Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Pathways of Transport in Bone

Patrick J. Kelly

10.1002/cphy.cp020312

Source: Supplement 8: Handbook of Physiology, The Cardiovascular System, Peripheral Circulation and Organ Blood Flow

Originally published: 1983

Published online: January 2011

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 51
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. 74; B from Lopez‐Curto, Bassingthwaighte, and Kelly 64
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. 88
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 64
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 64
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 64
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 64
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. 88
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. 15
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. 50
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 39, 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. 94
Figure 13. Figure 13.

Bone rigidity after tibial fracture for same dogs as in Fig. 12. By 120 days flow decreases and rigidity returns to normal.

From Rand, Kelly, et al. 94
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 19,38,49,61,62
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. 61
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 85. Flow values are given in Table 1 of ref. 85
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 47
Figure 20. Figure 20.

Plots of 85Sr and 42K washout. R(t), residue function vs. flow normalized in washout (cf. Fig. 23). 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. 61
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. 53
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. 61
Figure 26. Figure 26.

Washout curve of iodoantipyrine.
Figure 27. Figure 27.

Washout curve of 125I‐antipyrine.

From Kelly et al. 53


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 51


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. 74; B from Lopez‐Curto, Bassingthwaighte, and Kelly 64


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. 88


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 64


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 64


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 64


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 64


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. 88


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. 15


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. 50


Figure 12.

Clearance of 85Sr over 5‐min periods at standardized tibial fracture in dogs. Since net extraction does not change with increasing flow 39, 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. 94


Figure 13.

Bone rigidity after tibial fracture for same dogs as in Fig. 12. By 120 days flow decreases and rigidity returns to normal.

From Rand, Kelly, et al. 94


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 19,38,49,61,62


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. 61


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 85. Flow values are given in Table 1 of ref. 85


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 47


Figure 20.

Plots of 85Sr and 42K washout. R(t), residue function vs. flow normalized in washout (cf. Fig. 23). 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. 61


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. 53


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. 61


Figure 26.

Washout curve of iodoantipyrine.



Figure 27.

Washout curve of 125I‐antipyrine.

