Alpha-Defensin-1 in Synovial Fluid is Useful for Diagnosis of Joint Infection.

The distinction between bacterial infectious and noninfectious arthritis is typically challenging in the early stages; however, it is critical for treatment decision making. Here, we investigated the diagnostic relevance of alpha- and beta-defensin levels in serum and synovial fluid as biomarkers of joint infection in patients presenting with fever and arthritis. The study included 12 patients who presented with fever (≥37°C) and arthritis (pain in the knee or hip joint). The diagnostic criteria for periprosthetic joint infection proposed by the Musculoskeletal Infection Society were used to detect joint infection and categorize the patients into infection and non-infection groups. Alpha-defensin-1 and beta-defensin-3 levels in serum and synovial fluid were measured using enzyme-linked immunosorbent assay. No significant between-group difference was observed with respect to serum alpha-defensin-1 levels; however, synovial fluid alpha-defensin-1 levels were significantly higher in the infection group (33.6 ± 26.2 ng/ml) than in the non-infection group (0.9 ± 0.4 ng/ml). No significant between-group differences were observed with respect to serum or synovial fluid beta-defensin-3 levels. Furthermore, synovial fluid alpha-defensin-1 levels were increased in patients without prosthesis in the infection group. In conclusion, in patients with fever and arthritis, synovial fluid alpha-defensin-1 levels were significantly higher in patients with infectious arthritis than in those with noninfectious arthritis. Therefore, synovial fluid alpha-defensin-1 levels is a useful diagnostic marker for joint infection.

Differentiation Potential of Synovial Mesenchymal Stem Cells Isolated From Hip Joints Affected by Femoroacetabular Impingement Syndrome Versus Osteoarthritis.

PURPOSE: To establish the characteristics of synovium-derived mesenchymal stem cells (MSCs) from the hip joints of patients with femoroacetabular impingement syndrome (FAIS) and osteoarthritis (OA), particularly their proliferation and differentiation potentials. We further investigated their functional differences. METHODS: Synovium samples were harvested from 21 patients with FAIS who underwent hip arthroscopic surgery and from 14 patients with OA who underwent total hip arthroplasty. The MSC number, colony-forming units, cell viability, and differentiation potential were compared. Real-time polymerase chain reaction assessed the differentiation potential into adipose, bone, and cartilage tissues. RESULTS: The number of colonies at a density of 104 at passage 0 from OA synovium was significantly greater than that from FAIS synovium (P < .01). However, their proliferation and viability were significantly lower than those of FAIS synovium cells (P = .0495). The expression of lipoprotein lipase mRNA in OA synovium cells was greater than that in FAIS synovium cells (P < .01). Meanwhile, the fraction of colonies positive for von Kossa and alkaline phosphatase staining, as well as the level of bone gamma-carboxyglutamate protein expression in OA synovium cells, were greater than those in FAIS synovium cells (P < .01). In chondrogenic pellet culture experiments, the expression of COL10A1 mRNA was lower in OA synovium than in FAIS synovium (P < .01). CONCLUSIONS: Synovial MSCs from patients with OA had greater colony numbers but less viability and proliferative potential. They also showed greater osteogenic and adipogenic potentials, whereas those from patients with FAIS showed greater chondrogenic potential. CLINICAL RELEVANCE: MSCs from patients with FAIS exhibited good potential as cell sources for stem cell therapy in case of cartilage damage in the hip joint.

Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. METHODS: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1 and serum levels of bone metabolism biomarkers. RESULTS: All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. CONCLUSIONS: The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

Case Report and Literature Review of Periprosthetic Atypical Femoral Fractures After Total Hip Arthroplasty.

