Local alendronate increases fixation of implants inserted with bone compaction: 12-week canine study.

Bone compaction has been shown to increase initial implant fixation. Furthermore, bone compaction creates a peri-implant zone of autograft that exerts osteoconductive properties. We have previously shown that locally applied bisphosphonate (alendronate) at 4-week observation can preserve the autograft generated by bone compaction. We now investigate whether the increased amount of autograft, seen at 4 weeks, can increase implant osseointegration and biomechanical fixation. Porous-coated titanium implants were bilaterally inserted with bone compaction into the proximal part of tibia of 10 dogs. On the right side, local bisphosphonate was injected into the bone cavity prior to bone compaction immediately prior to implant insertion. On the left side, saline was used as control. Observation period was 12 weeks. Locally applied bisphosphonate significantly increased biomechanical implant fixation (approximately twofold), bone-to-implant contact (1.2-fold), and peri-implant bone volume fraction (2.3-fold). This study indicates that local alendronate treatment can increase early implant osseointegration and biomechanical fixation of implants inserted by use of bone compaction. Long term effects remain unknown.     

Local delivery of zoledronate from a poly (d,l‐lactide)‐coating increases fixation of hydroxy‐coated implants

Initial secure implant fixation predicts long‐term survival. Bisphosphonates are anti‐resorptive agents. They have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from a poly‐d ,l ‐lactide (PDLLA)‐coating could improve fixation and osseointegration of hydroxy‐apatite coated implants. Cylindrical hydroxy‐apatite coated implants were bilaterally inserted press‐fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The PDLLA coating was applied upon the hydroxy‐apatite coating. We used the contralateral implant as control. This implant was not coated with a poly‐d ,l ‐lactide. Observation period was 12 weeks. We evaluated implant fixation with histomorphometry and biomechanical push‐out test. Zoledronate resulted in an approximately threefold increase in all biomechanical parameters when comparing data with their respective controls. We found that zoledronate increased preservation of old lamellar bone and increased formation of new woven bone. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. Studies investigating different doses of zoledronate and longer follow‐up are needed. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:974–979, 2017.

     

Local delivery of zoledronate from a poly (D,L‐lactide)—Coating increases fixation of press‐fit implants

Early secure fixation of total joint replacements is crucial for long‐term survival. Antiresorptive agents such as bisphosphonates have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from poly‐D, L‐lactide (PDLLA)‐coated implants could improve implant fixation and osseointegration. Experimental titanium implants were bilaterally inserted press‐fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The contralateral implant was uncoated and used as control. Observation period was 12 weeks. Implant fixation was evaluated with histomorphometry and biomechanical push‐out test. We found an approximately twofold increase in all biomechanical parameters when comparing data from the zoledronate group with their respective controls. Histomorphometry showed increased amount of preserved bone and increased bone formation around the zoledronate implants. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:65–71, 2016.     

Fixation of hydroxyapatite‐coated revision implants is improved by the surgical technique of cracking the sclerotic bone rim

Revision joint replacement has poorer outcomes that have been associated with poorer mechanical fixation. We investigate a new bone‐sparing surgical technique that locally cracks the sclerotic bone rim formed during aseptic loosening. We inserted 16 hydroxyapatite‐coated implants bilaterally in the distal femur of eight dogs, using a controlled weight‐bearing experimental model that replicates important features of a typical revision setting. At 8 weeks, a control revision procedure and a crack revision procedure were performed on contralateral implants. The crack procedure used a splined tool to perform a systematic local perforation of the sclerotic bone rim of the revision cavity. After 4 weeks, the hydroxyapatite‐coated implants were evaluated for mechanical fixation by a push‐out test and for tissue distribution by histomorphometry. The cracking revision procedure resulted in significantly improved mechanical fixation, significantly more bone ongrowth and bone volume in the gap, and reduced fibrous tissue compared to the control revision procedure. The study demonstrates that the sclerotic bone rim prevents bone ingrowth and promotes fixation by fibrous tissue. The effect of the cracking technique may be due to improved access to the vascular compartment of the bone. The cracking technique is a simple surgical method that potentially can improve the fixation of revision implants in sclerotic regions important for obtaining the fixation critical for overall implant stability. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 996–1001, 2009     