From Kelly et al. 53
References
 1. Allen, T. H., H. J. Krzywicki, and J. E. Roberts. Density, fat, water and solids in freshly isolated tissues. J. Appl. Physiol. 14: 1005–1008, 1959.
 2. Anderson, D. W. Studies of the lymphatic pathways of bone and bone marrow. J. Bone Jt. Surg. Am. Vol. 42: 716–717, 1960.
 3. Ashton, B. A., H.‐J. Höhling, and J. T. Triffitt. Plasma proteins present in human cortical bone: enrichment of the α2HS‐glycoprotein. Calcif. Tissue Res. 22: 27–33, 1976.
 4. Baud, C.‐A. Submicroscopic structure and functional aspects of the osteocyte. Clin. Orthop. 56: 227–236, 1968.
 5. Baud, C.‐A., and P. W. Morgenthaler. Structure submicroscopique du rebord lacuno‐canaliculaire osseux. Gegenbaurs Morphol. Jahrb. 104: 476–486, 1963.
 6. Bauer, G. C. H., A. Carlsson, and B. Lindquist. Evaluation of accretion, resorption, and exchange reactions in the skeleton. K. Fysiogr. Saellsk. Lund Foerh. 25: 3–18, 1955.
 7. Bauer, G. C. H., L. Lindberg, Y. Naversten, and L.‐O. Sjöstrand. 85Sr radionuclide scintimetry in infected total hip arthroplasty. Acta Orthop. Scand. 44: 439–450, 1973.
 8. Bigler, R. E., and H. Q. Woodard. Skeletal distribution of mineralized bone tissue in humans. Health Phys. 31: 213–218, 1976.
 9. Bloom, J. D., R. H. Fitzgerald, Jr., J. A. Washington II, and P. J. Kelly. The transcapillary passage and interstitial fluid concentration of penicillin in canine bone. J. Bone Jt. Surg. Am. Vol. 62: 1168–1175, 1980.
 10. Bosch, W. J. Plasma 45Ca clearance by the tibia in the immature dog. Am. J. Physiol. 216: 1150–1157, 1969.
 11. Brookes, M. The Blood Supply of Bone: An Approach to Bone Biology. London: Butterworths, 1971.
 12. Casley‐Smith, J. R. The functioning and interrelationships of blood capillaries and lymphatics. Experientia 32: 1–12, 1976.
 13. Chiewitz, O., and G. Hevesy. [Cited by A. G. Mattar and B. A. Siegel. Bone tracers: radionuclide imaging and related techniques. In: Skeletal Research: An Experimental Approach, edited by D. J. Simmons and A. S. Kunin. New York: Academic, 1979, p. 455–486.]
 14. Cofield, R. H., J. B. Bassingthwaighte, and P. J. Kelly. Strontium‐85 extraction during transcapillary passage in tibial bone. J. Appl. Physiol. 39: 596–602, 1975.
 15. Cooper, R. R., J. W. Milgram, and R. A. Robinson. Morphology of the osteon: an electron microscopic study. J. Bone Jt. Surg. Am. Vol. 48: 1239–1271, 1966.
 16. Copp, D. H., and S. S. Shim. Extraction ratio and bone clearance of Sr85 as a measure of effective bone blood flow. Circ. Res. 16: 461–467, 1965.
 17. Crone, C. Does “restricted diffusion” occur in muscle capillaries? Proc. Soc. Exp. Biol. Med. 112: 453–455, 1963.
 18. Davies, D. R., J. B. Bassingthwaighte, and P. J. Kelly. Effect of lanthanum on transcapillary transport of 85Sr and [14C]sucrose in canine cortical bone (Abstract). Trans. 22nd Annu. Meet. Orthop. Res. Soc. 1: 127, 1976.
 19. Davies, D. R., J. B. Bassingthwaighte, and P. J. Kelly. Transcapillary exchange of strontium and sucrose in canine tibia. J. Appl. Physiol. 40: 17–22, 1976.
 20. Davies, D. R., J. B. Bassingthwaighte, and P. J. Kelly. Blood flow and ion exchange in bone. In: Skeletal Research: An Experimental Approach, edited by D. J. Simmons and A. S. Kunin. New York: Academic, 1979, p. 397–419.
 21. De Bruyn, P. P. H., P. C. Breen, and T. B. Thomas. The microcirculation of the bone marrow. Anat. Rec. 168: 55–68, 1970.
 22. Doty, S. B., and B. H. Schofield. Metabolic and structural changes within osteocytes of rat bone. In: Calcium, Parathyroid Hormone and the Calcitonins, Proc. Parathyroid Conf., 4th, Chapel Hill, North Carolina, 1971. Amsterdam: Excerpta Med. Found, 1972, p. 353–364. (Int. Congr. Ser. 243.)
 23. Driessens, M., and P. M. Vanhoutte. Vascular reactivity of the isolated tibia of the dog. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H904–H908, 1979.
