Kathleen S. Beebe

Long-term bisphosphonate usage and subtrochanteric insufficiency fractures

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures. This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.

Outcomes of a Modular Intercalary Endoprosthesis as Treatment for Segmental Defects of the Femur, Tibia, and Humerus

BackgroundResection of diaphyseal bone tumors for local tumor control and stabilization often results in an intercalary skeletal defect and presents a reconstructive challenge for orthopaedic surgeons. Although many options for reconstruction have been described, relatively few studies report on the functional outcomes and complications of patients treated with modular intercalary endoprostheses.Questions/purposesThe objectives of this study were to examine clinical outcomes after reconstruction with a modular intercalary endoprosthesis with a specific focus on (1) the rate of complication or failure; (2) differences in complication rates by anatomic site; (3) functional results as assessed by the Musculoskeletal Tumor Society System (MSTS); and (4) differences in complication rate between patients treated with cemented versus noncemented fixation.MethodsWe conducted a retrospective chart review of patients treated with a modular intercalary endoprosthesis from three musculoskeletal oncology centers from 2008 to 2013. The indication for use of this intercalary endoprosthesis was segmental bone loss from aggressive or malignant tumor with sparing of the joint above and below and deemed unsuitable for biologic reconstruction. No other implant was used for this indication during this period. During this period, 41 patients received a total of 44 intercalary implants, which included 18 (40%) humeri, 5 (11%) tibiae, and 21 (48%) femora. There were 27 (66%) men and 14 (34%) women with a mean age of 63 years (range, 18–91 years). Eight patients (20%) had primary bone tumors and 33 (80%) had metastatic lesions. Thirty-five (85%) patients were being operated on as an initial treatment and six (15%) for revision of a previous reconstruction. Twenty-nine (66%) procedures had cemented stem fixation and 15 (34%) were treated with noncemented fixation. The overall mean followup was 14 months (range, 1–51 months). Patients with primary tumors had a mean followup of 19 months (range, 4–48 months) and patients with metastatic disease had a mean followup of 11 months (range, 1–51 months). Causes of implant failure were categorized according to Henderson et al. [19] into five types as follows: Type I (soft tissue failure), Type II (aseptic loosening), Type III (structural failure), Type IV (infection), and Type V (tumor progression). At 2 years of followup, 38 (93%) of these patients were accounted for with three (7%) lost to followup. MSTS functional assessment was available for 39 of 41 patients (95%).ResultsAt latest followup of these 41 patients, 14 (34%) patients were dead of disease, two patients (5%) dead of other causes, seven (17%) are continuously disease-free, one (2%) shows no evidence of disease, and 17 (41%) are alive with disease. There were 12 (27%) nononcologic complications. Five (11%) of these were Type II failures occurring in noncemented implants between the stem and bone, and six (14%) were Type III failures occurring in cemented implants at the clamp-rod implant interface. One patient developed a deep infection (2%, Type IV failure) and underwent removal of the implant. Additionally, one patient (2%, Type V failure) was treated by amputation after local progression of his metastatic disease. Complications were more common in femoral reconstructions than in tibial or humeral reconstructions. Twelve of 21 patients (57%) with femoral reconstructions had complications versus 0% of tibial or humeral reconstructions (0 of 23; odds ratio [OR], 62; 95% confidence interval [CI], 3–1154; p < 0.0001). The mean overall MSTS score was 77%. Implants with cemented fixation (29) had higher mean MSTS scores when compared with implants with noncemented (15) fixation (84% versus 66%, p = 0.0017). The complication rate was 33% in noncemented cases and 21% in cemented cases (p = 0.39); however, Type II failure at the bone-stem interface was associated with noncemented fixation and Type III failure at the clamp-rod interface was associated with cemented fixation (OR, 143; 95% CI, 2.413–8476; p = 0.0022).ConclusionsThe results of this study indicate that this modular intercalary endoprosthesis yields equivalent results to other studies of intercalary endoprostheses in terms of MSTS scores. We found that patients treated with intercalary endoprostheses in the femur experienced more frequent complications than those treated for lesions in either the humerus or tibia and that the femoral complication rate of this endoprosthesis is higher when compared with other studies of intercalary endoprostheses for femoral reconstruction. Further studies are still needed to determine the long-term outcomes of this endoprosthesis in patients with primary tumors where longevity of the implant is of more importance than in the metastatic setting. We recommend cemented fixation for this intercalary modular endoprostheses because this provides improved MSTS scores and allows immediate return to weightbearing, which is of advantage to metastatic patients with limited lifespans.Level of EvidenceLevel III, therapeutic study.

