Transcutaneous osseointegration for amputees.

Transcutaneous osseointegration for amputees (TOFA) is an evolving technology that has the potential to revolutionize the interface between the amputee and their prosthesis, showing potential at many levels of amputation. While no amputation is without its challenges, TOFA requires a highly specialized prosthesis and a multidisciplinary team that includes specialized surgeons, physical therapists, wound care teams, and social workers who guide the amputee through surgery, postoperative rehabilitation, and the chronic wound care that goes into maintaining the prosthesis. The infrastructure required to facilitate care pathways that lead to reliable, successful outcomes are unique in each health care setting, including those in advanced health care systems such as the United States and Australia. This article details the emerging evidence supporting the use of this prosthetic interface design and many of the challenges that providers face when establishing programs to offer this type of care in the United States.

Bacteriophage therapy and current delivery strategies for orthopedic infections: A SCOPING review.

OBJECTIVES: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized. METHODS: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central. RESULTS: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described. CONCLUSIONS: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.

Retrograde Intramedullary Nailing Versus Locked Plating for Extreme Distal Periprosthetic Femur Fractures: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To compare clinical and radiographic outcomes after retrograde intramedullary nailing (rIMN) versus locked plating (LP) of "extreme distal" periprosthetic femur fractures, defined as those that contact or extend distal to the anterior flange. DESIGN: Retrospective review. SETTING: Eight academic level I trauma centers. PATIENT SELECTION CRITERIA: Adult patients with periprosthetic distal femur fractures at or distal to the anterior flange (OTA/AO 33B-C[VB1]) treated with rIMN or LP. OUTCOME MEASURES AND COMPARISONS: The primary outcome was reoperation to promote healing or to treat infection (reoperation for elective removal of symptomatic hardware was excluded from this analysis). Secondary outcomes included nonunion, delayed union, fixation failure, infection, overall reoperation rate, distal femoral alignment, and ambulatory status at final follow-up. Outcomes were compared between patients treated with rIMN or LP. RESULTS: Seventy-one patients treated with rIMN and 224 patients treated with LP were included. The rIMN group had fewer points of fixation in the distal segment (rIMN: 3.5 ± 1.1 vs. LP: 6.0 ± 1.1, P < 0.001) and more patients who were allowed to weight-bear as tolerated immediately postoperatively (rIMN: 45%; LP: 9%, P < 0.01). Reoperation to promote union and/or treat infection was 8% in the rIMN group and 16% in the LP group ( P = 0.122). There were no significant differences in nonunion ( P > 0.999), delayed union ( P = 0.079), fixation failure ( P > 0.999), infection ( P = 0.084), or overall reoperation rate ( P > 0.999). Significantly more patients in the rIMN group were ambulatory without assistive devices at final follow-up (rIMN: 35%, LP: 18%, P = 0.008). CONCLUSIONS: rIMN of extreme distal periprosthetic femur fractures has similar complication rates compared with LP, with a possible advantage of earlier return to weight-bearing. Surgeons can consider this treatment strategy in all fractures with stable implants and amenable prosthesis geometry, even extreme distal fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Antibiotic prophylaxis following low-velocity gunshot fractures: an updated review.

PURPOSE: Low-velocity gunshot fractures (LVGFs) are a common type of gunshot-induced trauma with the potential for complications such as infection and osteomyelitis. The effectiveness of antibiotic therapy in LVGFs remains uncertain, leading to ongoing debate about the appropriate treatment. In this review, we evaluate recent updates on the current understanding of antibiotic therapy in LVGFs, how previous studies have investigated the use of antibiotics in LVGFs, and the current state of institutional policies and protocols for treating LVGFs with antibiotics. METHODS: We conducted a review of PubMed, Embase, and Web of Science databases to identify studies that investigated the use of antibiotics in LVGFs after the last review in 2013. Due to the lack of quantitative clinical trial studies, we employed a narrative synthesis approach to analyze and present the findings from the included primary studies. We categorized the outcomes based on the anatomical location of the LVGFs. RESULTS: After evaluating 67 publications with the necessary qualifications out of 578 abstracts, 17 articles were included. The sample size of the studies ranged from 22 to 252 patients. The antibiotics used in the studies varied, and the follow-up period ranged from three months to ten years. The included studies investigated the use of antibiotics in treating LVGFs at various anatomic locations, including the humerus, forearm, hand and wrist, hip, femur, tibia, and foot and ankle. CONCLUSION: Our study provides updated evidence for the use of antibiotics in LVGFs and highlights the need for further research to establish evidence-based guidelines. We also highlight the lack of institutional policies for treating LVGFs and the heterogeneity in treatments among institutions with established protocols. A single-dose antibiotic approach could be cost-effective for patients with non-operatively treated LVGFs. We suggest that a national or international registry for gunshot injuries, antibiotics, and infections could serve as a valuable resource for collecting and analyzing data related to these important healthcare issues.