We describe a case of periprosthetic femoral fracture with 5 major features of an atypical femoral fracture (AFF) and localized cortical thickening at the fracture site, which is characteristic of an AFF. An 81-year-old female patient had undergone cementless total hip arthroplasty for a right femoral neck fracture at the age of 66, and had been taking oral alendronate since then. At the age of 79, she developed spontaneous right thigh pain. Radiographs showed lateral cortical thickening and pedestal formation around the end of the femoral component. She was advised to discontinue oral alendronate and change to eldecalcitol. At the age of 81, she developed sudden severe pain when standing up from a seated position and was not able to walk. Radiographs showed a periprosthetic femoral fracture with 5 major features of AFF at the site of localized cortical thickening. We diagnosed a Vancouver type B1 periprosthetic femoral fracture. She underwent open reduction and internal fixation (ORIF) with an NCB® Periprosthetic Femur Plate System with cable grips. Daily subcutaneous injection of teriparatide and low intensity pulsed ultrasound therapy were performed to stimulate bone healing. She was able to walk without assistance at 4 months after ORIF. Radiographs showed adequate bridging callus and a disappearing fracture line. This case was diagnosed as a periprosthetic atypical femoral fracture (PAFF), because a periprosthetic fracture is excluded from the definition of AFF. Similar to AFF, PAFF exhibits poor clinical outcomes. The approach to treating PAFF should be decided after considering the pathogenesis.

Systemic bone loss, impaired osteogenic activity and type I muscle fiber atrophy in mice with elastase-induced pulmonary emphysema: Establishment of a COPD-related osteoporosis mouse model.

Although it is suggested that chronic obstructive pulmonary disease (COPD) and bone are related, almost all of the pathological mechanisms of COPD-related osteoporosis remain unknown. There is a mouse model showing a deterioration of bone quality after cigarette smoke exposure; however, in smoking exposure models, various factors exist that affect bone metabolism, such as smoking and body weight loss (muscle and fat mass loss). We considered it appropriate to use an elastase-induced emphysema model to exclude factors influencing bone metabolism and to investigate the influence of pulmonary emphysema on bone metabolism. The purpose of this study was to establish a COPD/emphysema-related osteoporosis mouse model by using the elastase-induced emphysema model. The lumbar vertebrae and femurs/tibiae exhibited trabecular bone loss and impaired osteogenic activity in 24-week-old male elastase-induced emphysema model mice. In addition, the model mice showed atrophy of type I muscle fibers without atrophy of type II muscle fibers. We believe that the mice described in this experimental protocol will be accepted as a COPD/emphysema-related osteoporosis mouse model and contribute to further investigations.

Rapidly Progressive Osteolysis and a Large Cystic Lesion that Destroyed the Inner Table of the Iliac Bone Following Cementless Total Hip Arthroplasty: A Case Report.

We report a case of rapidly progressive osteolysis and a very large cystic lesion that destroyed the inner table of the iliac bone following cementless total hip arthroplasty (THA). A 59-year-old female patient developed left hip pain at 11 years after THA. Osteolysis surrounding the acetabular cup was pointed out. She was brought to our hospital by ambulance due to severe left hip pain at 12 years after THA. Computed tomography (CT) showed that a cystic lesion in the pelvic cavity had destroyed the inner table of the iliac bone. Magnetic resonance imaging (MRI) showed a high signal intensity area of the hemorrhagic cystic lesion in the iliac bone in both T1-weighted and T2-weighted images. She underwent a liner and femoral head exchange, and required bone grafting and revision of the cup. The cystic lesion was removed and block-like allograft bone grafts were stuffed into the bone defects. If osteolysis and cystic lesions occur at the same time, not only the bone area around the implant but also a distant area like the inner table of the iliac bone may be destroyed. Additional tests such as CT or MRI may be useful to detect the presence of distant or cystic lesions. Early diagnosis and treatment are important because severe complications may occur in cases where osteolysis and cystic lesions coexist after THA.

Hip arthroscopy enables classification and treatment of precollapse subchondral insufficiency fracture of the femoral head associated intra-articular pathology.

