Tibial Implants Research Articles

Effect of thin nano-hydroxyapatite coating on implant osseointegration in ovariectomized rats

The purpose of this study was to investigate the effect of the thin nano-hydroxyapatite (nano-HA) coating on implant osseointegration in an ovariectomized rat model. Implants were divided into a control group and a test group (nano-HA-coated group). Surface morphology was examined using field-emission scanning electron microscopy (FSEM). Surface roughness of both groups was performed. Sixteen ovariectomized rats randomly received 2 implants in both tibiae. After 12 weeks of implantation, tibias were retrieved and prepared for histomorphometric evaluation and removal torque tests (RTQ). Rodlike crystals uniformly covered the porous surfaces and the surface morphology of the implant was still clear. No significant differences were found in surface roughness between the 2 groups (P > .05). More bone tissue was formed around test implants compared with control implants. Test implants showed a significantly greater BIC, bone area within all threads, and RTQ values compared with control implants (P < .05). These results indicate the thin nano-HA coating by an electrochemical process has potential benefits to enhance implant osseointegration in ovariectomized rats.

Osteoconductivity and Hydrophilicity of TiO2Coatings on Ti Substrates Prepared by Different Oxidizing Processes

Various techniques for forming TiO2 coatings on Ti have been investigated for the improvement of the osteoconductivity of Ti implants. However, it is not clear how the oxidizing process affects this osteoconductivity. In this study, TiO2 coatings were prepared using the following three processes: anodizing in 0.1 M H3PO4 or 0.1 M NaOH aqueous solution; thermal oxidation at 673 K for 2 h in air; and a two-step process of anodizing followed by thermal oxidation. The oxide coatings were evaluated using SEM, XRD, and XPS. The water contact angle on the TiO2 coatings was measured as a surface property. The osteoconductivity of these samples was evaluated by measuring the contact ratio of formed hard tissue on the implanted samples (defined as the R B-I value) after 14 d implantation in rats' tibias. Anatase was formed by anodizing and rutile by thermal oxidation, but the difference in the TiO2 crystal structure did not influence the osteoconductivity. Anodized TiO2 coatings were hydrophilic, but thermally oxidized TiO2 coatings were less hydrophilic than anodized TiO2 coatings because they lacked in surface OH groups. The TiO2 coating process using anodizing without thermal oxidation gave effective improvement of the osteoconductivity of Ti samples.

In vivo ciprofloxacin release from hydroxyapatite-based bone implants in rabbit tibia: a preliminary study.

The present study deals with the preliminary evaluation of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia. The HAp-ciprofloxacin implants (2 × 2.5 mm) were prepared using various HAp-ciprofloxacin composites synthesized by precipitation technique and 1.5% w/v guar gum as a binder. 5 implants were implanted in artificial cortical bone window at the right proximal tibia of each rabbit. After 3- and 6-day intervals, the rabbits were euthanized. Bone marrow and serum concentrations of ciprofloxacin were determined from the harvested tibia using HPLC method. The results displayed the availability of elevated local antibiotic concentration at the implanted site with the limitation of systemic antibiotic exposure, which can be useful to minimize the risk of systemic toxicity-related side effects. This study is the preliminary investigation of the suitability of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia, after implantation, and these implants can be useful for the treatment of bacterial bone infections like osteomyelitis.

Removal Torque Analysis of Implants in Rabbit Tibia After Topical Application of Simvastatin Gel

The aim of this study was to evaluate the effects of topical application of simvastatin gel (7.5 mg) on the removal torque of titanium implants in the rabbit tibia. A total of 32 surgeries were performed on 16 New Zealand rabbits for the placement of 2 implants in 1 tibia of each rabbit. Only 1 of the surgical defects was injected with 30 mg/mL of simvastatin gel before implant placement. The initial torque was set at 20 N.cm, and removal torque testing was performed 28 and 56 days postoperatively with a Tonishi torque wrench. Surgical defects were divided into 4 groups: group IG-28 (test, 28 days), group IG-56 (test, 56 days), group I-28 (control, 28 days), and group I-56 (control, 56 days). Removal torque values were higher in group IG-56 than in groups IG-28, I-28, and I-56 (P < .05). Groups IG-28, I-28, and I-56 showed similar values (P > .05). Removal torque force increased under the influence of simvastatin, indicating that topical administration of a 7.5-mg dose of simvastatin gel is effective in improving the torque force required to remove implants inserted in the rabbit tibia.

