载阿仑膦酸钠骨水泥抑制钛磨屑诱导的假体周围骨溶解

目的 比较载阿仑膦酸钠丙烯酸骨水泥与皮下注射阿仑膦酸钠抑制钛磨眉诱导的骨溶解的效果.方法 48只成年雄性新西兰兔随机均分为无钛磨屑且无阿仑膦酸钠组(A组),有钛磨屑注射且无阿仑膦酸钠组(B组),钛磨屑分别注射0.1%、0.5%、1.0%载阿仑膦酸钠丙烯酸骨水泥组(C、I)、E组),钛磨屑注射且皮下手射阿仑膦酸钠组(F组),每组8只.将载阿仑膦酸钠骨水泥植入兔股骨远端.制备磨屑诱导骨溶解动物模型.术后8周对股骨行组织形态学分析、骨密度(bone mineral density,BMD)测定及界面力学测试结果 B组假体周围可见明显的骨溶解,而C、D、E、F组骨溶解明显少于B组.B组假体周围BMD和骨-骨水泥界面抗剪强度分别较A组下降17%和56%;D组假体周围BMD和界面抗剪强度较B组分别增加29%和62%;E组假体周围BMD和界画抗剪强度较B组分别增加37%和29%;F组假体周围BMD和界面抗剪强度较B组分别增加51%和69%;C组、D组、E组分别与F组比较,假体周围BMD和界面抗剪强度的差异均无统计学意义.结论 载阿仑瞵酸钠丙烯酸骨水泥与皮下注射阿仑瞵酸钠均可在一定程度上抑制磨屑诱导的骨吸收,增强界画抗剪强度.     

Antibacterial efficacy of a new gentamicin‐coating for cementless prostheses compared to gentamicin‐loaded bone cement

Cementless prostheses are increasingly popular but require alternative prophylactic measures than the use of antibiotic‐loaded bone cements. Here, we determine the 24‐h growth inhibition of gentamicin‐releasing coatings from grit‐blasted and porous‐coated titanium alloys, and compare their antibacterial efficacies and gentamicin release‐profiles to those of a commercially available gentamicin‐loaded bone cement. Antibacterial efficacy increased with increasing doses of gentamicin in the coating and loading with 1.0 and 0.1 mg gentamicin/cm² on both grit‐blasted and porous‐coated samples yielded comparable efficacy to gentamicin‐loaded bone cement. The coating had a higher burst release than bone cement, and also inhibited growth of gentamicin‐resistant strains. Antibacterial efficacy of the gentamicin coatings disappeared after 4 days, while gentamicin‐loaded bone cement exhibited efficacy over at least 7 days. Shut‐down after 4 days of gentamicin‐release from coatings is advantageous over the low‐dosage tail‐release from bone cements, as it minimizing risk of inducing antibiotic‐resistant strains. Both gentamicin‐loaded cement discs and gentamicin‐coated titanium coupons were able to kill gentamicin‐sensitive and ‐resistant bacteria in a simulated prothesis‐related interfacial gap. In conclusion, the gentamicin coating provided similar antibacterial properties to those seen by gentamicin‐loaded bone cement, implying protection of a prosthesis from being colonized by peri‐operatively introduced bacteria in cementless total joint arthroplasty. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1654–1661, 2011     

Low-magnitude high-frequency loading via whole body vibration enhances bone-implant osseointegration in ovariectomized rats

Osseointegration is vital to avoid long‐time implants loosening after implantation surgery. This study investigated the effect of low‐magnitude high‐frequency (LMHF) loading via whole body vibration on bone‐implant osseointegration in osteoporotic rats, and a comparison was made between LMHF vibration and alendronate on their effects. Thirty rats were ovariectomized to induce osteoporosis, and then treated with LMHF vibration (VIB) or alendronate (ALN) or a control treatment (OVX). Another 10 rats underwent sham operation to establish Sham control group. Prior to treatment, hydroxyapatite (HA)‐coated titanium implants were inserted into proximal tibiae bilaterally. Both LMHF vibration and alendronate treatment lasted for 8 weeks. Histomorphometrical assess showed that both group VIB, ALN and Sham significantly increased bone‐to‐implant contact and peri‐implant bone fraction (p < 0.05) when compared with group OVX. Nevertheless the bone‐to‐implant contact and peri‐implant bone fraction of group VIB were inferior to group ALN and Sham (p < 0.05). Biomechanical tests also revealed similar results in maximum push out force and interfacial shear strength. Accordingly, it is concluded that LMHF loading via whole body vibration enhances bone‐to‐implant osseointegration in ovariectomized rats, but its effectiveness is weaker than alendronate. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:733–739, 2012     

