The "Bag of Bones" Treatment of Comminuted Intra-articular Distal Humerus Fractures in the Elderly.

BACKGROUND: Extensively comminuted intra-articular distal humerus fractures in the elderly present a challenging therapeutic dilemma. The purpose of this study was to investigate the results of nonoperative treatment of these fractures in a select subset of patients. METHODS: Patients treated with nonoperative management for a comminuted intra-articular distal humerus fracture between 2007 and 2018 were reviewed. Patients were administered 3 elbow-specific functional outcomes instruments. RESULTS: A total of 8 patients (2 men, 6 women) were treated with brief immobilization followed by early range of motion. All had fractures with extensive comminution of the articular surface such that open reduction and internal fixation was not feasible. Average age was 70 years. At an average of 33 months postinjury, average flexion was 124°, and extension was -27°, with full forearm rotation. No patients required pain medications at the latest follow-up. At 33 months of follow-up, the average Mayo Elbow Performance Score was 92/100 (100 optimal), Oxford Elbow Score was 43/48 (48 optimal), and Quick Disabilities of the Arm, Shoulder, and Hand Score was 10/100 (0 optimal). All patients were satisfied with the nonsurgical treatment that they received. CONCLUSIONS: Nonoperative treatment for comminuted intra-articular distal humerus fractures results in acceptable functional outcome in elderly patients and should be considered when the fracture is not amenable to internal fixation and in lower-demand patients with higher surgical risk.

Editorial Commentary: Arthroscopic Shoulder Instability Surgery and Glenoid Bone Loss: A Paradigm Shift?

The successful treatment of shoulder instability, particularly in the setting of glenoid bone loss, is a challenging problem. There are several surgical options that are available for patients who have this clinical entity. Of these options, bone block procedures have become increasing common over the past several years, both for primary and revision surgery, with the aim to restore the native glenoid anatomy. The arthroscopic Eden-Hybinette procedure is a viable arthroscopic treatment option in patients who have anterior shoulder instability with anterior glenoid insufficiency. This technique has some distinct advantages over other bone block procedures, specifically the ability to avoid damage to the subscapularis and to preserve the coracoid process. In addition, the use of autograft has benefits over glenoid reconstruction procedures that use allograft, specifically pertaining to cost and availability.

Biomechanics Following Isolated Posterolateral Corner Reconstruction Comparing a Fibular-Based Docking Technique With a Tibia and Fibular-Based Anatomic Technique Show Either Technique is Acceptable.

PURPOSE: To analyze the biomechanical integrity of 2 posterolateral corner (PLC) reconstruction techniques using a sophisticated robotic biomechanical system that enables analysis of joint kinematics under dynamic external loads. METHODS: Eight cadaveric human knee specimens were tested. Five N·m external torque followed by 5 N·m varus torque was dynamically applied to each specimen. The 6 degrees of freedom kinematics of the joint were measured in 4 states (intact, PLC-deficient, fibular-based docking, and anatomic PLC reconstructed) at 30°, 60°, and 90° of flexion. Tibial external rotation (ER) and varus rotation (VR) were compared. RESULTS: Under external torque, ER significantly increased from the intact state to the PLC-deficient state across all flexion angles. At 30° of flexion, ER was not significantly different between the intact state (19.9°) and fibular-based (18.7°, P = .336) and anatomic reconstructions (14.9°, P = .0977). At 60°, ER was not significantly different between the intact state and fibular-based reconstruction (22.4°, compared with 19.8° in intact; P = .152) but showed overconstraint after anatomic reconstruction (15.7°; P = .0315). At 90°, ER was not significantly different between the intact state and anatomic reconstruction (15.4°, compared with 19.7° in intact; P = .386) but was with the fibular-based technique (23.5°; P = .0125). CONCLUSION: Both a fibular-based docking technique and an anatomic technique for isolated PLC reconstruction provided appropriate constraint through most tested knee range of motion, yet the fibular-based docking technique underconstrained the knee at 90°, and the anatomic reconstruction overconstrained the knee at 60°. Biomechanically, either technique may be considered for surgical treatment of high-grade isolated PLC injuries. CLINICAL RELEVANCE: This biomechanical study utilizing clinically-relevant dynamic forces on the knee shows that either a simplified fibular-based docking technique or a more complex anatomic technique may be considered for surgical treatment of high-grade isolated PLC injuries.

