Parathyroid & Bone

Question 1

What are 4 actions of PTH?

Answer 1

1. Stimulate bone resorption (indirectly through osteoblasts)
2. Stimulate renal reabsorption of Ca2+, Mg2+
3. Inhibit renal reabsorption of PO4- and HCO3-
4. Stimulate calcitriol (active vit D) synthesis therefore indirect intestinal Ca2+ absorption

Question 2

What are the 2 types of skeleton and where do they predominate?

Answer 2

Cortical- 80% of skeleton, shafts of long bones

Trabecular- vertebral bodies, ribs, pelvis and ends of long bones

Question 3

What mineral is necessary for the release of PTH and its action on target tissues?

Answer 3

Mg2+

Question 4

What are the 2 most common causes of hypercalcemia? What will PTH level look like for both?

Answer 4

1. Hyperparathyroidism (PTH high or normal)

2. Malignancy (PTH low)

Question 5

What will the dexascan show for a person with Primary Hyperparathyroidism?

Answer 5

preferentially affects cortical bone –> reduced wrist density; maintained lumbar spine

Question 6

What are 2 IV-given bisphosphonates? Mechanism and use? Which one is more potent?

Answer 6

Pamidronate & Zoledronic acid

• Reduce osteoclastic bone resorption
• Used for: Hypercalcemia of malignancy (normalized Ca2+ in 70-100%); Paget’s disease of bone; prevention of fractures in osteogenesis imperfecta
• Zoledronic acid is more potent and has a shorter infusion time

Question 7

What are some side effects of Pamidronate and Zoledronic acid? What is important regarding timing of dosing?

Answer 7

SE: Serum creatinine elevation; Fever, flu-like symptoms
-both take several days to see effect for lowering calcium (need to wait 7 days before administering another dose if complete response not achieved)

Question 8

Which agent may be used as an adjunct to hypercalcemia therapy in the acute setting? How and why?

Answer 8

• Increases urinary calcium excretion, inhibits bone reabsorption (can lower serum Ca2+ by 1-2mg/dl within 2-4 hrs)
• only used acutely due to tachyphylaxis in 2-3 days

Question 9

What class of drug may be used for hypercalcemia from vitamin D intoxication, granulomatous diseases or hematologic malignancies. Mechanism?

Answer 9

Corticosteroids

-Decreases production of 1,25 vitamin D; may inhibit growth of neoplastic lymphoid tissue

Question 10

What are 2 common causes of Secondary Hyperparathyroidism?

Answer 10

• Renal disease (at high concentrations phosphate can directly stimulate PTH secretion)
• Vitamin D deficiency (low serum 25(OH) stimulates PTH secretion)

Question 11

What may be used to treat Secondary Hyperparathyroidism from renal disease? From vitamin D deficiency?

Answer 11

• Renal Disease: Phosphate binders (Calcium carbonate, Calcium acetate, Sevelamer), low phosphate diet, vitamin D replacement, dialysis
• Deficiency: replace with 25(OH) vitamin D in the form of ergocalciferol or cholecalciferol

Question 12

What is the first thing that should be checked when a low Ca2+ is detected?

Answer 12

Albumin levels (40% serum Ca2+ binds to Albumin)
[should also check PTH and Mg2+]

Question 13

What is the most common cause of hypocalcemia where phosphorus, PTH and creatinine levels are high?

Answer 13

Chronic Renal Failure

Question 14

What will PTH, Ca2+ and PO4- levels look like in hypoparathyroidism? Treatment?

Answer 14

low PTH (except pseudohypoparathyroidism), low Ca2+, high PO4-
--> Treatment: Ca2+ and vitamin D supplementation in the low range of normal to avoid hypercalciuria

Question 15

What are 3 oral bisphosphonates used in the treatment of osteoporosis? Side effects? Special instructions?

Answer 15

Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)
-SE: Esophageal irritation
-need to be taken fasting, in the morning, w/ water and patient must remain upright for at least 30 min

Question 16

What is Raloxifene? Use? SE?

Answer 16

Selective Estrogen Receptor Modulator (SERM)

• Selectively activates certain estrogen receptors, but blocks others; decreases bone resorption
• used for osteoporosis
• SE: Increase risk of hot flashes, DVT

Question 17

What is an agent used in the treatment of osteoporosis that is no longer recommended due to increased risk of cancer?

Answer 17

Calcitonin
-No longer recommended for use in nasal spray form because of increased cancer risk. Can still use SQ or IM. Tachyphylaxis in 2-3 days; often used to bridge treatment for other medication

Question 18

What is the only anabolic agent approved for the treatment of osteoporosis? In what subset of patients is it used? Contraindications?

Answer 18

Teriparatide (PTH analog given SQ daily)

• reserved for pts at high risk of fracture or failure of other therapies
• Contraindicated in pts with increased risk of osteosarcoma (Pagets disease of bone, radiation)

Question 19

What agent is a RANK ligand inhibitor? What is its only contraindication?

Answer 19

Denosumab
(given SQ every 6 mos)
-Contraindication in hypocalcemia

Question 20

What is Paget’s disease of bone? Treatment?

Answer 20

• disorganized bone formation at one or more sites (typically pelvis, femur, skull, spine, tibia)
• affects males/females equally
• many asymptomatic, found on xray or high ALP
• Treatment: bisphosphonates

Question 21

What is Osteogenesis Imperfecta?

Answer 21

• inheritable disorder involving type 1 collagen (abundant in bone)
• usually presents with osteopenia causing recurrent fractures and skeletal deformity