Local administration of alendronate reduced peri‐tunnel bone loss and promoted graft‐bone tunnel healing with minimal systemic effect on bone in contralateral knee

Continued systemic administration of alendronate was reported to reduce peri‐tunnel bone resorption and promoted graft‐bone tunnel healing at the early stage post‐anterior cruciate ligament (ACL) reconstruction. However, systemic increase in bone mineral density (BMD) in the contralateral intact knee was observed. We tested if single local administration of alendronate into the bone tunnel during ACL reconstruction could achieve similar benefits yet without the systemic effect on bone. Seventy‐two rats with unilateral ACL reconstruction were divided into three groups: saline, low‐dose (6 μg/kg) and mid‐dose (60 μg/kg) alendronate. For local administration, alendronate was applied to the bone tunnels for 2 min before graft insertion and repair. At weeks 2 and 6, the reconstructed complex was harvested for high‐resolution computed tomography (vivaCT) imaging followed by biomechanical test or histology. Our results showed that local administration of low‐dose alendronate showed comparable benefits on the reduction of peri‐tunnel bone loss, enhancement of bone tunnel mineralization, tunnel graft integrity, graft osteointegration and mechanical strength of the reconstructed complex at early stage post‐reconstruction, yet with minimal systemic effect on mineralized tissue at the contralateral intact knee. A single local administration of alendronate at the low‐dose therefore might be used to promote early tunnel graft healing post‐reconstruction. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1897–1906, 2013     

Inhibition of particulate debris-induced osteolysis by alendronate in a rat model.

A rat model was used to study the efficacy of alendronate therapy in inhibition of particle-induced periprosthetic osteolysis. A prosthesis was simulated by inserting a cylindrical polymethylmethacrylate plug into the distal femur of 24 rats allowing the plug to communicate with the joint space. Intra-articular injections of irregularly-shaped ultra-high molecular weight polyethylene particles of 20-200 pm in diameter were administered at 2-week intervals. The rats were randomized into two groups (n=12 each). Group A rats received twice weekly subcutaneous injections of alendronate sodium while group B rats received injections of saline vehicle only. At 10 weeks all rats were sacrificed. The distal femurs were harvested and axial sections were prepared for histologic analysis. Each section was graded on a scale of 1-4, quantifying the degree of osteolysis surrounding the polymethylmethacrylate plug. Microscopic examination showed a significant (P<.0001) difference in the amount of periprosthetic bone. Femurs from group A treated with alendronate demonstrated mostly normal or near-normal periprosthetic trabeculations, whereas femurs from group B treated with saline showed extensive bone resorption. There was no qualitative difference in the inflammatory cellular response between the groups. This study established the ability of alendronate to inhibit the osteoclastic-mediated osteolysis around joint implants.     

Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle‐induced implant loosening: Evidence from a rat model

Particle‐induced implant loosening is a major challenge to long‐term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early‐stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri‐implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri‐implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri‐implant osteolysis. Implant fixation and peri‐implant bone mass were evaluated using biomechanical testing, micro‐CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push‐out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri‐implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri‐implant osteolysis, resulting in improved implant fixation and increased peri‐implant bone volume. Clinical significance: The innovative application of sequential treatment in peri‐implant osteolysis could be used clinically to improve the prognosis of patients with early‐stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489–1497, 2019.     