Fracture healing-orthobiologics: from basic science to clinical application.

Orthopaedics as a field and a profession is fundamentally concerned with the treatment of musculoskeletal disease, in all of its many forms. Our collective understanding of the cellular mechanisms underlying musculoskeletal pathology resulting from injury continues to evolve, opening novel opportunities to develop orthobiologic treatments to improve care. It is a long path to move from an understanding of cellular pathology to development of successful clinical treatment, and this article proposes to discuss some of the challenges to achieving translational therapies in orthopaedics. The article will focus on challenges that clinicians will likely face in seeking to bring promising treatments forward to clinical practice and strategies for improving success in translational efforts.

The epidemiology and management of iliopsoas hematoma with femoral nerve palsy: A descriptive systematic review of 174 cases.

INTRODUCTION: Iliopsoas hematoma with femoral nerve palsy is a rare phenomenon with no consensus treatment algorithm. The objective of this study was to perform a systematic review of all reported cases of femoral nerve palsy secondary to iliopsoas hematoma to better elucidate it's optimal treatment. MATERIALS AND METHODS: Queries of the PubMed, Embase, and Cochrane databases were performed for reports available in English of femoral nerve palsy secondary to iliopsoas, psoas, or iliacus hematoma. 1491 articles were identified. After removal of duplicated publications and review of abstract titles via a majority reviewer consensus, 217 articles remained for consideration. Dedicated review of the remaining articles (including their reference sections) yielded 122 articles representing 174 distinct cases. Clinical data including patient age, sex, medical history, use of pharmacologic anticoagulation, sensory and motor examination at presentation and follow-up, hematoma etiology and location, time to intervention, and type of intervention were collected. Descriptive statistics were generated for each variable. RESULTS: Femoral nerve palsy secondary to iliopsoas hematoma occurred at a mean age of 44.5 years old. A majority of patients (60%) were male, and a majority of hematomas (54%) occurred due to pharmacologic anticoagulation. Most hematomas (57%) were treated conservatively, and almost half (49%) - regardless of treatment modality - resulted in persistent motor deficits at final follow-up. A minority of patients treated surgically (34%) had residual motor deficit at final follow-up, while 66% of those treated medically had resultant motor deficits, although no direct statistical comparison was able to be performed. DISCUSSION AND CONCLUSIONS: The disparate available data on iliopsoas hematoma with femoral nerve palsy precludes the completion of a true metanalysis, and therefore any conclusions on an optimal treatment algorithm. Based on review of the literature, small to moderate hematomas are often treated conservatively, while larger hematomas with progressive neurological symptoms are usually managed with a percutaneous decompression or surgery. LEVEL OF EVIDENCE: IV.

Lack of Surgeon Standardization on Implant Selection in Ankle Fracture Fixation May Increase Costs and Decrease Contribution Margin.

BACKGROUND: Surgical standardization has been shown to decrease costs without impacting quality; however, there is limited literature on this subject regarding ankle fracture fixation. Methods. Between October 5, 2015 and September 27, 2017, a total of 168 patients with isolated ankle fractures who underwent open reduction, internal fixation (ORIF) were analyzed. Financial data were analyzed across ankle fracture classification type, implant characteristics, and surgeons. Bivariate analyses were conducted. One-way analysis of variance was used to compare hardware costs across all 5 surgeons. Linear regression analysis was used to determine if hardware cost differed by surgeon when accounting for fracture type. RESULTS: The mean contribution margin was $4853 (SD $6446). There was a significant difference in implant costs by surgeon (range, lowest-cost surgeon: $471 [SD $283] to $1609 [SD $819]; P < .001). There was no difference in the use of a suture button or locking plate by fracture type (P = .13); however, the cost of the implant was significantly higher if a suture button or locking plate was used ($1014 [SD $666] vs $338 [SD $176]; P < .001). There was an association between surgeon 3 (ß = 200.32 [95% CI 6.18-394.47]; P = .043) and surgeon 4 (ß = 1131.07 [95% CI 906.84-1355.30]; P < .001) and higher hardware costs. CONCLUSIONS: Even for the same ankle fracture type, a wide variation in implant costs exists. The lack of standardization among surgeons accounted for a nearly 3.5-fold difference, on average, between the lowest- and highest-cost surgeons, negatively affecting contribution margin. LEVELS OF EVIDENCE: Level IV.