Effect of zoledronate acid treatment on osseointegration and fixation of implants in autologous iliac bone grafts in ovariectomized rabbits

One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be able to invert the negative effect of osteoporosis on osseointegration and fixation of dental implants in autologous bone grafts. In this study, 56 rabbits received bilateral ovariectomy (OVX) (40 rabbits) or sham operation (16 rabbits). Three months later, 8 animals from each group were sacrificed for bone mineral density (BMD) examination. Then the remaining animals underwent bilateral autologous iliac bone grafting with simultaneous implantation of titanium implants in tibiae and were divided into 5 groups (n=8): Sham, OVX, Loc-ZOL (local treatment), Sys-ZOL (systemic treatment) and Loc+Sys-ZOL (local plus systemic) group. At 3 months after implantation, all animals were sacrificed and specimens were harvested for examinations. Both BMD and histological examinations of femurs showed osteoporotic changes after ovariectomy, while systemic treatment with ZOL restored mineralized bone. Micro-CT examination demonstrated that OVX group showed significant decrease of mineralized bone and implant-bone contact when compared with sham control, whereas both systemic and local treatments of ZOL significantly increased mineralized bone and implant-bone contact in ovariectomized animals. However, the best effects were observed in Loc+Sys-ZOL group (combined use of ZOL) and most of bone indices were similar to (IBCR, p>0.05) or higher than (BV/TV, Conn.D and Tb.N) (p<0.01) those of the sham group, except Tb.Th, which was still significantly lower (p<0.01), and Tb.Sp, which was further decreased (p<0.01). The aforementioned effects were also confirmed by histomorphometric analysis of bone indices on implant-bone contact and mineralized bone. In addition, biomechanical testing further supported the beneficial effect of ZOL treatment and maximal removal torque of titanium implants was observed in Loc+Sys-ZOL group. In conclusion, our study suggests that both systemic and local treatments with ZOL can invert negative effect of osteoporosis and promote osseointegration and fixation of dental implants in autologous bone grafts under osteoporotic condition. Combined systemic and local use of ZOL exerts best effects when compared to their single use.

All-Polyethylene Tibial Implant in Young, Active Patients: A Concise Follow-Up, 10 to 18 years

This is a long-term follow-up report of all-polyethylene tibial components in 60 years and younger, active patients. At the mean follow-up of 12.4 ± 2.7 (range, 10-18 years), no more patients were deceased or lost to follow-up, leaving 32 patients (44 knees) for final analysis. Good to excellent results were achieved in 96% of patients. The mean Western Ontario and McMaster Universities Osteoarthritis Index and Knee Society Score were 31 and 97, respectively. Sixty-two percent of patients were participating in sport activities such as running, gym exercises, and playing tennis or golf, with a mean UCLA score of 7.2. There were no cases of malalignment, aseptic loosening, excessive wear, or osteolysis. Seven patients (9 knees) had incomplete, nonprogressive demarcation at the zone 1 tibial interface. Kaplan-Meier survivorship at 10 years for revision due to mechanical reasons and for all failures was 97.7% and 95.5%, respectively.

Mechanical Stability of Cementless Tibial Components in Normal and Osteoporotic Bone

There is renewed interest in cementless total knee arthroplasty, yet the optimal tibial design remains elusive. The purpose of this study is to evaluate the stability of various tibial component designs in normal and osteoporotic bone. Two cementless tibial implants, a CoCr beaded keeled baseplate and a two-pegged, highly porous titanium design underwent mechanical testing in normal and osteoporotic bone models. Decreased stability was observed in both designs in the osteoporotic model compared with "normal" bone (p < 0.0017). Stability of the keeled design was greater than the two-peg design in both densities; however, this difference was statistically significant only in the "normal" bone model (p = 0.005). This study demonstrates that cementless tibial component stability is affected by both implant design and host bone quality.