Early biological fixation of porous implant coated with paste-retaining recombinant bone morphogenetic protein 2

The aim of this study was to evaluate the period required for stable initial bone-implant fixation with recombinant human bone morphogenetic protein 2 (rhBMP-2) in the bone marrow of a rabbit model. The porous implants being coated with β-tricalcium phosphate/polylactide-polyethylene glycol paste with 15, 30, or 60 μg of rhBMP-2 (n = 10) were implanted into animals in 3 experimental groups. In 2 control groups, the test implants were coated without rhBMP or no paste. In all groups, the implant was inserted for 3 and 6 weeks. At 3 weeks after implantation, the BMP-treated implants in the 2 lower dose groups had significantly more bone ingrowth to the implant surface than did the control groups, and the greatest effect occurred in the 30-μg rhBMP-2 group animals.     

Strontium ranelate treatment enhances hydroxyapatite‐coated titanium screws fixation in osteoporotic rats

Increased bone turnover with excessive bone resorption and decreased bone formation is known to impair implant fixation. Strontium ranelate is well known as an effective antiosteoporotic agent by its dual effect of antiresorbing and bone‐forming activity. This study was designed to evaluate the effect of systemic strontium ranelate (SR) treatment on fixation of hydroxyapatite (HA)‐coated titanium screws in ovariectomized (OVX) rats. Twelve weeks after being OVX (n = 30) or sham (n = 10) operated, 40 female Sprague–Dawley rats received unilateral implants in the proximal tibiae. The OVX rats were randomly divided into the following groups: OVX, OVX + SR_L (“_L” refers to low SR dose of 500 mg/kg/day), OVX + SR_H (“_H” refers to high SR dose of 1000 mg/kg/day).Twelve weeks after treatment, bone blocks with implants were evaluated with micro‐CT and biomechanical push‐out tests. Compared to OVX animals, SR treatment increased the bone volume ratio by 51.5% and 1.1‐fold, the percentage osteointegration by 1.0‐fold and 1.9‐fold in micro‐CT evaluation, and the maximal force by 1.9‐fold and 3.3‐fold in biomechanical push‐out test, for the low and high dose of SR, respectively. Significant correlation between micro‐CT and biomechanical properties demonstrated that trabecular parameters played an important role in predicting the biomechanical properties of implant fixation. Our findings suggest that SR treatment can dose‐dependently improve HA‐coated screw fixation in OVX rats and facilitate the stability of the implant in the osteoporotic bone. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:578–582, 2010     

Time course of peri‐implant bone regeneration around loaded and unloaded implants in a rat model

The time‐course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium‐coated polyether‐ether ketone (PEEK) implants on osseointegration using time‐lapsed, non‐invasive, in vivo micro‐computed tomography (micro‐CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague–Dawley rats. External cyclic loading (60 or 100 μm displacement, 1 Hz, 60 s) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high‐resolution micro‐CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post‐surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone‐formation rate (BFR) and bone‐resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0% and 37.2 ± 10.0%, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119% increase in pull‐out strength was measured in the loaded implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:997–1006, 2017.

     

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     

Development and initial validation of a novel smoothed‐particle hydrodynamics‐based simulation model of trabecular bone penetration by metallic implants

