Journal of Orthopaedic Research

Extracorporeal shock wave therapy (ESWT) is an increasingly popular therapeutic approach to the treatment of a number of soft tissue complaints. Whilst benefit has been demonstrated in calcific tendinitis, evidence is lacking for benefit in the management of non‐calcific rotator cuff disorders.

Aims: To perform a double‐blind placebo controlled trial of moderate dose ESWT in chronic lateral epicondylitis.

Methods: Adults with lateral epicondylitis were randomised to receive either active treatment (1500 pulses ESWT at 0.12 mJ/mm²) or sham therapy, monthly for three months. All were assessed before each treatment and one month after completion of therapy. Outcome measures consisted of visual analogue scores for pain in the day and at night.

Results: Seventy‐five subjects participated and there were no significant differences between the two groups at baseline. The mean duration of symptoms was 15.9 and 12 months in the ESWT and sham groups, respectively. Both groups showed significant improvements from two months. No significant difference existed between the groups with respect to the degrees of change in pain scores over the study period. In the ESWT group the mean (SD, range) pain score was 73.4 (14.5, 38–99) at baseline and 47.9 (31.4, 3–100) at three months. In the sham group the mean (SD, range) pain score was 67.2 (21.7, 12–100) at baseline and 51.5 (32.5, 3–100) at three months.

At three months, 50% improvement from baseline was noted in 35% of the ESWT group and 34% of the sham group with respect to pain.

Conclusions: There appears to be a significant placebo effect of moderate dose ESWT in subjects with lateral epicondylitis but there is no evidence of added benefit of treatment when compared to sham therapy.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

We evaluated femoral perfusion in a non‐traumatic rabbit serum sickness osteonecrosis (ON) model, using serial repetitive T2*‐weighted (T2*W) dynamic magnetic resonance imaging (MRI) and investigated prediction of ON occurrence in early stages, comparing T2*W dynamic MRI with non‐enhanced (T2‐, T1‐ and fat suppression T1‐weighted) and contrast‐enhanced MRI. Early microcirculatory injury or necrotic lesion was detected in 0% of femora (extravasation, 0/6) at 72 h, 33% (necrotic, 4/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using non‐enhanced MRI, and in 67% of femora (extravasation, 4/6) at 72 h, 58% (necrotic, 7/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using contrast‐enhanced MRI. In contrast, microcirculatory injury or necrotic lesion was detected in 83% of femora (extravasation, 5/6) at 72 h, 92% (necrotic, 11/12) at 1 week and 100% (necrotic, 14/14) at 3 weeks using T2*W dynamic MRI as no transient decrease or less marked transient decrease in signal intensity of regions of interest (ROIs), compared to normal femora, which showed a clear transient decrease in signal intensity of ROIs. These results indicate that T2*W dynamic MRI with optimal imaging parameters and a dose of contrast agent is the most sensitive of these three MRI methods and may be clinically useful for evaluating femoral perfusion in artery phase and predicting ON occurrence.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

We studied whether applying nucleus pulposus tissue, obtained from tail intervertebral discs that had been subjected to chronic mechanical compression, to the lumbar nerve roots produces hyperalgesia, which is thought to be a pain‐related behavior in the rat. An Ilizarov‐type apparatus was used for immobilization and chronically applied compression of the rat tail for eight weeks. Three weeks after application of extracted nucleus pulposus tissue on the lumbar nerve roots, motor function, sensitivity to noxious mechanical stimuli was measured. Eight weeks after application of the apparatus, the instrumented vertebrae were resected and sections were stained with hematoxylin and eosin to evaluate degeneration of the intervertebral disc. Mechanical hyperalgesia observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal and non‐compressed discs. The nucleus pulposus in the instrumented vertebrae showed some histological degeneration. In conclusion, chronic mechanical compression of nucleus pulposus, which resulted in degeneration to some extent, enhanced mechanical hyperalgesia, which was induced by application of nucleus pulposus on the nerve root in the rat. Degenerative intervertebral discs might induce more significant pain than normal intervertebral discs.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Mục tiêu. Khả năng cảm nhận vị trí của các đoạn chi là một chức năng cảm thụ chuyên biệt rất quan trọng cho việc kiểm soát chuyển động. Cảm giác proprioception đầu gối bất thường đã được phát hiện liên quan đến một số bệnh lý cơ xương khớp, nhưng liệu kích thích cảm giác đau có thể tạo ra những thay đổi proprioceptive này hay không vẫn còn chưa rõ. Nghiên cứu này đánh giá tác động của cơn đau đầu gối được gây ra một cách thực nghiệm đối với cảm giác vị trí khớp gối (JPS) ở những cá nhân khỏe mạnh.