PURPOSE: The purposes of this study were to investigate (1) the clinical, radiographic and arthroscopic presentation of patients with subchondral insufficiency fracture of the femoral head (SIFFH) and (2) the outcomes following arthroscopic treatment with internal fixation using hydroxyapatite poly-lactate acid (HA/PLLA) threaded pins and concomitant arthroscopic treatment of associated findings. METHODS: Nine patients (median age 49.0 years, range 43-65, five female and four male patients) with SIFFH who underwent arthroscopic treatment with labral repair, capsular closure and internal fixation of SIFFH using HA/PLLA pins were retrospectively reviewed. Inclusion criteria were adult patients with precollapse SIFFH with minimum 1-year follow-up (median follow-up 30.0 months, range 12-56). RESULTS: Acetabular labral tears were observed in all patients. The median BMI was 24.3 kg/m2 (range 20.1-31.8). Clinical presentations and radiographic measurements demonstrated mixed type FAI in six patients, borderline developmental dysplasia in two patients and pincer type FAI in one patient. The median MHHS significantly improved from preoperatively (67.1, range 36.3-78.0) to post-operatively (96.8, range 82.5-100; p = 0.001). The median NAHS significantly improved from preoperatively (34.0, range 17-63) to post-operatively (78.0 range 61-80; p = 0.001). CONCLUSION: SIFFH is associated with bony deformities and labral tears. Precollapse SIFFH can be treated with bioabsorbable pin stabilization of unstable lesions and treatment of associated intra-capsular pathology in those with stable lesions as determined by a new arthroscopic classification system with promising early outcomes. LEVEL OF EVIDENCE: IV.

In-vivo postoperative motion analysis of metal and ceramic bipolar hip hemiarthroplasty.

BACKGROUND: We hypothesized that ceramic bipolar shows less impingement between stem neck and outer head compared to metal bipolar, because of its low coefficient of friction with the acetabulum cartilage. In this paper, a three dimensional (3D) postoperative motion analysis has been used to assess the different motion characteristics of metal and ceramic bipolar hip hemiarthroplasty systems. METHODS: This study was conducted on 40 patients divided in two matched cohorts: 20 patients with metal bipolar and 20 patients with the ceramic bipolar. We obtained motion pictures from standing position to maximum abduction in flexion by fluoroscopy then analyzed by 2D-3D image matching method. The motion range of the "Outer head angle", "Stem neck angle" and the "Stem neck and outer head angle" was compared between the metal bipolar group and the ceramic bipolar group. RESULTS: The metal bipolar group's inner head's range of movement was greater than the ceramic bipolar group. Impingement between stem neck and outer head occurred in 30% of metal group patients. There were no impingement cases for the ceramic bipolar group. CONCLUSIONS: The ceramic bipolar shows less impingement between stem neck and outer head compared to the metal bipolar. Ceramic bipolar may reduce the typical bipolar related complication and exert less effect on the acetabular cartilage due to less surface coefficient of friction.

Endoscopic shelf acetabuloplasty can improve clinical outcomes and achieve return to sports-related activity in active patients with hip dysplasia.

PURPOSE: To investigate clinical outcomes and return to sports-related activity following endoscopic shelf acetabuloplasty combined with labral repair in the treatment of the active patients with developmental dysplasia of the hip (DDH). METHODS: Between 2011 and 2013, 32 patients (36 hips; 11 males and 21 females; 11 right 17 left 4 bilateral; median age 28.5, range 12-51 years), who underwent endoscopic shelf acetabuloplasty combined with labral repair and met the inclusion criteria were enrolled in this study. There was a minimum follow-up of 2 years (average 32.3 ± 3 months, range 24-48 months). Patient-reported outcome (PRO) scores including the modified Harris Hip Score (MHHS) and Non-Arthritis Hip Score (NAHS) were obtained preoperatively and at final follow-up for the assessment of surgical outcomes. RESULTS: The mean MHHS significantly improved from 68.4 ± 14.3 (range 23.1-95.7) preoperatively to 94.5 ± 8.5 (range 66-100) at final follow-up (p = 0.001). Similarly, the NAHS also significantly improved from 51.3 ± 11.9 (range 23-76) preoperatively to 73.0 ± 7.4 (range 44-80) at final follow-up (p = 0.001). The mean LCE angle significantly increased postoperatively but partially decreased at final follow-up (mean preoperative versus postoperative versus final follow-up: 16.0 range 5-24, versus 40.1 range 27-58, versus 30.1 range 20-41. p = 0.001, respectively). There were 3 patients who returned to a higher activity level, 20 patients who returned to the same activity level, and 6 patients who returned to a lower activity level. The mean period from surgery to return to play was 9.0 ± 3.5 months (range 5-18). CONCLUSION: Endoscopic shelf acetabuloplasty provides promising clinical outcomes and return to sports-related activity for active patients with DDH. LEVEL OF EVIDENCE: Level IV.

