Bone Metabolism

Question 1

PTH

Answer 1

• Produced by parathyroid glands in response to low iCa levels –> Ca-sensing receptors
• PTH secretion increased if iCa is low, decreased if high
• Secretion suppressed by 1,25-diOH Vit D
• Complex effects by magnesium (esp. hypomagnesemia)
• “Intact PTH” measured by sandwich ia, Ab to N-terminal epitope –>aa 1-6 biologically necessary but not always looked for in assays
• EDTA protects PTH from protease breakdown

Effects:
Bone = stimulates osteoclastic bone breakdown
Kidney = increases reabsorption of Ca (Phos exchange)
Intestines = increases Ca absorption via VitD

Question 2

Calcitonin

Answer 2

• Produced in parafollicular cells of thyroid gland
• Secretion stimulation by Ca and gastrin
• Measured by ia as a tumor marker for medullary thyroid cancer
• Countereffects PTH –> EXCEPT ALSO INHIBITS PO4 REABSORPTION (same as PTH)
• Used therapeutically in osteoporosis, Pagets Dz, bone metastases

Question 3

Parathyroid Disorders

Answer 3

• Primary hyperpara: benign hyperplasia or adenoma of para glands, elevated PTH, decalcification of bone
• -> can be independent or with inherited dz, treat by parathyroidectomy
• Secondary hyperpara: increased PTH due to refractory hypocalcemia (vitD deficiency, malabsorption, renal dz)
• Hypopara: less common, hypocalcemia w/ low PTH (hyperPO4 common), pseudo hypopara if PTH is elevated (receptor deficiency)

Question 4

Intra-operative PTH

Answer 4

• PTH testing done during surgery to very removal of hyperplastic gland(s)
• Baseline PTH drawn with samples at 5 & 10 minutes post-removal –> greater than 50% decline in PTH suggests successful removal of correct gland
• Sent as DIRE/STAT

Question 5

PTH-related peptide (PTH-rp)

Answer 5

• Significant sequence homology to PTH
• Secreted by some tumors but has no neg feedback from calcium –> paraneoplastic
• Typically unexplained hypercalcemia with suppressed PTH

Question 6

Bone Physiology & Disease

Answer 6

• Consists of collagen and hydroxyapatite, constant remodeling by osteoclasts and osteoblasts, BMD = bone mineral density
• Osteoporosis: loss of bone mass, asymptomatic until fracture; Osteopenia: precursor to osteoporosis, diagnosed by DEXA
• Decreased mineralization of bone: Rickets (children), Osteomalacia (adults)
  
  • –> usually from VitD deficiency, ALP commonly elevated
• Paget’s Dz: Increased osteoclastic activity plus disordered osteoblastic activity