Glenohumeral Dislocation Arthropathy: Etiology, Diagnosis, and Management.

Dislocation arthropathy describes the development of progressive degenerative changes of the glenohumeral joint in the setting of instability. Although the specific etiology remains unclear, the trauma of a single dislocation, repetitive injury associated with recurrent dislocations, changes in shoulder biomechanics, and complications associated with instability surgery have all been implicated in its development. Pain and restricted range of motion are the most common patient complaints. Conservative management, consisting of pain control, activity modification, and physical therapy, is the first-line treatment after the development of arthropathy. If conservative management fails, multiple surgical options exist. Arthroscopic débridement can be attempted in young, active patients and in those patients with mild-to-moderate arthropathy. Open subscapularis lengthening and capsular release can be done in patients with prior instability repairs that are overly tight. In young patients with minimal bone loss and glenoid wear, surface replacement arthroplasty and hemiarthroplasty are surgical options. In older patients with moderate-to-severe arthropathy, total shoulder or reverse shoulder arthroplasty is the preferred treatment option. Further study is needed to better predict which patients will develop dislocation arthropathy and will thus benefit from early surgical intervention.

Gravity Fluid Flow More Accurately Reflects Joint Fluid Pressure Compared With Commercial Peristaltic Pump Systems in a Cadaveric Model.

PURPOSE: To evaluate intra-articular fluid pressures and joint compliance generated by fluid management systems on cadaveric shoulders and knees under simulated arthroscopic conditions, and to compare joint compliance between knee and shoulder specimens. METHODS: Intra-articular pressures of 5 cadaver shoulders and 5 knees were recorded for 4 arthroscopic pumps (Stryker FloControl, Stryker CrossFlow, Arthrex DualWave, DePuy Mitek FMS Duo) and a gravity feed system. Each specimen was tested 6 times with a pressure transducer for 2 minutes at 0, 25%, and 50% suction. The average pressures were analyzed with 1-way analysis of variance and Tukey's honestly significant difference tests (P < .05). RESULTS: At all suction levels, all pumps exhibited significantly greater pressure than gravity feed (P = .001 to P < .001). At both 25% and 50% suction, FloControl displayed significantly greater pressures (Pmax 160.44 mm Hg) than the other pumps or gravity feed (Pmax 46.9 mm Hg). CrossFlow had the lowest net percentage error (36.8%, 18.4 mm Hg) when compared with the standard pressure of 50 mm Hg, followed by gravity feed. All pumps had large initial overshoot (ie, Pinitial CrossFlow 99.4 mm Hg) followed by settling time, whereas gravity feed did not (Pinitial 55.2 mm Hg). CONCLUSIONS: Gravity feed is an accurate, reliable delivery method for arthroscopic fluid with minimal overshoot and lower intra-articular pressure ranges than commercial pump systems. There was no evidence of plastic deformation of the joint capsule, because capsular compliance increased linearly in both knee and shoulder specimens throughout testing within the established safe range of intra-articular pressures. CLINICAL RELEVANCE: Arthroscopic flow management systems produce maximal and overshoot pressures that are not seen with gravity flow. Surgeons should understand intra-articular pressure and fluid delivery behavior during shoulder and knee arthroscopy to adapt to the variability and higher maximal pressures when using pump systems. Maintaining appropriate pressure could prevent fluid extravasation and possible neuromuscular dysfunction.

Relative Complications and Trends of Outpatient Total Shoulder Arthroplasty.

