IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse.

Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.

Metabolomics-based profiles predictive of low bone mass in menopausal women.

Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis. To do so, we enrolled healthy volunteer and osteoporosis patient female subjects, surveyed them with a questionnaire, measured their BMD, and then undertook a comprehensive metabolomics analysis of sera of the three groups named above. We identified 24 metabolites whose levels differed significantly between NN/LN and NN/LL groups, as well as 18 or 10 metabolites whose levels differed significantly between NN/LN and LN/LL, or LN/LL and NN/LN groups, respectively. Our data shows metabolomics changes represent useful markers to predict estrogen deficiency and/or bone loss.

A serum metabolomics-based profile in low bone mineral density postmenopausal women.

Osteoporosis is characterized as a metabolic disorder of bone tissue, and various metabolic markers are now available to support its diagnosis and evaluate treatment effects. Substances produced as end products of metabolomic activities are the correlated factors to the biological or metabolic status, and thus, metabolites are considered highly sensitive markers of particular pathological states, including osteoporosis. Here we undertook comprehensive serum metabolomics analysis in postmenopausal women with or without low bone mineral density (low BMD vs controls) for the first time using capillary electrophoresis/mass spectrometry. Among the metabolites tested, 57 were detected in sera. Levels of hydroxyproline, Gly-Gly and cystine, differed significantly between groups, with Gly-Gly and cystine significantly lower in the low BMD group and hydroxyproline, a reported marker of osteoporosis, significantly higher. Levels of TRACP5b, a bone resorption marker, were significantly higher in the low BMD group, supporting the study's validity. Taken together, our findings represent novel metabolomic profiling in low BMD in postmenopausal women.

Vitamin D Deficiency with High Intact PTH Levels is More Common in Younger than in Older Women: A Study of Women Aged 39-64 Years.

Low serum 25-hydroxyvitamin D (25(OH)D) levels are implicated as a risk factor for hip and spine fractures. Studies of the relation between 25(OH)D levels and fractures have primarily involved elderly osteoporosis patients or patients with fractures; however, the serum 25(OH)D and parathyroid hormone (PTH) status in younger adult populations remains largely unknown. We evaluated serum 25(OH)D and intact PTH levels in 411 women aged 39-64 years who were not receiving medication for osteoporosis or other bone diseases. Serum 25(OH)D levels were positively correlated with age (P = 0.019), whereas intact PTH levels were inversely correlated with 25(OH)D levels (P < 0.001). Thus, low vitamin D levels with high intact PTH levels were more common in younger than in older women. Our data show that serum 25(OH)D insufficiency could be a more serious concern in the younger population than had been previously anticipated. Because serum 25(OH)D insufficiency is reportedly a risk factor for hip and spine fracture, the number of fracture patients could increase in the future, suggesting that we may need to correct the serum vitamin D/intact PTH status to prevent future osteoporosis.

Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors.

The increasing number of osteoporosis patients is a pressing issue worldwide. Osteoporosis frequently causes fragility fractures, limiting activities of daily life and increasing mortality. Many osteoporosis patients take numerous medicines due to other health issues; thus, it would be preferable if a single medicine could ameliorate osteoporosis and other conditions. Here, we screened 96 randomly selected drugs targeting various diseases for their ability to inhibit differentiation of osteoclasts, which play a pivotal role in development of osteoporosis, and identified methotrexate (MTX), as a potential inhibitor. MTX is currently used to treat sarcomas or leukemic malignancies or auto-inflammatory diseases such as rheumatoid arthritis (RA) through its anti-proliferative and immunosuppressive activities; however, a direct effect on osteoclast differentiation has not been shown. Here, we report that osteoclast formation and expression of osteoclastic genes such as NFATc1 and DC-STAMP, which are induced by the cytokine RANKL, are significantly inhibited by MTX. We found that RANKL-dependent calcium (Ca) influx into osteoclast progenitors was significantly inhibited by MTX. RA patients often develop osteoporosis, and osteoclasts are reportedly required for joint destruction; thus, MTX treatment could have a beneficial effect on RA patients exhibiting high osteoclast activity by preventing both osteoporosis and joint destruction.

