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Biomedical subjects

J D Blaha

Publications and source records attributed to J D Blaha.

At least 19 recordsLinked to original sources

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: finite element model.

Many cementless implant designs rely upon a diaphyseal press-fit in conjunction with a porous coated implant surface to achieve primary or short term fixation, thereby constraining interface micromotion to such a level that bone ingrowth and consequent secondary or long-term fixation, i.e., osseointegration, can occur. Bone viscoelasticity, however, has been found to affect stem primary stability by reducing push-out load. In this investigation, an axisymmetric finite element model of a cylindrical stem and diaphyseal cortical bone section was created in order to parametrically evaluate the effect of bone viscoelasticity on stem push-out while controlling coefficient of friction (mu = 0.15, 0.40, and 1.00) and stem-bone diametral interference (delta = 0.01, 0.05, 0.10, and 0.50 mm). Based on results from a previous study, it was hypothesized that stem-bone interference (i.e., press-fit) would elicit a bone viscoelastic response which would reduce the initial fixation of the stem as measured by push-out load. Results indicate that for all examined combinations of mu and delta, bone viscoelastic behavior reduced the push-out load by a range of 2.6-82.6% due to stress relaxation of the bone. It was found that the push-out load increased with mu for each value of delta, but minimal increases in the push-out load (2.9-4.9%) were observed as delta was increased beyond 0.10 mm. Within the range of variables reported for this study, it was concluded that bone viscoelastic behavior, namely stress relaxation, has an asymptotic affect on stem contact pressure, which reduces stem push-out load. It was also found that higher levels of coefficient of friction are beneficial to primary fixation, and that an interference "threshold" exists beyond which no additional gains in push-out load are achieved.

Computer Simulation↗

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: an in-vitro model.

Cementless total hip femoral components rely on press-fit for initial stability and bone healing and remodeling for secondary fixation. However, the determinants of satisfactory press-fit are not well understood. In previous studies, human cortical bone loaded circumferentially to simulate press-fit exhibited viscoelastic, or time dependent, behavior. The effect of bone viscoelastic behavior on the initial stability of press-fit stems is not known. Therefore, in the current study, push-out loads of cylindrical stems press-fit into reamed cadaver diaphyseal femoral specimens were measured immediately after assembly and 24 h with stem-bone diametral interference and stem surface treatment as independent variables. It was hypothesized that stem-bone interference would result in a viscoelastic response of bone that would decrease push-out load thereby impairing initial press-fit stability. Results showed that push-out load significantly decreased over a 24 h period due to bone viscoelasticity. It was also found that high and low push-out loads occurred at relatively small amounts of stem-bone interference, but a relationship between stem-bone interference and push-out load could not be determined due to variability among specimens. On the basis of this model, it was concluded that press-fit fixation can occur at relatively low levels of diametral interference and that stem-bone interference elicits viscoelastic response that reduces stem stability over time. From a clinical perspective, these results suggest that there could be large variations in initial press-fit fixation among patients.

Adult↗

Estrogen potentiates the combined effects of transforming growth factor-beta and tumor necrosis factor-alpha on adult human osteoblast-like cell prostaglandin E2 biosynthesis.

Reports that estrogen treatment modulates arachidonic acid metabolism by bone and bone cells are found in the literature. However, conflicting indications of the relationship that exists between estrogen and arachidonic acid metabolism emerge from the analysis of those reports. The present studies were undertaken to determine if estrogen effected the production of prostaglandins (PG) in human osteoblast-like (hOB) cell cultures derived from adults, under basal or cytokine-stimulated conditions. A 48-hour estrogen pretreatment did not modify hOB cell PG biosynthesis on a qualitative basis, and PGE2 formation predominated under all tested conditions. Estrogen pretreatment did lead to increased PGE2 production in specimens stimulated conjointly with transforming growth factor-beta1 and tumor necrosis factor-alpha ( p < 0.001). No changes in PGE2 production were observed in estrogen pretreated specimens stimulated singly with either tested cytokine, nor in samples in which either TGFbeta or TNF was replaced by interleukin-1beta. Anti-estrogen (ICI 164,384) inclusion prevented the estrogen-dependent increase in PGE2 production in the TGFbeta plus TNF-stimulated samples. These results suggest that an estrogen effect on bone cell prostaglandin biosynthesis may be most evident and significant under conditions in which the cells are exposed to multiple osteotropic cytokines, a condition that applies during the bone remodeling process.

