Interspecies comparison of subchondral bone properties important for cartilage repair

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro‐CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:63–70, 2015.

     

微骨折+原位钻孔缝合法治疗股骨髁骨软骨骨折

目的探讨切开复位微骨折+原位钻孔缝合法治疗股骨髁负重区大面积骨软骨骨折的临床疗效。方法对15例股骨髁负重区大面积粉碎骨软骨骨折患者进行原位解剖复位、钻孔、可吸收缝线双隧道骨软骨块加强缝合,小的骨软骨块表面固定,骨折块间软骨缺损处予以微骨折术。术后3、6、12个月采用Lysholm评分评价膝关节功能。结果患者均获得随访,时间12~18个月。所有患者关节软骨面的平整结构恢复良好,骨软骨骨折均愈合。术后6个月膝关节Lysho Im评分为81~93(86.3±5.5)分,优良率86.7%,较术后3个月增加,差异有统计学意义(P0.05);术后12个月膝关节Lysholm评分为86~98(90.8±6.7)分,优良率93.3%,较术后6个月增加,差异有统计学意义(P0.05)。结论切开复位微骨折+原位钻孔缝合法治疗股骨髁负重区大面积骨软骨骨折操作简便,费用低廉,并发症少,功能恢复良好。     

Early health economic modelling of single‐stage cartilage repair. Guiding implementation of technologies in regenerative medicine

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair – such as autologous chondrocyte implantation (ACI) – plus increasing healthcare costs, and market competition, are forcing a shift in focus from two‐stage to single‐stage interventions that are more cost‐effective. Early health economic models are expected to provide essential insight in the parameters driving the cost‐effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost‐effectiveness ratio (ICER) of a new investigator‐driven single‐stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost‐effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One‐way sensitivity analysis was performed to identify those parameters that drive the cost‐effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost‐effective treatment option for smaller defects, a single‐stage tissue engineering procedure can replace ACI to improve the cost‐effectiveness for treating larger defects, especially if clinical non‐inferiority can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.     

Drilling and microfracture lead to different bone structure and necrosis during bone‐marrow stimulation for cartilage repair

Bone marrow stimulation is performed using several surgical techniques that have not been systematically compared or optimized for a desired cartilage repair outcome. In this study, we investigated acute osteochondral characteristics following microfracture and comparing to drilling in a mature rabbit model of cartilage repair. Microfracture holes were made to a depth of 2 mm and drill holes to either 2 mm or 6 mm under cooled irrigation. Animals were sacrificed 1 day postoperatively and subchondral bone assessed by histology and micro‐CT. We confirmed one hypothesis that microfracture produces fractured and compacted bone around holes, essentially sealing them off from viable bone marrow and potentially impeding repair. In contrast, drilling cleanly removed bone from the holes to provide access channels to marrow stroma. Our second hypothesis that drilling would cause greater osteocyte death than microfracture due to heat necrosis was not substantiated, because more empty osteocyte lacunae were associated with microfracture than drilling, probably due to shearing and crushing of adjacent bone. Drilling deeper to 6 mm versus 2 mm penetrated the epiphyseal scar in this model and led to greater subchondral hematoma. Our study revealed distinct differences between microfracture and drilling for acute subchondral bone structure and osteocyte necrosis. Additional ongoing studies suggest these differences significantly affect long‐term cartilage repair outcome. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1432–1438, 2009     

Trabecular Microfracture Precedes Cortical Shell Failure in the Rat Caudal Vertebra Under Cyclic Overloading

Microscopic tissue damage has been observed in otherwise healthy cancellous bone in humans and is believed to contribute to bone fragility and increased fracture risk. Animal models to study microscopic tissue damage and repair in cancellous bone would be useful, but it is currently not clear how loads applied to a whole animal bone are related to the amount and type of resulting microdamage in cancellous bone. In the current study we determine the relationship between applied cyclic compressive overloading and the resulting amount of microdamage in isolated rat tail vertebrae, a bone that has been used previously for in vivo loading experiments. Rat caudal vertebrae (C7–C9, n = 22) were potted in bone cement and subjected to cyclic compressive loading from 0 to 260 N. Loading was terminated in the secondary and tertiary phases of the creep-fatigue curve using custom data-monitoring software. In cancellous bone, trabecular microfracture was the primary form of microdamage observed with few microcracks. Trabecular microfracture prevalence increased with the amount of cyclic loading and occurred in nine out of 10 specimens loaded into the tertiary phase. Only small amounts of microdamage were observed in the cortical shell of the vertebrae, demonstrating that, under axial cyclic loading, damage occurs primarily in regions of cancellous bone before overt fracture of the bone (macroscopic cracks in the cortical shell). These experiments in isolated rat tail vertebrae suggest that it may be possible to use an animal model to study the generation and repair of microscopic tissue damage in cancellous bone.     

