Lin-Hsiu Weng

Treatment for osteonecrosis of the femoral head : Comparison of extracorporeal shock waves with core decompression and bone-grafting

BACKGROUND There is continuing controversy regarding the optimal treatment for patients with symptomatic early-stage osteonecrosis of the femoral head. We compared the results of noninvasive treatment with extracorporeal shock waves with those of core decompression and bone-grafting in similar groups of patients. METHODS Patients with stage-I, II, or III osteonecrosis were randomly assigned to be treated either with shock waves or with core decompression and nonvascularized fibular grafting. The shock-wave group consisted of twenty-three patients (twenty-nine hips), and the surgical group consisted of twenty-five patients (twenty-eight hips). The patients in the two groups had similar demographic characteristics, duration and stage of disease, and duration of follow-up. The patients in the shock-wave group received a single treatment with 6000 impulses of shock waves at 28 kV to the affected hip. The evaluation parameters included clinical assessment of pain with a visual analog pain scale, Harris hip scores, and an assessment of activities of daily living and work capacity. Radiographic assessment was performed with serial plain radiographs and magnetic resonance imaging. RESULTS Before treatment, the two groups had similar pain and Harris hip scores. At an average of twenty-five months after treatment, the pain and Harris hip scores in the shock-wave group were significantly improved compared with the pretreatment scores (p < 0.001). In this group, 79% of the hips were improved, 10% were unchanged, and 10% were worse. Of the hips treated with a nonvascularized fibular graft, 29% were improved, 36% were unchanged, and 36% were worse. In the shock-wave group, imaging studies showed regression of five of the thirteen lesions that had been designated as stage I or II before treatment and no regression of a stage-III lesion. Two stage-II and two stage-III lesions progressed. In the surgical group, four lesions regressed and fifteen (of the nineteen graded as stage I or II) progressed. The remaining nine lesions were unchanged. CONCLUSIONS Extracorporeal shock-wave treatment appeared to be more effective than core decompression and nonvascularized fibular grafting in patients with early-stage osteonecrosis of the femoral head. Long-term results are needed to determine whether the effect of this novel method of treatment for osteonecrosis of the femoral head endures.

Three-year changes in bone mineral density around the knee after a six-month course of oral alendronate following total knee arthroplasty. A prospective, randomized study.

BACKGROUND Bone mineral density decreases after total knee arthroplasty and is believed to affect prosthetic fixation. Treatment with alendronate has been shown to improve short-term bone mineral density after total knee arthroplasty; however, the long-term effects of this therapy are unknown. The purpose of this study was to evaluate the long-term effects of a six-month course of alendronate on bone mineral density after total knee arthroplasty. METHODS Sixty patients were randomly assigned to receive either oral alendronate at a dosage of 10 mg/day for six months or no alendronate. The bone mineral density in the distal aspect of the femur and the proximal aspect of the tibia was measured preoperatively and at six, twelve, and thirty-six months after total knee arthroplasty. RESULTS Fifty-four patients (twenty-nine in the alendronate group and twenty-five in the control group) completed the study. The alendronate group showed significant increases in bone mineral density in the distal aspect of the femur compared with the controls at six months (+4.8% and -14.2%, respectively; p < 0.01) and twelve months (+1.6% and -11.5%, respectively; p < 0.01). No significant difference in bone mineral density was detected between the groups at thirty-six months (-3.9% and -12.2%, respectively; p = 0.08). Similar trends in bone mineral density changes were also observed in the proximal aspect of the tibia. CONCLUSIONS A six-month course of alendronate initially increased bone mineral density at six and twelve months after total knee arthroplasty, but no difference was noted after thirty-six months. The effect of alendronate on bone mineral density after total knee arthroplasty may be limited after discontinuation of therapy.

Extracorporeal shockwave shows regression of osteoarthritis of the knee in rats.