From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology.

In 1943, Austin Moore developed the first endoprosthesis fashioned from Vitallium, providing the first alternative to traditional amputation as primary treatment of bone tumors. The success of the Vitallium endoprosthesis has since then led to the development of new materials and designs further advancing limb salvage and reconstructive surgery. Combined with the advent of chemotherapy use and imaging advances, conservative treatment of musculoskeletal tumors has expanded greatly. As the implantable options increased with the development of the Lewis expandable adjustable prosthesis and the noninvasive Phenix Growing prosthesis, receiving the diagnosis of a bone tumor no longer equates to automatic limb loss. Our review details the history and development of endoprostheses throughout orthopedic oncology in the treatment of musculoskeletal tumors.

Evaluation of a Noninvasive Expandable Prosthesis in Musculoskeletal Oncology Patients for the Upper and Lower Limb

The noninvasive expandable prosthesis is used for limb-salvage surgery following tumor resection in skeletally immature patients. The purpose of this retrospective study is to report our experience with the Repiphysis (Wright Medical Technology, Inc; Arlington, Tennessee) noninvasive expandable prosthesis for both the lower extremity and compassionate use in the upper extremity in 12 patients between 2003 and 2008. Twelve prostheses were implanted in 12 patients with an average follow-up of 38 months (range, 12-78 months). Nine patients underwent a total of 38 expansion procedures. Mean total expansion was 4.5 cm (range, 0.8-9.9 cm). No complications of lengthening occurred. Seven nononcologic complications were noted. One infection was reported in 12 patients. The mean MSTS score after rehabilitation was 24.5 (range, 13-30). The Repiphysis noninvasive prosthesis provides acceptable functional outcomes for both upper and lower extremity implantation and appears to have an advantage as compared to conventional expandable prosthetics, which require open procedures that can potentially increase the risk of infection from repeated hardware exposure.

Prophylactic Bilateral Intramedullary Femoral Nails for Bisphosphonate-associated Signs of Impending Subtrochanteric Hip Fracture

In the short and midterm, bisphosphonates have proven highly efficacious in the prevention of low-energy fractures, but long-term results and adverse effects have yet to be definitively identified. Of particular concern are emerging reports of long-term bisphosphonate users presenting with unusual low-energy subtrochanteric femur fractures. Perhaps associated with hyperactive bone remodeling leading to an eventually weakened bony architecture, the efficacy of longer-term bisphosphonate use has come into question, especially in those with >5 years of therapy.This article describes a case of a 65-year-old woman with a 10-year history of bisphosphonate use who presented with prodromal thigh pain and characteristic radiographic findings indicative of potential impending subtrochanteric insufficiency fracture. Supported by reports in the literature, unique characteristics of a certain clinical picture warn of potential bisphosphonate-associated subtrochanteric hip fracture; to our knowledge, we present the first reported prophylactic bilateral femoral intramedullary nailing to prevent fragility fracture. A deeper look into the biochemistry behind associated bony weakness caused by long-term incorporation of bisphosphonates is needed, especially if an endpoint to the therapy is to be determined. However, with mounting clinical evidence supporting the risk of bisphosphonate-associated fragility fracture, a characteristic radiographic appearance and clinical presentation cannot be ignored. In the interim, elective surgery may be an efficacious alternative in the treatment of an expected, readily preventable fracture.

Case Report: Elevated Serum Beta Human Chorionic Gonadotropin in a Woman With Osteosarcoma

Human chorionic gonadotropin is a glycoprotein hormone normally synthesized by placental syncytiotrophoblast cells. It also is secreted by gestational trophoblastic tumors, gonadal tumors, and even various nongonadal tumors, including bone and soft tissue sarcomas, as a paraneoplastic syndrome. The literature contains one case report of beta human chorionic gonadotropin production from a primary bone sarcoma occurring in a male patient. We report a woman of childbearing age who presented with a distal femur lytic lesion, clinical symptoms suggestive of pregnancy, and elevated serum beta human chorionic gonadotropin. Although the clinical diagnosis of a sarcoma was never in doubt, we present this case to emphasize a need to exclude pregnancy in women of childbearing age to avoid delay in biopsy and subsequent management. Positive immunohistochemical staining of the biopsy specimen established the tumor cells as the source of beta human chorionic gonadotropin.

Gender Comparison of Scholarly Production in the Musculoskeletal Tumor Society Using the Hirsch Index.