Effects of alendronate on particle-induced osteolysis in a rat model

BACKGROUND: Particle-induced osteolysis is currently a major problem affecting the long-term survivorship of total joint replacements. Alendronate is a third-generation bisphosphonate that blocks osteoclastic bone resorption. The objective of this study was to determine whether alendronate could prevent particle-induced osteolysis or restore (reverse) bone loss in established osteolysis. METHODS: A rat model of particle-induced osteolysis was used. A specially designed polyethylene implant was placed in the proximal part of the right tibia of seventy-two animals. Following four weeks of healing, the animals were randomized into control groups, a prevention group, or a treatment group. In the prevention group, animals received intra-articular injections of high-density polyethylene particles (mean size, 2 m; all <10 m) at four, six, and eight weeks postoperatively. Alendronate (0.01 mg/kg/day) was administered concomitantly through an implantable pump from the fourth week through the tenth week. In the treatment group, animals were also exposed to polyethylene particles at four, six, and eight weeks, to establish bone loss, but they received alendronate subsequently, from the tenth week through the sixteenth week, to treat the bone loss. Positive (particle-only) and negative (saline-solution-only) control groups were assessed as well. Tissues were harvested at ten weeks in the prevention group and at sixteen weeks in the treatment group. Histological analyses and histomorphometric determinations of the periprosthetic bone volume were carried out. RESULTS: Histological examination showed a rim of new bone (neocortex) around the implant in the untreated and saline-solution-treated control animals (no polyethylene particles). Treatment with saline solution (no polyethylene particles) did not affect periprosthetic bone. Animals exposed to polyethylene particles had bone loss. In those that received alendronate, the bone loss was either prevented or reversed, and the quantity of neocortical and trabecular bone was increased compared with that of the controls. Alendronate effectively preserved periprosthetic bone in both the prevention and treatment groups. In the prevention arm, the mean periprosthetic bone volume of the neocortex and the surrounding trabecular bone, as determined with histomorphometry, was 21.5% +/- 6.5% in the saline-solution-treated controls (no particles), 13.1% +/- 5.9% in the particle-treated animals, and 32.6% +/- 6.4% in the alendronate-treated animals (p < 0.001). In the treatment arm, the mean periprosthetic bone volume was 27.2% +/- 5.6% in the saline-solution-treated controls, 17.7% +/- 6.2% in the particle-treated animals, and 30.2% +/- 5.9% in the alendronate-treated animals (p = 0.002). CONCLUSIONS: In our model, the intra-articular injection of polyethylene particles caused substantial bone loss around a loaded implant. Alendronate effectively prevented and treated the particle-induced periprosthetic bone loss.     

Zementfreier Femurschaftwechsel mit der Modularen Revisions Prothese MRP-TITAN-Revisionsschaft

OBJECTIVE: Restoration of a painless hip joint capable of bearing weight by uncemented implantation of a rotationally stable, modular revision stem anchored in the diaphysis. INDICATIONS: Prosthetic stem loosening with osteolytic bone defects (defect classification types I-III according to Paprosky). Material failure with broken prosthesis. Sub- and/or periprosthetic femoral fractures. Tumors. CONTRAINDICATIONS: Extensive osteolysis preventing diaphyseal anchorage of the prosthesis. SURGICAL TECHNIQUE: Transgluteal approach to the hip joint. Removal of the loose prosthetic stem and, if cemented, the bone cement as well. Excision of intramedullary granulation tissue. Reaming of the medullary cavity with flexible reaming shafts and form-fit, uncemented implantation of the star-shaped modular revision stem with diaphyseal press fit. If there is extensive loss of metaphyseal bone stock, augmentation with autogenous/allogenic bone should be performed. POSTOPERATIVE MANAGEMENT: Mobilization on two underarm crutches from the 1st postoperative day. Removal of the Redon drains after 48 h. Partial loading with 20 kg for 6 weeks postoperatively. If plain radiographs show unchanged seating of the prosthesis after 6 weeks, loading can be increased by 10 kg per week until full weight bearing is achieved; thrombosis prophylaxis is continued throughout. Radiologic checkups after 3, 6, and 12 months. After that, the patient should be checked annually. RESULTS: 45 patients (n = 48 prostheses) with an average age of 67.2 years (min.-max. 42.4-87.4 years) were investigated. The average implantation time of the Modular Revision Prosthesis MRP-TITAN revision stem was 4.7 years (min.-max. 1.0-9.0 years). The Harris Hip Score for Paprosky bone defect types I-III had increased from 25.6 preoperatively to 71.4 postoperatively at the time of the final follow-up (< or = 0.05). Extensively defective bone was diagnosed preoperatively in 32 patients (> or = Paprosky IIB). Plain radiographs showed stable anchorage without migration in 44 patients. In one case, the stem (implantation time 2.36 years) was replaced due to increasing axial subsidence (> or = 5 mm). Good integration of bone graft with subsequent defect regeneration was seen in all patients with bone transplant (n = 30). Postoperative dislocation occurred in six patients and required closed reduction in four cases. Open reduction was performed in two patients, whereby the external rotation angle of the prosthetic neck was corrected without dismantling the distally anchored prosthetic stem components. The mechanical failure rate over the follow-up period of 9 years was one out of the 48 prospectively investigated prostheses. Rate of survival according to Kaplan-Meier was 97%.     