BACKGROUND This study investigated the effects of extracorporeal shockwave technology (ESWT) in osteoarthritis of the knee in rats. MATERIALS AND METHODS Thirty-six Sprague-Dawley rats were randomly divided into three groups with 12 rats in each group. Group I was the control group and received neither anterior cruciate ligament transection (ACLT) nor ESWT. In groups II and III, ACLT was performed in left knee and osteoarthritis (OA) was verified at 12 wk. Group II received no ESWT, and group III received ESWT at 12 wk after ACLT. Radiographs and bone mineral density (BMD) were obtained at 0, 12, and 24 wk. The animals were sacrificed at 24 wk. One half of the animals were subjected to bone strength test, and the other half for histomorphologic examination and immunohistochemical analysis. RESULTS Radiographs of the left knee showed progressive OA changes at 12 and 24 wk in group II, whereas, very subtle OA changes were noted in group I and group III. BMD and bone strength were significantly lower in group II compared with groups I and III, but no difference was noted between group I and group III. The cartilage degradations were significantly higher in group II compared with groups I and III, but no difference was noted between group I and group III. The subchondral bone remodeling was significantly less pronounced in group II compared with groups I and III, but no difference was noted between group I and group III. CONCLUSIONS Application of ESWT to the subchondral bone of the medial tibia condyle showed regression of osteoarthritis of the knees in rats.

pCMV-BMP-2-Transfected Cell-Mediated Gene Therapy in Anterior Cruciate Ligament Reconstruction in Rabbits

PURPOSE This study investigated the effect of plasmid cytomegalovirus (pCMV)-bone morphogenetic protein 2 (BMP-2) gene therapy on the healing of the tendon-bone interface after anterior cruciate ligament (ACL) reconstruction in rabbits. METHODS The pCMV-BMP-2 was synthesized from full-length human BMP-2 complementary deoxyribonucleic acid, followed by cloning into pCMV Script vector (Clontech Laboratories, Inc., San Jose, CA), and was delivered by a xenogeneic (rat kidney) cell line. The ACL was reconstructed by the transfer of extensor digital tendon in the proximal tibia. In the study group the pCMV-BMP-2 gene-transfected normal rat kidney cells mixed with calcium alginate gel were placed at the tendon-bone interface, whereas no pCMV-BMP-2 was used in the control group. The evaluations included radiography, bone mineral density, magnetic resonance imaging, biomechanical study, histologic examination, and immunohistochemical analysis. RESULTS Bone mineral density showed no significant difference between the groups (P > .05). Magnetic resonance imaging showed significantly better contact between tendon and bone in the study group compared with the control group (P < .0001). In the biomechanical study, significantly higher failure load and maximal graft tension were noted in the study group compared with the control group (P = .034). The modes of graft failure were rupture of the tendon proper in 78% and graft pullout from the bone tunnel in 22% of specimens in the study group versus graft rupture in 22% and graft pullout in 78% in the control group (P = .018). On histologic examination, the study group showed significantly better integration between tendon and bone, as well as more bone tissue around the tendon graft, than the control group (P = .0004). On immunohistochemical analysis, the study group showed significantly higher expressions of von Willebrand factor, vascular endothelial growth factor, proliferation cell nuclear antigen, and BMP-2 than the control group (P < .05). CONCLUSIONS The pCMV-BMP-2 gene therapy significantly improved the healing of tendon to bone and promoted angiogenesis and osteogenesis at the tendon-bone interface after ACL reconstruction in the rabbit model. CLINICAL RELEVANCE Application of pCMV-BMP-2 gene therapy may be an effective adjunct therapy in ACL reconstruction.

MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12

Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a expression within the articular compartment. Intra-articular injections with miR-128a antisense oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated articular tissue destruction, including cartilage erosion, synovitis, osteophyte formation, and subchondral plate damage. In vitro, miR-128 signaling hindered Atg12 expression, LC3-II conversion, and autophagic puncta formation through targeting the 3′-untranslated region of Atg12. It increased apoptotic programs, diminishing cartilage formation capacity of articular chondrocytes. Inactivating histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR-128a promoter and upregulated miR-128a transcription in inflamed chondrocytes. Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to accelerate miR-128a actions. Interruption of miR-128a signaling attenuated chondrocyte dysfunction and delayed OA development. Our data provide new insights into how miR-128a signaling affects chondrocyte survival and articular cartilage anabolism and highlight the potential of miR-128a targeting therapy to alleviate knee OA.