Adult↗

Stem surface roughness alters creep induced subsidence and 'taper-lock' in a cemented femoral hip prosthesis.

The clinical success of polished tapered stems has been widely reported in numerous long term studies. The mechanical environment that exists for polished tapered stems, however, is not fully understood. In this investigation, a collarless, tapered femoral total hip stem with an unsupported distal tip was evaluated using a 'physiological' three-dimensional (3D) finite element analysis. It was hypothesized that stem-cement interface friction, which alters the magnitude and orientation of the cement mantle stress, would subsequently influence stem 'taper-lock' and viscoelastic relaxation of bone cement stresses. The hypothesis that creep-induced subsidence would result in increases to stem-cement normal (radial) interface stresses was also examined. Utilizing a viscoelastic material model for the bone cement in the analysis, three different stem-cement interface conditions were considered: debonded stem with zero friction coefficient (mu=0) (frictionless), debonded stem with stem-cement interface friction (mu=0.22) ('smooth' or polished) and a completely bonded stem ('rough'). Stem roughness had a profound influence on cement mantle stress, stem subsidence and cement mantle stress relaxation over the 24-h test period. The frictionless and smooth tapered stems generated compressive normal stress at the stem-cement interface creating a mechanical environment indicative of 'taper-lock'. The normal stress increased with decreasing stem-cement interface friction but decreased proximally with time and stem subsidence. Stem subsidence also increased with decreasing stem-cement interface friction. We conclude that polished stems have a greater potential to develop 'taper-lock' fixation than do rough stems. However, subsidence is not an important determinant of the maintenance of 'taper-lock'. Rather subsidence is a function of stem-cement interface friction and bone cement creep.

Aged↗

Cement penetration in the proximal femur does not depend on broach surface finish.

In a cadaver study, we prepared 29 paired human cadaver femora using 3 different broaches of identical geometry but different surface characteristics. In one group of 20 pairs, preparation with chipped-toothed broaches was compared to diamond-shaped broaches; in the other group of 9 pairs, polished tamps for compaction of cancellous bone were compared with chipped-tooth broaches. Cancellous bone was irrigated with 1 liter pulsed lavage. The specimens were embedded in specially-designed pots. Palacos R and Simplex bone cements were used. After vacuum mixing, the cement was applied in a retrograde manner and subjected to a standard pressure protocol with a constant force of 3,000 N. Radiographs were taken and horizontal sections were obtained at predefined levels using a diamond saw. Microradiographs were taken, digitized and analyzed to assess cement penetration into cancellous bone. In 6 of 9 femora prepared using smooth tamps, femoral fractures occurred despite careful preparation technique. The microradiographic evaluation showed no significant morphometric differences between diamond and chipped-tooth or between polished and chipped-tooth broaches with regard to cement penetration into cancellous bone. Therefore, in the presence of pulsed lavage, one finds no significant effect of broach surface characteristics on cement penetration into cancellous bone of the proximal end of the femur.

Absorption↗

Lavage technique in total hip arthroplasty: jet lavage produces better cement penetration than syringe lavage in the proximal femur.

