Updated: 1/19/2018

Bone Formation

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Introduction
  • Bone formation (osteogenesis) can occur via two distinct processes that convert mesenchymal tissue to bone
    • endochondral ossification
      • mesenchymal tissue  cartilage intermediate  bone
    • intramembranous ossification
      • mesenchymal tissue  bone
  • Bone remodeling requires a  dynamic balance of formation and resorption that depends on multiple cell types
    • osteoblasts
    • osteocytes
    • osteoclasts
Endochondral Ossification
  • Overview
    • converts mesenchymal tissue to a cartilage intermediate and eventually to bone
    • occurs in several different osteogenic processes
      • embryonic long bone formation
      • longitudinal physis (growth plate) growth
      • non-rigid fracture healing
  • Steps
    • mesenchymal precursor cells commit to becoming cartilage cells (chondrocytes)
      • occurs via paracrine signaling
    • committed mesenchymal cells differentiate into chondrocytes
    • chondrocytes rapidly proliferate and secrete cartilage-specific extracellular matrix to form a cartilage model
    • chondrocytes die via apoptosis as the matrix calcifies
    • surrounding cells differentiate into osteoblasts to begin replacing degraded cartilage with bone matrix (osteoid)
    • blood vessels penetrate the diaphyseal cartilage core and osteoblasts form a primary ossification center
    • diaphyseal bone thickens and epiphyseal cartilage becomes calcified
    • blood vessels penetrate the epiphyseal cartilage core and osteoblasts form secondary ossification centers
      • initial bone is immature woven bone with irregular random collagen fibers
      • bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers
Intramembranous Ossification
  • Overview
    • converts mesenchymal tissue directly to bone
      • no cartilage intermediate
      • also known as Haversian remodeling
    • occurs in several different osteogenic processes
      • embryonic flat bone formation
        • skull
        • facial bones
        • clavicle
      • rigid fracture healing
  • Steps
    • mesenchymal cells proliferate and differentiate directly into osteoblasts
    • osteoblasts produce bone matrix (osteoid)
      • initial bone is immature woven bone with irregular random collagen fibers
      • bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers
Bone Remodeling
  • Multiple cell types are required for healthy bone remodeling
    • osteoblasts
      • function
        • bone-forming cells
          • produce a collagen-proteoglycan matrix that can bind calcium salts for osteoid calcification
      • origin
        • derived from fibroblasts
    • osteocytes
      • function
        • bone cells
          • transmit signals through bone
          • secrete growth factors to regulate activity of osteoblasts and osteoclasts
      • origin
        • derived from osteoblasts that become embedded in bone matrix
    • osteoclasts 
      • function
        • bone-resorbing cells
          • mobilize matrix minerals via acidification, then degrade matrix material via proteases
      • origin
        • derived from monocytes
  • clinical relevance
    • inadequate osteoblastic activity will lead to impaired bone mineralization
      • rickets/osteomalacia
    • excess osteoclastic activity will lead to increased bone resorption
      • osteoporosis
      • Paget disease of bone
      • osteitis fibrosa cystica
    • inadequate osteoclastic activity will lead to insufficient bone resorption
      • osteopetrosis
 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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