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.

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein-Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher's exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher's exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production.

Extracorporeal shockwave therapy shows a number of treatment related chondroprotective effect in osteoarthritis of the knee in rats.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) shows chondroprotective effect in osteoarthritis of the rat knees. However, the ideal number of ESWT is unknown. This study investigated the effects of different numbers of ESWT in osteoarthritis of the knee in rats. METHODS: Forty-five male Sprague-Dawley rats were divided into five groups. Group I underwent sham arthrotomy without anterior cruciate ligament transection (ACLT) or medial meniscectomy (MM) and received no ESWT. Group II underwent ACLT + MM and received no ESWT. Group III underwent ACLT + MM, and received ESWT once a week for one treatment. Group IV underwent ACLT + MM and received ESWT twice a week for 2 treatments. Group V underwent ACLT + MM and received ESWT three times a week for 3 treatments. Each treatment consisted of 800 impulses of shockwave at 14 Kv to the medial tibia condyle. The evaluations included radiographs of the knee, histomorphological examination and immunohistochemical analysis at 12 weeks. RESULTS: At 12 weeks, group II and V showed more radiographic arthritis than groups I, III and IV. On histomorphological examination, the Safranin O matrix staining in groups III and IV are significantly better than in groups II and V, and the Mankin scores in groups III and IV are less than groups II and V. Groups III and IV showed significant decreases of Mankin score and increase of Safranin O stain as compared to group I. Group V showed significant increases of Mankin score and a decrease of Safranin O stain as compared to group II. In articular cartilage, group II showed significant increase of MMP13 and decrease of collagen II as compared to group I. Groups III and IV showed significant decrease of MMP13 and increase of collagen II as compared to group I. Group V showed significant increase of MMP13 and decrease of collagen II as compared to group II. In subchondral bone, vWF, VEGF, BMP-2 and osteocalcin significantly decreased in groups II and V, but increased in groups III and IV relative to group I. CONCLUSIONS: ESWT shows a number of treatment related chondroproctective effect in osteoarthritis of the knee in rats.

Dkk-1 promotes angiogenic responses and cartilage matrix proteinase secretion in synovial fibroblasts from osteoarthritic joints.

OBJECTIVE: Synovial hypervascularity is a prominent pathologic feature in osteoarthritic (OA) joints. Wnt inhibitor Dkk-1 contributes to joint remodeling. We undertook this study to investigate whether Dkk-1 regulates cartilage destruction activities in OA synovial fibroblasts. METHODS: Synovial tissues were harvested from knees of patients with OA and from injured knees of non-OA patients who underwent arthroscopy. Expression of Dkk-1, angiogenic factors (stromal cell-derived factor 1 and colony-stimulating factor 1), and cartilage proteinases (ADAMTS-5 and matrix metalloproteinase 3 [MMP-3]) as well as vascularity in synovium and synovial fluid were quantified using enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and histomorphometry. Synovial fibroblasts were treated with interleukin-1ß (IL-1ß), anti-Dkk-1 antibody, and RNA interference to characterize their angiogenic activity. Rats with OA knees were administered Dkk-1 antisense oligonucleotide to verify synovial angiogenesis and cartilage integrity. RESULTS: OA synovium exhibited increased vascularity and expression of angiogenic factors and proteinases in association with up-regulated Dkk-1 levels. Neutralizing Dkk-1 reduced the inhibitory effects of OA synovial fluid on aggrecan expression in chondrocyte cultures. IL-1ß induction of Dkk-1 increased expression of hypoxia-inducible factor 1α (HIF-1α), angiogenic factors, ADAMTS-5, and MMP-3 in synovial fibroblasts and promoted angiogenesis in vascular endothelial cells. Knockdown of HIF-1α decreased Dkk-1 enhancement of angiogenic factor expression. Stabilization of glycogen synthase kinase 3ß phosphorylated at Ser(9) , ß-catenin, T cell factor 4, and ERK signaling attenuated Dkk-1 up-regulation of angiogenic factor and proteinase expression in synovial fibroblasts. In vivo, Dkk-1 interference reduced the expression of angiogenic factors and proteinases and ameliorated synovial vascularity and cartilage deterioration in knees of rats with OA. CONCLUSION: Dkk-1 promoted angiogenic and cartilage degradation activities in synovial fibroblasts, which accelerated synovial angiogenesis and cartilage destruction. Dkk-1 blockade has therapeutic potential for reducing OA-induced synovitis and joint deterioration.

Extracorporeal shockwave therapy shows chondroprotective effects in osteoarthritic rat knee.

