Endo (pt 7/7) Bone Mineral Homeostasis Flashcards

1
Q

___% of the 1-2 kg of Ca in the body is found in the bone.

A

98%

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2
Q

____% of the 1 kg of P in the body is found in the bone.

A

85%

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3
Q

How do Ca & P enter the body?

A

Via the intestine

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4
Q

How are Ca & P excreted?

A

Renally excreted to balance intestinal absorption

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5
Q

What are the three primary hormones of Ca & P homeostasis?

A

1) Parathyroid hormone (PTH)
2) Fibroblast Growth Factor 23 (FGF 23)
3) Vitamin D (prohormone)

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6
Q

What stimulates the production of the active metabolite of vitamin D (vit. D, 1,25 – dihydroxyvitamin D) in the Kidney?

A

Parathyroid Hormone (PTH)

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7
Q

What inhibits the production of 1,25 dihydroxyvitamin D by the kidney?

A

FGF23

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8
Q

1,25 dihydroxyvitamin D inhibits the production of ____ by the parathyroid glands, and stimulates release of ____ from the bone.

A

Parathyroid hormone; FGF23

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9
Q

What is the principal regulator of intestinal Ca & P absorption?

A

1,25 dihydroxyvitamin D

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10
Q

T/F: PTH and 1,25 dihydroxyvitamin D can only stimulate Osteoblast activity.

A

False; PTH & 1,25 vit D regulate bone formation and resorption. Each is capable of stimulating both processes (osteoblasts and osteoclasts)

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11
Q

Bone forming cells.
-Signaled by stem cells and preosteoblasts (and PTH and Active Vit D)

A

Osteoblasts

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12
Q

Break down bone.
-signaled by monocytes, and pre osteoclasts (and PTH and active Vit D).

A

Osteoclasts

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13
Q

What is the net effect of PTH secretion?

A

Increased Ca and Decreased P

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14
Q

What is the net effect of FGF23 Secretion?

A

Decreased P

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15
Q

What is the net effect of Vitamin D?

A

Increased Ca and P

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16
Q

What is the MOA of Calcitonin?

A

-Lower serum Ca & P by action on bone & kidney
-Inhibits osteoclastic bone resorption
-Reduces Ca & P reabsorption in the kidney
-Used in the treatment of: Paget’s disease, hypercalcemia, osteoporosis

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17
Q

How do glucocorticoid hormones alter bone mineral homeostasis?

A

-Antagonize Vitamin D-stimulated intestinal calcium transport
-Stimulate renal calcium excretion
-Block bone formation

18
Q

How do Estrogens regulate bone mineral homeostasis?

A

Given to prevent accelerated bone loss during the postmenopausal period.
-Selective estrogen receptor modulators (SERMs) were developed to retain the beneficial effects on bone while minimizing the deleterious effects of estrogen on breast, uterus, and the CV system.

19
Q

What is the MOA of the Bisphosphonates?

A

Multiple effects on bone mineral homeostasis:
-Inhibit bone resorption & secondary bone formation
-PO or IV form (PO is associated with adverse GI effects)
-Excreted in the urine
-Useful in the tx of hypercalcemia associated with malignancy, Paget’s Dz, or Osteoporosis

End in -dronate

20
Q

What is the MOA of RANK Ligand Inhibitors (RANKL)

A

-tx of postmenopausal osteoporosis
-Tx of prostate and breast Ca
-Limits development of bone mets or bone loss from other drugs that suppress gonadal function
-Denosumab

21
Q

What is the MOA of Cinacalcet (Calcium Receptor Agonist)?

A

Activates the calcium-sensing receptor (CaSR) of the parathyroid gland, increasing inhibition of PTH secretion
Approved for the treatment of secondary hyperparathyroidism in CKD & parathyroid carcinoma

22
Q

What is the MOA of Plicamycin (Mithramycin)?

A

-Cytotoxic antibiotic
-Seldom clinical use for: Paget’s disease & hypercalcemia (disorders of bone mineral metabolism)

23
Q

How do Thiazide Diuretics play a role in affecting bone mineral homeostasis?

A

Reduce renal Calcium excretion

24
Q

What are the major causes of hypercalcemia?