Highly Cross-Linked Polyethylene Reduces Osteolysis Incidence and Wear-Related Reoperation Rate in Cementless Total Hip Arthroplasty Compared With Conventional Polyethylene at a Mean 12-Year Follow-Up.

BACKGROUND: A number of studies on total hip arthroplasty have compared highly cross-linked polyethylene (HXLPE) with conventional polyethylene (CPE) liners beyond 10 years. However, the impact of HXLPE on the wear-related reoperation rate is unclear. The purpose of this study was to evaluate the clinical advantage of using a single manufacturer's HXLPE in terms of reducing the reoperation rate. METHODS: The study was a follow-up retrospective cohort study over a mean of 12 years that examined patients aged 45-70 years with cementless total hip arthroplasty using a 26-mm-diameter cobalt-chromium head. Sixty-seven patients (79 hips; HXLPE group = 41 hips, CPE group = 38 hips) were evaluated for a minimum 10-year follow-up. Kaplan-Meier survival analysis was performed, with wear-related reoperations and radiographic osteolysis serving as the end points. The polyethylene wear rate was also assessed. RESULTS: The mean 12-year follow-up rates of survivorship that were evaluated using wear-related reoperations as the end point were 100% and 91.4% in the HXLPE and CPE groups, respectively (P = .007), and the mean 12-year follow-up rates of survivorship with osteolysis as the end point were 100% and 36.2%, respectively (P < .001). Compared with the CPE group, the HXLPE group presented a significantly reduced wear rate (HXLPE group, 0.035 mm/y; CPE group, 0.118 mm/y). CONCLUSION: A unique strength of this study is that we assessed a single manufacturer's HXLPE while keeping most other implant parameters uniform. This study reveals the clinical advantage of using a single manufacturer's HXLPE in terms of a reduced wear-related reoperation rate at a mean 12-year follow-up.

Disruption of the Aldehyde Dehydrogenase 2 Gene Results in No Increase in Trabecular Bone Mass Due to Skeletal Loading in Association with Impaired Cell Cycle Regulation Through p21 Expression in the Bone Marrow Cells of Mice.

Approximately 45% of people of East Asian descent have the inactive aldehyde dehydrogenase 2 (ALDH2) phenotype. The enzyme defect of ALDH2 has been found to adversely influence the risk of osteoporosis. The aim of this study was to clarify the effect of skeletal loading on trabecular bone structure and dynamics in Aldh2-disrupted mice in the absence of alcohol consumption. Four-week-old male Aldh2-/- (KO) and Aldh2+/+ (WT) mice were divided into a ground control (GC) group and a climbing exercise (CE) group in each genotype. The trabecular bone mineral density of the distal femur measured by peripheral quantitative computed tomography in the wild-type CE (WTCE) group was significantly higher than that in the wild-type GC (WTGC) group; however, there was no significant difference between the knockout CE (KOCE) and knockout GC (KOGC) groups. Bone histomorphometry revealed that osteogenic parameters were significantly increased in the WTCE group compared with the WTGC group, but not increased in the KOCE group compared with the KOGC group. Quantitative reverse transcriptase polymerase chain reaction and flow cytometry revealed that mRNA and protein expression levels of p21 were significantly decreased in the WTCE group compared with those in the WTGC group, while these differences were not observed between the KOGC and KOCE groups. This study provides the first in vivo evidence that p21 expression in the bone marrow is not decreased after skeletal loading and osteoblast differentiation is impaired in the absence of Aldh2 gene.

Fifteen-Year Comparison of Wear and Osteolysis Analysis for Cross-Linked or Conventional Polyethylene in Cementless Total Hip Arthroplasty for Hip Dysplasia-A Retrospective Cohort Study.

