rainwater@mymelody.com || 1st semester, AY 2011-2012

9 - Metabolism of Bone

Biochemical Markers of Bone Metabolism

Key Points The plasma concentration of calcium, phosphate and

magnesium is dependent upon bone mineral absorption, resorption, intestinal absorption and renal excretion.

Regulating hormones are PTH, calcitonin and 1,25-dihydroxyvitamin D

80% of hypercalcemia is due to primary hyperparathyroidism (elevated PTH) or malignancy (decreased PTH)

Hypocalcemia is due to chronic renal failure and many others (acute pancreatitis)

Bio-intact PTH measures biologically active PTH; useful in patients with impaired renal functions and in surgical resection of parathyroid adenoma

Osteoporosis is the most common metabolic disease of the bone

Osteomalacia is a failure to mineralize newly formed osteoid in the mature skeleton

Bone Inorganic minerals= calcium and phosphorus Organic matrix = 90-95% type 1 collagen, 5-10% non-

collagenous proteins osteocalcin, osteopontin, thrombospondin, sialoproteins

Cells= osteoblast, osteoclast, osteocyte

Compact bone: 75% matrix, 25% air spaces

Cancellous bone: 95% air spaces, 5% matrix

Calcium Distribution, function, homeostasis: 99% in the

skeleton, needed for coagulation, contractility, enzymatic, integrity of cell membrane.

Analytical techniques: colorimetric, atomic absorption spectrophotometry (most accurate), indirect potentiometry (most popular)

Correction for hypoalbuminemia: total calcium + (normal albumin - patients albumin) x 0.8 (e.g., malignancy)

Normal range: total = 8.8 to 10.3 mg/dL(2.2 to 2.58 mmol/L); ionized = 4.6 to 5.3 mg/dL(1.16 to 1.32 mmol/L)

Phosphorus Distribution and function: organic

phosphates(phospholipids, phosphoproteins) and inorganic HPO4 and H2PO4; structural unit; oxidative phosphorylation

Homeostasis: small GIT, kidney, bone Analytical techniques: ammonium molybdate to form

phosphomolybdate complex Range: 2.8 to 4.5 md/dL(0.8 to 1.44 mmol/L)

Increase: serum calcium, absorption of calcium, osteoclast Hypocalcemia triggers release of PTH

Magnesium Distribution, function and homeostasis: 99% bone, 1%

ECF; enzymes; cellular energy, nerve conduction, transfers phosphates, maintains K+ intracellularly; renal and GIT

Analytical techniques: atomic absorption spectrophotometry

Range: 0.75 to 0.95 mmol/L

Hormones regulating mineral metabolism Parathyroid hormone = increases calcium, phosphate

from bone, renal calcium reabsorption, inhibition of renal phosphate reabsorption, stimulates renal vit D which increase intestinal absorption of calcium and phosphates. Over-all effect: increases calcium, decreases phosphate (chief cells, hyperparathyroid d/t adenoma most potent hormone in bone resorption)

Bio-intact PTH = used in uremia and CRF; 20 minute post-op S/P adenectomy

Parathyroid hormone-related peptide = increased in carcinomas; same receptors as PTH

Calcitonin = inhibits action of PTH and Vit D (decreases both calcium and phosphates); increased in medullary thyroid carcinoma

Vit D metabolites = increase calcium and phosphates

rainwater@mymelody.com || 1st semester, AY 2011-2012

Disorders of Mineral Metabolism Hypercalcemia

1. Primary hyperparathyroidism = asymptomatic; if (+) us. Nephrolithiasis (usually due to adenoma) (Dx late in the disease)

2. Secondary hyperparathyroidism = renal failure 3. Malignancy no PTH ( in PTH-like

substance) Hypocalcemia

Hypoparathyroidism Pseudohypoparathyroidism Chronic renal failure Early in hyperparathyroidism

Hyperphosphatemia and hypophosphatemia Hyper = ARF, CRF, intake of phosphates,

acidosis Hypo = alcohol abuse, antacids, shift of

phosphorous from extracellular into cells due to sepsis, salicylate poisoning

Hypermagnesemia and hypomagnesemia Hyper = rare; at risk are elderly, patients

with bowel disorders and renal insufficiency Hypo = loss of magnesium from GIT and

kidneys; diabetes

Bone resorption markers Pyridium crosslinks (pyridinoline and

deoxypyridinoline) = part of collagen; normal Pyr: Dpyr ratio is 3 to 3.5: 1. Dpyr is pronounced in metabolic bone disease

Crosslinked telopeptides = estimating risk of hip fracture; predicting complications of osteoporosis; renal osteodystrophy; attached to collagen fragment

Bone formation markers Alkaline phosphatase= proportional to collagen

formation; high in osteosarcoma and Pagets disease Osteocalcin= non-collagenous protein of bone;

increased in hyperparathyroidism; decreased in hypoparathyroidism

Metabolic bone disease Osteoporosis = decreased organic matrix with normal

mineralization Osteomalacia and rickets = decreased mineral

content; normal organic matrix Renal osteodystrophy = decreased organic matrix and

mineral content (hyperparathyroidism, osteomalacia); d/t retention of phosphate hypocalcemia increased resorption

Pagets disease = structurally and functionally abnormal bone; not a metabolic bone disease bulging bone ; paramyxovirus infection

A. Osteitis Fibrosa Cystica: compact bone is converted to cancellous bone osteomalacia end stage: renal osteodystrophy (spectrum of bone changes)

* Scalloping (thinning of trabeculae)

B. Chronic Renal Failure

* CC cutting cone

Chronic Renal Failure

Normal bone; osteoporotic

A. Osteomalacia

B. Renal Osteodystrophy

Fibrous tissue

Red stain: no scalloping d/t newly-formed osteoid

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