Sixteen paired human cadaver femora were prepared using conventional broaches. Cancellous bone was irrigated with 1 L pulsed lavage in one femur and 1 L syringe lavage in the contralateral femur. The specimens were embedded in specially designed pots, and vacuum-mixed bone-cements were applied in a retrograde manner. After application of a standard pressure to the pots, the femora were removed and radiographed, and horizontal sections were obtained and analyzed to assess cement penetration into cancellous bone and the ratio of the area of supported to unsupported cancellous bone (Rcb). Our results show that in equal quality bone, the use of jet lavage yields significantly (P < .0001) improved cement penetration and Rcb compared with syringe lavage specimens. Jet lavage should be considered routine to achieve interdigitation with cancellous bone in cemented total hip arthroplasty.

Arthroplasty, Replacement, Hip↗

Arachidonic acid metabolism by adult human osteoblast-like cells exhibits sexually dimorphic characteristics.

The eicosanoids, including prostaglandin E2 (PGE2) and other bioactive arachidonic acid metabolites, are important local mediators of bone remodeling. Presumably, the limited or excessive synthesis of the eicosanoids could compromise bone homeostasis. We have noted that the stimulated release of arachidonic acid by adult male donor derived human osteoblast-like (hOB) cells exceeded the stimulated release measured for female-derived hOB cells by 1.5-fold. Assays of PGE2 biosynthesis by cytokine-stimulated hOB cells also demonstrated a sex-linked difference, such that male hOB cell PGE2 production exceeded female cell production by 1.6-2.2-fold. The calcium-dependent cytoplasmic phospholipase A2 activity in subcellular fractions prepared from hOB cell homogenates was higher in both the cytosolic (1.6-fold) and particulate (1.5-fold) fractions from the male cells than in those prepared from female hOB cells, suggesting a molecular basis for the observed sexually dimorphic characteristics related to arachidonic acid metabolism by hOB cells. The relatively limited capacity of the female cells may limit needed intracellular and intercellular signaling during bone remodeling, thereby contributing to the development of bone pathology.

Adult↗

1,25-Dihydroxyvitamin D3 pretreatment limits prostaglandin biosynthesis by cytokine-stimulated adult human osteoblast-like cells.

The steroid derivative 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a regulator of bone biology, and there is evidence that 1,25(OH)2D3 modulates arachidonic acid metabolism in osteoblastic cell model systems and in bone organ cultures. In the present studies, 1,25(OH)2D3 decreased prostaglandin (PG) biosynthesis by normal adult human osteoblast-like (hOB) cell cultures by about 30%. The decrease was observed under basal incubation conditions, or in specimens stimulated by transforming growth factor-beta 1 (TGF-beta) or by tumor necrosis factor-alpha (TNF). The inhibition of the TGF-beta-stimulated PG production appeared to reflect a diminished efficiency of arachidonic acid conversion into PGs by the cells, while the efficiency of substrate utilization for PG biosynthesis was unaffected by 1,25(OH)2D3 pretreatment in the unstimulated samples, or in samples stimulated with TNF or with TNF plus TGF-beta. Free arachidonic acid levels were decreased following 1,25(OH)2D3 pretreatment in the TNF stimulated samples. hOB cell phospholipase A2 activity was measured in subcellular fractions, and this activity was decreased by 20-25% in the 1,25(OH)2D3 pretreated samples. The addition of the selective inhibitor AACOCF3 to the phospholipase A2 assays provided evidence that it was the cytoplasmic isoform of the enzyme that was affected by the 1,25(OH)2D3 pretreatment of the hOB cells. Thus, 1,25(OH)2D3 regulation of hOB cell biology includes significant effects on arachidonic acid metabolism. In turn, this could influence the effects of other hormones and cytokines whose actions include the stimulated production of bioactive arachidonic acid metabolites.

Adult↗

Cytokine regulation of adult human osteoblast-like cell prostaglandin biosynthesis.