Outpatient arthroplasty is an appealing option among select patient populations as a mechanism for reducing health care expenditure. The purpose of this study was to determine the nationwide trends and complication profile of outpatient total shoulder arthroplasty (TSA). The authors reviewed a national administrative claims database to identify patients undergoing TSA as outpatients and inpatients from 2007 to 2016. The incidence of perioperative surgical and medical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes. Multivariate logistic regression adjusted for age, sex, and Charlson Comorbidity Index was used to calculate odds ratios of complications among outpatients relative to inpatients undergoing TSA. The query identified 1555 patients who underwent outpatient TSA and 15,987 patients who underwent inpatient TSA. The median age was in the 70 to 74 years age group in both the outpatient and the inpatient cohorts, and the age distribution was comparable between the 2 cohorts (P=.287). The incidence of both outpatient (P<.001) and inpatient (P<.001) TSA increased during the study period. On adjustment for age, sex, and comorbidities, patients undergoing outpatient TSA had significantly lower rates of stiffness requiring manipulation under anesthesia (outpatient, 1.09%; inpatient, 2.35%; odds ratio, 0.52; 95% confidence interval, 0.38-0.71; P<.001) and higher rates of postoperative surgical site infections requiring reoperation (outpatient, 0.90%; inpatient, 0.65%; odds ratio, 1.65; 95% confidence interval, 1.15-2.35; P<.001) at 1 year. Rates of all other postoperative complications were comparable. Ambulatory TSA is increasing in incidence nationwide and is associated with an overall favorable postoperative complication profile. [Orthopedics. 2018; 41(3):e400-e409.].

Midshaft Fractures of the Clavicle: A Meta-analysis Comparing Surgical Fixation Using Anteroinferior Plating Versus Superior Plating.

OBJECTIVE: To compare the outcomes of clavicle fracture fixation using anteroinferior versus superior plate placement. METHODS: We performed a meta-analysis of studies that have reported on outcomes after superior or anteroinferior plate fixation for acute midshaft clavicle fractures (Orthopaedic Trauma Association 15-B). A computerized literature search in the Pubmed, Scopus, and Cochrane Library databases was used to identify relevant articles. Only full text articles without language restrictions were evaluated. The inclusion criteria consisted of: (1) fracture of the midshaft clavicle; (2) surgery for acute fractures (within 1 month of the fracture); (3) adult patients (16 years of age and older); and (4) open reduction and internal fixation with plate application in either the anteroinferior or superior position. Studies were excluded if they did not specify plate location, evaluated multitrauma patients, investigated minimally invasive procedures, or studied operations for revision, nonunion, malunion, or infection. The primary measured outcomes were symptomatic hardware (implant prominence or irritation) and surgery for implant removal. The secondary outcomes were time to union, fracture union, nonunion, malunion, Disabilies of the Arm, Shoulder and Hand score, Constant score, and implant failure. Frequencies and proportions of cases were recorded for binary outcomes, whereas mean and standard deviations were recorded for continuous outcomes. Other summary statistics provided were used to impute mean and standard deviations under the assumption of normality when these were not reported. Continuous outcomes were compared between groups using linear mixed effects models, whereas binary outcomes were compared using mixed effects logistic regression models, including fixed group effects and random study effects. P-values less than 0.05 were considered statistically significant. All analyses were performed using SAS v. 9.4 (SAS Institute Inc, Cary, NC). RESULTS: A total of 1428 articles were identified among the 3 databases, of which 897 remained after removing duplicates. From that pool, 57 relevant studies were evaluated. Articles were excluded because of an inability to specify plate location (6), a subject pool not exclusively consisting of acute fractures (4) or midshaft fractures (2), a minimally invasive surgical approach (6), use of nonstandard plates (1), poor reporting of functional outcomes (2), and a duplicate group of patients (2). This left 34 articles to be used in the meta-analysis. Of these, 8 studies reported on patients with anteroinferior plating (N = 390) and 27 studies reported on patients with superior plating (N = 1104). No significant differences were found with respect to the functional shoulder scores (Disabilies of the Arm, Shoulder and Hand and Constant) between the 2 groups. There was no significant difference between each group for the probability of having a union (P = 0.41), malunion (P = 0.28), nonunion (0.29), or implant failure (P = 0.39). Patients in the superior plating group had a significantly higher probability of suffering from symptomatic hardware (0.17) as compared to patients in the anteroinferior plating group (0.08), (P = 0.005). In addition, the superior plating group had a significantly higher rate of surgery for implant removal (0.11 vs. 0.05), (P = 0.008). CONCLUSIONS: The findings of this investigation demonstrate that plating along the superior and anteroinferior aspects of the clavicle lead to similar operative outcomes with respect to union, nonunion, malunion, and implant failure, as well as similar functional outcomes scores. Plates applied to the superior aspect of the clavicle are associated with higher rates of symptomatic hardware and more frequent implant removal. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