A novel computational model of implant migration in trabecular bone was developed using smoothed‐particle hydrodynamics (SPH), and an initial validation was performed via correlation with experimental data. Six fresh‐frozen human cadaveric specimens measuring 10 × 10 × 20 mm were extracted from the proximal femurs of female donors (mean age of 82 years, range 75–90, BV/TV ratios between 17.88% and 30.49%). These specimens were then penetrated under axial loading to a depth of 10 mm with 5 mm diameter cylindrical indenters bearing either flat or sharp/conical tip designs similar to blunt and self‐tapping cancellous screws, assigned in a random manner. SPH models were constructed based on microCT scans (17.33 µm) of the cadaveric specimens. Two initial specimens were used for calibration of material model parameters. The remaining four specimens were then simulated in silico using identical material model parameters. Peak forces varied between 92.0 and 365.0 N in the experiments, and 115.5–352.2 N in the SPH simulations. The concordance correlation coefficient between experimental and simulated pairs was 0.888, with a 95%CI of 0.8832–0.8926, a Pearson ρ (precision) value of 0.9396, and a bias correction factor Cb (accuracy) value of 0.945. Patterns of bone compaction were qualitatively similar; both experimental and simulated flat‐tipped indenters produced dense regions of compacted material adjacent to the advancing face of the indenter, while sharp‐tipped indenters deposited compacted material along their peripheries. Simulations based on SPH can produce accurate predictions of trabecular bone penetration that are useful for characterizing implant performance under high‐strain loading conditions. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1114–1123, 2018.

     

皮质外骨桥固定特制假体置换治疗肢体骨肿瘤

[目的]确定采用特制假体及特殊植骨方法固定后，假体与骨交界区能否有效形成皮质外骨桥，皮质外骨桥能否起到有效的辅助固定作用，皮质外骨桥的形成和重建有何规律。[方法]44例患者行皮质外骨桥加强固定，带有1～4am多孔表面区的特制假体置换。31例患者资料可供分析，以了解植入后固定的效果以及骨桥形成和重建的规律。[结果]31例患者中有25例（81％）形成了有效的骨桥固定，骨桥在股骨后侧和内侧的压应力区形成更为丰富。[结论]在假体与骨端交接区的珍珠面和骨皮质之间良好植骨可有效构建骨桥；骨桥的重建与应力和血运有关；髓内固定、珍珠面、皮质外植骨有利于形成有效的骨桥固定。     

可吸收双重内固定材料治疗髌骨骨折

2003年3月～2008年6月,笔者采用可吸收张力带内固定治疗髌骨骨折55例,疗效满意。1材料与方法1.1病例资料本组55例,男23例,女32例,年龄45～86岁。闭合性骨折54例,开放骨折1例;横形骨折18例,斜形和纵形骨折12例,粉碎性骨折25例;     

The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of prostate cancer

BACKGROUND: In men, prostate cancer frequently metastasizes to the bones, where it forms osteoblastic lesions with an osteolytic element that cause pain. However, the role of osteoclastogenesis in bone metastasis of human prostate cancer is unknown. Bisphosphonates are already known to be beneficical for treating osteolytic bone metastases, so we employed a model of osteoblastic bone tumor of human prostate cancer to investigate whether a new bisphosphonate (YM529: minodronate) could inhibit both the formation of bone tumors and the progression of established osteoblastic tumors. METHODS: Human prostate cancer cells (LNCaP) were injected into adult human bone implants in nonobese diabetic/severe combined immunodeficient mice, after which osteoblastic bone tumors developed. YM529 (1 microg/day) was administered subcutaneously every day for 2 weeks, starting either immediately or 2 weeks after implantation of the tumor cells, and the mice were sacrificed at 4 weeks after implantation. The bone tumors were examined histologically and the number of tartrate-resistant acid phosphatase-stained osteoclasts in each tumor focus was counted. RESULTS: Histomorphometric analysis revealed that YM529 markedly inhibited both the formation of bone tumors and the progression of established tumors, as well as markedly reducing the number of osteoclasts. CONCLUSIONS: YM529 reduced the tumor burden in bone by inhibiting both the formation of new lesions and the progression of existing tumors, suggesting that osteoclasts are involved in the formation of bone tumors by prostate cancer. Treatment with this bisphosphonate may potentially be beneficial for patients with bone metastases of prostate cancer.     

