Biomedical subjects

D W Howie

Publications and source records attributed to D W Howie.

At least 19 recordsLinked to original sources

PubMed2001

The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic osteolysis.

Extensive osteolysis adjacent to implants is often associated with wear particles of prosthetic material. We have investigated if RANKL, also known as osteoprotegerin ligand, osteoclast differentiation factor or TRANCE, and its natural inhibitor, osteoprotegerin (OPG), may be important in controlling this bone loss. Cells isolated from periprosthetic tissues containing wear particles expressed mRNA encoding for the pro-osteoclastogenic molecules, RANKL, its receptor RANK, monocyte colony-stimulating factor (M-CSF), interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, IL-6, and soluble IL-6 receptor, as well as OPG. Osteoclasts formed from cells isolated from periprosthetic tissues in the presence and absence of human osteoblastic cells. When osteoclasts formed in the absence of osteoblastic cells, markedly higher levels of RANKL mRNA relative to OPG mRNA were expressed. Particles of prosthetic materials also stimulated human monocytes to express osteoclastogenic molecules in vitro. Our results suggest that ingestion of prosthetic wear particles by macrophages results in expression of osteoclast-differentiating molecules and the stimulation of macrophage differentiation into osteoclasts.

Carrier Proteins↗

PubMed2000

The effect of particle phagocytosis and metallic wear particles on osteoclast formation and bone resorption in vitro.

Osteoclasts are multinucleated bone-resorbing cells that are formed from precursors that circulate in the monocyte fraction. This study has determined the effect of phagocytosis of metal particles on osteoclast formation and bone resorption in vitro. Human peripheral blood monocytes were cocultured for 21 days with osteoblast-like UMR 106 cells, in the presence of 1,25-dihydroxyvitamin D3, dexamethasone, and human macophage colony-stimulating factor. Cobalt-chrome alloy (CoCr), stainless steel (316L-SS), titanium alloy (TiAlV), and commercially pure titanium (cpTi) particles (size range, 0.5-3.0 microm) and 1.0-microm latex particles were added to the cocultures as a single dose at the beginning of each experiment. All 5 types of particles were readily phagocytosed by the monocytes. After 4 days' exposure to high concentrations of all the metal particles, some cell death was found in the cocultures. After 14 days, a reduction in the number of CD14+ cells was seen in cocultures exposed to high concentrations of metal particles, particularly CoCr and 316L-SS particles. Phagocytosis of latex particles by osteoclast precursors did not affect the ability of these cells to undergo osteoclast differentiation. In contrast, exposure to metal wear particle preparations caused a dose-dependent reduction in the number of vitronectin receptor-positive osteoclastic cells formed and a dose-dependent reduction in the bone resorption produced by these cells. This decrease in resorption was greater after exposure to CoCr and 316L-SS particles compared with TiAlV and cpTi particles. This in vitro cell culture system may provide a useful model to compare the effect of different prosthetic materials on human osteoclast formation and bone resorption.

Alloys↗

PubMed2000

Human bone-derived cells support formation of human osteoclasts from arthroplasty-derived cells in vitro.

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH)2 vitamin D3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH)2 vitamin D3 was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE2. Exogenous PGE2 (10(-8) to 10(-6) M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE2 by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening.

Acid Phosphatase↗

PubMed2000

The skeletal response to matt and polished cemented femoral stems.

We studied the effect of the surface finish of the stem on the transfer of load in the proximal femur in a sheep model of cemented hip arthroplasty. Strain-gauge analysis and corresponding finite-element (FE) analysis were performed to assess the effect of friction and creep at the cement-stem interface. No difference was seen between the matt and polished stems. FE analysis showed that the effects of cement creep and friction at the stem-cement interface on femoral strain were small compared with the effect of inserting a cemented stem.

Animals↗

PubMed1999

Macrophage colony-stimulating factor and interleukin-6 release by periprosthetic cells stimulates osteoclast formation and bone resorption.