BACKGROUND: Cross-linked polyethylene (XLPE) acetabular liners used in cementless total hip arthroplasty (THA) have demonstrated better wear resistance at 10 years compared with conventional polyethylene (CPE) liners. No clinical studies have compared XPLE to CPE liners beyond 10 years. METHODS: We performed a 15-year retrospective cohort study on cementless THA performed in patients with developmental hip dysplasia to measure the differences in polyethylene wear rates and the presence of osteolysis. Twenty-four THAs with XLPE and 17 THAs with CPE were evaluated. The mean age of patients was 55.9 years (41-68) in the XLPE group and 54.4 years (40-67) in the CPE group. The mean follow-up period was 15.1 years (13.9-16.1) in the XLPE group and 15.2 years (14.5-16.0) in the CPE group. RESULTS: The XLPE group had a significantly lower wear rate at 5 and 10 years compared with the CPE group; however, no significant difference was found at 15 years (XLPE group, 0.040 mm/y; CPE group, 0.034 mm/y). In addition, the incidence of osteolysis did not differ significantly between the groups. However, the incidence of excessive wear between 10 and 15 years after surgery in the XLPE group was significantly higher than that in the CPE group. CONCLUSION: XLPE demonstrated no advantage in the wear rate or the incidence of osteolysis at 15 years, despite having superior wear resistance up to 10 years. It is concerning that the incidence of excessive wear was higher in the XLPE group between 10 and 15 years, and this finding should alert the arthroplasty community to this possible problem with the more highly cross-linked polyethylene.

Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats.

An increase in the arthritis index as a marker of chronic inflammation and suppression of food intake are observed in adjuvant arthritic (AA) rats. Our previous study demonstrated that central oxytocin (OXT)-ergic pathways were activated potently in AA rats. In the present study, OXT-saporin (SAP) cytotoxin, which chemically disrupts OXT signaling was administered centrally to determine whether central OXT may be involved in the developments of chronic inflammation and alteration of feeding/drinking behavior in AA rats. The arthritis index was significantly enhanced in AA rats pretreated with OXT-SAP administered intrathecally (i.t.) but not intracerebroventricularly (i.c.v.). Suppression of food intake was significantly attenuated transiently in AA rats pretreated with OXT-SAP administered i.c.v. but not i.t. Suppression of drinking behavior was not affected by i.t. or i.c.v. administration of OXT-SAP in AA rats. In addition, intraperitoneal administration of an OXT receptor antagonist did not change the arthritis index or feeding/drinking behavior in AA rats. These results suggest that central OXT-ergic pathways may be involved in anti-inflammation at the spinal level and suppression of feeding behavior at the forebrain-brainstem level in AA rats.

Clinical and Radiographic Predictors for Worsened Clinical Outcomes After Hip Arthroscopic Labral Preservation and Capsular Closure in Developmental Dysplasia of the Hip.