Efficacy of etanercept for wear debris-induced osteolysis.

A major limitation of total joint arthroplasty is that up to 20% of patients require revision surgery to correct prosthetic loosening. Aseptic loosening is believed to result from the phagocytosis of wear debris particles by macrophages, which secrete proinflammatory cytokines that stimulate osteolysis. Tumor necrosis factor alpha (TNF-alpha) has been shown to be one of the prominent cytokines in this cascade and to be involved critically in the generation of particle-induced osteolysis. Etanercept is a soluble inhibitor of TNF-alpha, which is widely used for the treatment of rheumatoid arthritis. Here, we show this agent's ability to prevent wear debris-induced osteolysis. In vitro we show that Etanercept can inhibit directly osteoclastic bone resorption in a bone wafer pit assay, as well as cytokine production from titanium (Ti)-stimulated macrophages. Using a quantitative in vivo model of wear debris-induced osteolysis, we show that Etanercept prevents bone resorption and osteoclastogenesis. In mice treated with Etanercept at the time of osteolysis induction, bone resorption and osteoclast numbers were reduced to background levels in both normal and human TNF-alpha (hTNF-alpha) transgenic mice. In an effort to evaluate its effect on established osteolysis, Etanercept was administered 5 days after Ti implantation, and we observed that further osteolysis was prevented. These data support the concept that TNF-alpha is involved critically in osteoclastogenesis and bone resorption during periprosthetic osteolysis and suggest that soluble TNF-alpha inhibitors may be useful as therapeutic agents for the treatment of prosthetic loosening in humans.     

Alendronate did not inhibit instability-induced bone resorption : A study in rats

Alendronate is a bisphosphonate that can decrease osteoclastic activity. It has been suggested as treatment for periprosthetic osteolysis. We used 48 rats, of which 32 had a plate implant on one tibia, to study the effect of alendronate on bone resorption at an unstable implant-bone interface. The plate has a handle on top, which can be grasped through the skin and turned, to create a sliding motion of a titanium surface against the underlying bone. This is known to result in bone resorption, which was studied by histomorphometry. Osmotic minipumps were used to administer alendronate at 0.063 mg/kg/day or saline. The systemic effect of the treatment was assessed by ashing the proximal metaphyses of the tibia of the contralateral unoperated leg. The ash-weight was increased in the alendronate-treated group by 43% (p = 0.0001), corresponding to histological changes in the metaphyseal bone. There was no inhibition of the instability-induced bone resorption at the test surface by alendronate: bone was being resorbed and replaced by a tissue similar to a loosening membrane.     

Alendronate did not inhibit instability-induced bone resorption. A study in rats

Alendronate is a bisphosphonate that can decrease osteoclastic activity. It has been suggested as treatment for periprosthetic osteolysis. We used 48 rats, of which 32 had a plate implant on one tibia, to study the effect of alendronate on bone resorption at an unstable implant-bone interface. The plate has a handle on top, which can be grasped through the skin and turned, to create a sliding motion of a titanium surface against the underlying bone. This is known to result in bone resorption, which was studied by histomorphometry. Osmotic minipumps were used to administer alendronate at 0.063 mg/kg/day or saline. The systemic effect of the treatment was assessed by ashing the proximal metaphyses of the tibia of the contralateral unoperated leg. The ash-weight was increased in the alendronate-treated group by 43% (p = 0.0001), corresponding to histological changes in the metaphyseal bone. There was no inhibition of the instability-induced bone resorption at the test surface by alendronate: bone was being resorbed and replaced by a tissue similar to a loosening membrane.     