Periprosthetic bone loss is an important contributory factor for aseptic loosening of total joint replacements. It has recently been shown that osteoclast precursor cells are present in the wear particle-associated macrophage infiltrate found in the membrane surrounding loose implants and that these cells are capable of differentiating into osteoclastic bone-resorbing cells. Long-term co-culture of arthroplasty-derived macrophages and the rat osteoblast-like cell line, UMR-106, in the presence of 1,25(OH)2D3 results in the formation of numerous multinucleated cells that are positive for tartrate-resistant acid phosphatase and vitronectin receptor and capable of extensive lacunar bone resorption. The aim of this study was to determine the effect of cytokines/growth factors, known to be present in the arthroplasty membrane, on this process of osteoclast differentiation. During osteoclast formation, increased levels of macrophage colony-stimulating factor, interleukin-6, and to a lesser extent, interleukin-1beta, but not tumour necrosis factor alpha, were detected in the co-culture supernatants. Addition of neutralising antibodies to human interleukin-1beta or tumour necrosis factor alpha to the co-culture system did not inhibit osteoclast formation. In contrast, co-cultures to which neutralising antibodies to human macrophage colony-stimulating factor or interleukin-6 were added contained fewer cells positive for tartrate-resistant acid phosphatase and vitronectin receptor and formed significantly fewer resorption pits. Time-course studies showed that macrophage colony-stimulating factor and interleukin-6 increase osteoclast formation mainly in the early stages of osteoclast differentiation. These results indicate that the release of macrophage colony-stimulating factor and interleukin-6 by activated cells in the arthroplasty membrane is likely to contribute to pathological bone resorption associated with aseptic loosening by stimulating differentiation of mononuclear phagocyte osteoclast precursors into mature bone-resorbing cells.

Acetabulum↗

PubMed1999

A comparison of different surgical approaches for the periacetabular osteotomy.

The periacetabular osteotomy is a well established surgical procedure for the preventative treatment of degenerative joint disease caused by symptomatic acetabular dysplasia. Surgeons on several continents use varying surgical approaches to achieve the same effective osteotomy. Individual surgical approaches must provide accurate and adequate exposure for the osteotomy and the reorientation of the acetabular fragment. The aim of the surgical approach for such complex and expansive surgery is to minimize morbidity related to the approach. This article compares experiences among three common approaches including the modified Smith-Petersen, ilioinguinal, and direct anterior approaches and describes the double approach.

Acetabulum↗

PubMed1998

Effects of design changes on cemented tapered femoral stem fixation.

The effects of matte finish and modularity on loosening of tapered stems using the same cementing technique were studied prospectively. In 80 patients, 82 cemented Exeter primary stems were implanted at total hip revision by one surgeon using the same surgical and cementing technique throughout the series. The polished stems behaved differently than the matte surfaced stems behaved. Polished stems subsided in the cement mantle an average of 1 mm at 2 years after implantation, but without subsequent loosening of stems at as long as 12 years after implantation. Matte surfaced stems with metal centralizers had a higher loosening rate, and loss of fixation at the prosthesis to cement interface was identified as an early sign of loosening of these stems. At a mean 6-year followup, there were no revisions nor was there radiographic evidence of loosening of the polished modular stems. It is concluded that matte finish results in increased loosening of tapered stems but the introduction of modularity did not.

Aged↗

PubMed1998

Radiographic and histologic analysis of cemented double tapered femoral stems.

The macroscopic, radiographic, and histologic features of the prosthesis-cement and cementbone interfaces and adjacent bone were studied in 21 cemented hemiarthroplasties in sheep that had lived until sacrifice at 9 months. The features were compared with those immediately after implantation of the stem in the contralateral femur. The femoral stem was a double taper that was either polished collarless, matte collarless, or matte collared. There was no prosthesis to cement debonding or cement to bone radiolucent line immediately after implantation, and there was excellent interdigitation at the cement-bone interface. After 9 months there was no evidence of prosthesis to cement debonding and no stem with definite loosening. At 9 months after implantation there was evidence of bone remodeling with new bone filling what were presumed to be gaps at the cement-bone interface from immediately after implantation. Radiolucent lines at the cement-bone interface were found to represent trabeculation of the cortical bone rather than the presence of a complete fibrous interface, which was not seen. There was no difference between stem types. Sheep have been shown to be useful in a model of cemented hip arthroplasty and, although no differences were seen between stem types at 9 months after implantation, long term differences cannot be excluded.

