Calcium and Bone

Question 1

A correction for serum calcium must be performed if there is low serum _______.

Answer 1

Albumin

Question 2

What is the equation to calculate the serum calcium in the setting of low serum albumin?

Answer 2

adjusted serum Ca2+ = measured [Ca2+] + 0.8 x (4 - measured serum albumin)

Question 3

Is the gut good at absorbing calcium? What hormone helps it absorb more calcium?

Answer 3

Not good at it; most is pooped out. 1,25-dihydroxycholecalciferol (calcitriol/vitamin D3) helps the gut absorb more calcium via active transport mechanisms.

Question 4

How do acidemia and alkalemia affect ionized calcium levels, respectively?

Answer 4

Acidemia causes an increase in ionized calcium because fewer Ca2+ ions will be bound to albumin.

Alkalemia causes a decrease in ionized calcium because more Ca2+ ions will be bound to albumin.

Question 5

What is the relationship between calcium absorption in the gut and gastric acid?

Answer 5

Acid is needed for calcium absorption, so achlorhydria from old age or taking PPIs is a risk factor for being calcium deficient.

Question 6

Are the kidneys able to produce calcium-free urine?

Answer 6

No

Question 7

Where in the nephron is most calcium reabsorbed? By what mechanism?

Answer 7

PCT (paracellular)

Question 8

What segment of the nephron is responsive to PTH? Does PTH increase, or decrease calcium reabsorption?

Answer 8

DCT is PTH-responsive; PTH increases reabsorption

Question 9

What segment of the nephron has calcium-sensing receptors?

Answer 9

The thick ascending loop of Henle

Question 10

Osteoblasts make two soluble factors that regulate pre-osteoclasts. What are these factors and what do they do?

Answer 10

Osteoblasts make RANK-L and osteoprotegerin. RANK-L binds to RANK receptors on pre-osteoclasts, inducing their differentiation and activation into osteoclasts to resorb bone. Osteoprotegerin can sequester RANK-L to keep it from binding to RANK receptors on pre-osteoclasts –> less osteoclast reabsorption of bone.

Question 11

Name four things that increase PTH levels and four things that decrease PTH levels.

Answer 11

PTH release is stimulated by low [Ca2+], low vitamin D, high phosphate, low magnesium.

PTH is suppressed by high [Ca2+], high vitamin D (as long as Ca2+ is normal), low phosphate, very low Mg2+ levels (magnesium is a cofactor for making PTH)

Question 12

Which step in vitamin D synthesis is regulated by PTH? What enzyme is involved in this reaction?

Answer 12

Conversion of 25-OH-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (active D3) by 1-alpha hydroxylase in the kidney is regulated by PTH

Question 13

What effect does active vitamin D3 have on phosphate absorption in the gut?

Answer 13

It increases phosphate absorption

Question 14

Name two things that increase 1-alpha hydroxylase activity and three things that decrease its activity.

Answer 14

Increased 1-a-hydroxylase activity: PTH and hypophosphatemia

Decreased 1-a-hydroxylase activity: active D3, hyperphosphatemia, FGF-23

Question 15

Describe the physiology of how mechanical stress on bone results in bone strengthening.

Answer 15

Osteocytes, which constitutively secrete sclerostin, sense mechanical stress. After sensing stress, sclerostin is downregulated, allowing osteoblasts to lay down bone.

Question 16

Can exercise/weight training slow the rate of bone loss in older individuals?

Answer 16

Yeah

Question 17

What two things determine bone strength?

Answer 17

Bone quality and bone quantity

Question 18

What is the criteria for diagnosing osteoporosis?

Answer 18

Atramautic fracture, or a T-score of -2.5 or less as calculated from a DXA scan to determine bone mineral density

Question 19

What is the difference between a Z-score and T-score regarding bone mineral density.

Answer 19

T-score compares a patient to younger people, while the z-score compares the patient to others of the same age.

Question 20

What is the difference between osteoporosis and osteomalacia?

Answer 20

Osteoporosis is a lack of bone volume, while osteomalacia is due to defective bone mineralization (calcium phosphate deposition)

Question 21

What effect on calcium homeostasis do thiazides and lithium drugs have?

Answer 21

Thiazides decrease calcium excretion by the kidney –> hypercalcemia.

Lithium drugs reduce negative feedback of calcium on the parathyroid gland –> increased PTH levels –> hypercalcemia.

Question 22

What is the equation to calculate serum [Ca2+] in the setting of hypoalbuminemia?

Answer 22

corrected calcium = measured total serum calcium + 0.8(4 - measured albumin)

Question 23

Describe the mechanisms by which glucocorticoids cause osteoporosis.

Answer 23

Decreased Ca2+ absorption in the gut, increased activity of osteoclasts, increased apoptosis of osteoblasts

Question 24

What is the MOA of alendronate and what are its indications?

Answer 24

Inhibits osteoclasts, used for osteoporosis, Paget’s disease.

Question 25

What is the molecular defect involved in familial hypocalciuric hypercalcemia?

Answer 25

Calcium sensing receptor on parathyroid gland is less sensitive to calcium, so it takes a high level of calcium to negatively inhibit PTH production.