Thiết kế nghiên cứu. Thiết kế đo lặp lại, trong cùng một đối tượng.

Phương pháp. JPS đầu gối được thử nghiệm trên 16 cá nhân không có tiền sử bệnh lý đầu gối dưới ba điều kiện thí nghiệm: kiểm soát cơ bản, một nhiệm vụ phân tâm và đau đầu gối được gây ra bằng cách tiêm dung dịch muối ưu trương vào mỡ dưới đầu gối. JPS đầu gối được đo bằng cách sử dụng các phản ứng khớp cùng phía chủ động ở góc gập 20° và 60° trong tư thế không trọng lượng (NWB) và tư thế đứng một chân gập 20°. Trong suốt các nhiệm vụ, cảm giác chủ quan về phân tâm và mức độ đau được đo bằng cách sử dụng thang điểm số 11 điểm.

Photopolymerizing hydrogel systems provide a method to encapsulate cells and implant materials in a minimally invasive manner. Controlled release of growth factors in the hydrogels may enhance the ability to engineer tissues. IGF‐I and TGF‐β were loaded in PLGA microspheres using a double emulsion technique. 125 ng and 200 pg of active IGF‐I and TGF‐β, respectively, as measured by ELISA, were released over 15 days. The growth factor containing microspheres were photoencapsulated with bovine articular chondrocytes in PEO‐based hydrogels and incubated in vitro for two weeks. Statistically significant changes in glycosaminoglycan (GAG) production compared to control gels either without microspheres or with blank spheres were observed after a 14 day incubation with IGF‐I and IGF‐I/TGF‐β microspheres combined, with a maximum density of 8.41 ± 2.5% wet weight GAG. Total collagen density was low and decreased with the IGF‐I/TGF‐β microspheres after two weeks incubation, but otherwise remained unchanged in all other experimental groups. Cell content increased 10‐fold to 0.18 ± 0.056 × 10⁶ cells/mg wet weight and extracellular matrix (ECM) staining by H&E increased in hydrogels with IGF‐I/TGF‐β microspheres. In conclusion, photoencapsulation of microspheres in PEO‐based hydrogels provides a method to deliver molecules such as growth factors in porous hydrogel systems. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Pathologic fracture is a significant risk for patients afflicted with metastatic or benign skeletal tumors. The quandary for physicians who treat these patients is that after making the diagnosis they must try to predict the load bearing capacity of the involved bone and the fracture risk from images seen in radiological examinations. Since bone fails at a relatively constant strain independent of density we demonstrate that using a mechanics of materials approach that the cross‐sectional structural properties of the bone most affected by the lytic defect governs the load bearing capacity of the entire bone.

Homogeneous cylindrical cores of trabecular bone were harvested from the vertebral bodies of whale spines, and prepared with circular or slotted through‐hole defects of varying sizes to simulate lytic skeletal tumors. Each specimen was imaged using quantitative computed tomography (CT), dual energy X‐ray absorptiometry (DXA), and magnetic resonance imaging (MRI) to obtain data for calculating cross‐sectional structural properties: axial, flexural, and torsional rigidity. The specimens were then divided into groups uniformly distributed with respect to defect sizes and shapes, and subjected to uniaxial tension, four‐point bending or torsion until failure.