PURPOSE: This study investigated the effects of extracorporeal shockwave therapy (ESWT) on the subchondral bone and articular cartilage in the initiation of osteoarthritis of the knee in rats. METHODS: Anterior cruciate ligament transected (ACLT) osteoarthritis (OA) rat knee model was used in this study. Twenty-seven male Sprague-Dawley rats were divided into three groups. The control group underwent sham surgery without ACLT and received no ESWT. The ACLT group underwent ACLT, but received no ESWT. The ACLT plus ESWT group underwent ACLT and received ESWT immediately after surgery. The evaluation parameters included radiograph, bone mineral density, serum levels of cartilage oligometric protein and osteocalcin, and urinary concentration of C-telopeptide of type II collagen (CTX-II), and histomorphological examination. RESULTS: At 12 weeks, OA of the knee was radiographically verified in the ACLT group, but very subtle changes were noticed in the control and the ACLT plus ESWT groups. On articular cartilage, the ACLT group showed significant increases in cartilage degradation and chondrocyte apoptosis compared to the control and ACLT plus ESWT groups. The ACLT plus ESWT group demonstrated significant decrease in the cartilage degradation and an increase in chondrocyte activity comparable to the control. In subchondral bone, the ACLT group showed a significant decrease in bone remodeling as compared to the control and ACLT plus ESWT groups. The ACLT plus ESWT group showed significant improvement in bone remodeling comparable to the control. CONCLUSION: Extracorporeal shockwave therapy shows chondroprotective effect associated with improvement in subchondral bone remodeling in the initiation of ACLT OA knee model in rats.

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.

VEGF modulates angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits.

OBJECTIVE: Strong vascular endothelial growth factor (VEGF) expression of osteoprogenitors was found in callus site during fracture healing. The aim of this study was to investigate whether VEGF modulates the angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits. MATERIALS AND METHODS: Twenty-seven Japanese rabbits were used in the study. A fracture of left tibia with 5 mm gap was created, and the fracture was stabilized with an external fixator. The rabbits were randomly divided into three groups. Group I was the control group and received no shockwave therapy. Group II received shockwave therapy, and group III was pretreated with bevacizumab, a monoclonal antibody against VEGF, before receiving shockwave. Radiographs of the tibia were obtained at 1, 4, and 8 wk. Bone mineral density was performed at 8 wk. The rabbits were euthanized at 8 wk, and the bone specimens were subjected to histomorphological examination and immunohistochemical analysis. RESULTS: At 8 wk, radiographs showed considerably better bone healing and remodeling of the fracture in group II compared with groups I and III, whereas no discernable difference was noted between group I and group III. The BMD values were significantly higher in group II than groups I and III, but no difference noted between group I and group III. In histomorphological examination, significant increases in bone tissue was were noted in group II compared with groups I and III, but no difference was noted between group I and group III. In immunohistochemical analysis, significant increases in VEGF, vWF, PCNA, BMP-2 and osteocalcin, and a decrease in TUNEL expression were observed in group II compared with groups I and III, but no statistical difference was noted between group I and group III. CONCLUSION: Significant increases in VEGF and angiogenic and osteogenic growth factors were noted in shockwave-promoted bone healing. Pre-treatment with bevacizumab inhibited VEGF and in turn, attenuated the effect of shockwave. It appears that VEGF modulates angiogenesis and osteogenesis in shockwave-promoted bone healing in rabbits.

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.

Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees.

OBJECTIVE: Perturbation of Wnt signaling components reportedly regulates chondrocyte fate and joint disorders. The Wnt inhibitor Dkk-1 mediates remodeling of various tissue types. We undertook this study to examine whether control of Dkk-1 expression prevents joint deterioration in osteoarthritic (OA) knees. METHODS: Anterior cruciate ligament transection-and collagenase-induced OA in rat knees was treated with end-capped phosphorothioate Dkk-1 antisense oligonucleotide (Dkk-1-AS). Articular cartilage destruction, cartilage degradation markers, bone mineral density (BMD), and subchondral trabecular bone volume of injured knee joints were measured using Mankin scoring, enzyme-linked immunosorbent assay, dual x-ray absorptiometry, and histomorphometry. Dkk-1-responsive molecule expression and apoptotic cells in knee tissue were detected by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and TUNEL staining. RESULTS: Up-regulated Dkk-1 expression was associated with increased Mankin score and with increased serum levels of cartilage oligomeric matrix protein and C-telopeptide of type II collagen (CTX-II) during OA development. Dkk-1-AS treatment alleviated OA-associated increases in Dkk-1 expression, Mankin score, cartilage fibrillation, and serum cartilage degradation markers. Dkk-1-AS also alleviated epiphyseal BMD loss and subchondral bone exposure associated with altered serum levels of osteocalcin and CTX-I. The treatment abrogated chondrocyte/osteoblast apoptosis and subchondral trabecular bone remodeling in OA. Dkk-1 knockdown increased levels of nuclear beta-catenin and phosphorylated Ser(473)-Akt but attenuated expression of inflammatory factors (Toll-like receptor 4 [TLR-4], TLR-9, interleukin-1beta, and tumor necrosis factor alpha), the apoptosis regulator Bax, matrix metalloproteinase 3, and RANKL in OA knee joints. CONCLUSION: Interference with the cartilage- and bone-deleterious actions of Dkk-1 provides therapeutic potential for alleviating cartilage destruction and subchondral bone damage in OA knee joints.

