Comprehensive Physiology Wiley Online Library

Pathways of Transport in Bone

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Vascular Anatomy and Fluid Phase
1.1 Conduit Vessels to Bone
1.2 Capillaries of Bone
1.3 Fluid Transport
1.4 Physiological Implications
2 Bone Tissue Turnover
2.1 Bone Remodeling
2.2 Cells of Bone
2.3 Mineral Phase
2.4 Bone Repair
3 Transport of Ions and Molecules in Bone
3.1 Movement Into Bone From Bulk Extracellular Fluid (Influx)
3.2 Efflux
4 Methodology
4.1 Indicator‐Dilution Methods
4.2 Steady‐State Techniques (Volume of Distribution)
4.3 Blood Flow
5 Summary and Conclusions
Figure 1. Figure 1.

Blood supply of a long bone (A). B, C, and D: vessel arrangement in cancellous bone; B′, C′, and D′: cortical bone.

From Kelly and Peterson
Figure 2. Figure 2.

Radially arranged branches of descending nutrient artery that are conduit vessels to capillary bed of cortical bone. A: human tibia. India ink injection, cleared by Spalteholz technique. × 20. B: dog tibia. Microfil injection, cleared by Spalteholz technique. × 20.

A from Nelson, Kelly, et al. ; B from Lopez‐Curto, Bassingthwaighte, and Kelly
Figure 3. Figure 3.

Microangiogram of longitudinal section of cortical bone illustrating vasculature in dog. × 25.

From Peterson and Kelly. Surgical aspects of the blood supply of bone. In: American Academy of Orthopaedic Surgeons: Instructional Course Lectures, vol. 18, St. Louis, 1961, The C. V. Mosby Co.
Figure 4. Figure 4.

A: branch of nutrient artery penetrating cortex, then subdividing into smaller arterioles. Vessels at upper right are detailed in B. Microfil injection, cleared by Spalteholz technique. × 60. B: intracortical pattern and capillaries running longitudinally in haversian canals and radially toward periosteal surface in a Volkmann's canal. Microfil injection, cleared by Spalteholz technique. × 200.

From Lopez‐Curto, Bassingthwaighte, and Kelly
Figure 5. Figure 5.

Microvasculature of adult dog tibia. Photograph of specimen tipped at 30° angle. Microfil injection, cleared by Spalteholz technique. × 60.

From Lopez‐Curto, Bassingthwaighte, and Kelly
Figure 6. Figure 6.

Large conduit vessel (A) to cortical bone (cortex). Arrow points to smaller arteriole that enters endosteal sinusoid (S). Microfil injection, × 180.

From Lopez‐Curto, Bassingthwaighte, and Kelly
Figure 7. Figure 7.

Arteriole (A) and two small venules (V) en route to periosteum. Microfil injection, cleared by Spalteholz technique, × 120.

From Lopez‐Curto, Bassingthwaighte, and Kelly
Figure 8. Figure 8.

Microangiogram of dog femoral head. Injection medium, microopaque barium sulfate. × 45.

From Peterson and Kelly. Surgical aspects of the blood supply of bone. In: American Academy of Orthopaedic Surgeons: Instructional Course Lectures, vol. 18, St. Louis, 1961, The C. V. Mosby Co.
Figure 9. Figure 9.

Electron microradiography of cortical bone capillary. B, basement membrane; F, nerve fibers embedded in Schwann cells (S); R, red cell; arrows indicate nerves.

From Cooper et al.
Figure 10. Figure 10.

A: osteocytes and osteoblasts. B: extracellular fluid space outside capillary and surrounding canaliculi of the osteocyte.

Courtesy of B. Hall and R. Fitzgerald, unpublished observations
Figure 11. Figure 11.

Cortical bone from tibial diaphysis of 13‐yr‐old boy. Tetracycline was given twice 10 days apart. A: tetracycline‐labeled section under ultraviolet light. B: microradiograph of same section. × 100.

From Kelly et al.
Figure 12. Figure 12.

Clearance of 85Sr over 5‐min periods at standardized tibial fracture in dogs. Since net extraction does not change with increasing flow , clearance is a reasonable index of blood flow (blood flow = clearance/extraction). Paired observations for a tibial fracture fixed with a metal plate and a fracture fixed with an intramedullary rod.