Hydroxyapatite (HA) coating appears to be of benefit for implant durability of tibial components in primary total knee arthroplasty

Background It is unclear whether there is a clinical benefit to adding hydroxyapatite (HA) coatings to total knee implants, especially with the tibial component, where failure of the implant more often occurs. A systematic review of the literature was undertaken to identify all prospective randomized trials for determining whether the overall clinical results (as a function of durability, function, and adverse events) favored HA-coated tibial components.Methods A comprehensive literature search was performed for the years 1990 to September 16, 2010. We restricted our search to randomized controlled trials involving participants receiving either an HA-coated tibia or other forms of tibial fixation. The primary outcome measures evaluated were durability, function, and acute adverse events.Results Data from 926 evaluable primary total knee implants in 14 studies were analyzed. Using an RSA definition for durability, HA-coated tibial components (porous or press-fit) without screw fixation were less likely to be unstable at 2 years than porous and cemented metal-backed tibial components (RR = 0.58, 95% CI: 0.34–0.98; p = 0.04, I2 = 39%, M-H random effects model). There was no significant difference in durability, as measured from revision and evaluated at 2 and 8–10 years, between groups. Also, functional status using different validated measures showed no significant difference at 2 and 5 years, no matter what measure was used. Lastly, there was no significant difference in adverse events. Limitations included small numbers of evaluable patients (≤ 50) in 7 of the 14 trials identified, and a lack of “hard” evidence of durability with need for replacement (i.e. frank failure, pain, or loss of functionality).Interpretation In patients > 65 years of age, an HA-coated tibial implant may provide better durability than other forms of tibial fixation. Larger trials should be undertaken comparing the long-term durability, function, and adverse events of HA-coated implants with those of other porous-coated tibial implants in younger, more active OA patients.

Vertical Bone Augmentation With Simultaneous Implant Placement Using Particulate Mineralized Bone and Mesenchymal Stem Cells: A Preliminary Study in Rabbit

This study aimed to assess vertical bone augmentation with simultaneous implant placement in rabbit tibiae using particulate mineralized bone/fibrin glue/mesenchymal stem cell. Bone marrow was aspirated from tibiae of five 10-week-old New Zealand White male rabbits. Right and left tibiae of each rabbit were prepared, and a 3-mm protruding implant from tibial bone was placed in each side. Particulate allogenic bone/fibrin glue/mesenchymal stem cell combination was placed around test implants and particulate bone graft/fibrin glue around controls. Two months postoperatively, the animals were euthanized, and sections were prepared for histological analysis. The mean amount of vertical bone length was higher in the experimental group than the control group (2.09 mm vs 1.03 mm; P < .05). New supracrestal trabecular bone formation was also significantly higher in the test group (28.5 ± 4.5% vs 4.3 ± 1.8%; P < .05). Mesenchymal stem cell/particulate allograft/fibrin glue appears to be a promising combination for vertical bone augmentation around simultaneously inserted implants in rabbit tibia.

Osteoconductivity of thermal-sprayed silver-containing hydroxyapatite coating in the rat tibia

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement. At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating. These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.