A

-Hyperparathyroidism
-Cancer with or without bone metastases

25
Q

What is the potentially lethal S/Sx of Hypercalcemia?

A

CNS Depression

26
Q

What is the treatment for Hypercalcemia?

A

-Saline diuresis – 500 – 1L/h + loop diuretics (furosemide)
-Bisphosphonates – pamidronate 60 – 90mg IV over 2 – 4h; zoledronate 4mg IV over 15min
-Calcitonin
-Gallium nitrate – inhibits bone resorption
-Plicamycin (Mithramycin) – 25 – 50mcg/kg IV will lower serum calcium substantially within 24 – 48h. NOT first choice d/t toxicity!
-IV phosphate – fastest & surest way to reduce serum Ca but hazardous if IV administration is not done properly
-Glucocorticoids (not immediate tx, but help in chronic hyper Ca of sarcoidosis, Vit D intoxication, and some cancers do respond over the course of several days to glucocorticoid therapy)

27
Q

What are the major causes of Hypocalcemia?

A

Hypoparathyroidism
Vitamin D deficiency
CKD
malabsorption

28
Q

What are the S/Sx of Hypocalcemia?

A

Tetany, paresthesia, laryngospasm* (!!), muscle cramps, seizures

29
Q

What is the treatment for Hypocalcemia?

A

-Calcium (IV, IM, PO 🡪 Calcium carbonate (40% calcium) – Tums)
Calcium gluconate IV is less irritating to veins*

-Vitamin D
1,25(OH)2D3 (calcitriol) – vitamin D metabolite of choice to inc Ca within 24 – 48h

30
Q

What is the treatment of Hyperphosphatemia?

A

A common complication of renal failure.
Tx:
-Dietary restrictions
-Phosphate-binding gel – sevelamer
-Calcium supplements

Emergency: Dialysis, Insulin/Glucose

31
Q

What is hypophosphatemia associated with?

A

-Primary hyperparathyroidism
-Vitamin D deficiency
-Idiopathic hypercalciuria
-Inc bioactive FGF23 (x-linked & autosomal dominant hypophosphatemic rickets & tumor- induced osteomalacia)
-Renal phosphate wasting (Fanconi’s syndrome)
-Over use of phosphate binder
-TPN with inadequate phosphate content

32
Q

What is the treatment for Hypophosphatemia?

A

Avoid forms of therapy and treat causative conditions

33
Q

How can acute hypophosphatemia cause Rhabdomyolysis?

A

-Reduction of ATP, interfering with normal Hgb to tissue oxygen transfer.
-Long term proximal muscle weakness and abnormal bone mineralization (osteomalacia)

34
Q

What is the primary treatment for Primary Hyperparathyroidism?

A

Surgical resection of the Parathyroid Glands
(if associated with significant Hypercalcemia and Hypercalciuria, and symptoms of osteoporosis and kidney dz)

35
Q

What are the causes of Hypoparathyroidism?

A

-PTH Deficiency (either r/t surgical resection of the Parathyroid gland or idiopathic cause)
-Abnormal target tissue response to PTH (Pseudohypoparathyroidism)

36
Q

What are the electrolyte imbalances associated with Hypoparathyroidism?

A

Low Ca and Increased P

37
Q

What are the treatment aims for Hypoparathyroidism?

A

-Restore normocalcemia and normophosphatemia
-Vitamin D (25,000-100,000U 3x/wk) & dietary calcium supplements

38
Q

What are the nutritional levels of Vitamin D?

A

-Optimal: 30ng/mL
->10 ng/mL to prevent Rickets or Osteomalacia
-Range of 20 - 50 ng/mL safe

39
Q

What are the S/Sx of Chronic Kidney Disease (CKD)

A

-Deficient 1,25(OH)2D production (active Vit D) by the Kidneys
-Retention of Phosphate
-Reduction of Calcium
-Secondary hyperparathyroidism d/t low Ca and Low Vit D
-Increased FGF23 levels (has CV effects)
-Osteomalacia and osteoitis fibroasa of bone

40
Q

What is the Tx of Chronic Kidney Disease (CKD)

A

-2 analogs of calcitrol – doxercalciferol & paricalcitol – are approved for the treatment of secondary hyperparathyroidism of CKD
-Monitor labs (specifically serum Ca & P levels)