Journal of orthopaedic research : official publication of the Orthopaedic Research Society
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The vertebral column is the most frequent site of metastatic involvement of the skeleton with up to 1/3 of all cancer patients developing spinal metastases. Longer survival times for patients, particularly secondary to breast cancer, have increased the need for better understanding the impact of skeletal metastases on structural stability. This study aims to apply image registration to calculate strain distributions in metastatically involved rodent vertebrae utilizing µCT imaging. ⋯ Metastatically involved vertebrae had greater strain magnitude than control vertebrae. Strain concentrations at the dorsal wall in only the metastatic vertebrae, were consistent with higher incidence of burst fracture secondary to this pathology. Future use of image registration of whole vertebrae will allow focused examination of the efficacy of targeted and systemic treatments in reducing strains and the related risk of fracture in pathologic bones under simple and complex loading.
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Randomized Controlled Trial Comparative Study
Sensitivity of gait parameters to the effects of anti-inflammatory and opioid treatments in knee osteoarthritis patients.
The study aim was to address the need for objective markers of pain-modifying interventions by testing the hypothesis that selective gait measures of knee joint loading can distinguish differences between non-steroidal anti-inflammatory (NSAID), analgesic treatment (opioid-receptor agonist), and placebo in patients medial knee osteoarthritis (OA). A randomized, single-blind washout, double-blind treatment, double-dummy cross-over trial using three treatment arms placebo, opioid (Oxycodone), and NSAID (Celecoxib) in medial compartment knee OA patients. Six patients with Kellgren-Lawrence radiographic severity grades of 2 or 3 completed six testing sessions (gait and pain assessment) at 2-week intervals. ⋯ Self-reported function (WOMAC scores) was not different among treatments (p>0.05). The changes in total reaction moments and GRFs for only the NSAID suggest that greater increases in joint loading occurs when joint inflammation is treated in addition to pain. The total knee reaction moment, representing the magnitude of the extrinsic moment, appears to be a sensitive marker, more so than self-reported metrics, for evaluating knee OA treatment effects.
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Large, osseous, segmental defects heal poorly. Muscle has a propensity to form bone when exposed to an osteogenic stimulus such as that provided by transfer and expression of cDNA encoding bone morphogenetic protein-2 (BMP-2). The present study evaluated the ability of genetically modified, autologous muscle to heal large cranial defects in rats. ⋯ Although none of the defects were completely healed in this time, muscle grafts expressing BMP-2 deposited more than twice as much new bone as controls. Histology confirmed the anatomical integrity of the newly formed bone, which was comparable in thickness and mineral density to the original cranial bone. This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone.
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We examined the mechanical response of the distal radius pre-fracture and at fracture under dynamic impact loads. The distal third of eight human cadaveric radii were potted and placed in a custom designed pneumatic impact system. The distal intra-articular surface of the radius rested against a model scaphoid and lunate, simulating 45° of wrist extension. ⋯ The mean (SD) resultant impact reaction force (IRFr) at failure was 2,142 (1,229) N, resulting in high compressive strains at the distal (2,718 (1,698) µε) and proximal radius (3,664 (1,890) µε). We successfully reproduced consistent fracture patterns in response to dynamic loads. The fracture energy and forces reported here are lower and the strains are higher than those previously reported and can likely be attributed to the controlled, incremental, dynamic nature of the applied loads.
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The notochordal cell (NC) of the nucleus pulposus (NP) is considered a potential NP progenitor cell, and early intervertebral disk (IVD) degeneration involves replacement of NCs by chondrocyte-like cells (CLCs). Wnt/β-catenin signaling plays a crucial role in maintaining the notochordal fate during embryogenesis, but is also involved in tissue degeneration and regeneration. The canine species, which can be subdivided into non-chondrodystrophic and chondrodystrophic breeds, is characterized by differential maintenance of the NC: in non-chondrodystrophic dogs, the NC remains the predominant cell type during the majority of life, with IVD degeneration only occurring at old age; conversely, in chondrodystrophic dogs the NC is lost early in life, with concurrent degeneration of all IVDs. ⋯ Both NCs and CLCs showed nuclear and cytoplasmic β-catenin protein expression and axin2 gene expression, but β-catenin signal intensity and Wnt target gene expression were higher in the CLC-rich NP. Primary NCs in monolayer culture (normoxic conditions) showed Wnt/β-catenin signaling comparable to the in vivo situation, with increased cyclin D1 and c-myc gene expression. In conclusion, Wnt/β-catenin signaling activity in the NC within the NC-rich NP and in culture supports the role of this cell as a potential progenitor cell; increased Wnt/β-catenin signaling activity in early IVD degeneration may be a reflection of its dual role.