BACKGROUND: Patients with developmental dysplasia of the hip (DDH) have a greater risk of acetabular labral tearing and joint instability, which predispose them to developing osteoarthritis. The arthroscopic management of DDH, however, remains controversial. HYPOTHESIS: Specific clinical characteristics and radiographic parameters correlate with and predict a worsened clinical outcome after hip arthroscopic surgery for DDH. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Of patients with DDH who underwent an arthroscopic procedure between March 2009 and June 2011, there were 28 hips in 28 patients (6 male and 22 female) that met the inclusion criteria. The mean patient age was 28.4 years. Clinical and radiographic follow-up evaluations up to a minimum of 2 years after surgery were performed for all patients. Failure of the procedure was defined as conversion to subsequent surgery or having a Tönnis osteoarthritis grade of 2 and modified Harris Hip Score (mHHS) that remained <85, and success was defined as patients who did not need subsequent surgery and had an mHHS >85. Univariate analysis and Cox hazard proportional analysis were performed on the 2 subpopulations. RESULTS: There were 9 patients in the failure group (including 3 hips with T nnis grade 2) and 19 patients in the success group. In 22 of 28 patients, the mean mHHS significantly improved from 61.6 ± 18.8 (range, 12.0-85.0) preoperatively to 94.3 ± 7.0 (range, 73.7-100.0) at final follow-up, and the mean Non-Arthritic Hip Score (NAHS) improved from 56.2 ± 13.9 (range, 35.0-81.3) preoperatively to 92.7 ± 9.5 (range, 65.0-100.0) at final follow-up (P < .001, Wilcoxon signed-rank test). Univariate analysis showed that a broken Shenton line was significantly more prevalent in the failure group compared with the success group (8/9 [89%] vs 3/19 [16%] patients, respectively; P < .001). High-grade cartilage delamination (Multicenter Arthroscopy of the Hip Outcomes Research Network [MAHORN] grades 3-5) was significantly higher in the failure group than in the success group (8/9 [89%] vs 3/19 [16%] patients, respectively; P < .001). The median femoral neck-shaft (FNS) angle in the failure group was significantly higher than that in the success group (139° vs 134°, respectively; P = .01). Further, Cox hazard proportional analysis of the failure group showed that the predictors for a poor clinical outcome were the presence of a broken Shenton line, FNS angle >140°, center-edge (CE) angle <19°, body mass index (BMI) >23 kg/m(2), acetabular cartilage damage (MAHORN grades 3-5), and cartilage damage of the femoral head (International Cartilage Repair Society grades 2-4). The most important predictors for a poor clinical outcome at the time of surgery were a broken Shenton line and an FNS angle >140°. CONCLUSION: Patients with a broken Shenton line, FNS angle >140°, CE angle <19°, or BMI >23 kg/m(2) at the time of surgery are not good candidates for the arthroscopic management of DDH.

A novel non-invasive mechanical technique of cup and stem placement and leg length adjustment in total hip arthroplasty for dysplastic hips.

PURPOSE: This study assessed the accuracy of cup and stem positioning and limb length adjustment for developmental dysplasia of the hip (DDH) using our new mechanical technique compared with imageless navigation or a computed tomography (CT)-based navigation system. METHODS: One hundred thirteen primary total hip arthroplasties (THAs) for DDH were evaluated. At pre-operative positioning, patients were placed in a precise lateral decubitus position by tilting the surgical table using simple ready-made devices (two shot pipe, metal chain, level gauge and goniometer). During surgery, cups were intentionally placed at 45° inclination and 15° anteversion on radiograph by using a level gauge and goniometer. RESULTS: Cup inclination was 44.2° ± 3.4° (range, 32.0-51.2°), cup anteversion was 19.6° ± 6.1° (range, 3.0-33.1°), stem alignment was 0.04° ± 0.8° valgus (range, 2.1° varus to 1.9° valgus), and leg length discrepancy was -0.37 ± 3.7 mm (range, -12.8 to 8.8 mm) in postoperative radiographs. Outliers (outside ±10° from intentional position) occurred in 15 cases (13.3 %) in inclination or anteversion. Postoperative dislocation did not occur in any cases. CONCLUSIONS: Cup and stem positioning in THAs with our new mechanical technique yielded satisfactory results compared with previously reported imageless navigation or CT-based navigation. Our results were superior with regard to being non-invasive and low cost and involving minimum radiation exposure.

Disruption of aldehyde dehydrogenase 2 gene results in altered cortical bone structure and increased cortical bone mineral density in the femoral diaphysis of mice.