Revision Arthroplasty Versus Open Reduction and Internal Fixation of Vancouver Type-B2 and B3 Periprosthetic Femoral Fractures.

¼: Revision arthroplasty (RA) continues to be considered the gold standard in the surgical treatment of Vancouver type-B2 and B3 periprosthetic femoral fractures. However, open reduction and internal fixation (ORIF) has been associated with satisfactory outcomes. Thus, there is an ongoing discussion regarding the optimal surgical strategy for the treatment of these fractures. ¼: In this systematic review and meta-analysis, no significant differences in clinical and radiographic outcome were observed between ORIF and RA in the treatment of Vancouver type-B2 periprosthetic femoral fractures. ¼: ORIF of Vancouver type-B3 periprosthetic femoral fractures was associated with higher revision and reoperation rates than those after RA. ¼: Compared with RA, a significantly higher rate of subsidence was found in the ORIF group in Vancouver type-B2 periprosthetic femoral fractures whereas no significant difference in terms of loosening was observed. ¼: In the comparison of RA and ORIF for the treatment of Vancouver type-B2 and B3 fractures, the percentage of patients achieving full weight-bearing did not differ significantly. ¼: Mortality rates did not differ between RA and ORIF in the treatment of Vancouver type-B2 and B3 fractures. ¼: Overall complication rates did not differ between RA and ORIF in the treatment of Vancouver type-B2 and B3 fractures. ¼: We found a high heterogeneity in applied surgical and fixation techniques in the ORIF group.

Native Hip Septic Arthritis in the Setting of Postpartum Gynecologic Infection: A Case Report.

CASE: A 34-year-old healthy G3P3 woman, 1.5 weeks postpartum, presented with hip pain, fever, and a rash. Clinical examination, laboratory testing, and microbiologic cultures identified bacterial arthritis of the right hip; obstetric/gynecologic examination and cultures identified endometrial, vaginal, and urinary tract infections caused by the same pathogen, group A streptococcus, likely contracted from her 5-year-old son who had streptococcal pharyngitis. She underwent successful surgical decompression of the hip with concurrent medical management of toxic shock syndrome (TSS). CONCLUSIONS: Hematogenously spread septic arthritis may occur in the absence of positive blood cultures during the postpartum period, increasing the risk of developing TSS.

A Limited Fixation, Olecranon Sparing Approach, for Management of Geriatric Intra-Articular Distal Humerus Fractures.

PURPOSE: We propose that geriatric comminuted intra-articular distal humerus fractures can be effectively treated with a limited fixation approach aimed at achieving varus/valgus stability with columnar fixation, but allowing intra-articular comminution to heal by secondary congruency against an intact olecranon, thus avoiding an olecranon osteotomy. METHODS: Fifty-six elderly patients with AO 13-C type fractures, who underwent surgical fixation with ≥12-months of follow-up were retrospectively reviewed. Thirty patients were treated with intra-articular open reduction internal fixation (ORIF) with an olecranon osteotomy and 26 patients were treated with our limited fixation (L-ORIF) approach. Outcomes were range of motion (ROM), complications, additional surgery, and patient-reported outcome measures (PROMIS). RESULTS: At final follow-up, the average elbow ROM was 97° (40°-155°) in the ORIF group and 86.5° (20°-145°) in the L-ORIF group. There was a trend toward more complications and additional surgery in the ORIF group. PROMIS scores for pain were 53.1 and 52.14, and PROMIS functional scores were 41.7 and 41.4 in the ORIF and L-ORIF group respectively. No differences in outcomes were statistically significant. CONCLUSION: A limited fixation technique based on achieving varus/valgus stability with columnar fixation, demonstrated equivalent outcomes in elderly patients with intra-articular distal humerus fractures when compared to intra-articular ORIF with an olecranon osteotomy.

The utility of post-operative hip radiographs in patients treated with hip hemiarthroplasty for femoral neck fractures.