Nanostructured model implants for in vivo studies: influence of well-defined nanotopography on de novo bone formation on titanium implants

An implantable model system was developed to investigate the effects of nanoscale surface properties on the osseointegration of titanium implants in rat tibia. Topographical nanostructures with a well-defined shape (semispherical protrusions) and variable size (60 nm, 120 nm and 220 nm) were produced by colloidal lithography on the machined implants. Furthermore, the implants were sputter-coated with titanium to ensure a uniform surface chemical composition. The histological evaluation of bone around the implants at 7 days and 28 days after implantation was performed on the ground sections using optical and scanning electron microscopy. Differences between groups were found mainly in the new bone formation process in the endosteal and marrow bone compartments after 28 days of implantation. Implant surfaces with 60 nm features demonstrated significantly higher bone-implant contact (BIC, 76%) compared with the 120 nm (45%) and control (57%) surfaces. This effect was correlated to the higher density and curvature of the 60 nm protrusions. Within the developed model system, nanoscale protrusions could be applied and systematically varied in size in the presence of microscale background roughness on complex screw-shaped implants. Moreover, the model can be adapted for the systematic variation of surface nanofeature density and chemistry, which opens up new possibilities for in vivo studies of various nanoscale surface-bone interactions.

Importance of Ca2+ Modifications for Osseointegration of Smooth and Moderately Rough Anodized Titanium Implants – A Removal Torque and Histological Evaluation in Rabbit

Incorporation of Ca(2+) into the titania of anodized titanium surfaces has been found to enhance osseointegration. It provides a stable surface when the ions are incorporated into the oxide layer during the anodizing process. The Ca(2+) may suggestively be prominent sites for mineral induction, attract proteins, and catalyze intracellular cascades. The aim of the present study was to evaluate the osseointegration of smooth (S(a) < 0.5 µm) and moderately rough (S(a) 1.0-2.0 µm) commercially pure titanium implants, with and without Ca(2+) , in order to reflect on the importance of surface chemistry in relation to topography. Anodized implants with (OxCa) or without Ca(2+) (Ox), blasted implants (Bl), and blasted anodized implants, with (BlOxCa) or without Ca(2+) (BlOx), were inserted in rabbit femur and tibia. The implant surfaces were characterized using interferometry, scanning electron microscopy, and X-ray photoelectron spectroscopy prior to implant installation. Removal torque (RTQ) measurements were executed on all implants after a healing period of 12 weeks. The implants were, thereafter, removed en bloc with surrounding tissues and prepared for histological evaluations. RTQ measurements of tibial implants revealed significantly higher values for BlOxCa implants (90.7 ± 23.3 Ncm) compared to OxCa (64.6 ± 18.2 Ncm) and BlOx implants (69.7 ± 17.5 Ncm) (p = 0.029). Ca(2+) modification of smooth implants placed in the femur did not reveal any differences. Ca(2+) modification of smooth implants resulted in similar interfacial shear strength as moderately rough implants and Ca(2+) modification of moderately rough implants demonstrated the significantly strongest interfacial shear strength when placed in rabbit tibia. This possibly demonstrated surface chemistry compensating for lesser roughness.

Bone bonding bioactivity of Ti metal and Ti–Zr–Nb–Ta alloys with Ca ions incorporated on their surfaces by simple chemical and heat treatments

Ti15Zr4Nb4Ta and Ti29Nb13Ta4.6Zr, which do not contain the potentially cytotoxic elements V and Al, represent a new generation of alloys with improved corrosion resistance, mechanical properties, and cytocompatibility. Recently it has become possible for the apatite forming ability of these alloys to be ascertained by treatment with alkali, CaCl2, heat, and water (ACaHW). In order to confirm the actual in vivo bioactivity of commercially pure titanium (cp-Ti) and these alloys after subjecting them to ACaHW treatment at different temperatures, the bone bonding strength of implants made from these materials was evaluated. The failure load between implant and bone was measured for treated and untreated plates at 4, 8, 16, and 26weeks after implantation in rabbit tibia. The untreated implants showed almost no bonding, whereas all treated implants showed successful bonding by 4weeks, and the failure load subsequently increased with time. This suggests that a simple and economical ACaHW treatment could successfully be used to impart bone bonding bioactivity to Ti metal and Ti–Zr–Nb–Ta alloys in vivo. In particular, implants heat treated at 700°C exhibited significantly greater bone bonding strength, as well as augmented in vitro apatite formation, in comparison with those treated at 600°C. Thus, with this improved bioactive treatment process these advantageous Ti–Zr–Nb–Ta alloys can serve as useful candidates for orthopedic devices.

