Osteoporosis Flashcards
What are the Hormones involved in Ca homeostasis?
- Parathyroid Hormone (PTH)
- Calcitonin
- Vitamin D (Calcitriol)
- Thyroid hormones, growth hormone, androgens, estrogens, and glucocorticoids play a secondary role.
How is Parathyroid hormone involved in Ca homeostasis?
- Secreted in response to DECREASE in Ca or INCREASE in Phosphate.
- Secreted by parathyroid glands in thyroid.
- Mobilizes Ca from bone, Increases intestinal absorption (increase Vit. D synthesis). and decreases renal excretion.
- Suppresses Calcitonin release.
How is Calcitonin involved in Ca homeostasis?
- Secreted in response to HIGH blood Ca.
- Secreted by parafollicular C cells of thyroid. - Inhibits osteoclast-mediated bone resorption.
- Increases renal phosphate and Calcium excretion.
- Suppresses PTH release.
How is Vitamin D involved in Ca homeostasis?
- Promotes Ca absorption in intestine.
2. Promotes bone resorption.
What is the daily requirement for Ca in an adult?
1000 mg/day
Less than 1/3 is absorbed (~300mg)
What is the daily requirement for Ca in Women over 50 and Men over 70?
1200 mg/day
What is the daily requirement for Ca in adolescents?
1300 mg/day
-Median intake is 750 mg/day!
What are the upper limits for Ca intake?
3 g/day adolescents
2.5 g/day adults
2 g/d for elderly.
Where is most Ca obtained from?
75% obtained from dairy products.
What is the Bone turnover of Ca?
- 300 mg/day
How much Ca is lost in the urine and in the feces?
150 mg is lost in urine
-Can be increased by loop diuretics (furosemide)
150 mg is lost in feces, including as bile and sloughed cells.
How is Ca absorbed?
In proximal duodenum by active Vit D-Dependent transport.
-Can increase Ca absorption by 2 fold (up to 600 mg/day)
In all of small intestine by facilitated transport
-Accounts for majority of Ca uptake.
Where is most of the Phosphate in the body found?
80% of body phosphate is found in the bone.
-Complexed with Ca as hydroxyapatites (Ca10(PO4)6(OH)2)
Where is Phosphate absorbed?
Phosphate is absorbed in the intestine.
- Abundance in food prevents inadequate intake
- 2/3 of intake is absorbed
- Uptake is active transport, facilitated by Vit. D.
- Circulates in blood as NaH2PO4/Na2HPO4
- PO4 is excreted in urine
What increases phosphate excretion?
PTH increase excretion.
What plays an important role in Phosphate homeostasis?
FGF-23
-Secreted by osteoclasts in response to high phosphate.
-Promotes phosphate clearance by kidney
(inhibits reabsorption)
-Inhibits Vit D activation (1 alpha hydroxylation)
What doe elevated levels of FGF-23 cause?
Hypophosphatemic Rickets
- Impaired bone mineralization
- Low blood phosphate levels –> treat w/ vit D and oral phosphate.
What is the most common cause of primary hyperparathyroidism?
- Hypercalcemia
What is hyperparathyroidism?
- Hypersecretion of PTH due to parathyroid adenoma or hyperplasia.
- Characterized by hypercalcemia, osteoporosis, kidney stones, osteitis fibrosa cystica (replacement of bone with CT), Fatigue, weakness, depression –> seizures.
- Often hypophosphatemia.
- Frequently associated with low Vit D levels
- Currently treated by parathyroidectomy.
What is Familial Benign Hypercalcemia?
- Defect in Ca sensor.
- Very low Ca excretion in urine.
- PTH levels normal to slightly high.
- Relatively benign in most cases; not treated.
What are other causes of Hypercalcemia?
- Systemic malignancies that secrete PTH analogs, or promote bone resorption, or overproduce calcitriol.
- Granulomatous diseases
- Hypercalcemia of malignancy
What are Granulomatous Diseases?
- Tb, Sarcoidosis cause excess calcitriol synthesis by mononuclear cells.
- Leads to increased Ca absorption.
- Oral phosphate binds Ca; glucocorticoids also decreases ectopic calcitriol.
What is a Hypercalcemia of malignancy?
- Breast cancer metastatic to bone.
2. Treated by decreasing dietary Ca absorption; increasing urinary Ca; inhibiting bone resorption.
How is Acute Hypercalcemia treated?
- Treated by saline diuresis: IV saline + Ca wasting diuretic (furosemide)
- Long-term management w/ Bisphosphonates (pamidronate or zoledronate) and Calcitonin.
