Calcium homeostasis, Exercise and Osteoporosis Claudia Stanescu, Ph.D. Office Hours in Gittings 108 Tue 10-11am and Thurs 1-2pm or by appointmentObjectives: 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.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. Objectives: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) HormonesCalcium 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 - Kidney excretion – Intestinal absorptionCalcium homeostasis Greenspans’s Basic and Clinical endocrinolgy 8th edition. Metabolic Bone Disease Dolores Shoback, MD, Deborah Sellmeyer, MD, & Daniel D. Bikle, MD, PhD. 2007 ECF Ca2+ represents 1% of total body calcium yet it is highly regulatedHormones 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 calciumParathyroid 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 calciumNegative feedback 10 Blood Calcium (mg/dl) Calcitonin PTHVitamin 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 Vitamin D precursor 7-dehydrocholesterol Dietary Vitamin D3 Cholecalciferol Vitamin D3 Cholecalciferol Fish oil, Egg yolks, Milk UV Light 25-hydroxy- Cholecalciferol (Calcidiol) 1,25 dihydroxy- cholecalciferol (Calcitriol) Active form + Blood Liver Kidney + + PTH Low Blood Calcium Blood Skin Blood Intestine Vitamin D is converted to the active form only if PTH present or Ca is low in the blood SkinActions 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 calciumHow 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.htmBone mineral gain and loss across the life span Remodeling during different life stages Fracture ThresholdRole 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 coordinationHormones that influence bone Calcitonin Parathyroid Hormone Growth hormone (somatotropin) Thyroxine (T4) Estrogen / Testosterone Already discussed Act on osteoclasts Act on osteoblastsGrowth hormone (somatotropin) • Stimulates cell growth and protein synthesis (collagen) • Stimulates formation of Insulin Like Growth factors (IGFs)  stimulates osteoblast activity  stimulates bone formationSkeletal 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 closedThyroxine (T4) / Thyroid Hormone • Increases cell metabolism • Stimulates osteoblast activity  stimulates bone formationEstrogen / 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 ageOsteoporosis • Porous bones (reduced bone mass)  increased risk of fracturesLow-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 ([email protected])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 ([email protected])Detail of a trabecular bone element eroded by osteoclasts note extensive pitting and fragility of the bone By kind permission of Tim Arnett ([email protected])Detail of a trabecular bone element perforated