Fluid Space in Bone

Hughes, Sean; Davies, Rob; Khan, Ralph A. A.; Kelly, Patrick R.

doi:10.1097/00003086-197807000-00051

Cited by 27 publications

(17 citation statements)

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“…The ultrastructure of bone supports a compartmentalization of fluid spaces (15,19,20,22,38). Organic material in the Haversian canals separates bone fluid spaces into compartments of the vascular channel system and extracellular fluid of the mineralized matrix (39).…”

Section: W R Walsh and N Guzelsumentioning

confidence: 99%

Electrokinetic behavior of intact wet bone: Compartmental model

Walsh

Güzelsu

1991

Journal Orthopaedic Research

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Streaming potential experiments were performed on chemically-treated intact wet bone plugs equilibrated in potential-determining ion buffers. Comparison of calculated zeta (zeta) potentials from intact wet bone streaming potentials and bone particle electrophoresis indicates different values. Intact streaming potential experiments, where fluid is forced through the samples, represents flow, primarily through the vascular channel system, and contribution of the organically-lined channels to the electrokinetic zeta potential. Bone particle electrophoresis represents mainly the electrokinetic contribution of exposed mineralized matrix. The organic linings present in the vascular channel system limit potential-determining ions' access to the mineralized matrix. These linings may have an important role in mineral homeostasis and control of ion fluxes between bone compartments.

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Section: W R Walsh and N Guzelsumentioning

confidence: 99%

Electrokinetic behavior of intact wet bone: Compartmental model

Walsh

Güzelsu

1991

Journal Orthopaedic Research

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“…f The volumes of the vascular space, interstitial fluid, total bone fluid, bone cells, organic matrix, and hydroxyapatite crystals are assumed to be 1.3% (17,45), 4.0% (17,41,45), 20% (33,44,45), 1.5% (14), 35% (14,25,48), and 65% (14,25,32,48,54) of the total bone volume. The density of bone is assumed to be 1.0 g/ml.…”

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confidence: 99%

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation

Landersdorfer

Kinzig

Bulitta

et al. 2009

Antimicrob Agents Chemother

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Amoxicillin (amoxicilline)-clavulanic acid has promising activity against pathogens that cause bone infections. We present the first evaluation of the bone penetration of a beta-lactam by population pharmacokinetics and pharmacodynamic profiling via Monte Carlo simulations. Twenty uninfected patients undergoing total hip replacement received a single intravenous infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid before surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen with a cryogenic mill, including an internal standard. The drug concentrations in serum and total bone were analyzed by liquid chromatography-tandem mass spectrometry. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and a target time of the non-protein-bound drug concentration above the MIC for >50% of the dosing interval for near-maximal bactericidal activity in serum. The median of the ratio of the area under the curve (AUC) for bone/AUC for serum was 20% (10th to 90th percentile for betweensubject variability [variability], 16 to 25%) in cortical bone and 18% (variability, 11 to 29%) in cancellous bone for amoxicillin and 15% (variability, 11 to 21%) in cortical bone and 10% (variability, 5.1 to 21%) in cancellous bone for clavulanic acid. Analysis in S-ADAPT yielded similar results. The equilibration half-lives between serum and bone were 12 min for amoxicillin and 14 min for clavulanic acid. For a 30-min infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid every 4 h, amoxicillin achieved robust (>90%) probabilities of target attainment (PTAs) for MICs of <12 mg/liter in serum and 2 to 3 mg/liter in bone and population PTAs above 95% against methicillin-susceptible Staphylococcus aureus in bone and serum. The AUC of amoxicillin-clavulanic acid was 5 to 10 times lower in bone than in serum, and amoxicillin-clavulanic acid achieved a rapid equilibrium and favorable population PTAs against pathogens commonly encountered in bone infections.Osteomyelitis is difficult to diagnose and treat and may cause irreversible damage. Antibiotic treatment over weeks to months is required, often in addition to surgical debridement. To reduce the incidence of infections after orthopedic surgery, perioperative prophylaxis is standard practice. Each year more than a million hip replacements are done worldwide. Prosthetic devices are particularly susceptible to infections, more than 50% of which are due to Staphylococcus aureus or coagulase-negative staphylococci, such as S. epidermidis (38). It is vitally important that adequate surgical prophylaxis be used and that sufficient concentrations of antibiotic with activity against frequently encountered pathogens in bone be achieved.Amoxicillin (amoxicilline) in combination with clavulanic acid is active against pathogens commonly found in prosthesisrelated bone infections (MICs at which 90% of bacteria are inhibited [MIC 90 s], 1 mg/liter for methicillin-susceptible S. aureus [MSSA] and 8 mg/liter for S. epidermidis [28]). Successful treat...