Bcl6 promotes osteoblastogenesis through Stat1 inhibition.

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in significant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-deficient mice in vivo. Altered osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.

Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.

Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1ß in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.

Mycobacterium tuberculosis promotes arthritis development through Toll-like receptor 2.

Rheumatoid arthritis (RA) is a multifactorial disease caused by genetic and environmental factors: however, precise molecular mechanisms underlying its pathogenesis remain largely unknown. Treatment of RA patients with disease-modifying biological agents occasionally promotes Mycobacterium tuberculosis infection or recurrence of M. tuberculosis, although how infection promotes arthritis has not been characterized. Here, we found that arthritis phenotypes in a collagen-induced mouse model were evident only when killed M. tuberculosis was co-administered. Treatment of cultured macrophages with killed M. tuberculosis promoted production of IL-6, a major inflammatory cytokine in RA patients, while similar treatment of TLR2-deficient macrophages failed to induce IL-6 expression. Arthritis scores, joint destruction, and serum IL-6 levels were all significantly ameliorated in TLR2-deficient compared with wild-type mice, even in animals treated with killed M. tuberculosis. These results suggest that M. tuberculosis infection enhances arthritis development and that TLR2 could serve as a therapeutic target for some forms of the disease.

The vitamin D analogue ED71 but Not 1,25(OH)2D3 targets HIF1α protein in osteoclasts.

Although both an active form of the vitamin D metabolite, 1,25(OH)2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH)2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH)2D3, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH)2D3 or ED71 function in osteoclasts requires the vitamin D receptor (VDR). ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH)2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnß mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH)2D3 in vitro, were both significantly higher following treatment with 1,25(OH)2D3 than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH)2D3, could be a reliable read-out in either developing or screening reagents targeting osteoporosis.

HIF1α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis.

In women, estrogen deficiency after menopause frequently accelerates osteoclastic bone resorption, leading to osteoporosis, the most common skeletal disorder. However, mechanisms underlying osteoporosis resulting from estrogen deficiency remain largely unknown. Here we show that in bone-resorbing osteoclasts, estrogen-dependent destabilization of hypoxia-inducible factor 1 alpha (HIF1α), which is unstable in the presence of oxygen, plays a pivotal role in promoting bone loss in estrogen-deficient conditions. In vitro, HIF1α was destabilized by estrogen treatment even in hypoxic conditions, and estrogen loss in ovariectomized (Ovx) mice stabilized HIF1α in osteoclasts and promoted their activation and subsequent bone loss in vivo. Osteoclast-specific HIF1α inactivation antagonized bone loss in Ovx mice and osteoclast-specific estrogen receptor alpha deficient mice, both models of estrogen-deficient osteoporosis. Oral administration of a HIF1α inhibitor protected Ovx mice from osteoclast activation and bone loss. Thus, HIF1α represents a promising therapeutic target in osteoporosis.

An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion.

Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs.

Conditional inactivation of Blimp1 in adult mice promotes increased bone mass.

Bone resorption, which is regulated by osteoclasts, is excessively activated in bone destructive diseases such as osteoporosis. Thus, controlling osteoclasts would be an effective strategy to prevent pathological bone loss. Although several transcription factors that regulate osteoclast differentiation and function could serve as molecular targets to inhibit osteoclast formation, those factors have not yet been characterized using a loss of function approach in adults. Here we report such a study showing that inactivation of B-lymphocyte induced maturation protein 1 (Blimp1) in adult mice increases bone mass by suppressing osteoclast formation. Using an ex vivo assay, we show that osteoclast differentiation is significantly inhibited by Blimp1 inactivation at an early stage of osteoclastogenesis. Conditional inactivation of Blimp1 inhibited osteoclast formation and increased bone mass in both male and female adult mice. Bone resorption parameters were significantly reduced by Blimp1 inactivation in vivo. Blimp1 reportedly regulates immune cell differentiation and function, but we detected no immune cell failure following Blimp1 inactivation. These data suggest that Blimp1 is a potential target to promote increased bone mass and prevent osteoclastogenesis.

PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo.

Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor α (PDGFRα)-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGFß) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.

Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis.

Osteoporosis is a complex disease with various causes, such as estrogen loss, genetics, and aging. Here we show that a dominant-negative form of aldehyde dehydrogenase 2 (ALDH2) protein, ALDH2*2, which is produced by a single nucleotide polymorphism (rs671), promotes osteoporosis due to impaired osteoblastogenesis. Aldh2 plays a role in alcohol-detoxification by acetaldehyde-detoxification; however, transgenic mice expressing Aldh2*2 (Aldh2*2 Tg) exhibited severe osteoporosis with increased levels of blood acetaldehyde without alcohol consumption, indicating that Aldh2 regulates physiological bone homeostasis. Wild-type osteoblast differentiation was severely inhibited by exogenous acetaldehyde, and osteoblastic markers such as osteocalcin, runx2, and osterix expression, or phosphorylation of Smad1,5,8 induced by bone morphogenetic protein 2 (BMP2) was strongly altered by acetaldehyde. Acetaldehyde treatment also inhibits proliferation and induces apoptosis in osteoblasts. The Aldh2*2 transgene or acetaldehyde treatment induced accumulation of the lipid-oxidant 4-hydroxy-2-nonenal (4HNE) and expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that promotes adipogenesis and inhibits osteoblastogenesis. Antioxidant treatment inhibited acetaldehyde-induced proliferation-loss, apoptosis, and PPARγ expression and restored osteoblastogenesis inhibited by acetaldehyde. Treatment with a PPARγ inhibitor also restored acetaldehyde-mediated osteoblastogenesis inhibition. These results provide new insight into regulation of osteoporosis in a subset of individuals with ALDH2*2 and in alcoholic patients and suggest a novel strategy to promote bone formation in such osteopenic diseases.

Osteoclast stimulatory transmembrane protein and dendritic cell­specific transmembrane protein cooperatively modulate cell­cell fusion to form osteoclasts and foreign body giant cells.

Cell­cell fusion is a dynamic phenomenon promoting cytoskeletal reorganization and phenotypic changes. To characterize factors essential for fusion of macrophage lineage cells, we identified the multitransmembrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), and analyzed its function. OC-STAMP­deficient mice exhibited a complete lack of cell­cell fusion of osteoclasts and foreign body giant cells (FBGCs), both of which are macrophage-lineage multinuclear cells, although expression of dendritic cell specific transmembrane protein (DC-STAMP), which is also essential for osteoclast/FBGC fusion, was normal. Crossing OC-STAMP­overexpressing transgenic mice with OC-STAMP­deficient mice restored inhibited osteoclast and FBGC cell­cell fusion seen in OC-STAMP­deficient mice. Thus, fusogenic mechanisms in macrophage-lineage cells are regulated via OC-STAMP and DC-STAMP.