Inhibition of glycogen synthase kinase-3beta attenuates glucocorticoid-induced bone loss.

AIMS: Long-term glucocorticoid administration is known to induce bone deterioration. Glycogen synthase kinase-3beta (GSK-3beta) signaling reportedly participates in bone remodeling. This study investigated whether GSK-3beta inhibitor could regulate glucocorticoid-induced inhibition of osteoblast differentiation in vitro or bone mass in vivo. MAIN METHODS: MC3T3-E1 osteoblasts were treated with kinase-inactive GSK-3beta mutant and 6-bromoindirubin-3'-oxim (BIO) and then exposed to 1microM dexamethasone. Survival and osteoblast differentiation of cell cultures were assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling, quantitative RT-PCR, and von Kossa staining. Mineral density, biomechanical properties and microenvironments of BIO- and glucocorticoid-treated rat bone tissues were analyzed using dual-energy X-ray absorptiometry, material testing, and histomorphometry, respectively. KEY FINDINGS: Glucocorticoid decreased levels of phosphorylated Ser9-GSK-3beta and beta-catenin in osteoblast cultures. Kinase-inactive GSK-3beta mutant and BIO treatments attenuated dexamethasone-induced inhibition of beta-catenin, Runx2 abundance, and osteoblast differentiation but suppressed glucocorticoid-induced apoptosis of cell cultures. Exogenous BIO treatment alleviated methylprednisolone-induced impairment of mineral density, biomechanical strength, trabecular bone volume, osteoblast surface, and bone formation rate of rat bone tissue. BIO treatment also attenuated glucocorticoid-induced promotion of osteoclast surface and marrow adipocyte volume in bone tissue. Bone cells adjacent to glucocorticoid-stressed bone tissue displayed strong phosphorylated Ser9-GSK-3beta and beta-catenin immunostaining following BIO treatment. SIGNIFICANCE: Inhibition of GSK-3beta abrogated glucocorticoid-induced bone loss by increasing beta-catenin- and Runx2-mediated osteoblast differentiation. Controlling GSK-3beta signaling in bone cells may be a strategy for preventing glucocorticoid-induced osteopenia.

Functional outcomes of arthroscopic posterior cruciate ligament reconstruction: comparison of anteromedial and anterolateral trans-tibia approach.

INTRODUCTION: The hypothesis of this study is that anterolateral (A-L) trans-tibia approach is better than anteromedial (A-M) technique in posterior cruciate ligament (PCL) reconstruction. The purpose of this prospective clinical study was to compare the functional outcomes of A-M and A-L trans-tibia approach in arthroscopic PCL reconstruction. MATERIALS AND METHODS: Between 1999 and 2003, 55 patients (55 knees) with an average age of 30 +/- 11 years (range 16-60 years) underwent arthroscopic single-bundle reconstruction for symptomatic isolated PCL tear. Patients were randomly divided into two groups with 28 patients (28 knees) undergoing A-M trans-tibia approach on odd-numbered days, and 27 patients (27 knees) with A-L trans-tibia approach on even-numbered days. Hamstring auto grafts were used in all cases. All patients received the same rehabilitation program postoperatively. The evaluation parameters included clinical assessment, functional outcome, ligament laxity and radiographic changes of the affected knee. RESULTS: Significant improvements in pain and function of the knee were observed at an average follow-up of 48 +/- 15.9 months for A-M and 45.0 +/- 13.7 months for A-L approach. However, the difference between the two techniques was statistically not significant. In IKDC for symptom-activity level, normal or nearly normal knees were noted in 68% of A-M and 67% of A-L approach, respectively, but no difference was noted between the two groups. In ligament laxity, approximately two-thirds of the knees showed normal posterior laxity with no difference between the two groups. Radiographs of the knee showed no discernible difference in the overall alignment and degenerative changes as well as the sizes of bone tunnel between the two groups. CONCLUSION: A-M and A-L trans-tibia arthroscopic PCL reconstructions produced comparable clinical results in short-term follow-up. Contrary to our initial hypothesis, the theoretical disadvantages of A-M technique including graft failure were not observed during the follow-up period. Long-term results are needed to confirm the adverse effects of A-M trans-tibia approach in PCL reconstruction.

