BONE METABOLISM

Cortical / Compact most shafts of long bones, Haversian systems

Types of
most vertebral bodies and ends of long bones, greater surface area, remodelved more rapidly, lamellae
Bone Trabecular / Spongy
run parallel to bone surface
Bone Organic portion type I collagen, ground substance = proteoglycans (keratin sulfate, chondroitin sulfate, hyaluronic acid
Extracellular
Inorganic portion hydroxyapatite (Ca10(PO4)6(OH)2)
Matrix
Type I collagen major protein, 90-95% of organic material
Type V collagen small amounts (10%)
Bone Bone Specific Proteins CS-PG III, osteocalcin, bone sialoprotein, BMP
Proteins Non-collagen proteins
TRAMP Tyrosine-rich acidic matrix protein
Enzymes For collagen synthesis
mononuclear, mesenchymal precursors, depiosit new bone matrix (osteoid), becomes osteocytes,
Osteoblasts control mineralization by regulating passage of Ca and PO4 ions across membranes, synthesize Type I
collagen, growth factors, cytokines
Major bone
multinucleated, from pluripotent hematopoietic stem cells, resorb bone tissue via lysosomes and
cells Osteoclasts
H+ (via carbonic anhydrase) to resorb bone mineral at the ruffled border
connect with one another and lining cells on bone surface via cytoplasmic processes, running though
Osteocytes
canaliculi, sensors of mechanical strain, release signaling molecules (PGE, NO)
Alkaline phosphatase unclear role
Matrix vesicles at sites of
unclear role
Factors for mineralization
bone Type I collagen necessary
mineralizatio Acidic phosphoproteins
Poly Asp/Glu bind Ca, provide initial scaffold
n (bone sialoprotein)
Certain proteoglycans &
inhibit nucleation
glycoproteins
PU-I initial OC and monocyte differentiation
OC formation C-fos, NFkB differentiation of committed precursors to mature OC
and M-CSF OC and macrophage differentiation
Differentiatio RANKL, RANK promote differentiation of precursors to OC
n C-src lacuna formation
Osteoprotegerin inhibits OC formation
Molecules Carbonic anhydrase II formation of H+ within osteoclasts
Regulating TCIRGI encodes subunit of osteoclast proton pump
Osteoclast
Cathepsin K degrades collagen and other proteins
activity
regulatory molecule in pre-OB, key trigger for differentiation, activates coordinated gene expression
OB formation CBFA1
characteristic of OB phenotype
and
Osterix transcription factor for differentiation of mesenchymal cells into OB
Differentiatio
secretin protein, binds bone morphogenic proteins, promote bone formation by stimulating OB
n Sclerostin
precursor growth and differentiation
 Factors affecting OC & OB
↑ OC ↓ OC ↑ OB ↓ OB
PTH, Vit D corticosteroids PTH, Vit D Calcitonin, estrogen
Calcium Metabolism
 Occurrence: most abundant, 1.5-2% of body weight, 39% of total body minerals, 99% in bone and teeth, 1% in blood, ECF and soft tissues
 Distribution: Non-exchangeable pool – stable, unavailable for short-term regulation;
o Exchangeable pool – 1% involved in metabolic activities, 600-700 mg exchanged daily
 Total serum Ca: 8-8-10.8 mg/dL = Free/ionized – 50%, Anion bound to PO4, HCO3, citrate – 5%, Bound to albumin or globulin – 45%
 Absorption and utilization – mainly duodenum, 20-30% of ingested, VitD requiring, absorbable if water-soluble, unabsorbed is excreted
 Routes of Intestinal Calcium Absorption – Transcellular (active, saturable, proximal duodenum, vitD-dependent Ca BP (calbindin)),
Paracellular (passive, nonsaturable, vitD independent, throughout small intestine, diet-dependent)
 Factors affecting Absorption
Increase Absorption Decrease Absorption
Greater need, small supply, growth, pregnancy, lactation, deficiency, VitD deficiency, oxalic / phytic acid (binds with Ca  insoluble), fiber,
exercise, active VitD, acidic, lactose w/ normal lactase supply, moderate fat alkaline medium, excessive GI motility, stress, medications, aging
 Calcium Balance  Roles of PTH, Calcitonin and Vit D
Source Takes from ECF Gives to ECF Stimuli Effect
Bone 0.5 0.5 PTH ↓ Ca ↑ Ca (↑ resorption, ↓ excretion), Vit D
Intestine 0.2 0.2, excretes 0.8 Calcitonin ↑ Ca ↓ Ca (↓ resorption)
Kidney 10.0, excretes 0.2 9.8 Vit D PTH ↑ Ca absorption, ↑ Ca resorption
Metabolic / Genetic Diseases
Dwarfism ?
Rickets ↓ Vit D, children
Osteomalacia ↓ Vit D, adults
Hyperparathyroidism ?
Osteogenesis Imperfecta Mutated collagen (COL1A1, COL1A2)
Osteoporosis Hereditary, postmenopausal, collagen mutation, Vit D receptor gene
Osteoarthitis, Chondrodysplasia ?
Pfeifer syndrome FGFR1
Jackson-Weiss/Crongon FGFR2
Achondroplasia / Thanatophoric dysplasia FGFR3