bone is heavily used osteoblasts deposit new osseus tissue and thicken the boneOrderly remodeling of bone depends on precise balance between deposition and resorption

Mineral deposition process where calcium, phosphate and other ions are taken from the blood and deposited in bone tissueEctopic ossificationCalculusMineral resorption process of dissolving bone carried out by osteoclasts generate HCI with ph of 4 acid dissolves the bone minerals osteoclasts secrete acid phosphatase which digests the collagen of the bone matrixCalcium and Phosphate Homeostasis

Osseous tissue and ph balance acidosis exists when the ph of the blood drops below 7.35 urinary, respiratory and urinary systems maintain the bodys acid-base balance with acidosis the skeleton releases calcium phosphate which is a base and brings the ph back upChronic kidney disease state of chronic acidosis can cause damage to boneSkeleton is a reservoir for calcium and phosphorus these minerals are deposited in bone when the supply is ample and withdrawn when needed for other purposesAdult body contains about 1,100 g. of calcium with 99% of it in boneCalcium concentration of blood is 9.2 10.4 mg/dL. about 45% is in the ionized form and can diffuse through capillary walls and affect neighboring cells the rest is bound to plasma protein and not activeAverage adult has 500 - 800 g of phosphorus and 85% - 90% is in bone phosphorus concentration in plasma ranges between 3.5 and 4.0 mg/dL Changes in phosphorus concentration have very little immediate effect but changes in calcium concentration do have immediate effects hypocalcemia causes excessive excitability of nervous system and muscle spasm tetany tetany begins at a calcium level of 6 mg/dL Chvosteks sign carpalpedal spasm laryngospasm hypocalcemia causes an opening of sodium channels and influx of sodium into the cell causing muscle and nerve excitability

Hypercalcemia rare increases the charge difference across the cell membrane making the sodium channel less responsive which makes muscle and nerve less excitable than normal

Calcium phosphorus homeostasis is regulated by three compounds hormones

Calcitriol a form of vitamin DCalcitoninParathyroid hormoneCalcitriol Epidermal keratinocytes use ultraviolet light from the sun to make vitamin D3 liver converts it to calcidiol kidney converts it to calcitriol which is the most active form of vitamin D.Raises the blood calcium level in three waysIncreases calcium absorption by the small intestineIncreases calcium resorption from the skeletonPromotes calcium reabsorption by the kidneys

Parathyroid hormoneIncreases bone resorptionPromotes calcium reabsorption by the kidneysPromotes the final step of calcitriol synthesis in the kidneyInhibits collagen synthesis by osteoblasts and thus inhibits bone deposition

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Bone Diseases

Rickets Defective mineralization of bone in children usually as a result of insufficient sunlight or vitamin D sometimes due to a dietary deficiency of calcium or phosphorus or to liver or kidney disease causes bone softening and deformityOsteomalacia Adult form of rickets most common in poorly nourished women bones become soft and deformed Osteitis deformans Excessive proliferation of osteoclasts and resorption of excess bone osteoblasts try to compensate by depositng extra bone results in disorderly deformed bones causes pain most common in males over 50Osteomyelitis bone infection requires long term antibiotic therapyOsteogenesis Imperfecta defect in collagen deposition that renders the bones very brittle causes fractures at birth or childhood can cause hearing loss

Osteoma benign bone tumor usually in the skullOsteochondroma benign tumor of bone and cartilageOsteosarcoma most common and deadly form of bone cancer most often in the tibia, femur or humerus of males between the ages of 10-25 can be lethalChondrosarcoma slow growing cancer of hyaline cartilage requires surgical removalOsteoporsis The most common bone disease characterized by low bone mass, increased skeletal fragility, and susceptibility to fractures associated with lack of exercise or estrogen deficiency estrogen inhibits osteoclast activity loss of organic matrix and minerals affects spongy bone in particular frequently involves the hip, wrist and vertebraStatistics Half of all American women over the age of 50 will have an osteoporotic fracture at some time in their life 20 % of people suffering a hip fracture die within a year annual direct cost of osteoporotic fractures is about 17 billion dollars problem will worsen with aging population Peak bone mass women reach peak bone mass between age 20-30 they will then lose a small percent of their bone mass yearly until menopause when bone loss is accelerated women can lose 20 % of their bone mass in the 5-7 years after menopause failure to reach peak bone mass may contribute substantially to the development of osteoporosis Risk Factors For Osteoporosis

Personal history of fracture after age 50History of fracture in a first-degree relativeFemaleBeing thin or having a small frameEstrogen deficiency as a result of menopauseAbnormal absence of periods Anorexia nervosaLow lifetime calcium intakeVitamin D deficiency

Use of certain prescription medicines such as steroids, anticonvulsants and heparinExcessive use of antacids containing aluminumInactive life styleSmokingExcessive drinkingBeing Caucasian or AsianDiagnosis of Osteoporosis

Scanning for BMDNo available way to test for health of microarchitectureMany protocols for testing

Treatment of Osteoporosis Therapeutic and preventive

Estrogen inhibits osteoclastic activityBiphosphonates decrease bone resorption by inhibiting the formation and function of osteoblastsSERMS estrogen receptor agonist in boneCalcitonin suppresses osteoclastic activityParathyroid hormone given in pulsed injection it stimulates osteoblastic development and inhibits the death of osteoblasts