A strong positive relationship was found between measured tensile yield loads, bending, and torsional yield moments vs. axial, flexural and torsional structural rigidities respectively, calculated from QCT, DXA, and MRI data [QCT: tension r² = 0.951, bending r² = 0.909, torsion r² = 0.914 (p < 0.001); DXA: tension r² = 0.926, bending r² = 0.841, torsion r² = 0.916 (p < 0.001), MRI: tension r² = 0.916; bending r² = 0.856, torsion r² = 0.852 (p < 0.001)].

For cylindrical cores of trabecular bone with simulated lytic defects, the load bearing capacity of the entire core was directly proportional to the axial, bending, or torsional rigidity at the weakest cross‐section through the core containing the defect. Therefore structural rigidity analysis of cross‐sectional geometric data measured non‐invasively by QCT, DXA, and MRI of bones containing lytic defects may be used to predict the load bearing capacity of the involved bone and the relative fracture risk in vivo. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Mục tiêu của nghiên cứu này là xem xét vai trò của một trong các yếu tố tăng trưởng/sự phân hóa, GDF-5, trong quá trình hồi phục gân. Cụ thể, chúng tôi đã kiểm tra giả thuyết rằng sự thiếu hụt GDF-5 ở chuột sẽ dẫn đến việc sửa chữa gân Achilles bị chậm lại. Sử dụng các phân tích mô học, hóa sinh và siêu cấu trúc, chúng tôi chứng minh rằng các gân Achilles từ chuột đực GDF-5 –/– 8 tuần tuổi thể hiện sự chậm trễ ngắn hạn từ 1-2 tuần trong quá trình hồi phục so với các con cùng loại có hình thái bình thường. Các động vật đột biến mất nhiều thời gian hơn để đạt được mật độ tế bào cao nhất, hàm lượng glycosaminoglycan và hàm lượng collagen trong mô sửa chữa, và quá trình thay đổi kích thước sợi collagen cũng bị chậm lại. Quá trình tái sinh mạch máu ở chuột đột biến bị chậm lại 1 tuần. Gân Achilles thiếu GDF-5 cũng có chứa lượng mỡ nhiều hơn đáng kể trong mô sửa chữa ở tất cả các thời điểm được xem xét, và yếu hơn đáng kể so với mô kiểm soát sau 5 tuần phẫu thuật, nhưng sự khác biệt về độ mạnh không còn phát hiện được đến tuần thứ 12. Những dữ liệu này ủng hộ giả thuyết rằng GDF-5 có thể đóng vai trò quan trọng trong việc điều chỉnh quá trình sửa chữa gân, và phù hợp với những vai trò đã được đề xuất trước đó của GDF-5 trong việc thu hút tế bào, di chuyển/gắn kết, phân hóa, sinh sản, và tạo mạch. © 2003 Hiệp hội Nghiên cứu Chỉnh hình. Xuất bản bởi Elsevier Science Ltd. Đã được bảo lưu mọi quyền.