From Rand, Kelly, et al.
Figure 13. Figure 13.

Bone rigidity after tibial fracture for same dogs as in Fig. . By 120 days flow decreases and rigidity returns to normal.

From Rand, Kelly, et al.
Figure 14. Figure 14.

lc, Lining cells (osteocytes or osteoblasts); ec, endothelial cells of capillary; cap, capillary; bf, bone fluid; pvf, perivascular fluid; cm, mineral phase.

Courtesy of J. Day, unpublished data
Figure 15. Figure 15.

Comparison of ions and molecules by indicator‐dilution methods, including Sr2+ (85SrCl2), F (Na18F), pyrophosphate (99mTc‐PP), ethane‐1‐hydroxy‐1, 1‐diphosphonate (99mTc‐EHDP), ethylenediaminetetraacetate (51Cr‐EDTA), and sucrose [14C]sucrose). N, number of experiments in each group. Ordinate, mean values for PS/F; Abscissa, diffusion coefficients in dilute solution at 25°C.

Data from Kelly and colleagues
Figure 16. Figure 16.

PS/F, for 18F plotted against PS/Fs obtained simultaneously for 85Sr. Fs and S are the same for both tracers in each experiment so that the slope of a line from each datum point to origin represents a permeability ratio. Ratio of diffusion coefficients for fluoride and strontium is 1.05.

Data from Lemon, Kelly, et al.
Figure 17. Figure 17.

Effect of La3+ on blood flow (upper panel) and deposition of Sr2+ or Ca2+ (lower panel). Flow measured by iodoantipyrine washout. Abscissa, dose of LaCl3 (mg/g) of tibia.

From Paradis, Bassingthwaighte, and Kelly . Flow values are given in Table of ref.
Figure 18. Figure 18.

Broken line, free‐diffusion coefficient ratio of 85SrCl2 to [14C]sucrose.

Courtesy of D. R. Davies, unpublished observations
Figure 19. Figure 19.

A: cross section of tibia of intact dog. × 6. PE, preexperimental bone; P, new periosteal bone; and E, new endosteal bone. Lines show limit of preexperimental bone—i.e., bone formed prior to formation of new endosteal and periosteal bone that was labeled by tetracycline. B: cross section of tibia of thyroparathyroidectomized dog in which interstitial and surface remodeling has ceased. × 5. Resorption cavities and low‐density bone are decreased compared with A.

From Kelly
Figure 20. Figure 20.

Plots of 85Sr and 42K washout. R(t), residue function vs. flow normalized in washout (cf. Fig. ). Fp · t, plasma flow × time (ml/100 g).

Figure 21. Figure 21.

Whole blood volume vs. residue function. R(t), percent of calcium tracer 85Sr retained after first transcapillary passage; F, flow; F × t (flow × time in ml/100 g), total blood passing through tibia up to that time. If flow dominated exchange, plots of R(t) vs. volume of effluent would be superimposed; thus extravascular diffusion limits tracer washout.

Figure 22. Figure 22.

Outflow dilution curves. Upper panel, dilution curves; lower panel, fractional extraction curves. Instantaneous extraction is chosen at peak or one sample beyond peak of albumin curve. Because molecules such as strontium and fluoride can be separated from albumin, the capillary barrier is tight, indicating that large protein molecules are good reference tracers in first minutes. When the 85Sr2+ outflow dilution curve crosses the albumin curve, its ESr becomes negative. This does not occur with tracer 18F · Sr2+ crosses the reference at about 80 s; F does not cross albumin curve during 180‐s indicator‐dilution curve.

From Lemon, Kelly, et al.
Figure 23. Figure 23.

Thirty‐two iodoantipyrine washout curves from 10 dogs; f′ (flow) × t (time) = volume of blood per milliliter of bone that has left the bone since arbitrary time 0. Washout at different flow rates is shown by coded curves.

From Kelly et al.
Figure 24. Figure 24.

Removal of external periosteal surface (ps) and endos teal surface (es) ensures a more uniform sample for counting.

