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Bones

Skeleton essential for mechanical support of the body and its mineral homeostasis, houses the bone marrow, protects viscera, and determines the body’s size and shape.

Bones are constantly being remodelled to address the body’s calcium requirements and to repair microscopic damage.

The process of bone rebuilding takes place after an injury as well as during normal growth.

Normally, bone continuously breaks down and rebuild, with old bone resorbed and replaced with new bone.

The process keeps the skeleton strong and helps it to maintain a balance of minerals.

The cellular structure of bone consists of osteocytes within lacunae, and osteoblasts and osteoclasts at the periphery of the bone.

Osteoblasts and osteoclasts contribute to long-term bone remodeling.

The skeleton is replaced every 10 years in adults.

Around 10% of the skeleton is involved in bone remodelling at any one time.

Removal of existing bone is mediated by osteoclastic bone resorption and replacement with new bone is mediated by osteoblastic bone formation.

During skeletal growth, formation of bones rate exceeds resorption resulting in a net gain of bone.

Resorption rate exceeds formation rate later in life, particularly among estrogen deficient post menopausal females and all older people.

Resorption rate exceeds formation rate later in life, particularly among estrogen deficient post menopausal females and all older people.

Prolonged bone loss needs to low bone mineral density (BMD) and eventually osteoporosis.

Designed to be light and allowing for mobility.

Humans are born with approximately 300 bones that fuse to become 206 bones by age 25.

Skeleton composed of 206 bones.

Develop from mesencyhmal intramembranous ossification and endochondral ossification.

Flat bones develop from mesencyhmal in preexisting membranes.

Most bones develop from mesencyhmal that has condensed initially into cartilage.

The primary center for ossification occurs in the shaft of the bone, the diaphysis.

The ends of the bones, epiphyses, remain cartilaginous for several years after birth, during which the secondary centers of ossification appear.

Lengthening of bone occurs in the epiphyseal cartilage plate at the diaphysial-epiphyseal junction until it ossifies at about age 20.

Interconnected by joints that allow range of movement, structural stability and normally undergo mineralization.

Make blood cells, store minerals and play a key role in calcium homeostasis and perhaps energy metabolism.

Are mineralized connective tissue.

Bone provides rigid support for body weight and protects vital organs.

The cellular structure of native bone consists of osteocytes within lacunae, and osteoblasts and osteoclasts at the periphery of the bone.

Strength depends on structural and material properties, modulated by bone turnover.

The shape, strength and resilience of bones is determined by its organic matrix, the osteoid.

Hardness related to crystallization of hydroxyapatite (Ca10[PO4]6[OH]2) within the matrix.

Bones are made of a mixture of calcium, chondroitin sulfate and hydroxyapatite, the latter making up 70% of a bone.

Bone comprises approximately 70% mineral, 20% collagen protein, and 10% water.

Bone comprises about two-thirds mineral and one-third osteoid, most of which is type 1 collagen.

Hydroxyapatite is in turn composed of 39.8% of calcium, 41.4% of oxygen, 18.5% of phosphorus, and 0.2% of hydrogen by mass.

Chondroitin sulfate is a sugar made up primarily of oxygen and carbon.

Hardness improves weight bearing capacity, but increased brittleness of bones and increase risk of microfractures after repeated skeletal stress.

Microfracture repairs occur continuously through life and require resorption of bone and than deposition and mineralizaton of new bone,known as bone remodeling.

Microscopic cracking occurs on a daily basis from weight-bearing activity and these sites are repaired by remodeling.

3 cell types participate in bone remodeling and include osteoblasts, osteocytes and osteoblasts.

The two cell types contribute to long-term bone remodeling.

Large voids in bone can occur after traumatic fractures, pathologic fractures due to disease processes such as multiple myeloma, and iatrogenic bone resections.

These voids must be filled to restore structural form and integrity.

Osteoblasts are mesenchymal cells that synthesize new bone matrix and regulate mineralizaton.

Osteoblasts major source of type 1 collagen, which is synthesized and secreted as procollagen.

Estradiol has a stimulatory effect on osteblasts

Procollagen has propeptides which are removed before collgen is incorporated into osteoid.

Osteocytes detect microfractures and initiate the bone remodeling process.

Osteocytes are the main regulators of bone homeostasis between osteoclasts,which are responsible for bone resorption and osteoblasts, which are responsible for bone formation.

Osteocytes secrete cytokines that regulate the activity of osteoclasts and osteoblasts and include:

sclerostin, dickkopf WNT signaling pathway inhibitor 1 ((DKK1), receptor activated nuclear factor-KB (RANKL), and osteoprotegerin OPG, the decoy receptor of RANKL.

RANK-RANKL signaling activates a variety of a downstream signaling pathways required for osteoclast development and stimulates osteoclast differentiation and maturation.

Osteoclasts are hematopoietic cell that are responsible for bone resorption.

Osteocytes make up 90-95% of all bone cells, and osteoclasts and osteoblasts make up fewer than 10%.

Estimated that the entire skeleton undergoes bone remodeling each decade

The osteoid is composed of type-1 collagen, which makes up 90%, with osteocalcin, osteopenia, osteonectin, proteoglycans, glycosaminoglycans and lipids.

Structural properties dependent upon the size and shape of bones, cortical thickness, porosity, trabecular thickness, and micro cracks (damage).

Material properties are dependent on extent of mineralizaton, mineral crystal size, collagen cross links, proteins and fat.

Inorganic elements 65%, organic make up 35%.

Inorganic content: calcium hydroxyapatite, gives bone its strength and hardness and 99% of body’s stores of calcium, 85% of body’s phosphorus and 65% of the body’s sodium and magnesium.

99% of the body’s calcium supply is stored in the bones and teeth where it supports their structure and function

 

 

Bones undergo continuous remodeling, with constant resorption and deposition of calcium.

 

 

Bone resorption and deposition balance changes with age with formation exceeding resorption during childhood growth and adolescence.

 

 

Resorption and deposition of bone/calcium are relatively equal during  early and middle adulthood. 

Normal bone mass is maintained through a balance between osteoclasts, and osteoblasts.

Long bones can regenerate spontaneously, to restore full function without scarring.

Large segmental defects in long bones will fail to regenerate fully.

The skull bones lack the reparability in individuals older than two years of age.

Estrogen is the major steroid regulating bone resorption.

Regulators of osteoclast bone resorption include estrogen, the receptor activator of nuclear factor kb (RANK) receptor , the RANK ligand (RANKL), and the receptor osteoprotegerin.

Estrogen deficiency helps shift bone remodeling towards increased bone resorption by activating osteoclasts, decreases osteoclast apoptosis and increases osteoblast apoptosis.

Estrogen deficiency may increase osteoclastogenesis via up regulation of RANKL and down regulation of osteoprotegerin.

Estrogen deficiency as seen in menopause and with the use of aromatase inhibitors cause the formation of resorption cavities beyond which the osteoblasts can not completely repair resulting in loss of bone and bone integrity.

Tetracycline labeling can be used to examine bone remodeling as it binds the newly formed bone and fluorescent is in histologic samples: Patients are given to short courses of tetracycline separated by a 10 day period, and that is followed by iliac crest biopsy.

Tobacco smoking and alcohol abuse have both been associated with poor bone health.

Exposure to nicotine and other chemical components in cigarettes can lead to delayed healing, higher rates of nonunion, and decreased mechanical strength of bone.

Alcohol abuse has been associated with decreased bone mass and poor bone formation.

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