Bone Formation, Resorption and Remodeling

1. Bone Formation, Resorption and Remodeling

2. What are bones composed of? • Cartilage • In embryo and fetus – hyaline • In Adult – articular

3. Cartilage is also found isolated in the • Nose • Ears • Parts of ribs • Joints

4. Articular cartilage is a firm rubbery protein material covering the end of a bone acts as a cushion or shock absorber between the bones

5. Bone Formation in the Embryo and Fetus • Hyaline cartilage acts as the “model” and “mold” for the ossification process • .

6. Bone Formation The “bones” of an embryo begin formation at around 41 to 44 days postovulation.

7. Hyaline Cartilage Here, you can see both the bones, which are brightly imaged and shadows of bone, which are hyaline cartilage, as seen in this mouse embryo scan.

8. Ossification Term given to the process of bone formation. The mouse bones have been covered with bone matrix.

9. Bones in a child • Once the child is born, the only hyaline cartilage found is in the epiphyseal plates and articular cartilage

10. Ossification • Hyaline cartilage is digested by lysosomes in osteocytes (bone cells) which opens up the medullary cavity for osteoblast functioning.

11. How are flat bones formed?Intramembranous ossification • Intramembranous ossification involves the replacement of sheet-like connective tissue membranes with bony tissue. • Bones formed in this manner are called intramembranous bones. • They include certain flat bones of the skull and some of the irregular bones. • The future bones are first formed as connective tissue membranes. • Osteoblasts migrate to the membranes and deposit bony matrix around themselves. • When the osteoblasts are surrounded by matrix they are called osteocytes.

12. Bone Growth • Bone growth occurs on the inside of the articular cartilage at the superior and posterior regions and at the anterior region of the epiphyseal plate. Here, it would be just above the epiphyseal plate and below the end of the bone. • http://depts.washington.edu/bonebio/ASBMRed/growth.html

13. Bone Growth • Occurs both longitudinally and latitudinally (in other words both up and out!) • Osteoblasts add bone to the periosteum the same time that osteoclasts in the endosteum remove bone from the diaphysis – This is appositional growth. Go to http://student.ccbcmd.edu/c_anatomy/animations/BONEGROW/bonegrowth.gif for an animation of this form of growth

14. Epiphyseal Plates • Provide for longitudinal growth of long bones in childhood (which is why you get taller!) 1 and 2 are the epiphyseal plates

15. Bone Remodeling Bone is active tissue – small changes in bone architecture occur continuously – 5 to 7% of bone mass is recycled weekly – spongy bone is replaced every 3-4 years and compact bone approximately every 10 years Remodeling Units – adjacent osteoblasts and osteoclasts deposit and resorb bone at periosteal and endosteal surfaces

16. Growth hormone from the pituitary gland causes more osteoblast activity to occur during growth spurts between age 6 and puberty. Sex hormones increase osteoblast activity during puberty. Factors Affecting Bone Growth

17. Lack of Vitamins D and K and/or calcium causes ricketts Bones soften and bow outward Vitamin D calcium absorption in bone Vitamin K tells calcium where to go in body Lack of growth hormone Person will be shorter than others in his/her age cohort Treated by GH injections Factors that Affect Bone Growth

18. Pull of gravity Astronauts and bedridden patients lose bone mass Bone growth can be increased by pull of muscles The humerus size and mass of tennis players is different in each arm! More Factors

19. Cells Responsible for Bone Growth and Resorption http://www.argosymedical.com/Skeletal/samples/animations/Osteoporosis/index.html

20. Osteoclasts • derive from bone marrow mononuclear cells • characteristic feature is a ruffled edge where active resorption of bone takes place • You can see this on the picture.

21. Osteoclasts secrete bone-reabsorbing enzymes, which digest bone matrix. • Recruitment and inhibition is controlled by numerous hormonal and growth factors, such as PTH and calcitonin.

22. Estrogen receptors can be found on osteoclasts. • Decreases in estrogen promote osteoclast recruitment. • This is why osteoporosis is seen more often in post-menopausal women.

23. Osteoblasts Are bone-forming cells that deposit bone to replace the cartilage. These cells also help in bone reformation.

