Osteoblasts Osteocytes Osteoclasts Cells of Bone Osteoblasts Osteocytes Osteoclasts

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

Hormonal Influences

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

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?

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?)

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

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

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.

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 24-36 hours

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

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

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

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 (http://www.orthop.washington.edu/arthritis/types/pagets/01 ) Can lead to dementia, deafness, blindness

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

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

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.

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 40-45 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