Combination use of vitamin K<Subscript>2</Subscript> further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats

 Bisphosphonate is a potent inhibitor of bone resorption, which results in the increase of bone volume. However, bisphosphonate treatment may lead to extremely low bone turnover and abnormal bone microstructure. In this study, we examined whether the combination of bisphosphonate with vitamin K₂ treatment may have beneficial effects on bone turnover and trabecular microstructure as well as on bone volume loss by using tail-suspension model rats. In these model rats, bone mineral density (BMD) decreased with histological evidence of enhanced bone resorption and suppressed bone formation. By bisphosphonate treatment, BMD was increased compared with that of tail-suspended rats. Osteoclast surface per bone surface (Oc.S/BS) and number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and mineral apposition rate (MAR) decreased, suggesting extreme suppression of bone turnover. However, trabecular structure examined by microfocus CT was apparently abnormal. By contrast, combination of bisphosphonate with vitamin K₂ leads to further increase of bone volume. MAR and BFR as well as Oc.S/BS and N.Oc/B.Pm were increased compared with those of the bisphosphonate-treated group. However, abnormal structure of trabeculae in secondary spongiosa was not completely ameliorated. These data suggested that concomitant use of vitamin K₂ with bisphosphonate excessively ameliorates too much suppression of bone turnover while more efficiently preventing bone volume loss. Received: January 30, 2002 / Accepted: November 6, 2002 RID="*" ID="*"  Present address: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan Acknowledgments. This work was supported in part by a Special Grant for Medical Research from Ministry of Post and Telecommunications, Japan (to M.F.), a grant in aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (#13671115 to M.F.), and by a grant from the Research Society for Metabolic Bone Disease (to M.F.). We are grateful to Miss Sachiko Suzuki for technical assistance. Offprint requests to: M. Fukagawa     

Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta‐analysis

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post‐transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate‐treated kidney transplant recipients through meta‐analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow‐up duration was more than 6 months. We performed random‐effects meta‐analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm², 95% CI 0.012–0.099 and 0.053 g/cm², 95% CI 0.032–0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.     

Peri‐implant stress correlates with bone and cement morphology: Micro‐FE modeling of implanted cadaveric glenoids

Aseptic loosening of cemented joint replacements is a complex biological and mechanical process, and remains a clinical concern especially in patients with poor bone quality. Utilizing high resolution finite element analysis of a series of implanted cadaver glenoids, the objective of this study was to quantify relationships between construct morphology and resulting mechanical stresses in cement and trabeculae. Eight glenoid cadavers were implanted with a cemented central peg implant. Specimens were imaged by micro‐CT, and subject‐specific finite element models were developed. Bone volume fraction, glenoid width, implant‐cortex distance, cement volume, cement–cortex contact, and cement–bone interface area were measured. Axial loading was applied to the implant of each model and stress distributions were characterized. Correlation analysis was completed across all specimens for pairs of morphological and mechanical variables. The amount of trabecular bone with high stress was strongly negatively correlated with both cement volume and contact between the cement and cortex (r = ?0.85 and ?0.84, p < 0.05). Bone with high stress was also correlated with both glenoid width and implant‐cortex distance. Contact between the cement and underlying cortex may dramatically reduce trabecular bone stresses surrounding the cement, and this contact depends on bone shape, cement amount, and implant positioning. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1671–1679, 2015.

     

逆行可吸收拉力螺钉内固定治疗腕舟骨骨折

目的：探讨逆行可吸收拉力螺钉内固定治疗腕舟骨骨折的手术疗效。方法：2001年12月至2007年12月,18例腕舟骨骨折,男12例,女6例;年龄17～40岁,平均26岁。腕舟骨腰部骨折10例,近端骨折8例。采用逆行可吸收拉力螺钉内固定治疗。结果：18例患者获随访,时间12～36个月,平均25个月。18例中有17例愈合,1例不愈合,平均愈合时间为13周,平均腕关节活动度为健侧的90%,握力为健侧的95%。14例无疼痛,3例轻度疼痛,另外1例不愈合有中度疼痛,除1例不愈合外,其余都能胜任原工作。按Cooney评分标准：总评分由术前的（68.2±1.5）分提高到术后的（88.7±1.2）分,术后各项评分明显高于术前（P〈0.05）;优9例,良8例,差1例。结论：逆行可吸收拉力螺钉内固定治疗腕舟骨骨折手术操作简单,对腕舟骨残存的血运破坏小,固定牢靠,可缩短骨折愈合时间及提高骨折愈合率,是治疗腕舟骨骨折的一种有效的手术方法。     

