Parathyroids and Bone

Question 1

What are the key regulators of bone resorption? Which one inhibits bone resorption?

Answer 1

RANK ligand and its two receptors: RANK and OPG. OPG inhibits bone resorption.

Question 2

What are the effects of PTH?

Answer 2

1. Indirect stimulation of bone resorption by osteoclasts (via osteoblast stimulation).
2. Stimulation of renal tubular reabsorption of Ca and Mg.
3. Inhibition of renal tubular reabsorption of phosphate and bicarbonate.
4. Stimulation of calcitriol synthesis by activating 1alpha-hydroxylase in the kidney.

Question 3

What are calcitriol’s effects?

Answer 3

1. Increase efficiency of intestinal absorption of dietary calcium.
2. Stimulating stem cells in the bone to become mature osteoclasts.

Question 4

What usually causes primary hyperparathyroidism?

Answer 4

A benign, solitary adenoma.

Question 5

What causes Familial Hypocalciuric Hypercalcemia?

Answer 5

Loss of function mutation of the calcium-sensing receptor.

Question 6

How do you distinguish between FHH and primary hyperparathyroidism?

Answer 6

In FHH, the urinary calcium collection will be low.

Question 7

What is the first step in treating hypercalcemia?

Answer 7

Volume expansion with IV saline, since hypercalcemia leads to dehydration.

Question 8

What are the two bisphosphonates? Which is more potent? Which acts faster?

Answer 8

Pamidronate and zoledronic acid. Zoledronic acid is both faster and more potent.

Question 9

What can happen with repeated exposure to calcitonin?

Answer 9

Downregulation of calcitonin receptors on osteoclasts.

Question 10

How do corticosteroids help lower calcium levels?

Answer 10

Decrease vitamin D production.

Question 11

How does renal disease lead to secondary hyperparathyroidism?

Answer 11

The failing kidney retains phosphate (high phosphate can directly stimulate PTH secretion) and lacks 1alpha-hydroxylase activity.

Question 12

What is tertiary hyperparathyroidism?

Answer 12

When the parathyroid glands become autonomous after prolonged secondary hyperparathyroidism.

Question 13

What is the critical difference between secondary and tertiary hyperparathyroidism?

Answer 13

Secondary: low or normal plasma calcium
Tertiary: high plasma calcium

Question 14

What should always be checked when evaluating hypocalcemia in the lab?

Answer 14

Serum albumin levels.

Question 15

What are two vitamin D analogs?

Answer 15

Paracalcitol and doxercalciferol.

Question 16

What does hypoparathyroidism classically present with in the presence of normal renal function?

Answer 16

Hypocalcemia and hyperphosphatemia.

Question 17

What is a major concern in the treatment of hypoparathyroidism?

Answer 17

Hypercalciuria. This is because the absence of PTH results in the kidneys being unable to reabsorb calcium from the urine, meaning serum calcium levels should be kept on the low end of normal.

Question 18

How does magnesium affect PTH secretion?

Answer 18

An acute fall in magnesium will stimulate PTH secretion. During chronic or severe hypomagnesemia, PTH secretion is impaired, leading to hypocalcemia.

Question 19

What is the preferred treatment for symptomatic patients with acute hypocalcemia?

Answer 19

Calcium gluconate.

Question 20

What bisphosphonates are approved for osteoporosis?

Answer 20

Oral: alendronate, risedronate and ibandronate.
IV: Zolendronate.

Question 21

What are the Selective Estrogen Receptor Modulators?

Answer 21

Raloxifene, basedoxifene and lasofoxifene.

Question 22

What is a PTH analog that is used to treat osteoporosis?

Answer 22

Teriparatide. Short bursts of PTH stimulates both bone resorption and formation, resulting in a net increase in BMD and decrease in fractures.

Question 23

What does denosumab target?

Answer 23

RANK ligand inhibitor.