All-Arthroscopic Revision Eden-Hybinette Procedure for Failed Instability Surgery: Technique and Preliminary Results.

PURPOSE: To describe the technique of an all-arthroscopic Eden-Hybinette procedure in the revision setting for treatment of a failed instability procedure, particularly after failed Latarjet, as well as to present preliminary results of this technique. METHODS: Between 2007 and 2011, 18 shoulders with persistent instability after failed instability surgery were treated with an arthroscopic Eden-Hybinette technique using an autologous bicortical iliac crest bone graft. Of 18 patients, 12 (9 men, 3 women) were available for follow-up. The average follow-up was 28.8 months (range, 15 to 60 months). A Latarjet procedure was performed as an index surgery in 10 patients (83%). Two patients (17%) had a prior arthroscopic Bankart repair. RESULTS: Eight patients (67%) obtained a good or excellent result, whereas 4 patients (33%) reported a fair or poor result. Seven patients (58%) returned to sport activities. A positive apprehension test persisted in 5 patients (42%), including 2 patients (17%) with recurrent subluxations. The Rowe score increased from 30.00 to 78.33 points (P < .0001). The Walch-Duplay score increased from 11.67 to 76.67 points (P < .0001). The Western Ontario Shoulder Instability Index score showed a good result of 28.71% (603 points). The average anterior flexion was 176° (range, 150° to 180°), and the average external rotation was 66° (range, 0° to 90°). Two patients (16.67%) showed a progression of glenohumeral osteoarthritic changes, with each patient increasing by one stage in the Samilson-Prieto classification. All 4 patients (33%) with a fair or poor result had a nonunion identified on postoperative computed tomography scan. CONCLUSIONS: An all-arthroscopic Eden-Hybinette procedure in the revision setting for failed instability surgery, although technically demanding, is a safe, effective, and reproducible technique. Although the learning curve is considerable, this procedure offers all the advantages of arthroscopic surgery and allows reconstruction of glenoid defects and restoration of shoulder stability in this challenging patient population. In our hands, this procedure yields good or excellent results in 67% of patients. Successful outcome is correlated with bony healing of the iliac crest graft to the glenoid. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Three-dimensional planning and use of patient-specific guides improve glenoid component position: an in vitro study.

