ERM2 - Calcium and Bone

• 1. VitD hydroxylated in liver to 25vitD
• 2. 25VitD hydroxylated in kidney to 1,25(OH)2VitD
• -positive: PTH and hypophosphatemia
• -negative: FGF23

• -negative feedback
• -normal Ca = 10

• 
• -major regulator of intestinal absorption: vitD
• -major regulator of kidney reabsorption: PTH
• -major regulator of bone resporption: PTH

• -increase gut absorption of Ca
• -increase kidney reabsorption of Ca
• -increased resorption and formation of bone

• -increase gut absorption of Ca
• -increase kidney reabsorption of Ca
• -decrease bone formation
• -increase bone resorption

--> increase serum Ca

• -decrease gut absorption of Ca
• -decrease kidney reabsorption of Ca
• -increase bone formation
• -decrease bone resorption

--> decrease serum Ca

• 1. sustained PTH elevation --> bone resorption
• 2. intermittent PTH elevation --> bone formation (ie: injections)

• -eventually there is central downregulation of CT effets
• -chronic changes in CT don't effect Ca homeostasis

• -iCa signals through CaSR to inhibit PTH and stimulate CT secretion
• -most ppl have 4 parathyroid glands (can vary)
• -supplied by inferior thyroid artery

-peptic ulcers allow excess absorption of Ca into blood (milk, CaCO3)

-more Ca required to affect a given degree of PTH suppression (right shift)

-1/500 women, 1/2000 men

-asypmtomatic

• -stones
• -bones (painful resorption of bones = osteoitis)
• -groans (peptic ulcer, pancreatitis)
• -moans (fatigue, depression)
• -CV

• 1. Parathyroid Hyperplasia
• 2. Familial Hypocalciuric Hypercalcemia (FHH)
• 3. Lithium use

• -too many parathyroid cells
• -typically signal parathyroid adenoma
• -sometimes four gland hyperplasia
• -rarely carcinoma

-urine Ca is high (at risk for kidney stones)

• -CaSR mutation
• -inability of Ca signaling to inhibit PTH
• -Urine Ca is low (same CaSR mutation): not at risk for stones

-inhibits signaling downstream of CaSR

• -may be in the upper half of normal
• -inappropriate in the face of hypercalcemia

• 1. Artifactual (hyperproteinemia)
• 2. Malignancy
• 3. Drugs
• 4. Renal Disease
• 5. Endocrine
• 6. Granulomatous Disease
• 7. Immobilization

-iCa is normal, protein is elevated

• Causes
• -venous stasis
• -hyperalbuminemia (increased protein consumption)
• -hypergammaglobulinema (myeloma)

• -bone mets/myeloma
• -PTHrP production

• -VitD and VitA
• -Milk alkali syndrome
• -Li
• -Thiazides

• -ARF
• -tertiary hyperparathyroidism

• 1. Primary hyperparathyroidism
• 2. FHH
• 3. hyperthyroidism
• 4. adrenal insufficiency

• sarcoidosis
• coccidiomycosis
• TB
• histoplasmosis
• berrylliosis

• -Paget's disease
• -adolescence

• 1. hydration (protect kidneys)
• 2. CT injections (quick but temporary)
• 3. hemodialysis
• 4. Parathyroidectomy
• 5. Bisphosphonates/tumor resection
• 6. Glucocorticoids

-increase BMD while decreasing bone formation

-increase BMD while increasing bone resorption

-decreased bone formation is paradoxically coupled to increased resorption

--> double whammy for osteoporosis

• 1. Formation Markers (osteoblast origin)
• -alk phos
• -osteocalcin

• 2. Resorption Markers (osteoclast origin)
• -NTx, CTx

• -in high turnover states (adolescence and Paget's disease) immobilization leads to a sudden arrest of formation
• -ongoing resorption is unopposed
• --> hypercalcemia and kidney stones

in PT adenoma resection can have a sudden arrest of resorption and ongoing formation goes on unopposed --> hypocalcemia and hypophospatemia

• -turnover too slow
• -increased risk of fracture

• Causes
• 1. excessive use of bisphosphonates (block resorption)
• 2. hypophosphatemia (TNSAP mutation)
• 3. excessive use of 1,25D in renal failure (can over suppress PTH)

• Myeloma
• renal
• melanoma

• --> lead to hypercalcemia
• -cold on bone scan

• prostate
• breast
• lung

• --> lead to hypocalcemia and elevated alk phos
• -hot lesions

• -impaired mineralization due to:
•      -XLR
•      -renal failure
•      -D deficiency
•      -hypophosphatemia

• -dense bones
• -plates wide and jagged
• -richitic rosary beads

• males less than 3yrs, with short bowed legs
• -not nutritional defect
• -PHEX protease mutation --> elevated FGF23
• -phosphate wasting in urine (hypophosphatemia)
• -low 1,25D

1. osteoitis fibrosa cystica: secondary hyperparathyroidism (decreased Ca --> increased PTH --> osteoclast activity)

2. Osteomalacia (low Ca)

3. adynamic bone disease (tx with 1,25D)

4. osteoporosis

Tx: low phosphate diet

• -PTH driven hypercalcemia
• -usually single gland adenoma

• -increased PTH due to compensatory response
•      -Vit D deficienc
•      -renal failure
•      -PTH resistancce
• -blood calcium low or normal
• -typically 4 gland hyperplasia

• -when secondary hyperparathyroidism pick up mutations and become autonomous
• -hypercalcemia
• -very rare complication of renal failure