 24. Drinker, C. K., and K. R. Drinker. A method for maintaining an artificial circulation through the tibia of the dog, with a demonstration of the vasomotor control of the marrow vessels. Am. J. Physiol. 40: 514–521, 1916.
 25. Frederickson, J. M., A. J. Honour, and D. H. Copp. Measurement of initial bone clearance of Ca45 from blood in the rat (Abstract). Federation Proc. 14: 49, 1955.
 26. Galasko, C. S. B. Skeletal metastases and mammary cancer. Ann. R. Coll. Surg. Engl. 50: 3–28, 1972.
 27. Garlick, D. G., and E. M. Renkin. Transport of large molecules from plasma to interstitial fluid and lymph in dogs. Am. J. Physiol. 219: 1595–1605, 1970.
 28. Glimcher, M. J. A basic architectural principle in the organization of mineralized tissues. Clin. Orthop. 61: 16–36, 1968.
 29. Glimcher, M. J. Composition, structure, and organization of bone and other mineralized tissues and the mechanism of calcification. In: Handbook of Physiology. Endocrinology, edited by R. O. Greep and E. B. Astwood. Washington, DC: Am. Physiol. Soc., 1976, sect. 7, vol. VII, chapt. 3, p. 25–116.
 30. Göthman, L. Vascular reactions in experimental fractures: microangiographic and radioisotope studies. Acta Chir. Scand. Suppl. 284: 1–34, 1961.
 31. Greep, R. O., and E. B. Astwood (editors). Handbook of Physiology. Endocrinology. Washington, DC: Am. Physiol. Soc, 1976, sect. 7, vol. VII.
 32. Gross, P. M., D. D. Heistad, and M. L. Marcus. Neurohumoral regulation of blood flow to bones and marrow. Am. J. Physiol. 237 (Heart Circ. Physiol. 6): H440–H448, 1979.
 33. Grotte, G. Passage of dextran molecules across the blood‐lymph barrier. Acta Chir. Scand. Suppl. 211: 1–84, 1956.
 34. Haliburton, R. A., C. R. Sullivan, P. J. Kelly, and L. F. A. Peterson. The extra‐osseous and intra‐osseous blood supply of the talus. J. Bone Jt. Surg. Am. Vol. 40: 1115–1120, 1958.
 35. Heaney, R. P., and G. D. Whedon. Radiocalcium studies of bone formation rate in human metabolic bone disease. J. Clin. Endocrinol. Metab. 18: 1246–1267, 1958.
 36. Holmes, J. M., D. H. Davies, W. J. Meath, and R. A. Beebe. Gas adsorption and surface structure of bone mineral. Biochemistry 3: 2019–2024, 1964.
 37. Hughes, S., and M. Blount. The structure of capillaries in cortical bone (Abstract). Ann. R. Coll. Surg. Engl. 61: 312, 1979.
 38. Hughes, S. P. F., D. R. Davies, J. B. Bassingthwaighte, F. G. Knox, and P. J. Kelly. Bone extraction and blood clearance of diphosphonate in the dog. Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H341–H347, 1977.
 39. Hughes, S. P. F., G. J. Lemon, D. R. Davies, J. B. Bassingthwaighte, and P. J. Kelly. Extraction of minerals after experimental fractures of the tibia in dogs. J. Bone Jt. Surg. Am. Vol. 61: 857–866, 1979.
 40. Jowsey, J., B. L. Riggs, and P. J. Kelly. Mineral metabolism in osteocytes. Mayo Clin. Proc. 39: 480–484, 1964.
 41. Kaley, G., and B. M. Altura (editors). Microcirculation. Baltimore, MD: University Park, 1977, vol. I, 528 p.
 42. Kallius, H. U. Experimentelle Untersuchungen über die Lymphgefässe der Röhrenknochen. Bruns Beitr. Klin. Chir. 115: 109–124, 1932.
 43. Kane, W. J., and E. Grim. Blood flow to canine hind‐limb bone, muscle, and skin: a quantitative method and its validation. J. Bone Jt. Surg. Am. Vol. 51: 309–322, 1969.
 44. Karnovsky, M. J. The ultrastructural basis of capillary permeability studied with peroxidase as a tracer. J. Cell Biol. 35: 213–236, 1967.
 45. Kelly, P. J. Measurement of oxygen saturation in arterial and venous blood of bone in normal puppies and in puppies with arteriovenous fistula. Mayo Clin. Proc. 41: 95–102, 1966.
 46. Kelly, P. J. Anatomy, physiology, and pathology of the blood supply of bones. J. Bone Jt. Surg. Am. Vol. 50: 766–783, 1968.
 47. Kelly, P. J. Effects of thyroid and parathyroid deficiency on bone remodelling distal to a venous tourniquet. J. Anat. 110: 349–361, 1971.
 48. Kelly, P. J. Comparison of marrow and cortical bone blood flow by 125I‐labeled 4‐iodoantipyrine (I‐Ap) washout. J. Lab. Clin. Med. 81: 497–505, 1973.
