Endo (pt 7/7) Bone Mineral Homeostasis Flashcards
___% of the 1-2 kg of Ca in the body is found in the bone.
98%
____% of the 1 kg of P in the body is found in the bone.
85%
How do Ca & P enter the body?
Via the intestine
How are Ca & P excreted?
Renally excreted to balance intestinal absorption
What are the three primary hormones of Ca & P homeostasis?
1) Parathyroid hormone (PTH)
2) Fibroblast Growth Factor 23 (FGF 23)
3) Vitamin D (prohormone)
What stimulates the production of the active metabolite of vitamin D (vit. D, 1,25 – dihydroxyvitamin D) in the Kidney?
Parathyroid Hormone (PTH)
What inhibits the production of 1,25 dihydroxyvitamin D by the kidney?
FGF23
1,25 dihydroxyvitamin D inhibits the production of ____ by the parathyroid glands, and stimulates release of ____ from the bone.
Parathyroid hormone; FGF23
What is the principal regulator of intestinal Ca & P absorption?
1,25 dihydroxyvitamin D
T/F: PTH and 1,25 dihydroxyvitamin D can only stimulate Osteoblast activity.
False; PTH & 1,25 vit D regulate bone formation and resorption. Each is capable of stimulating both processes (osteoblasts and osteoclasts)
Bone forming cells.
-Signaled by stem cells and preosteoblasts (and PTH and Active Vit D)
Osteoblasts
Break down bone.
-signaled by monocytes, and pre osteoclasts (and PTH and active Vit D).
Osteoclasts
What is the net effect of PTH secretion?
Increased Ca and Decreased P
What is the net effect of FGF23 Secretion?
Decreased P
What is the net effect of Vitamin D?
Increased Ca and P
What is the MOA of Calcitonin?
-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
How do glucocorticoid hormones alter bone mineral homeostasis?
-Antagonize Vitamin D-stimulated intestinal calcium transport
-Stimulate renal calcium excretion
-Block bone formation
How do Estrogens regulate bone mineral homeostasis?
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.
What is the MOA of the Bisphosphonates?
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
What is the MOA of RANK Ligand Inhibitors (RANKL)
-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
What is the MOA of Cinacalcet (Calcium Receptor Agonist)?
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
What is the MOA of Plicamycin (Mithramycin)?
-Cytotoxic antibiotic
-Seldom clinical use for: Paget’s disease & hypercalcemia (disorders of bone mineral metabolism)
How do Thiazide Diuretics play a role in affecting bone mineral homeostasis?
Reduce renal Calcium excretion
What are the major causes of hypercalcemia?
-Hyperparathyroidism
-Cancer with or without bone metastases
What is the potentially lethal S/Sx of Hypercalcemia?
CNS Depression
What is the treatment for Hypercalcemia?
-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)
What are the major causes of Hypocalcemia?
Hypoparathyroidism
Vitamin D deficiency
CKD
malabsorption
What are the S/Sx of Hypocalcemia?
Tetany, paresthesia, laryngospasm* (!!), muscle cramps, seizures
What is the treatment for Hypocalcemia?
-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
What is the treatment of Hyperphosphatemia?
A common complication of renal failure.
Tx:
-Dietary restrictions
-Phosphate-binding gel – sevelamer
-Calcium supplements
Emergency: Dialysis, Insulin/Glucose
What is hypophosphatemia associated with?
-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
What is the treatment for Hypophosphatemia?
Avoid forms of therapy and treat causative conditions
How can acute hypophosphatemia cause Rhabdomyolysis?
-Reduction of ATP, interfering with normal Hgb to tissue oxygen transfer.
-Long term proximal muscle weakness and abnormal bone mineralization (osteomalacia)
What is the primary treatment for Primary Hyperparathyroidism?
Surgical resection of the Parathyroid Glands
(if associated with significant Hypercalcemia and Hypercalciuria, and symptoms of osteoporosis and kidney dz)
What are the causes of Hypoparathyroidism?
-PTH Deficiency (either r/t surgical resection of the Parathyroid gland or idiopathic cause)
-Abnormal target tissue response to PTH (Pseudohypoparathyroidism)
What are the electrolyte imbalances associated with Hypoparathyroidism?
Low Ca and Increased P
What are the treatment aims for Hypoparathyroidism?
-Restore normocalcemia and normophosphatemia
-Vitamin D (25,000-100,000U 3x/wk) & dietary calcium supplements
What are the nutritional levels of Vitamin D?
-Optimal: 30ng/mL
->10 ng/mL to prevent Rickets or Osteomalacia
-Range of 20 - 50 ng/mL safe
What are the S/Sx of Chronic Kidney Disease (CKD)
-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
What is the Tx of Chronic Kidney Disease (CKD)
-2 analogs of calcitrol – doxercalciferol & paricalcitol – are approved for the treatment of secondary hyperparathyroidism of CKD
-Monitor labs (specifically serum Ca & P levels)