Mathematical Modeling of Spatio‐Temporal Dynamics of a Single Bone Multicellular Unit

During bone remodeling, bone‐resorbing osteoclasts and bone‐forming osteoblasts are organized in bone multicellular units (BMUs), which travel at a rate of 20–40 μm/d for 6–12 mo, maintaining a cylindrical structure. However, the interplay of local BMU geometry with biochemical regulation is poorly understood. We developed a mathematical model of BMU describing changes in time and space of the concentrations of proresorptive cytokine RANKL and its inhibitor osteoprotegerin (OPG), in osteoclast and osteoblast numbers, and in bone mass. We assumed that osteocytes surrounding a microfracture produce RANKL, which attracted osteoclasts. OPG and RANKL were produced by osteoblasts and diffused through bone, RANKL was eliminated by binding to OPG and RANK. Osteoblasts were coupled to osteoclasts through paracrine factors. The evolution of the BMU arising from this model was studied using numerical simulations. Our model recapitulated the spatio‐temporal dynamics observed in vivo in a cross‐section of bone. In response to a RANKL field, osteoclasts moved as a well‐confined cutting cone. The coupling of osteoclasts to osteoblasts allowed for sufficient recruitment of osteoblasts to the resorbed surfaces. The RANKL field was the highest at the microfracture in front of the BMU, whereas the OPG field peaked at the back of the BMU, resulting in the formation of a RANKL/OPG gradient, which strongly affected the rate of BMU progression and its size. Thus, the spatial organization of a BMU provides important constraints on the roles of RANKL and OPG as well as possibly other regulators in determining the outcome of remodeling in the BMU.     

Microfracture of chondral lesions of the glenohumeral joint

Objective:

To determine if microfracture is successful in treating chondral lesions of the shoulder.

Design:

Case series.

Setting:

Tertiary referral practice.

Patients:

From June 2005 to November 2006, eight patients underwent shoulder arthroscopy with arthroscopic microfracture to treat full-thickness chondral lesions of less than 4 cm² size. The study group consisted of six men and two women. The mean age at surgery was 37 years (range: 27–55 years).One patient (12.5%) had an isolated chondral defect and seven patients (87.5%) had associated conditions treated simultaneously: two patients had arthroscopic subacromial decompressions, two had capsular plications for multidirectional instability, and three had anterior stabilization done (one with an associated superior labrum anterior to posterior repair and one with repair of a small rotator cuff tear). Five patients had humeral head defects and three had glenoid defects.

Intervention:

Microfracture.

Main outcome measures:

Constant score and Oxford score.

Results:

The mean follow-up period was 15.4 months, with a range of 12–27 months. The mean preoperative Constant score was 43.88 (range: 28–70) and at final follow-up the mean Constant score was 90.25 (range: 85–100); this difference was significant (P<0.005). The mean preoperative Oxford score was 25.75 (range: 12–37) and the mean postoperative Oxford score at final follow-up was 17 (range: 11–27); the difference was significant (P<0.005).There were no complications. Two patients underwent reoperation which allowed assessment of the lesion; in both cases the lesions showed good filling with fibrocartilage.

Conclusion:

Microfracture has been shown to be a reliable method of treatment for chondral lesions within the knee. We believe that this technique may also be applied to the shoulder; however, further study is required to assess its efficacy in this joint.

Level of evidence:

IV     

The role of the microfracturetechnique in the treatment of full-thickness chondral injuries

Microfracture is indicated for both traumatic and degenerative full-thickness chondral defects. The technique isuseful for both unipolar and “kissing” (bipolar) lesions in both the primary treatment and revision settings. There are no contraindications to the technique based on the size or location of the lesion, although smaller (<400 mm²), acute (<12 weeks from injury) femoral and trochlear lesions have the most predictable results. Relative contraindications to microfracture include chondral defects greater than 5 to 10 mm deep and the presence of a malaligned limb. Clinical studies have shown significant (P < .05) improvement in all functional parameters studied following the use of microfracture for the treatment of full-thickness, traumatic chondral defects. Of note, improvement in symptoms of pain and swelling continue to be seen until 2 years after surgery following microfracture. The microfacture technique is a cost-effective, technically feasible, highly efficacious procedure available to all surgeons who perform arthroscopy of the knee. It is a reasonable first approach to the treatment of chondral defects, because it does not burn any bridges with regard to future procedures such as a mosaic-plasty or autologous chondrocyte transplantation if the microfracture should fail.