 49. Kelly, P. J., and J. B. Bassingthwaighte. Studies on bone ion exchanges using multiple‐tracer indicator‐dilution techniques. Federation Proc. 36: 2634–2639, 1977.
 50. Kelly, P. J., J. Jowsey, and B. L. Riggs. A comparison of different morphologic methods of determining bone formation. Clin. Orthop. 40: 7–11, 1965.
 51. Kelly, P. J., and L. F. A. Peterson. The blood supply of bone. Heart Bull. 12: 96–99, 1963.
 52. Kelly, P. J., L. F. A. Peterson, D. C. Pease, and L. Zamboni. Circulation of bone. In: Blood Vessels and Lymphatics, edited by D. I. Abramson. New York: Academic, 1962, p. 531–554.
 53. Kelly, P. J., T. Yipintsoi, and J. B. Bassingthwaighte. Blood flow in canine tibial diaphysis estimated by iodoantipyrine‐125I washout. J. Appl. Physiol. 31: 38–47, 1971.
 54. Kelly, R. G., E. A. Peets, S. Gordon, and D. A. Buyske. Determination of C14 and H3 in biological samples by Schöniger combustion and liquid scintillation techniques. Anal. Biochem. 2: 267–273, 1961.
 55. Kolodny, A. The relation of the bone marrow to the lymphatic system: its rôle in the spreading of carcinomatous metastases throughout the skeleton. Arch. Surg. Chicago 11: 690–707, 1925.
 56. Kornblum, S. S., and P. J. Kelly. The lacunae and Haversian canals in tibial cortical bone from ischemic and nonischemic limbs: a comparative microradiographic study. J. Bone Jt. Surg. Am. Vol. 46: 797–810, 1964.
 57. Kretsinger, R. H. Evolutionary considerations of calcium pumping by biological membranes. In: Membrane Transport Processes, edited by D.C. Tosteson and Yu. A. Ovchinnikov. New York: Raven, 1977, vol. 2, p. 253–260.
 58. Landis, E. M., and J. R. Pappenheimer. Exchange of substances through the capillary walls. In: Handbook of Physiology. Circulation, edited by W. F. Hamilton. Washington, DC: Am. Physiol. Soc., 1963, sect. 2, vol. II, chapt. 29, p. 961–1034.
 59. Laurnen, E. L., and P. J. Kelly. Blood flow, oxygen consumption, carbon‐dioxide production and blood‐calcium and pH changes in tibial fractures in dogs. J. Bone Jt. Surg. Am. Vol. 51: 298–308, 1969.
 60. Lemon, G. J., J. B. Bassingthwaighte, and P. J. Kelly. Influence of parathyroid state on calcium uptake in bone. Am. J. Physiol. 242 (Endocrinol. Metab. 5): E146–E153, 1982.
 61. Lemon, G. J., D. R. Da vies, S. P. F. Hughes, J. B. Bassingthwaighte, and P. J. Kelly. Transcapillary exchange and retention of fluoride, strontium, EDTA, sucrose, and antipyrine in bone. Calcif. Tissue Int. 31: 173–181, 1980.
 62. Lemon, G. J., B. Maltby, D. R. Da vies, S. P. F. Hughes, J. B. Bassingthwaighte, and P. J. Kelly. Transcapillary exchange and washout of 42K compared with ions and molecules that concentrate in bone (Abstract). Trans. 26th Annu. Meet. Orthop. Res. Soc. 5: 49, 1980.
 63. Lloyd, E., and D. Hodges. Quantitative characterization of bone: a computer analysis of microradiographs. Clin. Orthop. 78: 230–250, 1971.
 64. Lopez‐Curto, J. A., J. B. Bassingthwaighte, and P. J. Kelly. Anatomy of the microvasculature of the tibial diaphysis of the adult dog. J. Bone Jt. Surg. Am. Vol. 62: 1362–1369, 1980.
 65. Lopez‐Curto, J. A., S. P. F. Hughes, J. B. Bassingthwaighte, and P. J. Kelly. Interstitial fluid space in bone (Abstract). Federation Proc. 35: 850, 1976.
 66. Mahin, D. T., and R. T. Lofberg. A simplified method of sample preparation for determination of tritium, carbon‐14, or sulfur‐35 in blood or tissue by liquid scintillation counting. Anal. Biochem. 16: 500–509, 1966.
 67. Majno, G. Ultrastructure of the vascular membrane. In: Handbook of Physiology. Circulation, edited by W. F. Hamilton. Washington, DC: Am. Physiol. Soc., 1965, sect. 2, vol. III, chapt. 64, p. 2293–2375.
 68. Manning, J. W., K. Wasserman, A. E. Taylor, and H. S. Mayerson. Capillary permeability and mechanism of transport: a salute to Professor Hymen S. Mayerson. Physiologist 23 (1): 34–43, 1980.