Murine model of prosthesis failure for the long-term study of aseptic loosening.

We examined a novel mouse model of wear debris-induced prosthesis instability and osteolysis, and its application for the evaluation of therapy. A stainless steel or titanium-alloy pin was implanted into the proximal tibia to form a contiguous surface with the articular cartilage. In some mice, titanium particles were injected into the tibial canal during the surgery, followed by monthly intraarticular injection. MicroCT scans revealed that the implants without particle challenge were stable without bone mineral density changes for 6 months. Histological analysis showed new bone formation around the implant at 6 weeks postsurgery. Periprosthetic soft tissue with inflammatory cells was a ubiquitous finding at the interface between the implant and surrounding bone in samples exposed to titanium particles, and expression of IL-1beta, TNFalpha, and CD68 was common in these joints. Pullout tests indicated that an average 5N load was required to pull out stable implants from surrounding bone. However, particle stimulation dramatically reduced the pullout force to less than 0.4 N. The feasibility of in vivo gene transfer on this model was confirmed by X-gal staining of synovial membrane and periprosthetic tissue after injection of AAV-LacZ in the prosthetic joint. This murine model of weight-bearing knee prosthesis provides an economical, reproducible, and easily obtained means to study joint arthroplasty failure. The ability to evaluate the biomechanical properties of the prosthetic joint, in addition to histological and biochemical examination, results in a useful model to investigate many of the properties of prosthetic joint components during the response to debris-associated osteolysis.     

Uncemented femoral revision arthroplasty using the modular revision prosthesis MRP-TITAN revision stem

Objective  Restoration of a painless hip joint capable of bearing weight by uncemented implantation of a rotationally stable, modular revision stem anchored in the diaphysis. Indications  Prosthetic stem loosening with osteolytic bone defects (defect classification types I–III according to Paprosky), material failure with broken prosthesis, sub-and/or periprosthetic femoral fractures, and tumors. Contraindication  Extensive osteolysis preventing diaphyseal anchorage of the prosthetic stem. Surgical technique  Transgluteal approach to the hip joint. Removal of the loose prosthetic stem and, if cemented, the bone cement as well. Excision of intramedullary granulation tissue. Reaming of the medullary cavity with flexible reaming shafts and formfit, uncemented implantation of the star-shaped modular revision stem with diaphyseal press-fit. If there is extensive loss of metaphyseal bone stock, augmentation with autogenous-allogenic bone should be performed. Postoperative management  Mobilization on two underarm crutches from the 1st postoperative day. Removal of the Redon drains after 48 hours. Partial loading with 20 kg for 6 weeks postoperatively. If plain radiographs show unchanged seating of the prosthesis after 6 weeks, loading can be increased by 10 kg per week until full weight bearing is achieved; thrombosis prophylaxis is continued throughout. Radiologic checkups will be done after 3, 6, and 12 months. After that, the patient should be checked annually. Results  Forty-five patients (N = 48 prostheses) with an average age of 67.2 years (min/max: 42.4–87.4 years) were investigated. The average implantation time of the Modular revision prosthesis MRP-TITAN revision stem was 4.7 years (min/max: 1.0–9.0 years). The Harris hip score for Paprosky bone defect types I–III had increased from 25.6 preoperatively to 71.4 postoperatively at the time of the final follow-up (p ³ 0.05). Extensively defective bone was diagnosed preoperatively in 32 patients (¹Paprosky IIB). Plain radiographs showed stable anchorage without migration in 44 patients. In one case, the stem (implantation time 2.36 years) was replaced due to increasing axial subsidence (¹5 mm). Good integration of bone graft with subsequent defect regeneration was seen in all patients with bone trans-plant (N = 30). Postoperative dislocation occurred in six patients and required closed reduction in four cases. Open reduction was performed in two patients, whereby the external rotation angle of the prosthetic neck was corrected without dismantling the distally anchored prosthetic stem components. The mechanical failure rate over the follow-up period of 9 years was 1 out of the 48 prospectively investigated prostheses. The rate of survival according to Kaplan-Meier was 97%.     