Animals↗

PubMed1998

Loosening of matt and polished cemented femoral stems.

We have compared prospectively the incidence of loosening of 20 femoral stems with a matt surface with that of 20 polished stems of an otherwise identical tapered, non-modular design of Exeter hip replacement. The stems were inserted using the same technique at operation and radiographs showed no difference in the adequacy of the cement mantle or of fixation. All the patients were reviewed regularly and none was lost to follow-up. After a minimum follow-up of nine years, four matt but no polished stems had been revised for aseptic loosening. Polished stems subsided slightly within the cement mantle early, but did not loosen.

Acetabulum↗

PubMed1998

Variation in cytokines induced by particles from different prosthetic materials.

Particles of prosthetic material stimulate macrophages to release cytokines, which may cause bone loss and loosening of the prosthesis. This study investigates the possibility that particles of different prosthetic materials may induce different cytokines and thus have different effects on bone remodeling. The in vitro response of human monocytes to particles of cast and forged cobalt chrome alloy, stainless steel, and titanium aluminum vanadium alloy were compared. There was no difference in the biologic response to cobalt-chrome particles derived from cast or forged material. Cobalt-chrome particles were toxic to the cells, but titanium aluminum vanadium particles did not affect cell viability. Stainless steel particles were approximately 10 times more toxic than were cobalt-chrome particles. All particles induced the release of tumor necrosis factor and interleukin 1 beta; stainless steel particles were the most potent stimulators of interleukin 1 beta; titanium aluminum vanadium particles were the strongest stimulators of interleukin 6 and prostaglandin 2. The study showed that particles derived from prosthetic materials of different metal compositions can elicit significantly different biologic responses. Understanding these different responses may help identify materials better suited for prostheses.

Alloys↗

PubMed1997

The role of polyethylene wear in joint replacement failure.

Aseptic loosening is the major cause of failure of joint replacement prostheses. Polyethylene implants removed at revision surgery regularly show wear. It is proposed that the polyethylene particles released into the tissues as a consequence of this wear induce a tissue response that precedes aseptic loosening. This paper presents the results of recent in vivo and in vitro studies of the biological response to polyethylene wear particles undertaken in the authors' laboratories. A clinical perspective is provided by the inclusion of the authors' recent observations of retrieval analyses of joint replacement implant wear and the tissue response to polyethylene in humans.

Animals↗

PubMed1997

In vitro human monocyte response to wear particles of titanium alloy containing vanadium or niobium.

Our aim was to determine whether in vitro studies would detect differences in the cellular response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 microm in diameter representative of those found adjacent to failed prostheses. Exposure of human monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10(7) particles/ml produced a mean prostaglandin E2 release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials.

Alloys↗

PubMed1997

Continuous passive motion after primary total knee arthroplasty. Does it offer any benefits?

We report a prospective randomly controlled trial to examine the effectiveness of continuous passive motion (CPM) in improving postoperative function and range of movement after total knee arthroplasty (TKA). We allocated 53 patients (57 knees) to one of three postoperative regimes: no CPM (n = 19); CPM at 0 to 40 degrees (0 to 40 CPM; n = 18); and CPM at 0 to 70 degrees (0 to 70 CPM; n = 20). Those in the CPM groups had CPM for 48 hours and all patients had an identical regime of physiotherapy. There was an even distribution of various cemented and cementless TKAs in each group. Patients were assessed preoperatively and at one week and at one year postoperatively. At one week, there was a statistically significant increase in the range of flexion and total range of movement in the 0 to 70 CPM group compared with the no-CPM group. At one year we found no significant differences in mean flexion, overall range of movement, fixed flexion deformity or functional results in the three groups. Those who had CPM had a significant increase in analgesic requirement (p = 0.04). There was an increased mean blood drainage postoperatively in those who had 0 to 70 CPM (1558 ml) compared with those with no CPM (956 ml) (t = 2.96, p = 0.005) and with 0 to 40 CPM (1017 ml) (t = 2.62, p = 0.01). Our findings show that CPM had no significant advantage in terms of improving function or range of movement, and that its use increased blood loss and analgesic requirements.

Aged↗

PubMed1997

Regulation of bone cells by particle-activated mononuclear phagocytes.

