Bone Formation, Maintenance, Breakage, and Repair: An Overview

1. How do we form bones, maintain bones, break bones and repair bones? 10/9 FRIDAY: Special talk by WSU Library: be there if you want the 5 points for attendance that day only. • What is ossification? • What are the three ways to form bone? • Why is it critical to maintain serum calcium? • What mechanisms allow calcium regulation? • What are some classic bone diseases? • What is osteoporosis and why are women effected? • What are the types of fracture? • When bones are broken and how are they repaired? • Contrast of healing bone with healing the integument

2. Flat bones form as a set of trabeculae within fibrous connective tissues. • 1) Osteoblasts collect and deposit bone matrix • 2) Bone is woven into trabeculae (no osteons) • 3) Surrounding connective tissue creates periosteum • 4) Periosteum stimulates underlying osteoblasts to create compact bone sheath (NO osteons) • 5) Blood vessels inside become red bone marrow (hemopoietic)

3. What are the effects of gravity and exercise on the balance of calcium deposition and osteoporosis in regards to osteoblasts and osteoclasts? Why do trabeculae form in the pattern that they do?The Trick: osteoblast activity is stimulated by load (tension/compression) and osteoclast activity is stimulated by lack of tension.

4. Why is blood calcium level tightly regulated? • What are some of the actions of calcium? • High blood calcium: “HYPERCALCEMIA” • Low blood calcium: “HYPOCALCEMIA” • Calcium solubility product: • Muscle contraction- • Nerve cell function- • Bone formation- • How do we regulate blood calcium with vitamins and special hormones? • Negative Feedback Loops!

5. It is easy to see why the bones of a person with osteoporosis become very brittle! Which trabeculae will compress more easily (i.e. vertebrae)?

6. How much calcium enters and leaves your body each day?By what routes does Ca++ enter/exit from your body? RAPIDLY CHANGEABLE POOL: Ca++ IN CELLS AND IN BLOOD

7. Three hormones control the uptake and excretion of calcium in your body. How is this a type of homeostasis? What are the functions of parathyroid hormone, vitamin D, and Calcitonin?

8. Vitamin D is only required (a vitamin) if your skin gets no exposure to sunlight! Explain rickets. Excess consumption of Vitamin D is extremely toxic because it is fat soluble! The liver converts D3 and calciferol into 25-OH-cholecalciferol (active)

9. Vitamin D is also called calcitriol if you make it in your body: what does this steroid-structure hormone do? • Exocytosis, secretion, and muscle contraction cannot occur if there is insufficient Ca++ in the plasma or cytosol! • The story of “milk fever” in cows with calves • Calcitriol is produced in the body to improve calcium availability and conserve calcium losses! • 1) Increase intestinal Ca++ and Phosphate absorption • 2) Decrease Ca++ loss from kidney • 3) Increase bone osteoclast activity • We take Vitamin D when we lack sufficient sunlight! • Where do we spend our urban hours? Who is at risk? • Why are kids most sensitive to Rickets (bow legged appearance) ? • Why do may adults develop osteomalacia (brittle bones)?

10. Vitamin D: A little is “good” and a lot must be “better” right??????? • This is a sad but fatal statement for many. • Vitamin D promotes Ca++ and Phosphate uptake needed for osteoblasts to build bone and also causes osteoclasts to remove bone from unused areas. • Vitamin D potentially increases blood Ca++ in two ways! • Why not take unlimited amounts? • Vitamin D is a lipid and very toxic at high doses (toxic at only at about X5 RDA) • Vitamin D accumulates in adipocytes • So once you have “too much” its tough to get rid of vitamin D • Why does Excess Vitamin D lead to atherosclerosis and soft tissue calculi? Why do some of these kids die of a heart attack?

11. What are the other two primary hormones that promote calcium homeostasis? Parathyroid Hormone (PTH): peptide from parathyroid gland that prevents low plasma Ca++ • Increase osteoclast activity • Increase renal Ca++ uptake • Increase calcitriol (Vit D) synthesis • Inhibit collagen synthesis in bone: prevent new bone Calcitonin: peptide hormone secreted from thyroid gland when Ca++ levels are “TOO” high • Action: lowers Ca++ and phosphate levels • + Osteobast Activity (-) Osteoclast activity • No deficiency diseases known to exit however

12. What are some diseases related to improper calcium and bone metabolism? • Osteoporosis: • Kyphosis: • Osteogenesis imperfecta: • Achondroplastic dwarfism: • Ricketts/Osteomalacia: • Osteoma/ Osteosarcoma: • Radiation toxicity: • Leukemia chemotherapy treatments kill hemopeotic cells in red bone marrow, this requires a bone marrow transplant to be able to produce blood cells (hemopoeisis), osteocytes tend to be left more intact.

13. It is easy to see why the bones of a person with osteoporosis become very brittle! Which trabeculae will compress more easily (i.e. vertebrae)?

14. Osteoporosis is a primary factor leading to death in the elderly, what leads to this disease state? Why do events after the fracture kill the person? • When does your bone density peak? • What alters bone density in youth? • What happens at menopause in women? • What happens to exercise ability as we age? • Bones can become so brittle they collapse under their own weight! • What happens to the density of the trabeculae? • What are some at risk groups for broken bones based on these factors? • WHAT IF: Ca++ loss: 1.2 grams/day Ca++ intake: 1.0 g/day RDA Ca++ total of about 1000 g……how long will it take to reduce Ca++ mass to 50% or original? Math: (500 grams loss)/ (0.2 g/day)=2,500 days = about 6-7 years

15. What types of fracture do orthopedic surgeons evaluate?Fracture Types: Open is often called “Compound”Please Add “Closed”: a fracture contained within skin

16. The healing of a fracture is an amazing process completed under the harshest of circumstances! • How does the fracture occur? • What is effect of inflammation and pain? • Four Main Steps: • 1) Hematoma formation and angiogenesis: • 2) Granulation tissue formation: • 3) Callus formation: Fibrocartilage then Soft Callus then Bony Callus- • 4) Remodeling: • What happens when break is repeated?? clavicles

17. When a fracture occurs blood immediately rushes out of the blood vessels into the fracture site creating a hematoma, clotting, and inflammation. Healing a fracture takes from days to months to years to occur!

19. Contrast: Healing the Integument • Phases of Healing Integument: • 1) Inflammatory Phase • Clot unites wound and vasodilation brings warmth, rubor, leukocytes and nutrients • 2) Migratory Phase • Fibroblasts migrate through clot and angiogenesis begins creating granulation tissue • 3) Proliferation Phase • Epithelial cells grow underneath scab and fibroblasts lay down excess collagen • 4) Maturation Phase • Scab sloughed off when epithelial cells complete migration/proliferation and fibroblast numbers/activity drop Remodeling: May occur to some degree over time, but skin seldom returns to its original “perfect state”