1. Bone Development a. Osteogenesis (Ossification)- bone tissue formation b. Stages i.

Bone formation- begins in the 2nd month of development ii. Postnatal bone growth- until early adulthood 1. After adolescence iii. Bone remodeling and repair- lifelong 2. Two Types of Ossification a. Intramembranous Ossification (Inside membrane) i. Membrane bone develops from fibrous membrane ii. Forms flat bones, e.g. clavicles(collarbones) and cranial bones b. Endochondral Ossification (forms inside cartilage) i. Cartilage( endochondral) bones form by replacing hyaline cartilage ii. Forms most of rest of skeleton 3. Endochondral Ossifications a. Uses Hyaline Cartilage models b. Requires breakdown of hyaline cartilage prior to ossification c. Dont walk around after birth because hyaline cartilage in epiphysis of long bones has not calcified. They are too soft and cannot support weight d. Long bones grow in length via epiphyseal plate cartilage 4. Postnatal Bone Growth a. Interstitial growth: i. Increase length of long bones ii. Endochondral Ossification b. Appositional growth i. Increase thickness and remodeling of all bones by osteoblasts and osteoclasts on bone surfaces ii. Intramembranous ossification 5. Growth in Length of Long Bones a. Epiphyseal plate cartilage organizes into four important functional zones: i. Proliferation (growth) ii. Hypertrophic iii. Calcification iv. Ossification (osteogenic) 6. Hormonal Regulation of Bone Growth a. Growth hormone stimulates epiphyseal plate activity b. Thyroid hormone modulates activity of growth hormone c. Testosterone and estrogens (at puberty) i. Promote adolescent growth spurts ii. End growth by inducing epiphyseal plate closure

iii. Osteoclasts destroy bones to reshape bone to adapt to the lengthening of bones 1. It resorbs the bone 7. Bone Deposit a. Occurs where bone is injured or added strength is needed b. Requires a diet rich in protein; vitamins C, D, and A; calcium; phosphorus; magnesium; and manganese c. Sites of new matrix deposit are revealed by the i. Osteoid seam 1. Unmineralized name of matrix ii. Calcification front 1. The abrupt transmission zone between the osteoid seam and the older mineralized bone 8. Bone Resorption a. Osteoclasts secrete i. Lysosomal enzymes (digest organic matrix) 1. Acid hydrolases a. Breaks down substances by adding water ii. Acids (convert calcium salts into soluble forms) b. Dissolved matrix is transcytosed across osteoclasts, enters interstitial fluid and then blood c. Gets inorganic substance into blood 9. Control of Remodeling a. What controls continual remodeling of bone? i. Hormonal mechanisms that maintain calcium homeostasis in the blood ii. Mechanical and gravitational forces 10. Hormonal Control of Blood Ca2+ a. Calcium is necessary for i. Transmissions of nerve impulses ii. Muscle contraction iii. Blood coagulation iv. Secretion by glands and nerve cells v. Cell division b. Primarily controlled by parathyroid hormone (PTH) i. Drop in Blood Ca2+ levels ii. Parathyroid glands release PTH iii. PTH stimulates osteoclasts to degrade bone matrix and release Ca2+ iv. Rise in in Blood Ca2+ levels c. May be affected to a lesser extent by calcitonin i. Rise in Blood Ca2+ levels