INTRODUCTION: Aldehyde dehydrogenase 2 (ALDH2) degrades acetaldehyde produced by the metabolism of alcohol. The inactive ALDH2 phenotype is prevalent in East Asians, and an association between this ALDH2 polymorphism and osteoporosis has been reported. In our previous study, we found that alcohol consumption results in decreased trabecular bone volume in aldh2 knockout (aldh2(-/-)) mice compared with the volume in wild-type (aldh2(+/+)) mice. However, the effect of aldh2 gene on the skeletal phenotype in the absence of alcohol consumption remains unknown. The aim of this study was to clarify the effect of aldh2 disruption on femoral bone structure and dynamics in aldh2-disrupted mice in the absence of alcohol consumption. MATERIALS AND METHODS: We examined aldh2(-/-) and aldh2(+/+) mice at the ages of 4, 8 and 12weeks. The femoral bone length and bone mineral density (BMD) were measured using peripheral quantitative computed tomography. The mechanical strength was assessed by the three-point bending test at 12weeks, and cortical bone histomorphometry at the femur diaphysis was performed at all three time points. Osteogenic activities in aldh2(-/-) and aldh2(+/+) mice were assessed by osteoblast culture from calvariae of the neonatal mice. Bilateral femoral and tibial bones containing no bone marrow cells of 8-week-old mice were used for analysis of mRNA expression. In addition, mRNA expression in aldh2(-/-) and aldh2(+/+) mice after tail suspension or climbing exercise for 7days from 8weeks was analyzed to clarify the response to mechanical loading. RESULTS: At 12weeks, there were no significant differences in femoral bone length, trabecular BMD in the distal metaphyses of the femurs, or mechanical strength between aldh2(-/-) and aldh2(+/)(+) mice, whereas cortical BMD and cortical thickness were significantly increased and cross-sectional area and bone marrow area were significantly decreased in the femoral diaphysis of aldh2(-/-) mice relative to the corresponding values in aldh2(+/+) mice. At 8weeks, bone formation rate and mineral apposition rate on the periosteal and endocortical surfaces were significantly increased in aldh2(-/-) mice relative to the rates in aldh(+/+) mice. Calvarial osteoblast culture study revealed that the percentage of alkaline phosphatase stained cells was significantly higher in aldh2(-/-) mice compared to that in aldh(+/+) mice. Quantitative real-time RT-PCR revealed a significant increase in the expressions of bmp2, osterix, runx2, and col1a1 mRNA in aldh2(-/-) mice, along with an increase in the expression of wnt5a mRNA and the lrp5/sost mRNA ratio. The mRNA expressions of bmp2, osterix, runx2 and pthr in aldh2(-/-) mice were significantly decreased after climbing exercise compared to those in the control, although the mRNA expressions of bmp2, osterix, runx2 were not significantly decreased and pthr mRNA expression was increased in aldh(+/+) mice after climbing exercise. CONCLUSION: Our results show that disruption of aldh2 gene resulted in altered cortical bone structure and dynamics in mice. Cross-sectional area was decreased. Cortical BMD was increased owing to the promotion of cortical bone formation on the periosteal and endocortical surfaces of the femoral diaphysis. The possible mechanisms underlying altered cortical bone structure in aldh2(-/-) mice were gene-related higher osteogenic activity of osteoblasts and weakened osteogenice response to mechanical loading in growth period.

15-year comparison of cementless total hip arthroplasty with anatomical or high cup placement for Crowe I to III hip dysplasia.

This study compared radiological and clinical results of Mallory-Head (Biomet, Warsaw, Indiana) cementless total hip arthroplasty (THA) by anatomical (AP group) or high cup placement (HP group) for Crowe I to III developmental dysplasia of the hip. Of the 68 hips studied, 43 hips were available for 15.3-year follow-up. Ten cups were placed at anatomical center with bulk bone grafting, and 33 cups were at high hip center without bulk bone grafting. No acetabular or femoral components showed loosening in either group. One standard polyethylene liner in a highly placed cup was revised due to excessive wear after 11 years. The average rate of polyethylene wear was 0.128 mm/year in the AP group and 0.148 mm/year in the HP group (except for the revision case). The extent of grafted bone coverage was 34.6% in the AP group. Hip center height was 24.5 mm from the inter-teardrop line in the HP group. The center of the hip horizontal location in the AP group (24.5 mm) and HP group (26.4 mm) was significantly shorter than in normal hips (35.6 mm). Postoperative center-edge angle was 11° (except grafted bone) in the AP group and 25° in the HP group. Mean Harris Hip Score in the AP group improved from 38 points preoperatively to 82 points postoperatively and in the HP group improved from 40 points preoperatively to 88 points postoperatively. Survivorship was 100% in the AP group and 97% in the HP group. Our results indicate that moderate high cup placement without bulk bone grafting at a horizontal locus more medial than that of a normal hip is an alternative durable solution.

Reduced bone formation in alcohol-induced osteopenia is associated with elevated p21 expression in bone marrow cells in aldehyde dehydrogenase 2-disrupted mice.