BACKGROUND: Patients treated with hip hemiarthroplasty for low energy femoral neck fractures routinely undergo hip radiographs at each postoperative clinic visit regardless of history and physical findings. No studies to date have evaluated the effectiveness of this accepted practice. The goal of this study was to identify the postoperative utility of both history and physical (H/P) and hip radiographs in the treatment course of patients treated with hip hemiarthroplasty for low energy femoral neck fractures. METHODS: A retrospective chart review was performed on consecutive patients treated with hip hemiarthroplasty for low energy femoral neck fractures. An abnormal H/P and hip radiographs as well as a change in treatment course were recorded at each clinic or emergency department visit. RESULTS: Five hundred and eighty-three patients met inclusion criteria, consisting of 1177 clinic and 50 emergency department (ED) visits. An abnormal radiograph in the presence of a normal H/P did not lead to a change in treatment course. An abnormal H/P alone changed treatment course in 28 (3%) clinic visits and 18 (36%) ED visits. An abnormal H/P and the presence of an abnormal hip radiograph changed the treatment course in 23 (2%) clinic visits and 18 (36%) ED visits. In only one case - 0.3% of abnormal radiographs or 0.08% of 1177 clinic visits - did an abnormal hip radiograph change treatment course in the setting of an abnormal H/P within 6 months from surgery. The average cost of a series of hip and pelvis radiographs was $242. CONCLUSIONS: Abnormal radiographs do not change treatment course in the presence of a normal H/P. Hip radiographs obtained in clinic within 6 months of surgery rarely lead to a change in treatment course and thereby are a source of excess cost and radiation exposure to the patient.

Diagnostic Modalities for Acute Compartment Syndrome of the Extremities: A Systematic Review.

IMPORTANCE: Acute compartment syndrome (ACS) can cause catastrophic tissue damage leading to permanent muscle and nerve loss. Acute compartment syndrome is a clinical diagnosis, with intracompartmental pressure (ICP) used in equivocal cases. There are no reliable diagnostic methods. The clinical evaluation is impossible to standardize, and the threshold for ICP has been known to be unreliable; thus, guidelines for diagnosis can result in overtreatment or delayed diagnosis. OBJECTIVE: To present and review the advantages and disadvantages of each diagnostic modality and identify gaps that need to be addressed in the future and to review the most used and appropriate animal and human ACS models. EVIDENCE REVIEW: We included clinical studies and animal models investigating diagnostic modalities for ACS of the extremities. A MEDLINE and Web of Science search was performed. The protocol for the study was registered on PROSPERO (CRD42017079266). We assessed the quality of the clinical studies with Newcastle-Ottawa scale and reported level of evidence for each article. FINDINGS: Fifty-one articles were included in this study, reporting on 38 noninvasive and 35 invasive modalities. Near-infrared spectroscopy and direct ICP measurement using a Stryker device were the most common, respectively. Cadaveric studies used saline infusions to create an ACS model. Most studies with human participants included injured patients with acquired ACS or at risk of developing ACS. In healthy human participants, tourniquets formed the most commonly used ACS model. Application of tourniquets and infusion of saline or albumin were the most used ACS models among animal studies. CONCLUSIONS AND RELEVANCE: This article reports on the most common as well as many new and modified diagnostic modalities, which can serve as inspiration for future investigations to develop more effective and efficient diagnostic techniques for ACS. Future studies on diagnostic modalities should include the development of tools for continuous assessment of ICP to better identify the earliest alterations suggestive of impending ACS. With the advent of such technologies, it may be possible to develop far less aggressive and more effective approaches for early detection of ACS.

Implant cut-out following cephalomedullary nailing of intertrochanteric femur fractures: Are helical blades to blame?

INTRODUCTION: Implant cut-out remains a common cause of cephalomedullary nail (CMN) failure and patient morbidity following surgical treatment of intertrochanteric femur fractures. Recent studies have suggested an increased rate of CMN cut-out with helical blades as opposed to lag screws. We compared rates of overall cut-out between helical blades and lag screws and used bivariate and multivariate analysis to determine the role of proximal fixation method among other variables on risk for cut-out. Subgroup analysis was performed on the basis of failure mechanism; superior migration (Fig. 2) versus medial perforation (Fig. 3). METHODS: Three-hundred and thirteen patient charts were retrospectively reviewed over an 8-year period; 245 patients were treated with helical blades and 68 with lag screws. Radiographs were reviewed for fracture pattern, Tip-Apex Distance (TAD), Parker's Ratio (PR) and reduction quality. Rate of implant cut-out was compared between groups and multiple logistic regression was used to analyze the ability of several independent variables to predict implant cut-out. RESULTS: Twenty cut-outs occurred; 15 with helical blades and 5 with lag screws. No difference in the rate of cut-out was observed between the two groups (p = 0.45). Poor fracture reduction was found to be a significant predictor of implant failure via bivariate and multiple logistic regression analysis (p = <0.01, OR 23.573). Helical blade fixation, fracture instability, TAD ≥ 25, and PR ≥ 0.45 were not predictive of implant cut-out during multivariate analysis. Similarly, patient smoking status and surgeon trauma fellowship training did not significantly increase the odds of implant cut-out. Failure by medial perforation occurred in 12 instances, all involving helical blades. Failure by superior migration occurred at a significantly higher rate with lag screws than helical blades (p = 0.02). CONCLUSION: CMN cutout is likely multifactorial. A direct association between helical blade fixation and implant cut-out was not observed in our study. Amongst modifiable risk factors for implant failure, poorer fracture reduction was predictive of failure by cut-out. Subgroup analysis highlights differing modes of failure between lag screws and helical blades which warrants further investigation. Ideal TAD during helical blade fixation remains unknown.