Prostaglandin (PG) biosynthesis by cytokine stimulated normal adult human osteoblast-like (hOB) cells was evaluated by thin layer chromatography, high performance liquid chromatography, and specific immunoassays. PGE2 was the predominant PG formed under all incubation conditions tested. Control samples produced measurable amounts of PGE2, and the measured level of this metabolite increased by 22-fold (from 7 to 152 ng/ml) following a 20 h treatment with the combination of TGF beta and tumor necrosis factor-alpha(TNF). The production of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) and of PGF2 alpha were each increased by about five-fold (from about 0.5 to 2.5 ng/ml) in samples treated with the cytokines. Thus, TGF beta and TNF exerted a regulation of hOB cell PG biosynthesis that was principally directed towards an increased PGE2 biosynthesis, with lesser effects on the production of other PG metabolites. COX-2 mRNA levels were increased within 2 h of cytokine stimulation, reached a maximum at 6-12 h, and levels had appreciably diminished by 24 h after treatment. Both TGF beta and TNF could independently increase COX-2 mRNA levels and PG biosynthesis. However, the increased production of PGE2 resulting from TNF stimulation was blocked by the addition of an interleukin-1 beta (IL-1 beta) neutralizing antibody, suggesting that TNF regulation of hOB cell PG synthesis was secondary to its capacity to increase hOB cell IL-1 beta production. TGF beta regulation of PG production was not affected by the addition of the neutralizing antibody. These studies support the proposition that PGs can be important autocrine/paracrine mediators of bone biology, whose production by hOB cells is responsively regulated by osteotropic cytokines.

Adult↗

Influence of delayed injection time on the creep behavior of acrylic bone cement.

It has been proposed that creep of acrylic bone cement may contribute to loosening of cemented total joint replacements. If true, it is important that factors affecting creep of bone cement are identified. The objective of this study was to evaluate the effect of an operator-controlled variable, injection time, on the creep behavior of acrylic bone cement. Results from this investigation showed that injection time significantly (p < 0.0001) influenced creep behavior of bone cement. "Delayed" injection time of acrylic bone cement increased creep by approximately 5 times in 24 h compared to specimens prepared according to standard injection procedures.

Acrylates↗

Estrogen pretreatment increases arachidonic acid release by bradykinin stimulated normal human osteoblast-like cells.

Eicosanoids are multifunctional autocrine/paracrine regulators of bone that are enzymatically derived from arachidonic acid (AA). The rate-limiting step in the eicosanoid biosynthetic pathways may be the release of AA from membrane glycerophospholipids by activated phospholipases. Free AA can serve as the substrate for cyclooxygenase(s) or lipoxygenases that catalyze the commitive steps in eicosanoid synthesis; alternatively, free AA may be used in reacylation processes, resulting in its reincorporation into cellular lipids. The hormones 17 beta-estradiol (17 beta-E2), dexamethasone (a synthetic glucocorticoid), and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have been identified as regulators of AA metabolism, at various levels, in several tissues including bone. The possibility that these osteotropic steroids modulate the availability of free AA in bone cells was studied in the human osteoblast-like (hOB) cell model system. Following a 48-h steroid pretreatment, bradykinin or the calcium ionophore A23187 were used as agonists to stimulate hOB cell release of AA. The principal findings from these investigations were that (1) 17 beta-E2 pretreatment potentiated the appearance of free AA following bradykinin stimulation of the cells but, did not alter their response to A23187 stimulation; (2) dexamethasone pretreatment limited bradykinin-induced increases in free AA levels but did not alter cell response to A23187 stimulation; (3) hOB cells derived from different trabecular bone compartments (manubrium of the sternum, femoral head) differed quantitatively in their responses to bradykinin stimulation of AA release; and (4) 1,25(OH)2D3 did not effect AA release stimulated by either agonist. The ability of the steroids to modulate AA release by hOB cells suggests that these hormones may indirectly mediate bone cell responses to other osteotropic hormones that act through eicosanoid-dependent processes.

Arachidonic Acid↗

Axisymmetric finite element analysis of a debonded total hip stem with an unsupported distal tip.