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAIV) stimulated MNP to release interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, IL-6 and prostaglandin E2 (PGE2). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteoblastic cells, was reduced. Experiments with blocking antibodies showed that TNFalpha was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1beta stimulated cell proliferation and differentiation. Both IL-1beta and TNFalpha stimulated IL-6 and PGE2 release from the osteoblast-like cells. Our results suggest that, particle-activated mononuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms.

Alkaline Phosphatase↗

PubMed1996

Drug inhibition of the macrophage response to metal wear particles in vitro.

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.

Ammonium Chloride↗

PubMed1996

Biologic effects of cobalt chrome in cell and animal models.

The literature on animal and cellular models used to study the response to cobalt chrome alloy implants and wear and corrosion products is reviewed. Animal studies show that in solid form cobalt chrome alloy is relatively well tolerated. Injections of large numbers of particles in a single bolus lead to acute inflammation and necrosis, followed by a chronic inflammatory response. Macrophages are the predominant cell type and may persist in the tissues for years. Long term studies have failed to confirm the induction of tumors. In vitro studies confirm the toxic effects of cobalt chrome alloy corrosion products and wear particles, especially cobalt, and show that intracellular corrosion is an important mechanism for early release of cobalt ions. In vitro studies show that cobalt chrome alloy particles induce the release of inflammatory mediators from macrophages before causing cell death. These mediators have significant effects on osteoblastlike cells, as well as inducing bone resorption. Variations in the cell types, implantation site, and characteristics of the particles used in experimental models make interpretation of the results difficult. Standardized methods to control for size, shape, and number of particles for testing are proposed. It is important that in vitro and in vivo findings not be taken in isolation, but be compared with the results of human studies.

Animals↗

PubMed1996

Treatment of humeral shaft fractures with the Seidel intramedullary nail.

BACKGROUND: The use of intremedullary nails for the management of humeral shaft fractures has been controversial. Recently, the Seidel nail has become available. The purpose of this study was to review our initial experience with the Seidel nail. METHODS: A retrospective clinical and radiographic review of 25 consecutive patients treated with Seidel intramedullary humeral nail was performed. The nail was used for non-union in 10 patients, delayed union in four, acute fracture in eight and pathological fracture in three. Eighteen of the 19 survivors were clinically reviewed at an average of 15 months (range 8-15). Pain, function, satisfaction, shoulder power, range of motion and clinical outcome were graded using the UCLA shoulder score. RESULTS: Pain was present at the shoulder in four patients and at the fracture site in nine. Average shoulder abduction was 99 degrees and nine patients could not abduct the shoulder past 90 degrees. Sixty-six percent of patients reviewed were graded as only fair or poor using the UCLA shoulder score. In three patients rotational control was not achieved with the distal locking device at the time of surgery. Complications included non-union in 10 patients and three intra-operative fractures. CONCLUSIONS: Non-union was more likely to occur if rotational control was not obtained, or if the patient had the nail inserted for a previous non-union. Use of the Seidel nail frequently leads to shoulder pain and dysfunction. The distal locking device is unreliable and predisposes to non-union. We do not recommend the continued use of the Seidel nail.

Adolescent↗

PubMed1993

A method for production and characterization of metal prosthesis wear particles.

The wear of joint prostheses generates wear particles that produce an inflammatory response in the surrounding tissues and may contribute to bone resorption resulting in prosthetic loosening. Although the effects of particles produced from prosthetic materials have been studied extensively in vitro and in vivo, little attention has been paid to the standardisation of methods for the generation and characterization of these particles. This paper describes a reproducible method for generation of metal particles by the abrasive shaking of joint replacement components. Particular attention was given to the production of metal particles that closely resembled particles found around solid and loose human prostheses. To achieve this, particle size, size distribution, chemical composition, and shape were characterized. Particles that were 0.5-3.0 microns in diameter were isolated by differential sedimentation, and the distribution of particle sizes was determined with use of a Coulter Multisizer. Chemical composition was measured by atomic absorption spectrophotometry, and transmission electron microscopy was used to characterize particle shape. The techniques were shown to be reproducible, since there was little variation between batches over a lengthy time period. These or similar methods of particle production and characterization should be an essential part of future in vitro and in vivo studies of wear particles.

Alloys↗