Calcium homeostasis Exercise and Osteoporosis Claudia Stanescu Ph D Office Hours in Gittings 108 Tue 10 11am and Thurs 1 2pm or by appointment Objectives 1 Describe the dietary factors that influence bone 2 Describe the roles of calcitonin and parathyroid hormone in the regulation of blood calcium 3 Describe the vitamin D pathway and the role of calcitriol in calcium homeostasis 4 Describe the role of dietary calcium in maintenance of bone mass and know the recommended allowance for calcium intake for young adults Objectives 5 Describe how exercise can affect bone mass 6 Describe the role of growth hormone thyroxine and sex hormones in modulating bone mass 7 Describe the skeletal disorders that arise from abnormal levels of human growth hormone 8 Define osteoporosis and identify the risk factors for development of the disease Offer strategies for prevention of osteoporosis Factors that influence bone 1 Dietary Minerals calcium and phosphorus also magnesium fluoride and manganese Vitamins Vitamin A stimulates activity of osteoblasts Vitamin C needed for collagen synthesis Vitamin D stimulates calcium absorption Vitamins K B12 needed for synthesis of bone proteins 2 Exercise 3 Hormones Calcium homeostasis Goal regulate blood calcium within a normal range 8 5 11 0 mg dl Why Calcium has important physiological roles Membrane excitability Blood clotting Intracellular activity second messenger How Control calcium entry into and exit from blood Bone storage Intestinal absorption Kidney excretion Calcium homeostasis ECF Ca2 represents 1 of total body calcium yet it is highly regulated Greenspans s Basic and Clinical endocrinolgy 8th edition Metabolic Bone Disease Dolores Shoback MD Deborah Sellmeyer MD Daniel D Bikle MD PhD 2007 Hormones involved in calcium homeostasis Calcitonin Parathyroid hormone Calcitriol Vitamin D Calcitonin Stimulus high blood calcium Source thyroid gland parafollicular cells Target tissue bone kidney intestine Actions goal is to decrease blood Ca Inhibits osteoclast activity decreased bone resorption Increases excretion of calcium at kidney Inhibits absorption of calcium at intestine End result decrease blood calcium Parathyroid Hormone Stimulus low blood calcium Source parathyroid gland Target tissues bone kidney intestine Actions goal is to increase calcium Stimulates osteoclast activity increased bone resorption Decreases excretion of calcium at kidney Stimulates intestinal absorption of calcium and promotes calcitriol Vit D action End result increase blood calcium Negative feedback Calcitonin Blood Calcium mg dl 10 PTH Vitamin D Calcitriol active form of vitamin D 1 25 dihydroxycholecalciferol or 1 25 dihydroxy vitamin D3 Vitamin D is a steroid hormone derived from cholesterol lipophillic hydrophobic Vitamin D pathway Skin Vitamin D precursor 7 dehydrocholesterol PTH UV Light Skin Kidney Liver Vitamin D3 Cholecalciferol Blood 25 hydroxyCholecalciferol Calcidiol Blood Active form Blood Intestine Dietary Vitamin D3 Cholecalciferol 1 25 dihydroxycholecalciferol Calcitriol Low Blood Calcium Fish oil Egg yolks Milk Vitamin D is converted to the active form only if PTH present or Ca is low in the blood Actions of Calcitriol active form of vitamin D Stimulates osteoclast activity increases bone resorption Decreases calcium excretion at the kidney Increases calcium absorption at the intestine works well with PTH to stimulate absorption End result increase blood calcium How much calcium should you have per day Young adults 19 50 years old need 1000mg calcium from diet and supplements to avoid bone loss Check out the Bone Builders website for more information http ag arizona edu maricopa fcs bb index htm Remodeling during different life stages Fracture Threshold Bone mineral gain and loss across the life span Role of exercise Goal reach the fracture threshold later in life Exercise early in life increase peak bone mass Exercise later in life prevent bone loss Other benefits of exercise fall prevention Improved strength Improved balance and coordination Hormones that influence bone Calcitonin Already discussed Parathyroid Hormone Act on osteoclasts Growth hormone somatotropin Thyroxine T4 Estrogen Testosterone Act on osteoblasts Growth hormone somatotropin Stimulates cell growth and protein synthesis collagen Stimulates formation of Insulin Like Growth factors IGFs stimulates osteoblast activity stimulates bone formation Skeletal disorders associated with GH Pituitary dwarfism children with low levels of Growth Hormone slow epiphyseal growth short stature Pituitary giantism hypersecretion of Growth Hormone in childhood accelerated epiphyseal growth tall stature Acromegaly hypersecretion of Growth Hormone after puberty appositional growth thickening of bones in the skull hands feet Epiphyseal plates of long bones already closed Thyroxine T4 Thyroid Hormone Increases cell metabolism Stimulates osteoblast activity stimulates bone formation Estrogen Testosterone Both stimulate osteoblast activity stimulate bone formation Levels increase at puberty Bone growth growth spurts Eventually cause closure of the epiphyseal plates because osteoblast osteoclast activity is slightly greater than chondroblast activity Levels decrease with older age Osteoporosis Porous bones reduced bone mass increased risk of fractures Low power scanning electron microscope image of normal bone architecture in the 3rd lumbar vertebra of a 30 year old woman marrow and other cells have been removed to reveal thick interconnected rods of bone By kind permission of Tim Arnett t arnett ucl ac uk Low power scanning electron microscope image of osteoporotic bone architecture in the 3rd lumbar vertebra of a 71 year old woman marrow and other cells have been removed to reveal eroded fragile rods of bone By kind permission of Tim Arnett t arnett ucl ac uk Detail of a trabecular bone element eroded by osteoclasts note extensive pitting and fragility of the bone By kind permission of Tim Arnett t arnett ucl ac uk Detail of a trabecular bone element perforated by osteoclast action note perforation By kind permission of Tim Arnett t arnett ucl ac uk DXA Dual X ray Absorptiometry DXA Dual X ray Absorptiometry Physical changes accompanying bone loss and vertebral fractures What causes reduced bone mass Any factor that stimulates bone resorption or inhibits bone formation or both Osteoclast activity Osteoblast activity bone resorption bone formation Osteoporosis Risk Factors Calcium Vitamin D deficiency Older age