A tapered femoral total hip stem with a debonded stem-cement interface and an unsupported distal tip subjected to constant axial load was evaluated using two-dimensional (2D) axisymmetric finite element analysis. The analysis was performed to test if the mechanical condition suggest that a "taper-lock" with a debonded viscoelastic bone cement might be an alternative approach to cement fixation of stem type cemented hip prosthesis. Effect of stem-cement interface conditions (bonded, debonded with and without friction) and viscoelastic response (creep and relaxation) of acrylic bone cement on cement mantle stresses and axial displacement of the stem was also investigated. Stem debonding with friction increased maximum cement von Mises stress by approximately 50 percent when compared to the bonded stem. Of the stress components in the cement mantle, radial stresses were compressive and hoop stresses were tensile and were indicative of mechanical taper-lock. Cement mantle stress, creep and stress relaxation and stem displacement increased with increasing load level and with decreasing stem-cement interface friction. Stress relaxation occur predominately in tensile hoop stress and decreased from 1 to 46 percent over the conditions considered. Stem displacement due to cement mantle creep ranged from 614 microns to 1.3 microns in 24 hours depending upon interface conditions and load level.

Biomechanical Phenomena↗

Creep characteristics of hand- and vacuum-mixed acrylic bone cement at elevated stress levels.

Compressive creep testing of cylindrical specimens machined from two commercial self-polymerizing acrylic bone cements demonstrated measurable creep strains with higher creep strains for the hand-mixed cement specimens compared to vacuum-mixed cement ones. The average creep strains of hand-mixed cement, after 6 h of constant load, ranged from 0.11% at 10.5 MPa to 14.0% at 50 MPa of applied stress. Vacuum mixing reduced the average creep strain to 6.7% after 6 h of applied stress at 50 MPa. There were no significant differences in the creep response between the two types of acrylic cements. The difference in creep resistance of the two cements was reduced after vacuum mixing (P = .013), which also significantly reduced the cement's internal porosity.

Bone Cements↗

1,25-Dihydroxyvitamin D3 or dexamethasone modulate arachidonic acid uptake and distribution into glycerophospholipids by normal adult human osteoblast-like cells.

The effects of treatment with the osteotropic steroids 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 17 beta-estradiol, or dexamethasone on [1-14C]arachidonic acid (AA) uptake and distribution into glycerophospholipid classes by normal adult human osteoblast-like (hOB) cells were investigated. Total uptake of [1-14C]AA was decreased in cells treated with dexamethasone when assayed after a 24-, 48-, or 96-h exposure to the hormone. Specific radiolabel incorporation into phosphatidylcholine was reduced by a 48-h treatment with dexamethasone with a concurrent increase in the radiolabeling of phosphatidylethanolamine. However, these changes were transient, and by 96 h of dexamethasone treatment the distribution of the radiolabeled fatty acid had reequilibrated to resemble the pattern found for vehicle treated samples. Total uptake of [1-14C]AA was diminished by 96-h treatment with 1,25(OH)2D3 (79 +/- 3% of control, P < 0.01); at that time point, a significant decrease in the proportional radiolabeling of the phosphatidylinositol pool was identified (92 +/- 2% of control, P < 0.05). The 1,25(OH)2D3-dependent decrease in total uptake and in phosphatidylinositol incorporation of [1-14C]AA were found to be hormone dose dependent. Treatment with 24,25(OH)2D3 was without effect on either total [1-14C]AA uptake or the specific [1-14C]AA radiolabeling of the phosphatidylinositol pool. 1,25(OH)2D3 treatment decreased hOB cell uptake of [1-14C]oleic acid and decreased its proportional incorporation into the phosphatidylinositol pool. Gas chromatographic analyses revealed no 1,25(OH)2D3-dependent effects on total phosphatidylinositol lipid mass or on the mole percent of arachidonic acid within the phosphatidylinositol pool, leaving the mechanism of the effects of the secosteroid on hOB cell AA metabolism unexplained. 17 beta-Estradiol had no effects on the parameters of AA metabolism measured. As a consequence of their modulation of arachidonic acid uptake and its distribution into hOB cellular phospholipids, steroids might alter the biological effects of other hormones whose actions include the stimulated production of bioactive AA metabolites, such as prostaglandins or the various lipoxygenase products.