Osteolysis in cemented titanium alloy hip prosthesis

We evaluated 132 consecutively implanted cemented titanium alloy stems (Ti6-Al7-Nb, SLS-88) after a mean follow-up of 6.6 years (range 5-7 years). Almost 30% of the stems showed significant osteolysis, mainly in the proximal stem area. The amount of osteolysis correlated significantly to a typical pain pattern: dull, circular, and occurring at rest. Six stems had already been revised, and another 7 stems were loose clinically and radiologically, which resulted in a Kaplan-Meier survivorship of 95% for stem revisions and 88% for stem failures (revisions plus loose stems). We found that smaller stem sizes tend to increase the development of osteolysis and loosening. Two factors seem to play a role in early loosening of cemented titanium alloy stems: i) increased elasticity of titanium, which leads in small stem sizes to micromotion between the stem and cement and to cement breakage, and ii) corrosion of the cemented titanium alloy stem and subsequent osteolysis in the adjacent bone. The combination of both factors (high elasticity plus corrosion) accelerates the degradation of the bone anchorage of the stem and initiates early loosening. We advise against the further use of cemented SLS-88 titanium alloy stems.     

Systemic alendronate treatment improves fixation of press-fit implants: a canine study using nonloaded implants.

Bone resorption associated with local trauma occurring during insertion of joint prostheses is recognized as an early event. Being an osteoclastic inhibitor, alendronate is a potential candidate means to decrease early periprosthetic bone resorption and thereby improve implant fixation. We investigated the influence of oral alendronate treatment on early implant fixation in two implant interface settings representing sites of an implant that are in contact with surrounding bone, and other sites without intimate bone contact. One plasma-sprayed cylindrical titanium implant (6 mm diameter) was inserted into each proximal tibia of 16 dogs. On one side the implant was inserted press-fit whereas on the contralateral side, the implants were surrounded by a 2 mm concentric gap. Oral alendronate (0.5 mg/kg/day) was given 2 weeks following surgery to eight dogs. The dogs were euthanized after 10 weeks of alendronate treatment. Bone ongrowth (bone in contact with implant surface) was estimated using the linear intercept technique and shear strength was calculated as the slope on a load-displacement curve. For the press fit implants, alendronate treatment significantly increased bone ongrowth from 24% to 29% and significantly increased ultimate shear strength from 1.26 to 3.72 MPa. Also, the fraction of periprosthetic bone significantly increased from 10% to 18%. For implants surrounded by a gap, alendronate neither stimulated nor impaired implant fixation, bone ingrowth, or new bone formation in the gaps. Because early implant stability is an important predictor of longevity, systemic alendronate treatment could be an important clinical tool to positively influence the early stages of implant incorporation.     

Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.     

The effect of alendronate doped calcium phosphates on bone cells activity

This study demonstrates that octacalcium phosphate (OCP) is a suitable substrate for alendronate local action towards bone cells. The results of the structural, spectroscopic, and microscopic investigation show that soaking OCP into alendronate solutions provoked the deposition of long crystalline rod-shaped formations, most likely a calcium alendronate complex, onto the calcium phosphate. The amount of alendronate loaded onto OCP increased as a function of the bisphosphonate concentration in solution. Osteoblast and osteoclast response was tested in single and in co-cultures on OCP containing 6.4 wt.% AL (OCP-AL), and for comparison on hydroxyapatite (HA) containing a similar amount (5.9 wt.%) of AL (HA-AL), as well as on pure OCP and HA as reference materials. Alendronate loaded materials displayed a beneficial effect on osteoblast activity and differentiation, whereas they inhibited osteoclast proliferation and differentiation. Crosstalking between osteoblast-like MG63 cells and human osteoclasts enhanced their response to alendronate. Moreover, OCP displayed a greater stimulating effect than HA on osteoblast differentiation, and AL promotion of osteoblast differentiation and mineralization was enhanced in OCP-AL with respect to HA-AL.     