The Effect of Hip Positioning on the Projected Femoral Neck-Shaft Angle: A Modeling Study.

OBJECTIVES: To determine and test mathematical models of the relationship between hip flexion-extension, femoral rotation, and NSA. We hypothesized that hip flexion-extension and femoral rotation would result in NSA measurement error. METHODS: Two mathematical models were developed to predict NSA in varying degrees of hip flexion-extension and femoral rotation. The predictions of the equations were tested in vitro using a model that varied hip flexion-extension while keeping rotation constant, and vice versa. The NSA was measured from an anterior-posterior radiograph obtained with a C-arm. Attributable measurement error based on hip positioning was calculated from the models. RESULTS: The predictions of the model correlated well with the experimental data (correlation coefficient = 0.82-0.90). A wide range of patient positioning was found to result in <5-10 degrees error in the measurement of NSA. Hip flexion-extension and femoral rotation had a synergistic effect in measurement error of the NSA. Measurement error was minimized when hip flexion-extension was within 10 degrees of neutral. CONCLUSIONS: This study demonstrates that hip flexion-extension and femoral rotation significantly affect the measurement of the NSA. To avoid inadvertently fixing the proximal femur in varus or valgus, the hip should be positioned within 10 degrees of neutral flexion-extension with respect to the C-arm to minimize positional measurement error.

Runx2-Smad signaling impacts the progression of tumor-induced bone disease.

Runx2, a master regulator of osteogenesis, is abnormally expressed in advanced prostate cancer. Here, we addressed Runx2 contribution to formation of prostate cancer-related osteolytic and osteoblastic bone lesions by mediating TGFß/BMP signaling through direct interaction with Smads. Further, we examined involvement of the Runx2-Smad complex in mediating tumor growth and distal metastasis. To identify Runx2-Smad-specific mechanisms of prostate tumor activity in bone, we generated PC3 prostate cancer cell lines expressing Runx2-WT or one of two mutant proteins (Runx2-HTY and Runx2-ΔC) that each disrupt the Runx2-Smad interaction, either directly through a point mutation or by deletion of the functional C-terminus, respectively. Intratibial tumors generated from these cells revealed that Runx2-WT-expressing cells resulted in predominantly osteolytic disease, whereas cells expressing mutant proteins exhibited tumors with mixed osteolytic/osteoblastic lesions. Extent of bone loss and woven bone formation was assessed by radiography and micro-computed tomography. Bioluminescent imaging showed the presence of labeled prostate cancer cells in the lung at the latest time point examined, with Runx2-WT group exhibiting increased incidence of tumor cells in lung. Notably, disruption of the Runx2-Smad interaction significantly reduced incidence and size of lung tumors. Altered expression of Runx2 target genes involved in invasion, growth, adhesion and metastasis supported our findings. Thus, our studies demonstrate that Runx2 in prostate cancer cells plays a significant role in intratibial prostate cancer-related tumor growth and bone loss through mechanisms mediated by the Runx2-Smad signaling pathway. This work expands upon the potential importance of Runx2 as a therapeutic target in cancer.

Three-part head-splitting proximal humerus fracture through a unicameral bone cyst.