Figure 25. Figure 25.

Instantaneous maximum extraction of F and Sr2+ in dogs with known diaphyseal flow perfused by a pump via tibial nutrient artery. Extraction decreases with increasing flow.

Data from Lemon, Kelly, et al.
Figure 26. Figure 26.

Washout curve of iodoantipyrine.

Figure 27. Figure 27.

Washout curve of 125I‐antipyrine.

From Kelly et al.


Figure 1.

Blood supply of a long bone (A). B, C, and D: vessel arrangement in cancellous bone; B′, C′, and D′: cortical bone.

From Kelly and Peterson


Figure 2.

Radially arranged branches of descending nutrient artery that are conduit vessels to capillary bed of cortical bone. A: human tibia. India ink injection, cleared by Spalteholz technique. × 20. B: dog tibia. Microfil injection, cleared by Spalteholz technique. × 20.

A from Nelson, Kelly, et al. ; B from Lopez‐Curto, Bassingthwaighte, and Kelly


Figure 3.

Microangiogram of longitudinal section of cortical bone illustrating vasculature in dog. × 25.

From Peterson and Kelly. Surgical aspects of the blood supply of bone. In: American Academy of Orthopaedic Surgeons: Instructional Course Lectures, vol. 18, St. Louis, 1961, The C. V. Mosby Co.


Figure 4.

A: branch of nutrient artery penetrating cortex, then subdividing into smaller arterioles. Vessels at upper right are detailed in B. Microfil injection, cleared by Spalteholz technique. × 60. B: intracortical pattern and capillaries running longitudinally in haversian canals and radially toward periosteal surface in a Volkmann's canal. Microfil injection, cleared by Spalteholz technique. × 200.

From Lopez‐Curto, Bassingthwaighte, and Kelly


Figure 5.

Microvasculature of adult dog tibia. Photograph of specimen tipped at 30° angle. Microfil injection, cleared by Spalteholz technique. × 60.

From Lopez‐Curto, Bassingthwaighte, and Kelly


Figure 6.

Large conduit vessel (A) to cortical bone (cortex). Arrow points to smaller arteriole that enters endosteal sinusoid (S). Microfil injection, × 180.

From Lopez‐Curto, Bassingthwaighte, and Kelly


Figure 7.

Arteriole (A) and two small venules (V) en route to periosteum. Microfil injection, cleared by Spalteholz technique, × 120.

From Lopez‐Curto, Bassingthwaighte, and Kelly


Figure 8.

Microangiogram of dog femoral head. Injection medium, microopaque barium sulfate. × 45.

From Peterson and Kelly. Surgical aspects of the blood supply of bone. In: American Academy of Orthopaedic Surgeons: Instructional Course Lectures, vol. 18, St. Louis, 1961, The C. V. Mosby Co.


Figure 9.

Electron microradiography of cortical bone capillary. B, basement membrane; F, nerve fibers embedded in Schwann cells (S); R, red cell; arrows indicate nerves.

From Cooper et al.


Figure 10.

A: osteocytes and osteoblasts. B: extracellular fluid space outside capillary and surrounding canaliculi of the osteocyte.

Courtesy of B. Hall and R. Fitzgerald, unpublished observations


Figure 11.

Cortical bone from tibial diaphysis of 13‐yr‐old boy. Tetracycline was given twice 10 days apart. A: tetracycline‐labeled section under ultraviolet light. B: microradiograph of same section. × 100.

From Kelly et al.


Figure 12.

Clearance of 85Sr over 5‐min periods at standardized tibial fracture in dogs. Since net extraction does not change with increasing flow , clearance is a reasonable index of blood flow (blood flow = clearance/extraction). Paired observations for a tibial fracture fixed with a metal plate and a fracture fixed with an intramedullary rod.

From Rand, Kelly, et al.


Figure 13.

Bone rigidity after tibial fracture for same dogs as in Fig. . By 120 days flow decreases and rigidity returns to normal.

From Rand, Kelly, et al.


Figure 14.

lc, Lining cells (osteocytes or osteoblasts); ec, endothelial cells of capillary; cap, capillary; bf, bone fluid; pvf, perivascular fluid; cm, mineral phase.