ii. Parafollicular cells of thyroid release calcitonin iii. Osteoblasts deposit calcium salts iv. Drop in Blood Ca2+ levels d. Leptin has also been shown to influence bone density by inhibiting osteoblasts 11. Response to mechanical Stress a. Wolffs Law: A bone grows or remodels in response or demands placed upon it b. Observations supporting Wolffs Law i. Handedness (right or left handed) results in bone of one upper limb being thicker and stronger ii. Curved bones are thickest where they are most likely to buckle iii. Trabeculae form along lines of stress iv. Large, bony projections occur where heavy, active muscles attach c. Young guys shouldnt play heavy contact sports because we risk the separation of the epiphyseal plate because the hyaline cartilage is soft 12. Classification of Bone Fractures a. Bone fractures may be classified by four either/or classifications: i. Position of bone ends after fracture: 1. Nondisplaced- ends retain normal position 2. Displaced- ends out of normal alignment ii. Completeness of the break 1. Complete- Broken all the way through 2. Incomplete- not broken all the way through iii. Orientation to the break of the long axis of the bone 1. Linear- parallel to the long axis of the bone 2. Transverse- perpendicular to the long axis of the bone iv. Whether or not bone ends penetrate skin 1. Compound (open)- bone ends penetrate skin 2. Simple (closed)- bone ends dont penetrate skin 13. Common types of fractures a. Location b. External appearance c. Nature of break 14. Stages in the healing of a bone fracture a. Hematoma forms i. Hematoma- localized collection of loose blood outside blood vessel, can form bruises ii. This is why bruising occurs where bones are broken b. Fibrocartilaginous callus forms i. Phagocytic cells clear debris ii. Osteoblasts begin forming spongy bone within one week

iii. Fibroblasts secrete collagen fibers to connect bone ends iv. Mass of tissue repair is not called fibrocartilaganous callus 1. Fibrocartilaganous callus is why movement may feel awkward or bone cannot resist to as much tension as before while bone is still not fully repaired because the callus isnt as hard as bone c. Bony Callus formation i. New trabeculae form a bony (hard) callus ii. Bony callus formation continues until firm union is formed in ~2 months d. Bone remodeling i. In response to mechanical stressors over several months ii. Final structure resembles original 15. Common Types of Fractures a. Comminuted i. Bone fragments into three or more pieces ii. Particularly common in the aged, whose bones are more brittle b. Spiral i. Ragged break occurs when excessive twisting forces are applied to a bone ii. Common sports fracture c. Depressed i. Broken bone portion is pressed inward ii. Typical of skull fracture d. Compression i. Bone is crushed ii. Common in porous bones (i.e., osteoporotic bones) subjected to extreme traumas, as in falls e. Epiphyseal i. Epiphysis separates from the diaphysis along the epiphyseal plate ii. Tends to occur where cartilage cells are dying and calcification of the matrix is occurring f. Greenstick i. Bone breaks incompletely, much in the way a green twig breaks. Only one side of the shaft breaks; the other side bends ii. Common in children, whose bones have relatively more organic matrix and are more flexible that those of adults 16. Homeostatic Imbalances a. Osteomalacia and rickets i. Calcium salts not deposited ii. Rickets (childhood disease) causes bowed legs and other bone deformations iii. Cause: Vitamin D deficiency or insufficient dietary calcium

b. Osteoporosis i. Loss of bone mass- bone resorption outpaces deposit ii. Spongy bone of spine and neck of femur become most susceptible to fracture iii. Causes 1. Lack of estrogen, calcium, or Vitamin D; petite body form; immobility; low levels of TSH; 17. Osteoperosis: Treatment and prevention a. Calcium, vitamin D, and fluoride supplements b. Increase weight bearing exercises throughout life c. Hormone (estrogen) replacement therapy (HRT) slows bone loss d. Some drugs (Fosamax, SERMs, and statins) increase bone mineral density 18. Pagets disease a. Excessive haphazard bone formation and breakdown, usually in spine, femur, pelvis, or skull b. Pagetic bone has a very high ratio of spongy bone to compact bone and reduced mineralization i. Results in a softer bone that is more susceptible to tension and compression which could result in chronic fractures and broken bones c. Unknown cause (probably viral) d. Treatments include calcitonin and bisphosphonates 19. Developmental Aspects of Bone a. Embryonic skeleton ossifies predictably so fetal age is easily determined from X rays or Sonograms b. At birth, most long bones are well ossified (except long bones) c. Nearly all bones completely ossified at age 25 i. We stop growing d. Bone mass decreases in age beginning in 4th decade e. Rate of loss determined by genetics and environmental factors f. In old age, resorption predominates i. Which could lead to osteoperosis