Unicameral bone cysts are rare in adults and are most often found incidentally on radiographs. However, they can persist from the adolescent period and may be present in locations that predispose to or exacerbate fractures.This article describes a case of a healthy 40-year-old woman who sustained a proximal humerus trauma that involved a large unicameral bone cyst, resulting in a 3-part head-splitting fracture. The epiphyseal location of the cyst contributed to the severity and extent of the fracture that resulted from a simple fall. Given the age of the patient, open reduction and internal fixation with a locking plate and lag screws was performed. The patient chose open reduction and internal fixation to preserve a hemiarthroplasty procedure in case of future revision. Successful humeral head reconstruction was achieved, and the patient fully recovered. One year postoperatively, the patient underwent arthroscopic debridement to alleviate subjective stiffness and decreased range of motion.Multipart head-splitting fractures require complex repair strategies. The gold standard for the treatment of these injuries is hemiarthroplasty. However, the decision process is difficult in a young patient given the average survival of autoplastic prostheses and the added difficulty of later revision. The current case demonstrates the complexity of decision making resulting from a rare injury in a young, healthy patient and shows that open reduction and internal fixation can provide acceptable reconstruction in such situations.

Biomechanical effects of harvesting bone graft with the Reamer/Irrigator/Aspirator on the adult femur: a cadaver study.

OBJECTIVES: Test the biomechanical properties of femurs that have undergone reaming with the Reamer Irrigator Aspirator (RIA) device with an aim to prove no difference in torsional strength between matched pairs. METHODS: Intact femurs were harvested from embalmed cadavers, representing 19 matched pairs. One femur from each pair was randomly selected to undergo reaming using the RIA to 15 mm. The bones were then cut and potted using a uniform jig for testing. Each specimen was tested in torsion and torsional stiffness was calculated for each pair. Samples were loaded until fracture or 11 3 N·m of torque. RESULTS: Nine of the reamed specimens and 13 of the unreamed samples remained intact until the machine limit of 113 N·m was reached, representing approximately four times the peak torque of 30N·m seen with stair climbing [Garino J, Beredjiklian P. Core Knowledge in Orthopaedics: Adult Reconstruction and Arthroplasty. Chapter 1, page 33. Mosby, 2007]. Mean torsional stiffness for the reamed group was 532.1 N·m/rad (SD = 208.2), and the unreamed was 546.2 N·m/rad (SD=206). Torsional load capacity was calculated for all specimens and compared in groups in which both reamed and unreamed specimens failed. In these five groups, mean load capacity was 80.6 Nm (SD = 9.5) for the reamed group, and 85 Nm (SD = 16.1) for the unreamed group. CONCLUSIONS: 17 of our reamed specimens and all of our unreamed specimens withstood normal physiologic load seen with stair climbing. In addition, 16 of 19 reamed specimens remained intact at twice this load. The specimen in the reamed group with the lowest torsional load capacity was eccentrically reamed in the distal anterior cortex highlighting potential complications. Given these findings, reaming the cortex of the femur with the RIA device for the purpose of harvesting bone graft does not appear to dramatically diminish the mechanical properties of the cortex or require postoperative weight bearing restrictions. However, careful attention must be paid to technique as eccentric reaming either proximally or distally may result in catastrophic failure. Careful attention must be paid to the use of irrigating fluid and post operative blood loss, and a thorough discussion of risk factors including postoperative fracture should be covered when obtaining informed consent.

The histone deacetylase inhibitor, vorinostat, reduces tumor growth at the metastatic bone site and associated osteolysis, but promotes normal bone loss.

Vorinostat, an oral histone deacetylase inhibitor with antitumor activity, is in clinical trials for hematologic and solid tumors that metastasize and compromise bone structure. Consequently, there is a requirement to establish the effects of vorinostat on tumor growth within bone. Breast (MDA-231) and prostate (PC3) cancer cells were injected into tibias of SCID/NCr mice and the effects of vorinostat on tumor growth and osteolytic disease were assessed by radiography, micro-computed tomography, and histologic and molecular analyses. Vorinostat-treated and control mice without tumors were also examined. Tumor growth in bone was reduced ∼33% by vorinostat with inhibited osteolysis in the first few weeks of the experiment. However, osteolysis became more severe in both the vehicle and vorinostat-treated groups. Vorinostat increased the expression of tumor-derived factors promoting bone resorption, including PTHrP, IL-8, and osteopontin. After 4 weeks of vorinostat therapy, the non-tumor-bearing contralateral femurs and limbs from vorinostat-treated tumor-free SCID mice showed significant bone loss (50% volume density of controls). Thus, our studies indicate that vorinostat effectively inhibits tumor growth in bone, but has a negative systemic effect reducing normal trabecular bone mass. Vorinostat treatment reduces tumor growth in bone and accompanying osteolytic disease as a result of decreased tumor burden in bone. However, vorinostat can promote osteopenia throughout the skeleton independent of tumor cell activity.