INTRODUCTION: High consumption of alcohol is one of the risk factors for osteoporosis. Approximately 45% of Chinese and Japanese individuals have the inactive aldehyde dehydrogenase 2 (Aldh2) phenotype. The absence of the ALDH2*2 allele is found to adversely influence the risk of osteoporosis. The aim of this study is to clarify the effects of alcohol consumption on osteoblast differentiation in bone marrow and trabecular bone formation in Aldh2-disrupted mice. MATERIALS AND METHODS: Seven-week-old male Aldh2 knockout mice (Aldh2(-/-)) and wild-type (Aldh2(+/+)) mice were fed with water (groups Aldh2(-/-)/Wa and Aldh2(+/+)/Wa) or with 5% ethanol (groups Aldh2(-/-)/Al and Aldh2(+/+)/Al) for 4 weeks. At the age of 12 weeks, bone histomorphometry was performed at the secondary spongiosa of the tibias. Bone marrow cells from the bilateral femurs and tibias were used for mRNA expression analysis. RESULTS: Histomorphometrical study revealed that trabecular bone was significantly reduced in the Aldh2(-/-)/Al group compared with that in the Aldh2(-/-)/Wa and Aldh2(+/+)/Wa groups. Bone formation rate was significantly decreased in Aldh2(-/-)/Al compared with the other three groups. Quantitative RT-PCR revealed a significant decrease in type I collagen, osterix, osteopontin, and osteocalcin mRNA expressions in Aldh2(-/-)/Al compared with Aldh2(-/-)/Wa. In bone marrow cell cultures, mineralized nodule formation in Aldh2(-/-)/Al was significantly decreased compared with that in Aldh2(+/+)/Wa and Aldh2(-/-)/Wa, while PAK18, a p21-activated kinase inhibitor, recovered the decreased mineralized nodule formation in Aldh2(-/-)/Al. CONCLUSION: Alcohol consumption suppressed the differentiation and mineralization of osteoblasts and then reduced trabecular bone formation and bone volume in association with the elevated p21 expression in bone marrow cells, especially in aldehyde dehydrogenase 2-disrupted mice.

The anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status in bone in ovariectomized mice.

We hypothesized that the anabolic action of parathyroid hormone (PTH) with the anti-catabolic agents cathepsin K inhibitor and alendronate differs depending on the remodeling status in the bone. C57/BL/6J mice, 8 weeks of age, were subjected to ovariectomized (OVX) or sham surgery. At 6 weeks after surgery, the mice were treated with cathepsin K inhibitor, alendronate, or a vehicle (daily, for 8 weeks), with or without PTH (1-34) (5 times/week, for the last 4 weeks). We assessed the bone chemical markers of the serum and urine, bone mineral density (BMD), histomorphomery in the primary and secondary spongiosa of the proximal tibia after fluorescence labeling, primary cell culture, and mRNA expressions in bone marrow cells. Cathepsin K inhibitor and alendronate significantly increased the BMD and the bone volume of the primary and secondary spongiosa, with a reduction of the urinary C-telopeptide of type I collagen that was increased by OVX, respectively. Cathepsin K inhibitor augmented the anabolic action of PTH on the BMD and bone volume at both the primary and secondary spongiosa, while alendronate had the same effect on the BMD and bone volume only at the primary spongiosa. Cathepsin K inhibitor did not decrease serum osteocalcin with or without PTH, while alendronate did decrease it. Cathepsin K inhibitor did not decrease the values of osteoclast number or bone formation rate with or without PTH, while alendronate decreased those values and increased osteoclast apoptosis. The combination of PTH and cathepsin K inhibitor increased alkaline phosphatase-positive CFU-f formation and c-fos, osterix, and osteocalcin mRNA expressions of bone marrow cells as well as PTH alone, while the combination of PTH and alendronate decreased those values. This study demonstrated that alendronate enhances the anabolic action of PTH at the primary spongiosa, but blunts it in the remodeling trabecular bone, while cathepsin K inhibitor enhances the action at both sites in OVX mice. In conclusion, the anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status of bone in OVX mice.

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells.

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.