大颗粒聚乙烯对人工关节假体周围组织影响的实验研究

目的　制作松动人工关节的动物模型 ,了解大颗粒聚乙烯对实验动物人工关节假体周围骨组织的影响 ,并初步探讨其作用机制。　方法　选用健康新西兰白兔 2 0只 ,雌雄各半 ,体重 2 .3～ 2 .7kg。从两侧膝关节向股骨置入钴 -铬 -钼棒 ,分别于术后 2、4、6、8及 10周向一侧膝关节腔内注射聚乙烯微粒 (直径 10 0 μm)悬液 1.5 ml(实验侧 ) ,向另一侧膝关节腔内注射生理盐水 1.5 ml(对照侧 )。术后第 10周摄双下肢 X线片 ,了解假体周围是否有骨溶解和假体松动。术后第 12周处死动物。取 13只兔检查聚乙烯颗粒在关节囊分布情况 ,假体有否松动 ,周围有无新骨及界膜形成 ;取5只兔双侧股骨、膝关节囊作组织学检查 (实验过程中有 2只动物死亡 )。　结果　 1肉眼观察 :实验侧有 4侧金属假体被新生骨组织覆盖 ,9侧被纤维膜覆盖 ;对照侧有 11侧金属假体被新生骨组织覆盖 ,2侧被纤维膜覆盖 ,差异有统计学意义(P<0 .0 5 )。2 X线片观察 :假体位于股骨髓腔远端 ,其周围未见明显新生骨组织和骨溶解征像。3组织学观察 :实验侧关节囊见大量异物颗粒被成纤维细胞和多核巨细胞包绕 ,假体近端髓腔周围见成纤维细胞和纤维组织或新生骨组织形成 ,未见异物颗粒和多核巨细胞 ,靠近关节面部分见异物颗粒被成纤维细胞和多核巨细胞包绕     

The significance of wear and material fatigue in loosening of hip prostheses

Particles created by wear and disintegration of implant materials give rise to foreign body reactions in the tissue surrounding joint endoprostheses. Histiocytes and foreign body giant cells phagocytize the particles released and form granulomas, which lead in turn to remodelling and resorption of the bone at the interface between implant and bone. As a consequence of this, osteolysis develops, which may lead to loosening and complete failure of fixation of the implant. Radiographically, the areas of osteolysis appear as localized, round, oval or oblong scalloping defects or as radiolucent lines in the endosteal sections of the bone immediately adjacent to the implants. This paper reports on 21 hip joint endoprostheses in which polyethylene and bone cement particles induced large areas of osteolysis at the bone/cement interface. In 8 cases the polyethylene particles originated from the convex joint surfaces of ball heads in "soft-top" endoprostheses (with or without simultaneous replacement of the acetabulum by a metal cup), and in 5 cases they originated from the anchoring surfaces of non-cemented cone-shaped screw-in sockets (Endler type); osteolysis and loosening of these endoprostheses appeared on average 48.2 and 76.6 months after implantation, respectively. The bone cement fragments came from the bone cement mantle of the femur, which had become fractured, disrupted and crushed, in 8 cases of total hip replacement with cemented prostheses; osteolysis appeared on average 87 months after primary implantation in these cases. Tissue samples taken at revision surgery from the joint capsule, the bone/cement interface and the osteolytic areas were processed into histological sections for microscopy and examined in the usual way. The type and amount of phagocytized material were subjected to semiquantitative analysis. We were able to show that osteolysis at the bone/cement interface can be induced by foreign body reactions to abraded polyethylene particles alone as well as by reactions to fragmented bone cement. The morphology of the tissue reaction to particles of the different materials is quite similar. The effect of the foreign body granulomas depends less on the type of the polymer than on the amount of abrasion and fragmentation products released into the surrounding tissue. This again proves that the life-time of joint endoprostheses depends essentially on factors influencing the wear rate. Polymer materials, with low wear resistance, are unsuitable for convex joint surfaces and for direct fixation to bone.(ABSTRACT TRUNCATED AT 400 WORDS)