Management of nonunion associated with broken intramedullary nail of the femur.

This study analyzed 14 patients with 17 broken intramedullary nails for the treatment of femoral fractures. Average distance from the fracture site was 7.9 cm in cases in which nail breakage occurred at the junction between the cylindrical and cloverleaf portions and 6.4 cm in cases in which nail breakage occurred at the screw hole. Eleven patients with 14 broken nails were treated with exchange nailing and bone grafting, 2 were treated with plating and bone grafting, and 1 was treated with extracorporeal shock wave therapy. Nonunion or delayed union is the main cause of nail breakage. Exchange nailing with bone grafting is a safe and effective method of treatment for a broken intramedullary nail with nonunion.

Clinical significance of muscular deep-vein thrombosis after total knee arthroplasty.

BACKGROUND: The definition of gastrocneumus and soleus deep-vein thrombosis (DVT) remains controversial. The purpose of this study was to evaluate the clinical significance of muscular deep-vein thrombosis after total knee arthroplasty (TKA). METHODS: This study consisted of 359 consecutive patients undergoing TKA evaluated for DVT by ascending venography. Venographies were performed 5 to 7 days after surgery. Those patients showing positive DVT underwent a follow-up venographic study at 3 months. The evaluation parameters included clinical symptoms, late DVT, thrombus propagation and pulmonary embolism. The data from patients with isolated muscular DVT were compared statistically with those patients with DVT of the leg veins and combined DVT. RESULTS: Of 359 patients, 175 (49%) developed venographic DVT including 160 with distal and 15 with proximal DVT. Of the 160 cases with distal DVT, 83 (52%) involved the gastroneumus and soleus muscular veins. Of these 83 cases, 38 (46%) were isolated muscular DVT and 45 (54%) involved muscular branches and major leg veins including the anterior and posterior tibial and peroneal veins. Patients with isolated muscular DVT showed comparable rates of clinical symptoms, late DVT, thrombus propagation and no pulmonary embolism compared with patients with DVT in the major leg veins (p = 0.874, 0.398 and 1.000) and patients with combined DVT (p = 0.155, 0.592 and 1.000). CONCLUSION: The clinical significance of isolated muscular DVT is comparable to that of the major leg veins and combined DVT. Muscular DVT in the calf is considered a significant clinical entity and should be treated accordingly.

Extracorporeal shockwave for chronic patellar tendinopathy.

BACKGROUND: Chronic patellar tendinopathy is an overuse syndrome with pathologic changes similar to tendinopathies of the shoulder, elbow, and heel. Extracorporeal shockwave was shown effective in many tendinopathies. HYPOTHESIS: Extracorporeal shockwave therapy may be more effective than conservative treatment for chronic patellar tendinopathy. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 2. METHODS: This study consisted of 27 patients (30 knees) in the study group and 23 patients (24 knees) in the control group. In the study group, patients were treated with 1500 impulses of extracorporeal shockwave at 14 KV (equivalent to 0.18 mJ/mm(2) energy flux density) to the affected knee at a single session. Patients in the control group were treated with conservative treatments including nonsteroidal anti-inflammatory drugs, physiotherapy, exercise program, and the use of a knee strap. The evaluation parameters included pain score, Victorian Institute of Sports Assessment score, and ultrasonographic examination at 1, 3, 6, and 12 months and then once a year. RESULTS: At the 2- to 3-year follow-up, the overall results for the study group were 43% excellent, 47% good, 10% fair, and none poor. For the control group, the results were none excellent, 50% good, 25% fair, and 25% poor. The mean Victorian Institute of Sports Assessment scores were 42.57 +/- 10.22 and 39.25 +/- 10.85, respectively, before treatment (P = .129) and 92.0 +/- 10.17 and 41.04 +/- 10.96, respectively, after treatment (P < .001). Satisfactory results were observed in 90% of the study group versus 50% of the control group (P < .001). Recurrence of symptoms occurred in 13% of the study group and 50% of the control group (P = .014). Ultrasonographic examination showed a significant increase in the vascularity of the patellar tendon and a trend of reduction in the patellar tendon thickness after shockwave treatment compared with conservative treatments. However, no significant difference in the appearance, arrangement, and homogeneity of tendon fibers was noted between the 2 groups. There were no systemic or local complications or device-related problems. CONCLUSION: Extracorporeal shockwave therapy appeared to be more effective and safer than traditional conservative treatments in the management of patients with chronic patellar tendinopathy.