Adolescent↗

Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group.

A randomized, parallel-group, open-label clinical trial (the physicians, patients, and staff were not blinded with regard to the regimen that had been used) was conducted, between December 1988 and September 1990, to compare the safety and efficacy of enoxaparin, a low-molecular-weight heparin, with the safety and efficacy of unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. Six hundred and ten patients were randomized, and 607 patients received one of the study medications. The evaluations of efficacy included contrast-media venography, non-invasive vascular examination, and clinical examination. Data on efficacy were available for 604 patients, who had been assigned to one of three treatment groups: thirty milligrams of enoxaparin every twelve hours (194 patients), forty milligrams of enoxaparin once daily (203 patients), or 5000 units of unfractionated heparin every eight hours (207 patients). All drugs were administered subcutaneously. Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient. Treatment was initiated within twenty-four hours after the operation and continued for a maximum of seven days. The primary safety outcome was the occurrence of bleeding episodes. An intent-to-treat patient analysis revealed that deep venous thrombosis occurred in nine (5 per cent) of the 194 patients who received thirty milligrams of enoxaparin every twelve hours, thirty (15 per cent) of the 203 patients who received forty milligrams of enoxaparin once daily, and twenty-four (12 per cent) of the 207 patients who received unfractionated heparin. The rate of deep venous thrombosis was significantly lower in the group that received thirty milligrams of enoxaparin every twelve hours than in the group that received unfractionated heparin (p = 0.03) and in the group that received forty milligrams of enoxaparin once daily (p = 0.0002). No clinically symptomatic pulmonary embolism was observed during the treatment or follow-up phase of this study in the group that received thirty milligrams of enoxaparin every twelve hours. Analysis of evaluable patients revealed a marked reduction in the rate of deep venous thrombosis in the group that received thirty milligrams of enoxaparin every twelve hours (eight [6 per cent] of 136 patients) compared with the group that received heparin (twenty-one [15 per cent] of 145 patients) (p = 0.10); however, this difference was not significant because of the small number of patients included in this analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Histomorphometric assessment of the mechanisms for rapid ingrowth of bone to HA/TCP coated implants.

The purpose of this work is to use dynamic histomorphometry to evaluate the basic biological mechanisms by which hydroxyapatite/tricalcium phosphate (HA/TCP) implant coatings accelerate bone formation rates. Twenty-five rabbits had an HA/TCP coated cylindrical titanium fiber metal mesh implant surgically placed in the subchondral bone of the proximal tibia and a noncoated implant placed in the contralateral tibia. Twenty-two of these animals had HA/TCP coated cylindrical solid titanium implants placed in the distal femur and an uncoated implant placed in the contralateral femur. The animals were double labeled with vital stains, and sacrificed at 3, 6, 16, or 26 weeks after surgery. Histomorphometric analyses were done of the bone implant interfaces. Both static and dynamic histomorphometric parameters indicate that HA/TCP coatings stimulate faster bone ingrowth to coated fiber metal implants through the early production of woven bone and by subsequent rapid lamellar bone formation rates. Coated fiber metal implants demonstrated significantly more bone ingrowth than noncoated implants through 16 weeks postimplantation, but not by 26 weeks. In solid implants, the differences between coated and noncoated implants are less pronounced and not statistically significant, although there is a trend toward increased bone apposition to the surface of the implants over the first 16 weeks following implantation. The clinical significance of these results is that coated implants may allow earlier return to normal weightbearing.

Alloys↗