Retracted: Melatonin stimulates the growth of new bone around implants in the tibia of rabbits

This study evaluated the effect of the topical application of melatonin in accelerating bone formation associated with implants 2 months after their application to the tibiae of rabbits. Twenty New Zealand rabbits were used. Twenty implants treated with melatonin and 20 control implants without melatonin were placed in the proximal metaphyseal area of each tibia. Studies of new bone formation were subsequently made at 15, 30, 45 and 60 days. Cortical width and cortical length of new bone formation were measured. Following implantation, an anteroposterior and lateral radiologic study was carried out. Collected samples were sectioned at 5 μm and stained using hematoxylin-eosin, Masson's trichromic and Gordon-Switt reticulin stains. After a 60 day treatment period, melatonin increased the length of cortical bone (95.13±0.42%) versus that around control implants (62.91±1.45%). Related to the perimeter of cortical bone of the tibiae, melatonin induced new bone 88.35±1.56% versus 60.20±1.67% in the control implants. Melatonin regenerated the width and length of cortical bone around implants in tibiae of rabbits more quickly than around control implants without the addition of melatonin.

A FUNCTIONAL AND ROENTGENOGRAPHIC PRELIMINARY COMPARATIVE STUDY USING METAL-BACKED AND ALL-POLYETHYLENE TIBIAL COMPONENTS IN TOTAL KNEE ARTHROPLASTY

Objective: To describe and clinically and radiographically compare patients who underwent total knee arthroplasty (TKA) with all-polyethylene (ALP) and metal-backed (MTB) tibial implants. Methods: Patients who underwent TKA between January 1988 and December 2004 were grouped according to the type of implant received: all-polyethylene or metal-backed. Sixty patients came for evaluations, totaling 82 operated knees. Among these, 22 patients had undergone TKA only with ALP (12 unilateral and 10 bilateral cases), 33 patients only with MTB (26 unilateral and 7 bilateral cases) and five patients underwent TKA with ALP in one knee and MTB in the other. The knees were divided thus: group 1, 37 knees with ALP; and group 2, 45 knees with MTB. Results: There were no differences in clinical or functional evaluations between the groups. The mean radiolucency in the femur was 0.838 mm for the patients in group 1 and 0.356 mm for the patients in group 2 (p = 0.049). For the tibia, in the AP view, there was a mean value of 2.703 mm for group 1 and 0.733 mm for group 2 (p = 0.000). In the lateral view, the mean values for osteolysis was 0.405 mm for group 1 and 0.200 mm for group 2 (p = 0.074). Conclusions: There were no differences between the groups in the functional and clinical evaluations. However, greater radiolucency was observed in the arthroplasties with ALP, both in the femur in the lateral view and in the tibia in the AP view. Level of evidence IV – case series study.

Imageless computer assisted versus conventional total knee replacement. A Bayesian meta-analysis of 23 comparative studies

We have undertaken a meta-analysis of the English literature, to assess the component alignment outcomes after imageless computer assisted (CAOS) total knee arthroplasty (TKA) versus conventional TKA. We reviewed 23 publications that met the inclusion criteria. Results were summarised via a Bayesian hierarchical random effects meta-analysis model. Separate analyses were conducted for prospective randomised trials alone, as well as for all randomised and observational studies. In 20 papers (4,199 TKAs) we found a reduction in outliers rate of approximately 80% in limb mechanical axis when operated with the CAOS. For the coronal femoral and tibial implants positions, the analysis included 3,058 TKAs. The analysis for the femoral implant showed a reduction in outliers rate of approximately 87% and for the tibial implant a reduction in outliers rate of approximately 80%. Imageless navigation when performing TKA improves component orientation and postoperative limb alignment. The clinical significance of these findings though has to be proven in the future.