 69. Mayerson, H. S., C. G. Wolfram, H. H. Shirley, Jr., and K. Wasserman. Regional differences in capillary permeability. Am. J. Physiol. 198: 155–160, 1960.
 70. McInnis, J. C., R. A. Robb, and P. J. Kelly. The relationship of bone blood flow, bone tracer deposition, and endosteal new bone formation. J. Lab. Clin. Med. 96: 511–522, 1980.
 71. McLean, F. C. The ultrastructure and function of bone. Science 127: 451–456, 1958.
 72. Morris, M. A., and P. J. Kelly. Use of tracer microspheres to measure bone blood flow in conscious dogs. Calcif. Tissue Int. 32: 69–76, 1980.
 73. Morris, M. A., J. A. Lopez‐Curto, S. P. F. Hughes, K.‐N. An, J. B. Bassingthwaighte, and P. J. Kelly. Fluid spaces in canine bone and marrow. Microvasc. Res., in press.
 74. Nelson, G. E., Jr., P. J. Kelly, L. F. A. Peterson, and J. M. Janes. Blood supply of the human tibia. J. Bone Jt. Surg. Am. Vol. 42: 625–636, 1960.
 75. Neuman, M. W., and W. F. Neuman. On the measurement of water compartments, pH, and gradients in calvaria. Calcif. Tissue Int. 31: 135–145, 1980.
 76. Neuman, W. F., M. W. Neuman, and C. R. Myers. Blood:bone disequilibrium. III. Linkage between cell energetics and Ca fluxes. Am. J. Physiol. 236 (Cell Physiol. 5): C244–C248, 1979.
 77. Neuman, W. F., and W. K. Ramp. The concept of a bone membrane: some implications. In: Cellular Mechanisms for Calcium Transfer and Homeostasis, edited by G. Nichols, Jr. and R. H. Wasserman. New York: Academic, 1971, p. 197–206.
 78. Nordin, B. E. C., D. H. Marshall, M. Peacock, and W. G. Robertson. Plasma calcium homeostasis. In: Calcium‐Regulating Hormones, Proc. Parathyroid Conf, 5th, Oxford, London, 1974. Amsterdam: Excerpta Med. Found., 1975, p. 239–253. (Int. Congr. Ser. 346.)
 79. Norimatsu, H. Rapid action of calcitonin in lining bone cells (osteocytes). Bone Metab. 13: 407–416, 1980.
 80. Owen, C. A., Jr., and M. H. Power. Intercellular plasma of centrifuged human erythrocytes as measured by means of iodo131‐albumin. J. Appl. Physiol. 5: 323–329, 1953.
 81. Owen, M., and J. T. Triffitt. Extravascular albumin in bone tissue. J. Physiol. London 257: 293–307, 1976.
 82. Paaske, W. P. Permeability of capillaries in muscle, skin, and subcutaneous tissue. Physiologist 23 (1): 75–78, 1980.
 83. Palade, G. E. Fine structure of blood capillaries (Abstract). J. Appl. Phys. 24: 1424, 1953.
 84. Pappenheimer, J. R. Passage of molecules through capillary walls. Physiol. Rev. 33: 387–423, 1953.
 85. Paradis, G. R., J. B. Bassingthwaighte, and P. J. Kelly. Inhibition of transport of 47Ca and 85Sr by lanthanum in canine cortical bone. J. Appl. Physiol. 36: 221–225, 1974.
 86. Pasternak, H. S., P. J. Kelly, and C. A. Owen, Jr. Metabolic rate in tibia of normal and thyrotoxic dogs. J. Lab. Clin. Med. 71: 240–246, 1968.
 87. Peacocke, A. R., and P. A. Williams. Binding of calcium, yttrium and thorium to a glycoprotein from bovine cortical bone. Nature London 211: 1140–1141, 1966.
 88. Peterson, L. F. A., and P. J. Kelly. Surgical aspects of the blood supply of bone. In: American Academy of Orthopaedic Surgeons: Instructional Course Lectures, edited by F. C. Reynolds. St. Louis, MO: Mosby, 1961, vol. 18, p. 221–233.
 89. Peterson, L. F. A., and P. J. Kelly. Microangiography. In: The Encyclopedia of X‐Rays and Gamma Rays, edited by G. L. Clark. New York: Reinhold, 1963, p. 595–597.
 90. Posner, A. S. Crystal chemistry of bone mineral. Physiol. Rev. 49: 760–792, 1969.
 91. Posner, A. S., F. Betts, and N. C. Blumenthal. Formation and structure of synthetic and bone hydroxyapatites. Prog. Cryst. Growth Charact. 3: 49–64, 1980.
 92. Price, P. A., J. W. Lothringer, and S. K. Nishimoto. Absence of the vitamin K‐dependent bone protein in fetal rat mineral: evidence for another γ‐carboxyglutamic acid‐containing component in bone. J. Biol. Chem. 255: 2938–2942, 1980.
 93. Price, P. A., and S. K. Nishimoto. Radioimmunoassay for the vitamin K‐dependent protein of bone and its discovery in plasma. Proc. Natl. Acad. Sci. USA 77: 2234–2238, 1980.
