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Question 1

Estrogen

Answer 1

Metabolic Effects-
Maintain skin and blood vessels, periods, promote apoptosis of osteoclasts and go against pro-osteoclast factors like IL-6 and PTH, stimulate leptin, higher plasma triglycerides and change cholesterol levels

Enhance blood coagulation, induce synthesis of progesterone receptors for behavior and libido

Question 2

PTH

Answer 2

Increased serum Ca and decrease serum phosphate

Stimulates osteoclasts by making osteoblasts secrete RANKL, net bone resorption

Denosumab is an antibody against RANKL

Calcium and phosphate resorption increased by high doses, low doses may increase bone formation

Question 3

Vitamin D

Answer 3

1,25(OH)2D

Induce RANKL in osteoblasts

Stimulate intestinal calcium and phosphate transport, bone resorption

Fibroblast Growth Factor 23: inhibits 1,25(OH)2D and phosphate reabsorption in the kidney, made by osteoblasts and osteocytes

Question 4

Calcitonin

Answer 4

Lower serum calcium and phosphate by actions on bone and kidney

Inhibits osteoclast bone resorption, over time bone formation is reduced too

Mechanism of Action: bind GPC to suppress osteoclastic bone resorption and inhibit PTH secretion

Indications: first line for Paget’s with bisphosphonates

Reduces calcium and phosphate reabsorption in the kidneys

Adverse Effects: gastric erosion and bleeding due to lower prostaglandin synthesis

Question 5

Estrogen, SERMs, and Glucocorticoids on Bone

Answer 5

1. Glucocorticoids-
   Antagonize vitamin D stimulated intestinal calcium transport, stimulates renal calcium excretion, blocks bone formation

Prolonged use leads to osteoporosis and can cause stunted skeletal growth in kids

2. Estrogen-
   Prevent bone loss, reduce bone reasorption action of PTH

Use for postmenopausal osteopenia, long term use has can cause breast cancer so use Selective Estrogen Receptor Modulators instead

3. SERMs- Raloxifene
   Prevents osteoporosis, same effects on bone resorption as estrogen without increased cancer risk

Adverse Effects: increased risk for thromboembolism

4. RANKL Inhibitors- Denosumab
   Osteoporosis

Mechanism of Action: antibody that binds to RANKL and prevents osteoclast differentiation

Increased risk of infection since parenteral administration

Question 6

Bisphosphonates

Answer 6

Alendronate, Risedronate, and Ibandronate

Increase bone density and reduce fractures

Pyrophosphate bond with C instead of O, potent inhibitors of bone resorption by inhibiting farnesyl pyrophosphate Synthesis for osteoclast activity

Poor absorption and need to take on an empty stomach, gastric irritation but can have with glass of water and remain upright after take, can do IVs

Little adverse effects but rarely causes osteonecrosis of the jaw and femoral fractures, can cause a dynamic bone with little bone turnover

Question 7

Other Bone Drugs

Answer 7

1. Calcimetrics (Ca Receptor Agonist)- Cinacacelt
   Activates calcium sensing receptor in parathyroid gland to inhibit PTH secretion

Indication: Secondary hyperparathyroidism from chronic kidney problem or parathyroid carcinoma

Adverse Effects: nausea

2. Teripartide-
   Recombinant form of PTH 1-34 treats osteoporosis, stimulates new bone formation

Adverse Effects: hypercalcemia and hypercalciuria

Question 8

Vitamin D, Metabolites, and Analogs

Answer 8

Calcitrol and cholecalciferol

Indications: osteoporosis, osteomalacia, Rickets, Vitamin D deficiency, renal insufficiency

Mechanism of Action: Increase intestinal Ca absorption, bone resorption, and renal Ca/Phosp reabsorption

Raises serum conc. of both Ca and phosp

Decrease PTH hormone

Adverse Effects: hypercalcemia and hypercalciuria

Question 9

Types of Skeletal Muscle Fibers

Answer 9

Type I-
Slow red oxidative, smallest diameter, many mitochondria and red myoglobin, oxidative phosphorylation of FAs, postural muscles of back

Type IIa-
Fast intermediate oxidative-glycolytic, many myoglobin and lots of myoglobin/glycogen, walking or sprinting

Type IIb-
Fast white glycolytic, largest diameter, fewer mitochondria but lots of glycogen (pale color), glycolysis, weight lifting, throw ball

Question 10

Connective Tissue around Skeletal Muscle

Answer 10

Endomysium- surrounded each muscle fiber/cell

Perimysium- thicker, surrounds fascicle

Epimysium- DCT that surrounds the entire Muscle like biceps brachii

Question 11

Types of Muscle Contraction

Answer 11

1. Isotonic-
   A: Concentric- tension generated overcomes resistance of the object, Muscle shortens

B: Eccentric- Muscle is lengthened, tension generated can’t overcome resistance

2. Isometric-
   Tension generated not enough to exceed resistance of the object to be moved, Muscle doesn’t change shape