Unicondylar knee replacement with a new tensioner device: clinical results of a multicentre study on 168 cases

Ligament balancing is an established surgical technique in total knee arthroplasty with good clinical results. A similar technique for unicondylar knee arthroplasty was developed. The aim of this study was to asses the outcomes of a unicondylar knee replacement implanted with a ligament tensor. A prospective multicentre study of 168 medial compartment unicondylar knee prosthesis with a minimum follow-up of 2 years. Clinically, the knee society score was recorded. For subjective assessment, the visual analogue scale (VAS) for pain and satisfaction was used. Radiographic analysis was performed to determine radiolucent lines. The surgical technique was based on a ligament-orientated procedure. With this technique, the femoral orientation, flexion/extension gaps and limb alignment is determined with a unique ligament tensor. The total KSS increased from 110.9 +/- 27.5 points preoperative to 176.5 +/- 21.1 points after 24 months. VAS for pain decreased from 6.0 +/- 1.9 preoperative to 2.8 +/- 1.7 after 24 months. VAS for satisfaction increased in the same period from 4.3 +/- 1.9 to 8.9 +/- 1.7. Four tibia implants had thin continuous radiolucent lines. Nine adverse events are reported. One patient died of unrelated causes. Five polyethylene inlays dislocated, one of five dislocated due to a fall. Three unicondylar knee prostheses were revised to a total knee arthroplasty, one because of undiagnosed pain, one for infection and one for femoral component malalignment. We have demonstrated the efficacy of a tension-controlled ligament-balanced surgical technique for unicompartmental knee prosthesis that gives satisfying and reproducible short-term results.

The effect of a single remote injection of statin-impregnated poly (lactic- co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia

The aim of this study was to evaluate the effects of newly developed injectable poly (lactic- co-glycolic acid) (PLGA) microspheres containing fluvastatin on osteogenesis around titanium implants in the rat tibia. After confirmation of the sustained-release profile of fluvastatin from the microspheres by an in vitro assay, the microspheres were administered to the back skin of the rats by a single transdermal injection. At 2 and 4 weeks after the implant surgery, the fluvastatin groups showed enhanced new bone formation around the titanium implants without any influence on the serum biochemistry. In addition, the fluvastatin groups showed increased three-point bending strengths of their femurs. The results of this study indicate that a single remote injection of PLGA/fluvastatin microspheres safely and successfully stimulated bone formation around titanium implants and increased the mechanical properties of bone.

Degradation behaviour and mechanical properties of magnesium implants in rabbit tibiae

To investigate the initial mechanical strength and the degradation behaviour with the associated changes in mechanical properties of magnesium-based osteosynthesis implants, 30 rabbits were implanted with cylindrical pins of the alloys MgCa0.8 (magnesium with 0.8 wt% calcium), LAE442 (magnesium with 4 wt% lithium, 4 wt% aluminium and 2 wt% rare earths) and WE43 (magnesium with 4 wt% yttrium and 3 wt% rare earths). The implants were inserted into the medullary cavity of both tibiae. After 3 and 6 months, each half of the animals was euthanized, respectively, and the implants were taken out. A determination of volume, three-point bending tests, scanning electron microscopy (SEM) and energy dispersive X-ray analyses as well as metallographic and μ-computed tomography examinations were accomplished. All implants were clinically well tolerated. MgCa-implants showed the least initial strength and the highest loss in volume after 6 months. SEM- and μ-computed tomography examinations revealed a pronounced pitting corrosion. Therefore, their use as degradable implant material seems to be limited. LAE442 has the best initial strength which seems to be sufficient for an application in weight-bearing bones. The degradation behaviour is very constant. However, possible unknown side effects of the rare earths have to be excluded in further investigations on biocompatibility. Considering all results of WE43, its application as osteosynthesis material for fracture repair is ineligible due to its heterogeneous and unpredictable degradation behaviour.

Simvastatin enhances bone formation around titanium implants in rat tibiae

Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0.125, 1, 5 or 10 mg kg(-1) of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0.125 and 1 mg kg(-1) groups. In contrast, in both the 5 and 10 mg kg(-1) groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0.01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg(-1) or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated.