Journal of Orthopaedic Research

Cervical spine disorders such as spondylotic radiculopathy and myelopathy are often related to osteophyte formation. Bone remodeling experimental—analytical studies have correlated biomechanical responses such as stress and strain energy density to the formation of bony outgrowth. Using these responses of the spinal components, the present study was conducted to investigate the basis for the occurrence of disc‐related pathological conditions. An anatomically accurate and validated intact finite element model of the C4‐C5‐C6 cervical spine was used to simulate progressive disc degeneration at the C5‐C6 level. Slight degeneration included an alteration of material properties of the nucleus pulposus representing the dehydration process. Moderate degeneration included an alteration of fiber content and material properties of the anulus fibrosus representing the disintegrated nature of the anulus in addition to dehydrated nucleus. Severe degeneration included decrease in the intervertebral disc height with dehydrated nucleus and disintegrated anulus. The intact and three degenerated models were exercised under compression, and the overall force—displacement response, local segmental stiffness, anulus fiber strain, disc bulge, anulus stress, load shared by the disc and facet joints, pressure in the disc, facet and uncovertebral joints, and strain energy density and stress in the vertebral cortex were determined. The overall stiffness (C4‐C6) increased with the severity of degeneration. The segmental stiffness at the degenerated level (C5‐C6) increased with the severity of degeneration. Intervertebral disc bulge and anulus stress and strain decreased at the degenerated level. The strain energy density and stress in vertebral cortex increased adjacent to the degenerated disc. Specifically, the anterior region of the cortex responded with a higher increase in these responses. The increased strain energy density and stress in the vertebral cortex over time may induce the remodeling process according to Wolff's law, leading to the formation of osteophytes. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Osteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor‐β, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin‐1 (IL‐1). The problems associated with selective delivery of the growth factor to chondrocytes, undesirable side‐effects on joint tissues, and short biological half‐life have led us to explore modalities aimed at activating transforming growth factor‐β that is stored in the cartilage as latent complexes. Photodynamic therapy is a two‐step protocol of tissue sensitization with a light‐activatable chemical called a photosensitizer followed at some interval by irradiation with the appropriate wavelength visible light. Biological effects are typically elicited through oxygen‐dependent photochemistry without heat generation. Transforming growth factor‐β1 can be activated by oxidative mechanism(s), prompting us to explore whether photodynamic technology can be harnessed to modulate cartilage metabolism. Disks of bovine articular cartilage were photosensitized by incubation with a chlorin_e6‐succinylated polylysine conjugate and irradiated with 1–2 J/cm² red light (λ_max = 671 nm). This two‐step regimen dramatically inhibited IL‐1‐stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor‐β1 in culture medium. This research may lead to the development of minimally invasive photodynamic therapy in which light is delivered to locally activate a chondroprotective program in photosensitized cartilage in the context of OA. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

The use of modular interlocking components is a central design feature of total joint replacements. In this investigation we hypothesized that clinically available ceramic–metal modular connections used in total hip arthroplasty release more metal through fretting corrosion than traditional metal–metal modular connections. This was investigated using an in vitro comparison of ceramic (zirconia, ZrO₂) and metal (Co‐alloy) femoral‐head fretting upon Co‐alloy stem components. In vitro fretting corrosion testing consisted of potentiodynamic monitoring and analysis of metal release from zirconia and Co‐alloy 28 mm femoral heads with similar surface roughnesses (Ra = 0.46 μm) on identical Co‐alloy stems at 2.2 kN for 1 × 10⁶ cycles at 2 Hz. In contrast to our original hypothesis, we found greater metal release (approximately 11‐fold increase in Co and 3‐fold increase in Cr) and potentiodynamic fretting of metal–metal modular junctions when compared to ceramic–metal. Potentiodynamic testing demonstrated that lower initial voltages (−266 < 153 mV), greater maximum voltage changes (116 > 56 mV, p < 0.05, t‐test) and voltage variability (3 > 0.5 mV, p < 0.05, t‐test) were associated with the open circuit potentials of Co‐alloy on Co‐alloy junctions when compared to zirconia on Co‐alloy junctions. In this study of a single total hip replacement stem and head design, zirconia heads mated with Co‐alloy stems produced less fretting than Co‐alloy heads mated with Co‐alloy stems. Although further studies are necessary with a variety of implant designs and under different experimental conditions, the evidence presented here should, in part, alleviate concerns of increases in fretting corrosion at modular junctions of ceramic–metal coupled components. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Avascular zones of tendons are predisposed for degenerative changes and spontaneous rupture. Therefore, we analyzed the expression of the endogenous angiogenesis inhibiting factor endostatin in human fetal and adult tendons by immunohistochemical and biochemical methods. Moreover, to elucidate factors involved in the regulation of vascularity, we exposed primary cultures of rat tendon cells to intermittent hydrostatic pressure (0.2 MPa, 0.1 Hz for 24 h), and measured the endostatin content by ELISA and the effect of the conditioned medium to the proliferation of human umbilical vein endothelial cells (HUVEC).