Factors affecting anterior knee pain following anatomic double-bundle anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study was to evaluate the prevalence of anterior knee pain in anatomic double-bundle anterior cruciate ligament (ACL) reconstruction and to identify critical factors affecting postoperative anterior knee pain development. METHODS: Subjects comprised 171 patients (171 knees) who underwent anatomic double-bundle ACL reconstruction with a follow-up period of ≥2 years. The procedure used bone-patellar tendon-bone plus gracilis tendon (BTB-G) in 56 knees, semitendinosus tendon (ST) in 71 knees, and ST-G in 44 knees. Clinical results and prevalence and severity of anterior knee pain were assessed at 3 months and 2 years postoperatively. Clinical variables influencing anterior knee pain development at each postoperative period were subjected to univariate analysis, followed by logistic regression analysis to identify risk factors for anterior knee pain. RESULTS: Overall prevalences of anterior knee pain at 3 months and 2 years postoperatively were 42.0 and 11.1%, respectively. Use of BTB-G graft represented the highest prevalence of anterior knee pain between the 3 different grafts (P = 0.001); however, this statistical significance disappeared at 2 years postoperatively. Prevalence of postoperative extension deficit was significantly higher in anterior knee pain-positive cohort than in anterior knee pain-negative cohort at 3 months postoperatively. Level of quadriceps strength was significantly lower, and Lysholm score was significantly worse in anterior knee pain-positive cohort than in anterior knee pain-negative cohort at 2 years postoperatively. According to logistic regression analysis, knee extension deficit was a predisposing factor for the development of anterior knee pain at 3 months postoperatively (odds ratio, 2.76; P = 0.004); however, there was no significant predisposing factor for anterior knee pain at 2 years postoperatively. CONCLUSIONS: Knee extension deficit was an important predisposing factor for postoperative anterior knee pain in the early postoperative period, and anterior knee pain was associated with impaired quadriceps function and inferior subjective results over 2 years postoperatively. Early recovery of full extension may prevent postoperative development of anterior knee pain and achieve successful outcomes for ACL reconstruction. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Effects of four different surgical approaches on intra-operative joint gap in posterior-stabilized total knee arthroplasty.

PURPOSE: The effects of surgical approaches and patellar positions on joint gap measurement during total knee arthroplasty (TKA) remain unclear. We hypothesized that joint gap changes with different knee flexion angles would not be consistent within four different approaches and two different patellar positions. METHODS: This study enrolled 80 knees undergoing posterior-stabilized TKA. For 60 varus knees, parapatellar, midvastus, and subvastus approaches were used in 20 knees each. For 20 valgus knees, a lateral subvastus approach was used. Component gap length and inclination were measured intra-operatively using a specific tensor device under 40 lb with the patella reduced or shifted laterally, at 0°, 45°, 90°, and 135° of knee flexion. RESULTS: Mean gap lengths at 45° and 90° of knee flexion were significantly larger with the parapatellar approach than with midvastus or lateral subvastus approaches (P < 0.05). Regarding gap inclination, varus angle increased linearly through the entire arc of flexion in all four approaches. When the patella was shifted laterally, gap lengths at 45°, 90°, and 135° were significantly reduced compared with those for the patella reduced in the subvastus approach, whereas gap length was constant in the parapatellar approach, regardless of patellar position. CONCLUSION: Joint gap kinematics was not consistent within four different approaches and two different patellar positions. Relatively large gaps at 45° and 90° were unique features for the parapatellar approach. Surgeons should be aware that the flexion gap is reduced when the patella is shifted laterally in vastus medialis-preserving approaches such as the subvastus approach. LEVEL OF EVIDENCE: II.

Anatomic double-bundle anterior cruciate ligament reconstruction using bone-patellar tendon-bone and gracilis tendon graft: a comparative study with 2-year follow-up results of semitendinosus tendon grafts alone or semitendinosus-gracilis tendon grafts.