Courtesy of J. Day, unpublished data


Figure 15.

Comparison of ions and molecules by indicator‐dilution methods, including Sr2+ (85SrCl2), F (Na18F), pyrophosphate (99mTc‐PP), ethane‐1‐hydroxy‐1, 1‐diphosphonate (99mTc‐EHDP), ethylenediaminetetraacetate (51Cr‐EDTA), and sucrose [14C]sucrose). N, number of experiments in each group. Ordinate, mean values for PS/F; Abscissa, diffusion coefficients in dilute solution at 25°C.

Data from Kelly and colleagues


Figure 16.

PS/F, for 18F plotted against PS/Fs obtained simultaneously for 85Sr. Fs and S are the same for both tracers in each experiment so that the slope of a line from each datum point to origin represents a permeability ratio. Ratio of diffusion coefficients for fluoride and strontium is 1.05.

Data from Lemon, Kelly, et al.


Figure 17.

Effect of La3+ on blood flow (upper panel) and deposition of Sr2+ or Ca2+ (lower panel). Flow measured by iodoantipyrine washout. Abscissa, dose of LaCl3 (mg/g) of tibia.

From Paradis, Bassingthwaighte, and Kelly . Flow values are given in Table of ref.


Figure 18.

Broken line, free‐diffusion coefficient ratio of 85SrCl2 to [14C]sucrose.

Courtesy of D. R. Davies, unpublished observations


Figure 19.

A: cross section of tibia of intact dog. × 6. PE, preexperimental bone; P, new periosteal bone; and E, new endosteal bone. Lines show limit of preexperimental bone—i.e., bone formed prior to formation of new endosteal and periosteal bone that was labeled by tetracycline. B: cross section of tibia of thyroparathyroidectomized dog in which interstitial and surface remodeling has ceased. × 5. Resorption cavities and low‐density bone are decreased compared with A.

From Kelly


Figure 20.

Plots of 85Sr and 42K washout. R(t), residue function vs. flow normalized in washout (cf. Fig. ). Fp · t, plasma flow × time (ml/100 g).



Figure 21.

Whole blood volume vs. residue function. R(t), percent of calcium tracer 85Sr retained after first transcapillary passage; F, flow; F × t (flow × time in ml/100 g), total blood passing through tibia up to that time. If flow dominated exchange, plots of R(t) vs. volume of effluent would be superimposed; thus extravascular diffusion limits tracer washout.



Figure 22.

Outflow dilution curves. Upper panel, dilution curves; lower panel, fractional extraction curves. Instantaneous extraction is chosen at peak or one sample beyond peak of albumin curve. Because molecules such as strontium and fluoride can be separated from albumin, the capillary barrier is tight, indicating that large protein molecules are good reference tracers in first minutes. When the 85Sr2+ outflow dilution curve crosses the albumin curve, its ESr becomes negative. This does not occur with tracer 18F · Sr2+ crosses the reference at about 80 s; F does not cross albumin curve during 180‐s indicator‐dilution curve.

From Lemon, Kelly, et al.


Figure 23.

Thirty‐two iodoantipyrine washout curves from 10 dogs; f′ (flow) × t (time) = volume of blood per milliliter of bone that has left the bone since arbitrary time 0. Washout at different flow rates is shown by coded curves.

From Kelly et al.


Figure 24.

Removal of external periosteal surface (ps) and endos teal surface (es) ensures a more uniform sample for counting.



Figure 25.

Instantaneous maximum extraction of F and Sr2+ in dogs with known diaphyseal flow perfused by a pump via tibial nutrient artery. Extraction decreases with increasing flow.

Data from Lemon, Kelly, et al.


Figure 26.

Washout curve of iodoantipyrine.



Figure 27.

Washout curve of 125I‐antipyrine.

From Kelly et al.
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Patrick J. Kelly. Pathways of Transport in Bone. Compr Physiol 2011, Supplement 8: Handbook of Physiology, The Cardiovascular System, Peripheral Circulation and Organ Blood Flow: 371-396. First published in print 1983. doi: 10.1002/cphy.cp020312