Long-term results of extracorporeal shockwave treatment for plantar fasciitis.

BACKGROUND: Extracorporeal shockwave treatment has shown mixed short-term results for plantar fasciitis. However, the long-term results are not available. HYPOTHESIS: Long-term results of shockwave treatment are comparable with short-term results. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: This prospective study consisted of 149 patients (168 heels) with an established diagnosis of chronic plantar fasciitis, including 79 patients (85 heels) in the shockwave treatment group and 70 patients (83 heels) in the control group. In the shockwave group, patients received 1500 impulses of shockwaves at 16 kV to the affected heel in a single session. Patients in the control group received conservative treatment consisting of nonsteroidal anti-inflammatory drugs, orthotics, physical therapy, an exercise program, and/or a local cortisone injection. Patients were evaluated at 60 to 72 months (shockwave group) or 34 to 64 months (control group) with a 100-point scoring system including 70 points for pain and 30 points for function. The clinical outcomes were rated as excellent, good, fair, or poor. RESULTS: Before treatment, the groups showed no significant differences in the scores for pain and function. After treatment, the shockwave group showed significantly better pain and function scores as compared with the control group. The overall results were 69.1% excellent, 13.6% good, 6.2% fair, and 11.1% poor for the shockwave group; and 0% excellent, 55% good, 36% fair, and 9% poor for the control group (P < .001). The recurrence rate was 11% (9/81 heels) for the shockwave group versus 55% (43/78 heels) for the control group (P < .001). There were no systemic or local complications or device-related problems. CONCLUSION: Extracorporeal shockwave treatment is effective and safe for patients with plantar fasciitis, with good long-term results.

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.

Posterior cruciate ligament reconstruction using hamstring tendon graft with remnant augmentation.

Despite good early functional results, the posterior laxity of the knee is not completely eliminated after posterior cruciate ligament (PCL) reconstruction. The PCL can retain the normal tension only when the injured ligament is maintained anatomically. This article describes a technique of PCL reconstruction using hamstring tendon graft with PCL remnant augmentation. The harvested hamstring tendons were quadrupled, sized, and pretensioned before use. The PCL remnants and the synovium were preserved. Minimal debridement was performed to gain access to the insertion sites. The tibia and femoral tunnels were created with graft size-matched reamers. The graft was transfixed at 70 degrees of knee flexion with a 15-lb anterior drawer force on the proximal tibia. This surgical technique has several advantages. The hamstring graft acts as an independent PCL reconstruction and maintains the PCL remnant tension. The PCL remnants and synovium may be beneficial to ligament healing and postoperative rehabilitation. The procedure is technically feasible and cosmetically acceptable. The selection of autograft precludes the risks of allograft and artificial ligament. The short-term results are encouraging, but long-term results are needed to confirm the value of this technique for PCL reconstruction.

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.

The effect of shock wave treatment at the tendon-bone interface-an histomorphological and biomechanical study in rabbits.

PURPOSE: This study was performed to investigate the effect of shock wave treatment on the healing at tendon-bone interface in rabbits. MATERIALS AND METHODS: Thirty-six New Zealand White rabbits were used in this study. The anterior cruciate ligament was excised and replaced with the long digital extensor. The right knees (study group) were treated with 500 impulses of shock waves at 14 kV, while the left knees (control group) received no shock waves. Histomorphological studies were performed in 24 rabbits at 1, 2, 4, 8, 12 and 24 weeks. Biomechanical studies were performed in 12 rabbits at 12 and 24 weeks. RESULTS: There was significantly more trabecular bone around the tendons noted in the study group compared with the control group at different time intervals after 4 weeks (P<0.05). The contacting between bone and tendon was significantly better in the study group than the control group after 8 weeks (P<0.05). The tensile strength of the tendon-bone interface was significantly higher in the study group than the control group at 24 weeks (P=0.018), whereas similar modes of graft failure were noted between the two groups. CONCLUSION: Shock wave treatment significantly improves the healing rate of the tendon-bone interface in a bone tunnel in rabbits. The effect of shock waves appears to be time-dependent.