BACKGROUND: Glenoid component positioning is a key factor for success in total shoulder arthroplasty. Three-dimensional (3D) measurements of glenoid retroversion, inclination, and humeral head subluxation are helpful tools for preoperative planning. The purpose of this study was to assess the reliability and precision of a novel surgical method for placing the glenoid component with use of patient-specific templates created by preoperative surgical planning and 3D modeling. METHODS: A preoperative computed tomography examination of cadaveric scapulae (N = 18) was performed. The glenoid implants were virtually placed, and patient-specific guides were created to direct the guide pin into the desired orientation and position in the glenoid. The 3D orientation and position of the guide pin were evaluated by performing a postoperative computed tomography scan for each scapula. The differences between the preoperative planning and the achieved result were analyzed. RESULTS: The mean error in 3D orientation of the guide pin was 2.39°, the mean entry point position error was 1.05 mm, and the mean inclination angle error was 1.42°. The average error in the version angle was 1.64°. There were no technical difficulties or complications related to use of patient-specific guides for guide pin placement. Quantitative analysis of guide pin positioning demonstrated a good correlation between preoperative planning and the achieved position of the guide pin. CONCLUSION: This study demonstrates the reliability and precision of preoperative planning software and patient-specific guides for glenoid component placement in total shoulder arthroplasty.

Patient-reported Outcomes of Tarsal Coalitions Treated With Surgical Excision.

PURPOSE: There are little patient-reported data on functional outcomes of tarsal coalition resection in children and adolescents. The purpose of this study is to evaluate the medium-term (>2 y) outcomes in patients who have had surgical excision of their symptomatic tarsal coalition and to compare patient-based outcomes in patients who have calcaneonavicular (CN) coalitions to those with talocalcaneal (TC) coalitions. METHODS: A billing query was conducted to identify patients who had surgical excision of their tarsal coalition between 2003 and 2008. Eligible patients were mailed questionnaires consisting of a modified American Orthopaedic Foot and Ankle Society (AOFAS) score and the University of California at Los Angeles (UCLA) activity scale. Patients were also specifically asked if their activity level was limited by their foot pain. Only patients who returned questionnaires were included. Demographics and diagnostic images were reviewed. A nonresponder analysis was completed. Complications such as infection and reoperation were reported. RESULTS: Sixty-three patients (22 females, 41 males) who returned questionnaires were included in the analysis. Twenty-four patients had bilateral surgery. TC coalitions were present in 20 patients (32%); CN coalitions were present in 43 patients (68%).Overall, mean modified AOFAS score was 88.3 and mean UCLA activity score was 8.33 at an average of 4.62 years after surgery. Patients who had TC coalitions had similar modified AOFAS scores (88.4) and UCLA activity scores (8.4) when compared with those with CN coalitions (88.0 and 8.3, both not significant).Of the 73% (46/63) patients who reported that their activity levels were not limited by their foot pain, the mean AOFAS score was 93.9 and the mean UCLA activity score was 8.9; 32 of these were CN and 14 were TC coalitions. Of the 27% (17/63) patients who reported that their activity levels were limited by their foot pain, the mean AOFAS score was 72.9 and the mean UCLA activity score was 6.9; 11 of these were CN and 6 were TC coalitions. There was a statistically significant difference in these groups both in modified AOFAS score (P<0.0001) and UCLA activity score (P=0.006). There was no difference in outcomes between those who were treated for a TC and CN coalition. CONCLUSIONS: Patient-reported outcomes after surgical excision of tarsal coalition reveal that >70% of patients' activities are not limited by pain and their functional outcome is terrific. A few patients continue to have problems with ongoing foot pain and activity limitations. The type of coalition does not seem to be an indicative factor in determining outcome.

Surgical treatment for avulsion injuries of the humeral lesser tuberosity apophysis in adolescents.