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“…Tissue fluid from Haversian capillaries flowing into the canalicular-lacunar complex has been studied histologically using molecular markers. The principle mechanism of exchange between blood and the interstitial fluid has been assumed to be passive diffusion (Hughes et al, 1978). However, observations from the present and other studies (Seliger, 1970, Dillaman, 1984Montgomery et al, 1988) indicate that there is a transport system other than simple diffusion since overall flow was predominantly in a centrifugal manner with clear front(s).…”

Section: Discussionmentioning

confidence: 51%

“…These methods have provided important information on the kinetics of solute movement and the relative sizes of compartments in the long bone blood vessels. However, they are limited to the observation of macroscopic effects due to trapping of the 15µm spheres in microvascular vessels (Hughes et al, 1978). The permeability through the network of canaliculi, lacunae, and the much finer microporosity of the collagen-hydroxyapatite matrix has received less attention.…”

mentioning

confidence: 99%

Histomorphological study on pattern of fluid movement in cortical bone in goats

et al. 1999

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Streaming potential is considered one of the most important mechanisms to moderate the function of osteoblasts and osteocytes in bone growth, remodeling and fracture repair. The present study was designed to demonstrate the fluid flow pattern in the cortical bone matrix in an animal model using undecalcified histological techniques. Immediately after injection of ferritin into the tibia nutrient artery of four adult goats, the animals were euthanized. Undecalcified transverse and longitudinal blocks of cortical bone obtained from the tibial diaphysis were immersed in Perl's reagent and embedded in methyl methacrylate. Sections were cut and ground to 30-50 µm thickness for histomorphological evaluation at different magnifications and focusing levels. A serial grinding technique was used to validate the observations made at different focusing levels. As expected, ferritin was observed in the interstitial compartment in both transverse and longitudinal sections. In osteons sectioned transversely, the pattern of centrifugal movement of ferritin marker was demonstrated as single or multiple halos around the Haversian canal. The most apparent halo in osteons with multiple halos was the one found closest to the Haversian canal. The total number of identifiable single or multiple halos increased or was altered when counting was made with higher magnification or at different focusing levels, respectively. Irregular and incomplete ferritin halos indicated structural complexity of the osteons. Overall, the pattern of ferritin movement was consistent with bulk interstitial fluid flow influenced by both hydrostatic pressure and transudation. This study demonstrated for the first time multiple concentric halos of the fluid flow marker ferritin around Haversian canals in the cortical interstitial compartment. The results suggest that the undecalcified technique might be a useful method for qualitative and quantitative studies on cortical fluid flow. Anat Rec 255: 380-387, 1999. 1999 Key words: fluid flow; cortical bone; ferritin transudation; undecalcification; histology; microscopy Mature cortical bone is structurally organized into osteons. Each osteon is roughly cylindrical in shape with concentric lamellae around the vasculature-containing Haversian canal. Between the lamellae lie the ellipsoidal lacunae where the osteocytes reside. Cortical bone has a hierarchical network of flow channels, i.e. the longitudinal Haversian and the transverse Volkmann's canals to the tiny lacunae-canaliculi channels around the bone cells, and the microporosity of the collagen-hydroxyapatite bone matrix (Cooper et al

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Fluid Space in Bone

Cited by 27 publications

References 0 publications

Electrokinetic behavior of intact wet bone: Compartmental model

Electrokinetic behavior of intact wet bone: Compartmental model

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation

Histomorphological study on pattern of fluid movement in cortical bone in goats

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