PURPOSE: The purpose of this study was to assess the clinical results of anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by use of bone-patellar tendon-bone and gracilis tendon (BPTB-G) grafts and to compare them with the results of double-bundle ACL reconstruction by use of semitendinosus tendon (ST) or semitendinosus-gracilis tendon (ST-G) grafts, with particular emphasis on the postoperative incidence of anterior knee pain. METHODS: The study comprised 144 patients who underwent unilateral anatomic double-bundle ACL reconstruction with 3 graft types, including 55 BPTB-G, 56 ST, and 33 ST-G grafts. A traumatic graft rupture occurred within 2 years postoperatively in 5 patients (1 BPTB-G, 3 ST, and 1 ST-G). Clinical results and incidence and severity of anterior knee pain were assessed and compared among the 3 different graft groups at 2 years postoperatively. Potential variables influencing postoperative anterior knee pain development were subjected to univariate analysis, followed by logistic regression analysis to identify risk factors for anterior knee pain. RESULTS: Both subjective and objective clinical results in anatomic double-bundle ACL reconstruction with BPTB-G graft were similar to those using ST or ST-G graft at 2 years postoperatively. The incidences of anterior knee pain at 2 years' follow-up were 18.5%, 9.4%, and 9.3% in the BPTB-G, ST, and ST-G groups, respectively, indicating no statistically significant difference among the 3 groups. Multivariate logistic regression analyses showed that BPTB graft harvest and patellofemoral cartilage defect failed to be significant factors for anterior knee pain whereas quadriceps peak torque at 60°/s was the only significant factor for anterior knee pain at 2 years. CONCLUSIONS: Clinical results including the incidence of anterior knee pain 2 years after anatomic double-bundle ACL reconstruction with BPTB-G grafts were comparable to those after ACL reconstruction with ST or ST-G grafts. LEVEL OF EVIDENCE: Level III, therapeutic, retrospective comparative study.

Clinical and radiographic outcomes of minimally invasive total knee arthroplasty through a lateral approach.

PURPOSE: With increasing confidence and surgical experience, minimally invasive surgery (MIS) in total knee arthroplasty (TKA) is now being applied to more complicated cases. The present study assessed the feasibility of MIS-TKA using a lateral approach for valgus knees. METHODS: Subjects comprised 26 patients with valgus knees who underwent MIS-TKA using a lateral subvastus approach. Five cases required a 1-cm snip of vastus lateralis obliquus, to shift the patella medially without eversion. Clinical scores and radiographic parameters of lateral MIS-TKA were examined and compared with those of 26 medial MIS-TKAs matched for preoperative patient characteristics. RESULTS: The lateral MIS-TKA group showed slightly longer operative time and larger skin incision than the medial MIS-TKA group. Nevertheless, myoglobin index and pain on a visual analog scale on postoperative day 7 were significantly lower in the lateral MIS-TKA group than in the medial MIS-TKA group. Postoperative improvement of clinical scores was quite comparable between lateral and medial MIS-TKA groups. Radiographic assessment revealed that tibiofemoral mechanical axis aligned within ±3° from ideal in 24 of 26 patients after lateral MIS-TKA. MIS technique-related complications occurred in only 1 patient presenting with subsidence of the tibial component, due to malpositioning of the tibial component. CONCLUSION: From the perspectives of postoperative pain, clinical scores, radiographic accuracy, and postoperative complication rate, lateral MIS-TKA achieved comparable or superior results to medial MIS-TKA. This technique may offer a promising technical option that can be utilized for most patients with valgus knee deformity.

Medial patellofemoral ligament reconstruction with hanger lifting procedure.

Medial patellofemoral ligament (MPFL) reconstruction has become a common surgical procedure in the treatment of recurrent dislocation of the patella. A technique of MPFL reconstruction with the "hanger lifting procedure" using extra-articular arthroscopy is presented. After conventional intra-articular arthroscopy, an incision about 1 cm long is made at the superomedial edge of the patella. A bone tunnel is created with a guide pin and overdrilling method, from this portal to the subcutaneous surface of the patella. Using a semi-loop-shaped hanger, the harvested Gracillis tendon is passed through the bone tunnel using a passing pin. Under extra-articular arthroscopy with the "hanger lifting procedure", this tendon is then led back to the superomedial portal. Both ends of the Gracillis tendon are then led to the femoral fixation site posterosuperior to the medial epicondyle with a tendon passer, and fixed by an absorbable interference screw. This procedure can be performed under a minimum incision using a hanger, but control radiographs should be taken to confirm appropriate placement of bone tunnels.