游离腓骨骨皮瓣加单臂外固定架治疗胫骨骨缺损

目的 探讨游离腓骨骨皮瓣治疗胫骨骨缺损的方法和临床疗效.方法 采用吻合血管的游腓骨骨皮瓣移植加单臂外固定架治疗12例因创伤、慢性骨髓炎导致的胫骨骨缺损患者.结果 患者腓骨骨皮瓣携带皮岛血运均良好,切口均一期愈合.12例均获随访,时间12~48个月.全部骨性愈合,患者恢复行走功能.结论 吻合血管的游离腓骨骨皮瓣移植加单臂外固定架治疗胫骨骨缺损临床疗效满意.     

Particle‐induced osteolysis is not accompanied by systemic remodeling but is reflected by systemic bone biomarkers

Particle‐induced osteolysis is caused by an imbalance in bone resorption and formation, often leading to loss of implant fixation. Bone remodeling biomarkers may be useful for identification of osteolysis and studying pathogenesis, but interpretation of biomarker data could be confounded if local osteolysis engenders systemic bone remodeling. Our goal was to determine if remote bone remodeling contributes to biomarker levels. Serum concentrations of eight biomarkers and bone remodeling rates at local (femur), contiguous (tibia), and remote (humerus and lumbar vertebra) sites were evaluated in a rat model of particle‐induced osteolysis. Serum CTX‐1, cathepsin K, PINP, and OPG were elevated and osteocalcin was suppressed in the osteolytic group, but RANKL, TRAP 5b, and sclerostin were not affected at the termination of the study at 12 weeks. The one marker tested longitudinally (CTX‐1) was elevated by 3 weeks. We found increased bone resorption and decreased bone formation locally, subtle differences in contiguous sites, but no differences remotely at 12 weeks. Thus, the skeletal response to local particle challenge was not systemic, implying that the observed differences in serum biomarker levels reflect differences in local remodeling. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:967–973, 2014.     

一期手术经后路病灶清除植骨融合内固定治疗胸椎结核

目的探讨一期手术经后路结核病灶清除植骨融合内固定治疗胸椎结核的效果。方法 12例胸椎结核患者均采用一期经后路病灶清除、前后路植骨融合和后路钉棒系统内固定术。术后定期复查X线片了解Cobb角变化和椎间植骨融合情况,采用ASIA分级评定术后脊髓功能恢复情况。结果术中无大血管或脊髓损伤。患者均获随访,时间16～38个月。结核症状均消失无复发,无切口感染、窦道形成或内固定失败等并发症发生;复查血沉均正常。术后4～8个月X线片提示椎间植骨均融合,后路植骨融合时间6～9个月,内固定在位。末次随访Cobb角为18°～36°。脊髓功能ASIA分级:B级5例中有2例恢复至C级、3例无恢复,C级5例均恢复至D级,D级2例均恢复至E级。结论一期经后路清除胸椎结核病灶彻底,椎管减压可靠,行自体或同种异体骨植骨钉棒系统内固定可有效重建胸段脊柱的稳定性,矫形效果显著。     

单侧双臂外固定支架治疗长骨开放性骨折

目的探讨单侧双臂外固定支架治疗长骨开放性骨折的临床效果。方法采用单侧双臂外固定支架治疗严重长骨开放性骨折30例。所有患者均在急诊手术时行外固定支架固定。二期手术行植皮、转移皮瓣和骨延长治疗。结果开放性骨折均治愈,骨缺损同时纠正。结论单侧双臂外固定支架治疗长骨开放性骨折是一种手术创伤小、操作简单、疗效可靠的方法。