24. Osteoblasts • secrete a collagen rich ground substance essential for later mineralization of hydroxyapatite and other crystals • collagen actually strands to form osteoids: spiral fibers of bone matrix.

25. Osteoblasts • cause calcium salts and phosphorus to precipitate from the blood • these minerals bond with the newly formed osteoid to mineralize the bone tissue.

26. Bone Formation Osteoblasts continue to create osteocytes both within the spongy bone layer and the compact bone layer the endosteum.

27. This animation shows a slice through a piece of bone about a millimeter long. • It lasts 13 seconds and shows 30 months of "real time." • The view is similar to the view seen under the microscope of a bone biopsy from a patient. • There are about 10 BMU's (basic multicellular unit) in this view, each at a different stage. • The bone formation rate in this movie is a bit above average, but within the normal range. • The shades of green represent the mineralization density: newly formed bone is not very dense (pale green) and older bone is denser (dark green).

28. Go to http://courses.washington.edu/bonephys/Gallery/movies/normal.swf

29. This animation shows one BMU. • It lasts about 11 seconds and represents about 6 months of real time. • A micro-crack starts the process, the osteocytes (not shown here) sense damage and send signals into the marrow space. • Preosteoclasts turn into multi-nucleated osteoclasts and start resorption, • Meanwhile preosteoblasts turn into osteoblasts and start forming osteoid (orange) which then mineralizes (green). For details go to physiology

30. Bone resorption and formation after a microcrack forms Go to http://courses.washington.edu/bonephys/Gallery/movies/newBMUbu.swf

31. Go to the website below to review bone physiology • http://courses.washington.edu/bonephys/physremod.html • Reviews steps involved in bone remodeling • Click the “NEXT” on the drawing to view the steps.

32. Osteocytes • Osteoblasts that have been trapped in the osteoids produced by other surroundings osteoblasts are called Osteocytes.

33. Mouse Embryos • The bones seen here contain osteocytes.

34. Osteocytes • maintain bones from within • play a role in controlling the extracellular concentration of calcium and phosphate • are directly stimulated by calcitonin and inhibited by PTH (Parathyroid hormone

35. Side Trip to Hormone Land!!!

36. Thyroid and Parathyroid Locations Thyroid Gland

37. Calcitonin • Calcitonin is a hormone secreted • predominately by the C cells of the thyroid gland, but can also • be secreted by tissues of the lungs and intestinal tract • Functions to • control calcium and phosphorus metabolism (here, the loss of calcium and phosphorus) by suppressing osteoclasts in the bones and • inhibits their resorption in the kidney tubules.

38. C cell locations in Thyroid Gland

39. PTH or Parathyroid Hormone • is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid • is secreted from cells of the parathyroid glands • if calcium ion concentrations in extracellular fluid (such as blood plasma and interstitial fluid between cells) fall below normal, PTH brings them back within the normal range

40. How do these hormones get near the osteocytes? • Via the circulatory blood vessels that run in and out of the bones and through the canaliculi

41. PTH regulates calcium and phosphorus in three ways 1. stimulates osteoclasts to resorb bone mineral, liberating calcium and phosphate into blood.

42. 2. Enhancing absorption of calcium from the small intestine indirectly by stimulating production of the active form of vitamin D in the kidney. Vitamin D induces synthesis of a calcium-binding protein in intestinal epithelial cells that facilitates efficient absorption of calcium into blood.

43. 3. Suppression of calcium loss in urine by kidney tubule resorption. What problem can this cause in the kidney if too much calcium is retained?

44. PTH Diagram

45. Figure 6.13 Factors that Alter the Concentration of Calcium Ions in Body Fluids Figure 6.13a

46. Hypocalcemia • http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypocalcemia/

47. Figure 6.13 Factors that Alter the Concentration of Calcium Ions in Body Fluids Figure 6.13b

48. Hypercalcemia • http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001404/

49. Homeostasis of Remodeling • Two control loops regulate bone remodeling • Hormonal mechanisms that maintain calcium homeostasis in the blood • Mechanical and gravitational forces acting on the skeleton

50. Hormonal Mechanism • Rising blood Ca2+ stimulates the thyroid to release calcitonin • Calcitonin stimulates calcium salt deposition