3. Osteoblasts Osteocytes Osteoclasts
Cells of Bone
Osteoblasts Osteocytes Osteoclasts

4. Calcium Homeostasis & Bone Tissue
Skeleton is a reservoir of Calcium & Phosphate
Calcium ions involved with many body systems
nerve & muscle cell function
blood clotting
enzyme function in many biochemical reactions
Small changes in blood levels of Ca+2 can be deadly (plasma level maintained 9-11mg/100mL)
cardiac arrest if too high
respiratory arrest if too low

5. Hormonal Influences

6. Calcium and Bone Physiology
Serum Ca+2 derived from:
diet (active transport in intestine)
active transport in renal tubules
breakdown of bony matrix
Ca+2 homeostasis maintained by:
Parathyroid hormone
Calcitonin
Vitamin D

7. Physiological roles of PTH
Receptors present in kidney, gut, bone, other tissues
Activ. of receptors on osteoblasts = release of cytokines = stim. of osteoclast activity
Demineralization of bones leads to elevated Ca+2 in blood
Vit D required for PTH effects on bone
Recruiter of osteoblasts?

8. Physiological effects of PTH, cont’d.
Increases renal tubular reabsorption of Ca+2
Enhances vitamin D synthesis in kidney
Enhances intestinal uptake of Ca+2 (indirect effects thru vitamin D?)

9. Calcitonin Produced by thyroid gland:
Release stimulated by elevation of blood Ca+2 levels (hypercalcemia)
Other factors (e.g., gastrin) stimulate its release
Calcitonin levels rise in response to feeding

10. Calcitonin
Activ of receptors by calcium stimulates calcitonin secretion (opposite of what occurs w/PTH)
Receptors present on skeletal tissue, kidney, and Leydig cells
At level of bone, calcitonin acts directly on osteoclasts to inhibit their activity

11. Think, pair, share
How will calcitonin and PTH secretion change in response to the injection of EDTA (a calcium chelator)?
A chelator is a substance that binds particular ions, removing them from solution, e.g., EDTA is a chelator of divalent cations such as Mg+2.
Draw a schematic illustration the demonstrates the mechanism of regulation by calcium of hormone secretion at the cellular level.

12. Other roles of calcitonin
May serve as satiety factor
Inject calcitonin into rats, monkeys > inhibit food intake
Inject calcitonin into humans > reduce body weight within hours

13. Vitamin D
Can be made from dietary or endogenous (part of the internal environment of an organism) substances
Precursor of steroidlike hormones that activate nuclear receptors
Renal enzyme production stimulated by PTH

14. Physiological roles of Vitamin D
Facilitates Ca+2 absorption from intestines; “recruits” osteoblasts
Vitamin D actions are necessary for proper bone growth (evidence: rickets)
Mechanisms of action:
Can promote mineralization(stimulates osteoblasts to do their work)
Can enhance PTH actions
Stimulates reabsorption of Ca+2 in kidney

15. Osteomalacia (rickets)
Failure of normal bone mineralization
Retards growth in children
Causes skeletal abnormalities in adults

16. Paget’s disease Abnormal osteoclast and osteoblast activity
Excessively rapid and uncoordinated turnover of bone
Detected due to elevated alkaline phosphatase levels in blood (the work of Vit D)
Pain, skull enlargement, scoliosis ( )
Can lead to dementia, deafness, blindness

17. Estrogen effects on bone
Inhibits cytokine release (interleukins) from osteoblasts (result: less bone resorption)
Reduces osteoclast lifespan
Lengthens osteoblast lifespan
Reduces rate of activation of new bone remodeling sites

18. Bone Remodeling
Remodeling is the ongoing replacement of old bone tissue by new bone tissue.
Old bone is constantly destroyed by osteoclasts, whereas new bone is constructed by osteoblasts.
In orthodontics teeth are moved by braces. This places stress on bone in the sockets causing osteoclasts and osteoblasts to remodel the sockets so that the teeth can be properly aligned

19. EXERCISE AND BONE TISSUE
Within limits, bone has the ability to alter its strength in response to mechanical stress by increasing deposition of mineral salts and production of collagen fibers.
Removal of mechanical stress leads to weakening of bone through demineralization (loss of bone minerals) and collagen reduction.
reduced activity while in a cast
astronauts in weightless environment
bedridden person
Weight-bearing activities, such as walking or moderate weightlifting, help build and retain bone mass.

20. AGING AND BONE TISSUE
Of two principal effects of aging on bone, the first is the loss of calcium and other minerals from bone matrix (demineralization), which may result in osteoporosis.
very rapid in women as estrogens levels decrease
in males, begins after age 60
The second principal effect of aging on the skeletal system is a decreased rate of protein synthesis
decrease in collagen production which gives bone its tensile strength
decrease in growth hormone
bone becomes brittle & susceptible to fracture