Bone Metabolism Flashcards
What three hormones are involved in calcium homeostasis?
Calcium levels tightly controlled by complex endocrine system: Parathyroid hormone (PTH) Vitamin D (see Nutrition slides) Calcitonin? (probably non-physiologic)
Bone serves as a ________ for calcium.
Bone Resevoir
Where are the parathyroid glands?
Four parathyroid glands, near or
w/in thyroid
Not related to thyroid gland except
by proximity
Possess Ca-sensing receptors that:
Inc. PTH secretion with low (free, ionized) calcium
Dec. PTH secretion with high calcium
1,25-diOH vit. D suppresses PTH secretion
Complex effects by Mg2+, esp. hypomagnesemia
Ectopic parathyroid glands are not uncommon (thoracic)
Function of PTH?
84 amino acid protein
Plasma half-life ~4 minutes
Bone
—–Stimulates osteoclasts which break down bone
——–Raises serum calcium raises phosph
Kidney
- –Increases tubular reabsorption of calcium
- –Decreases tubular reabsorption of phosphate
- –Induces 1α-hydroxylase which forms 1,25 diOH D lowers phosph
Intestine
—–Increases calcium absorption via 1,25-diOH vit. D increas phosph
OVERALL PTH inc Ca and dec P
How is PTH measured?
Measured by sandwich immunoassay
Reference interval: 10-65 pg/mL
Assays should measure “intact” PTH
—One Ab vs N-terminal epitope, other vs C-terminal
—1-34 aa (N-terminus) req’d for biological activity
—7-84 commonly measured in commercial assays
—“Bio-active” – measures 1-84 (limited availability)
—Controversial necessity
EDTA protects PTH from protease breakdown
Describe Calcitonin
32 aa peptide produced in parafollicular (C) cells of the thyroid gland
Secretion stimulated by Ca2+, (penta)gastrin
Actual physiological role in human calcium regulation unclear
Measured more as a tumor marker for medullary thyroid cancer
Measure by immunoassay
What are the actions of calcitonin?
Counteracts effects of PTH
- –Inhibits intestinal calcium absorption
- –Inhibits osteoclast activity in bone
- –Stimulates osteoblast activity in bone
- –Inhibits tubular reabsorption of Ca2+ in kidney
- –Inhibits tubular reabsorption of PO4 in kidney (= PTH)
Used therapeutically in treatment of:
- –Postmenopausal osteoporosis
- –Paget’s disease
- –Bone metastases
What is Primary Hyperparathyroid?
Disorder of the parathyroid
Primary Hyperparathyroidism (“hyperpara”)
Hyperplasia or adenoma of one or more glands
Elevated serum PTH
Hypercalcemia, hypophosphatemia, hypomagnesemia
Decalcification of bone
Occurs independently or as component of inherited disease (multiple endocrine neoplasia)
Treat by parathyroidectomy of affected gland(s)
What is Intra operative PTH?
PTH testing done during surgery to verify removal of hyperplastic gland(s)
Baseline PTH sample before suspect gland(s) removed
Samples at 5 and/or 10 min post removal
Send to lab for “super-stat” testing (or in OR)
>50% PTH decline indicates successful removal of hyperplastic gland(s)
What is secondary hyperparathroidism?
Secondary hyperparathyroidism
Increased PTH due to refractory hypocalcemia
Vitamin D deficiency
Malabsorption (of Ca or vitamin D)
Renal dz (reduced 1,25-diOH D production)
Characterized by
High PTH
Low or normal Ca
High phosphorus if not an absorption problem
What is PTH-related Peptide (PTH-rp)?
Significant sequence homology to PTH
Secreted by some tumors, but no negative feedback by calcium
“Paraneoplastic” – from tumor secretion, not mass
Typified by unexplained hypercalcemia with suppressed PTH
Measure by specific immunoassay
Does not identify tumor type or source
What is hypoparathyroidism
Much less common than hyperparathyroidism
Characterized by hypocalcemia with low PTH
—–Hyperphosphatemia common
Pseudohypoparathyroidism:
—Hypocalcemia with elevated PTH
—Target organ PTH receptor deficiency/defect
Describe bone physiology?
Bone consists of collagen and hydroxyapatite (Ca10(PO4)6(OH)2)
Constant “re-modeling”
Osteoclasts – cells that induce bone resorption
Osteoblasts – cells that induce bone formation
Bone mineral density (BMD)
Determined by special X-ray
What is osteoporosis? Osteopenia?
Osteoporosis – loss of bone mass
Usually asymptomatic until fracture (inappropriate)
Osteopenia – loss of bone mass
What diseases result form decreased bone mineralization?
Decreased mineralization of bone (formation)
Rickets – occurring in childhood
—Skeletal deformities common (e.g., bowed legs)
Osteomalacia – occurring in adults
—-Skeletal deformities uncommon
Usually result from vitamin D deficiency
–Formation (skin, hepatic, renal) or intake/absorption
–Inherited defect of metabolism or action
–Anticonvulsants – forms inactive vitamin D metabolites
Alkaline phosphatase(marker of ostoblastic activity) commonly elevated, but not diagnostic due to many origins.