 94. Rand, J. A., K. N. An, E. Y. S. Chao, and P. J. Kelly. A comparison of the effect of open intramedullary nailing and compression‐plate fixation on fracture‐site blood flow and fracture union. J. Bone Jt. Surg. Am. Vol. 63: 427–442, 1981.
 95. Reynolds, J. J. Bone turnover, vitamin D and plasma calcium homeostasis. In: Calcium‐Regulating Hormones, Proc. Parathyroid Conf, 5th, Oxford, London, 1974. Amsterdam: Excerpta Med. Found., 1975, p. 254–261. (Int. Congr. Ser. 346.)
 96. Rhinelander, F. W., C. L. Stewart, and J. W. Wilson. Bone vascular supply. In: Skeletal Research: An Experimental Approach, edited by D. J. Simmons and A. S. Kunin. New York: Academic, 1979, p. 367–395.
 97. Robinson, R. A. Physicochemical structure of bone. Clin. Orthop. 112: 263–315, 1975.
 98. Robinson, R. A., and S. R. Elliott. The water content of bone. I. The mass of water, inorganic crystals, organic matrix, and CO2 space components in a unit volume of dog bone. J. Bone Jt. Surg. Am. Vol. 39: 167–187, 1957.
 99. Root, W. S. The flow of blood through bones and joints. In: Handbook of Physiology. Circulation, edited by W. F. Hamilton. Washington, DC: Am. Physiol. Soc., 1963, sect. 2, vol. II, chapt. 47, p. 1651–1665.
 100. Roufosse, A. H., W. J. Landis, W. K. Sabine, and M. J. Glimcher. Identification of brushite in newly deposited bone mineral from embryonic chicks. J. Ultrastruct. Res. 68: 235–255, 1979.
 101. Rowland, R. E. Exchangeable bone calcium. Clin. Orthop. 49: 233–248, 1966.
 102. Seliger, W. G. Tissue fluid movement in compact bone. Anat. Rec. 166: 247–255, 1970.
 103. Semb, H. Bone marrow blood flow studied by iodoantipyrine clearance technique. Surg. Gynecol. Obstet. 133: 472–474, 1971.
 104. Taleisnik, J., and P. J. Kelly. The extraosseous and intraosseous blood supply of the scaphoid bone. J. Bone Jt. Surg. Am. Vol. 48: 1125–1137, 1966.
 105. Talmage, R. V., and S. A. Grubb. A laboratory model demonstrating osteocyte‐osteoblast control of plasma calcium concentrations: table model for plasma calcium control. Clin. Orthop. 122: 299–306, 1977.
 106. Talmage, R. V., and R. A. Meyer, Jr. Physiological role of parathyroid hormone. In: Handbook of Physiology. Endocrinology, edited by R. O. Greep and E. B. Astwood. Washington, DC: Am. Physiol. Soc., 1976, sect. 7, vol. VII, chapt. 14, p. 343–351.
 107. Tonna, E. A. Electron microscopic study of bone surface changes during aging: the loss of cellular control and biofeedback. J. Gerontol. 33: 163–177, 1978.
 108. Triffitt, J. T., U. Gebauer, B. A. Ashton, M. E. Owen, and J. J. Reynolds. Origin of plasma α2HS‐glycoprotein and its accumulation in bone. Nature London 262: 226–227, 1976.
 109. Trueta, J., and M. H. M. Harrison. The normal vascular anatomy of the femoral head in adult man. J. Bone Jt. Surg. Br. Vol. 35: 442–461, 1953.
 110. Van Dyke, D., H. O. Anger, Y. Yano, and C. Bozzini. Bone blood flow shown with F18 and the positron camera. Am. J. Physiol. 209: 65–70, 1965.
 111. Watson, P. D. The interstitial matrix as a barrier in blood‐to‐lymph solute movement. Physiologist 23 (1): 86–89, 1980.
 112. Weinman, D. T., P. J. Kelly, C. A. Owen, Jr., and A. L. Orvis. Skeletal clearance of Ca47 and Sr85 and skeletal blood flow in dogs. Proc. Staff Meet. Mayo Clin. 38: 559–570, 1963.
 113. Whiteside, L. A., P. A. Lesker, and D. J. Simmons. Measurement of regional bone and bone marrow blood flow in the rabbit using the hydrogen washout technique. Clin. Orthop. 122: 340–346, 1977.
 114. Wootton, R., J. Reeve, and N. Veall. The clinical measurement of skeletal blood flow. Clin. Sci. Mol. Med. 50: 261–268, 1976.
 115. Zierler, K. L. Equations for measuring blood flow by external monitoring of radioisotopes. Circ. Res. 16: 309–321, 1965.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Pathways of Transport in Bone
 

How to Cite

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