Bone morphogenetic protein 3 (BMP3) is a potent osteoinductive growth factor belonging to the TGF‐β superfamily. In this study, we engineered a recombinant BMP3 protein to include an auxiliary collagen‐targeting domain derived from von Willebrand coagulation factor (vWF). The collagen‐targeted BMP3 fusion protein (rhBMP3‐C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo. The renatured rhBMP3‐C fusion protein bound tightly to collagen matrices and inhibited DNA synthesis in normal rat calvaria cells and in two out of three human osteosarcoma cell lines tested. Alkaline phosphatase activity was increased in rat calvarial cells and was decreased in osteosarcoma cells in vitro in a dose‐dependent manner. Collagen sponges impregnated with rhBMP3‐C and implanted subcutaneously in Fischer‐344 rats induced dose‐dependent dystrophic calcification of the collagen matrix, with no evidence of ectopic bone formation. However, local injection of rhBMP3‐C infused in a collagen suspension induced new bone formation on the periosteal surface of rat calvaria. Finally, in a rat cranial defect model, surgical implantation of rhBMP3‐C arrayed on either collagen sponges or on porous ceramics coated with Type I collagen exhibited marked osteoinductive properties. Taken together, these results demonstrate the feasibility of engineering and manufacturing targeted‐BMPs which exhibit an integral gain‐of‐function that may be exploited to therapeutic advantage in (i) the enhancement of effective local concentrations, (ii) the prevention of systemic biodistribution and side effects, and (iii) the design of improved osteoinductive matrices. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Little is known about the contribution of innervation to ligament healing after traumatic disruption, although there is good evidence of an important role for the peripheral nervous system in the healing of fractures and skin injuries.

Tissues such as ligament, with a low resting blood supply, are dependent on substantial increases in blood flow and vascular volume during the initial stages of repair. We hypothesized that this initial healing response would be strongly promoted by neurogenic inflammation. Since the saphenous nerve (a major sensory branch of the femoral nerve) supplies the medial half of the knee joint, we elected to use femoral nerve transection as a model to determine the role of sensory and autonomic innervation in the initial outcome of repair of the injured medial collateral ligament. Twelve adult, female NZW rabbits underwent right medial collateral ligament transection. Of these, six rabbits underwent right femoral nerve transection to disrupt the somatic sensory and autonomic nerve supply to the knee joint and six were kept neurologically intact (controls). At six weeks post‐injury, the animals were assessed by laser Doppler perfusion imaging (LDI) to determine the local blood flow, at both the injury site and at the uninjured contralateral ligament. The animals were then killed, the knee joints were removed and the biomechanical characteristics of the healing bone–median collateral ligament (MCL)–bone complexes assessed. In a separate cohort of 16 rabbits, vascular volumes of the injured ligaments were measured by infusion of a carmine red/gelatin solution.

At six weeks post‐injury, in vivo measurement of perfusion with LDI revealed that normally innervated ligaments had an almost three‐fold higher average blood flow. Carmine red/gelatin infusion revealed a 50% higher density of blood vessels as compared to denervated ligaments. The force required for ultimate failure was found to be 50% higher in normally innnervated MCL's as compared to denervated MCL's: 153.14 ± 20.71 N versus 101.29 ± 17.88 N (p < 0.05). Static creep was increased by 66% in denervated MCL's: 2.83 ± 0.45% versus 1.70 ± 0.12% (p < 0.05). Total creep was increased by 45% in denervated MCL's: 5.29 ± 0.62% compared to 3.64 ± 0.31% in innervated MCL's (p < 0.05).

We conclude that intact innervation makes a critical contribution to the early healing responses of the MCL of adult rabbits.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Retrieval studies indicate that cemented stem loosening in femoral components of total hip replacement can initiate at the stem‐cement interface. The etiology of the crack propagation process from the stem‐cement interface is not well understood, but cracks are typically associated with thin cement mantles. In this study, a combination of experimental and computational methods was used to investigate the fatigue crack propagation process from the stem‐PMMA cement interface using a novel torsional loading model. Constructs with thin (1 mm), medium (3 mm) or thick (7 mm) cement mantles were evaluated. Crack growth was stable for all cases and the rate of crack growth diminished with increasing crack length. Crack growth rate did not depend on mantle thickness (p > 0.05) over the first 1 mm of crack length, but cracks in thin mantles reached the full thickness of the mantle in the fewest number of loading cycles. The fracture mechanics‐based finite element models indicated decreased stress intensity factors with increasing crack length and were consistent with the experimental findings. When combined with a fatigue crack growth Paris‐law for PMMA cement, the finite element models provided reasonable predictions of the crack growth process. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.