In fetal tendons high endostatin levels could be quantified by ELISA whereas low levels were found in adult tissue. In fetal tendons endostatin could also be immunostained in endothelial cells but mainly in fibroblasts. In adult Achilles tendons endostatin immunostaining was restricted to endothelial cells. In the tibialis posterior tendon—as an example for “wrap around”—endostatin immunostaining remained positive in the fibrocartilage adjacent to the medial malleolus. Fibrochondrocytes of the type II collagen positive fibrocartilage were intensively stained with the endostatin antibody. Factor VIII immunostaining showed that this region was largely avascular. Monolayer cultures of tendon cells released measurable amounts of endostatin into their culture supernatants. Application of intermittent hydrostatic pressure increased endostatin expression significantly. The conditioned media of tendon fibroblasts cultivated under intermittent hydrostatic pressure inhibited the proliferation of HUVEC in a dose dependent way.

The spatial expression of endostatin in adult gliding tendons suggests that mechanical factors are involved in the regulation of this anti‐angiogenic factor. In accordance, tendon cells exposed to intermittent hydrostatic pressure inhibit endothelial cell proliferation via humoral factors and produce endostatin. These findings support the view that the development and maintenance of avascular zones in tendons might be caused by a mechanically induced upregulation of anti‐angiogenic factors. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

The influence of torsional loading on the fatigue life of cortical bone was investigated by conducting in vitro testing. Fatigue tests were conducted on cylindrical dumbbell bovine cortical bone specimens in an environmental chamber under axial loading, torsional loading and various combinations of axial‐torsional loading where the phase relationship and relative magnitudes of axial and torsional loadings were systematically varied. It was found that the superposition of torque on axial loading reduced the fatigue life of cortical bone. The reduction in fatigue life was significant when the maximum shear stress was greater than 59% of the maximum normal stress. The magnitude of reduction in the fatigue life of bone at low as well as high levels of axial loading depended on the magnitude of torsional loading, but was independent of the phase angle by which the torsional loading lagged the axial loading. Furthermore, oblique fracture profiles, characteristic of torsion‐induced failure, were observed for combined axial‐torsional load cases. Based on these results, it is suggested that torsional loading plays a significant role in determining the fatigue life of cortical bone. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen‐replete (sham‐operated) and estrogen‐deplete (ovariectomized) female rats. Eight month old, retired breeder, sham‐operated and ovariectomized Sprague‐Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham‐operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham‐operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5–4.5‐fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine‐treated rats than in vehicle‐treated rats. However, differences were not detected between the high dose nicotine‐ and vehicle‐treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.

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

Roentgen stereophotogrammetric analysis (RSA) can be used to measure changes in anterior–posterior (A–P) knee laxity after anterior cruciate ligament (ACL) reconstruction. Previous measurements of A–P knee laxity using RSA have employed a tibial coordinate system with the origin placed midway between the tips of the tibial‐eminences. However, the precision in measuring A–P knee laxity might be improved if the origin was placed on the flexion–extension axis of rotation of the knee. The purpose of this study was to determine whether a center‐of‐rotation tibial coordinate system with the origin placed midway between the centers of the posterior femoral condyles, which closely approximates the flexion–extension center‐of‐rotation of the knee, improves the precision in measuring A–P knee laxity compared to the tibial‐eminence‐based coordinate system. A–P knee laxity was measured using each coordinate system six times in three human cadaveric knees implanted with 0.8‐mm diameter tantalum markers. For each laxity measurement, the knee was placed in a custom loading apparatus and biplanar radiographs were obtained while the knee resisted a 44 N posterior shear force and 136 N anterior shear force. A–P knee laxity was determined from the change in position of the tibia, with respect to the femur, resulting from the posterior and anterior shear forces. The precision for each coordinate system was calculated as the pooled standard deviation of A–P knee laxity measurements. The precision of the center‐of‐rotation coordinate system was 0.33 mm, which was about a factor of 2 better than the 0.62mm precision of the tibial‐eminence coordinate system (p = 0.006). The 0.33mm precision with the center‐of‐rotation coordinate system suggests that an observed change of either 0.56mm (i.e. 1.7 standard deviations) or greater in A–P knee laxity over time is a real change and not due to measurement error when the new tibial coordinate system is used and other factors contributing to variability are controlled as was done in this study. Accordingly, clinicians and researchers should consider the use of this alternate tibial coordinate system when making serial measurements of A–P knee laxity using RSA because the improved precision allows for the observation of smaller differences. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.