BACKGROUND: There is little published information regarding avulsion fractures of the humeral lesser tuberosity in adolescents, and no consensus exists on optimal treatment. The purpose of this study was to investigate the demographics, injury mechanisms, and results of operative treatment of lesser tuberosity avulsion fractures in skeletally immature patients. METHODS: Eight patients were treated with open reduction and internal fixation (ORIF) for lesser tuberosity avulsion fractures from 2000 through 2010. Data were collected regarding patient demographics, mechanisms of injury, operative findings, and early clinical results. Preoperative radiographic studies were evaluated, and patient-derived functional outcome scores were obtained. The mean age of the patients was 13.3 years. All patients were male and sustained sports-related injuries, typically from forceful shoulder abduction and external rotation with eccentric subscapularis load. The dominant extremity was injured in six patients. Six patients had initial radiographs that were interpreted as normal. Time from injury to surgery ranged from two weeks to five months. Surgical treatment consisted of ORIF with use of suture anchors (in six patients) or transosseous sutures (in two patients). RESULTS: All patients achieved pain relief, and there were no neurovascular complications. All patients had full return of internal rotation strength, negative lift-off tests, and negative belly-press tests postoperatively. Average time to return to sports was 4.4 months postoperatively. Return of full external rotation occurred in five patients at an average of 4.9 months postoperatively. There were no refractures. Patient-derived functional outcomes scores at an average of 24.6 months after surgery demonstrated excellent shoulder function and high patient satisfaction. CONCLUSIONS: Humeral lesser tuberosity avulsion fractures do occur in adolescents, typically from high-energy sports injuries. Careful physical examination and magnetic resonance imaging (MRI) evaluation aid in achieving a timely diagnosis. Surgical reduction and suture fixation is safe and effective in restoring subscapularis function and return to sports, even in cases of delayed treatment. Full recovery of shoulder external rotation may not be seen until six months postoperatively.

Postarthroscopic arthrofibrosis of the shoulder.

Arthrofibrosis after shoulder surgery may be challenging to treat. Certain factors, including diabetes and history of keloid formation, predispose patients to the development of postoperative arthrofibrosis. Etiologies include rotator cuff repair, labral repair, capsulorrhaphy, shoulder arthroplasty, and proximal humerus fracture fixation. Systematic evaluation with thorough history and physical examination is essential to determine the proper treatment and to counsel patients on expectations for recovery. Nonoperative treatment focused on physical therapy is the first step in management. Manipulation under anesthesia may be an effective treatment for failure of physical therapy regimens in idiopathic adhesive capsulitis, however it is less successful in cases of postsurgical adhesions. In cases of postoperative stiffness, treatment options include arthroscopic and open capsular releases. Adequate postoperative pain control and adherence to a rigorous physical therapy regimen are integral to the success of surgical release. Surgical treatment is effective in the majority of patients with postsurgical arthrofibrosis.

Ulnar-sided wrist pain. Part I: anatomy and physical examination.

Ulnar-sided wrist pain is a common complaint, and it presents a diagnostic challenge for hand surgeons and radiologists. The complex anatomy of this region, combined with the small size of structures and subtle imaging findings, compound this problem. A thorough understanding of ulnar-sided wrist anatomy and a systematic clinical examination of this region are essential in arriving at an accurate diagnosis. In part I of this review, ulnar-sided wrist anatomy and clinical examination are discussed for a more comprehensive understanding of ulnar-sided wrist pain.

Ulnar-sided wrist pain. II. Clinical imaging and treatment.

Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed.

Differential expression of type X collagen in a mechanically active 3-D chondrocyte culture system: a quantitative study.

OBJECTIVE: Mechanical loading of cartilage influences chondrocyte metabolism and gene expression. The gene encoding type X collagen is expressed specifically by hypertrophic chondrocytes and up regulated during osteoarthritis. In this study we tested the hypothesis that the mechanical microenvironment resulting from higher levels of local strain in a three dimensional cell culture construct would lead to an increase in the expression of type X collagen mRNA by chondrocytes in those areas. METHODS: Hypertrophic chondrocytes were isolated from embryonic chick sterna and seeded onto rectangular Gelfoam sponges. Seeded sponges were subjected to various levels of cyclic uniaxial tensile strains at 1 Hz with the computer-controlled Bio-Stretch system. Strain distribution across the sponge was quantified by digital image analysis. After mechanical loading, sponges were cut and the end and center regions were separated according to construct strain distribution. Total RNA was extracted from the cells harvested from these regions, and real-time quantitative RT-PCR was performed to quantify mRNA levels for type X collagen and a housing-keeping gene 18S RNA. RESULTS: Chondrocytes distributed in high (9%) local strain areas produced more than two times type X collagen mRNA compared to the those under no load conditions, while chondrocytes located in low (2.5%) local strain areas had no appreciable difference in type X collagen mRNA production in comparison to non-loaded samples. Increasing local strains above 2.5%, either in the center or end regions of the sponge, resulted in increased expression of Col X mRNA by chondrocytes in that region. CONCLUSION: These findings suggest that the threshold of chondrocyte sensitivity to inducing type X collagen mRNA production is more than 2.5% local strain, and that increased local strains above the threshold results in an increase of Col X mRNA expression. Such quantitative analysis has important implications for our understanding of mechanosensitivity of cartilage and mechanical regulation of chondrocyte gene expression.

Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation.

Osteocytes are thought to orchestrate bone remodeling, but it is unclear exactly how osteocytes influence neighboring bone cells. Here, we tested whether osteocytes, osteoblasts, and periosteal fibroblasts subjected to pulsating fluid flow (PFF) produce soluble factors that modulate the proliferation and differentiation of cultured osteoblasts and periosteal fibroblasts. We found that osteocyte PFF conditioned medium (CM) inhibited bone cell proliferation, and osteocytes produced the strongest inhibition of proliferation compared to osteoblasts and periosteal fibroblasts. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the inhibitory effects of osteocyte PFF CM, suggesting that a change in NO release is at least partially responsible for the inhibitory effects of osteocyte PFF CM. Furthermore, osteocyte PFF CM stimulated osteoblast differentiation measured as increased alkaline phosphatase activity, and l-NAME decreased the stimulatory effects of osteocyte PFF CM on osteoblast differentiation. We conclude that osteocytes subjected to PFF inhibit proliferation but stimulate differentiation of osteoblasts in vitro via soluble factors and that the release of these soluble factors was at least partially dependent on the activation of a NO pathway in osteocytes in response to PFF. Thus, the osteocyte appears to be more responsive to PFF than the osteoblast or periosteal fibroblast with respect to the production of soluble signaling molecules affecting osteoblast proliferation and differentiation.

Polyamines modulate nitric oxide production and COX-2 gene expression in response to mechanical loading in human adipose tissue-derived mesenchymal stem cells.

For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) display a bone cell-like response to mechanical loading. We have shown earlier that this response includes increased nitric oxide (NO) production and cyclooxygenase-2 (COX-2) gene expression, both of which are intimately involved in mechanical adaptation of bone. COX-2 gene expression is likely regulated by polyamines, which are organic cations implicated in cell proliferation and differentiation. This has led to the hypothesis that polyamines may play a role in the response of adipose tissue-derived MSCs (AT-MSCs) to mechanical loading. The aim of this study was to investigate whether genes involved in polyamine metabolism are regulated by mechanical loading and to study whether polyamines modulate mechanical loading-induced NO production and COX-2 gene expression in human AT-MSCs. Human AT-MSCs displayed a bone cell-like response to mechanical loading applied by pulsating fluid flow (PFF), as demonstrated by increased NO production and increased gene expression of COX-2. Furthermore, PFF increased gene expression of spermidine/spermine N (1)-acetyltransferase, which is involved in polyamine catabolism, suggesting that mechanical loading modulates polyamine levels. Finally, the polyamine spermine was shown to inhibit both PFF-induced NO production and COX-2 gene expression, suggesting that polyamines modulate the response of human AT-MSCs to mechanical loading. In conclusion, this is the first study implicating polyamines in the response of human AT-MSCs to mechanical loading, creating opportunities for the use of polyamines in tissue engineering approaches targeting skeletal defects.

Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone.

OBJECTIVE: Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E2-induced anorexia. RESEARCH METHODS AND PROCEDURES: We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high-fat diet. RESULTS: We confirmed E2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia. E2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2-induced anorexia. High-fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week. DISCUSSION: The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.