OBJECTIVE Despite an increase in the proportion of female medical school graduates, the number of women in orthopedic surgery remains low. To examine the presence of gender disparities in scholarly production, the authors used the Hirsch index (h-index) to assess members of the Musculoskeletal Tumor Society (MSTS), a well-defined subspecialty of orthopedic surgery. DESIGN Using the MSTS Membership Directory, the authors assessed those practicing at an academic institution in the United States. Members׳ sex and rank was obtained from their departments website, and their h-index and years since initial publication was collected from the Scopus database. SETTING Research was performed at New Jersey Medical School, an institution, using online databases. PARTICIPANTS A total of 247 members of the MSTS were eligible, of whom 125 practiced at a US academic medical center and were included in the study. RESULTS The MSTS is composed of 247 members, 28 (11%) of whom are women. Within US academic medical centers, there are 125 members, including 17 (14%) women. Mean h-indices increased with rising academic rank from 5.42 for assistant professors to 19.28 for professors. Publication ranges showed an increase from 11.03 years for assistant professors to 29.52 years for professors. The h-index and publication years of chairpersons were nearly equal to those of professors. Using the h-index, it was found that men outproduce women-13.4:7.9. Men outnumber women at every rank, increasingly so at higher ranks. The authors found that there was a significant difference in productivity between ranks (p < 0.01) and between sexes (p = 0.035), but not between sexes at the assistant professor, associate professor, or professor levels (p = 0.147, 0.581, and 0.263, respectively). CONCLUSIONS The h-index shows differing production among the sexes and ranks in the MSTS. No significant difference exists between the sexes when members are organized by academic title.

Primary alveolar soft part sarcoma of fibula demonstrating ASPL–TFE3 fusion: a case report and review of the literature

Alveolar soft part sarcoma is a rare soft tissue tumor typically affecting young adults. These tumors are most often seen in the deep soft tissues of the extremities and patients generally present with advanced disease. Primary bone involvement is extremely rare and has only been reported in seven cases. This is the first case of alveolar soft part sarcoma in bone documenting the ASPL-TFE3 gene product. Herein, we report a rare presentation of alveolar soft part sarcoma presenting as a primary bone neoplasm involving the proximal fibula in a 41-year-old woman.

Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis

PURPOSE Intergroup 9514 reported promising outcomes with neoadjuvant chemoradiotherapy for large extremity/trunk soft tissue sarcoma (ESTS). One decade later, optimum integration of chemotherapy and radiotherapy into the perioperative management of ESTS remains to be defined. METHODS The National Cancer Data Base was used to identify 3422 patients who underwent resection for large (>8cm) high-grade STS between 2004 and 2013. Chi-square analysis was used to evaluate distribution of patient and tumor related factors within treatment groups while multivariate analyses were used to determine the impact of these factors on patient outcome. The Kaplan Meier method and Cox proportional hazards model were utilized to evaluate overall survival according to treatment regimen, with a secondary analysis based on propensity score matching to control for prescription bias and potential confounders imbalance. RESULTS Hazard ratio for death was reduced by 35% with radiotherapy and 24% with chemotherapy, compared to surgery alone. Combination therapy incorporating both modalities improved 5-yr survival (62.1%) compared to either treatment alone (51.4%). The sequencing of chemotherapy and radiotherapy or whether they were delivered as adjuvant vs. as neoadjuvant therapy did not affect their efficacy. Age>50years, tumor size>11cm, and tumor location on the trunk/pelvis were poor prognostic factors. CONCLUSION Our analysis suggests that adjunctive modalities are both critical in the treatment of large high-grade ESTS, improving survival when used individually and demonstrating synergy in combination, regardless of sequencing relative to each other or relative to surgery; thus providing a framework for future randomized trials.

Comparison of Phenol and Argon Beam Coagulation as Adjuvant Therapies in the Treatment of Stage 2 and 3 Benign–Aggressive Bone Tumors

Argon beam photocoagulation has gained popularity as an adjuvant therapy for the treatment of giant cell tumors of bone and other stage 2 or 3 benign-aggressive bone tumors. Although argon beam photocoagulation has been considered a safe and reasonable adjuvant treatment with acceptable recurrence rates, it has never been directly compared with the commonly described phenol as adjuvant. The purpose of this study was to determine whether argon beam photocoagulation is as effective as phenol in preventing recurrence without affecting functional outcome as an adjuvant to surgical curettage. We retrospectively reviewed 93 consecutive patients with a minimum 10-month follow-up between 1992 and 2007 who were treated with curettage and either phenol or argon beam photocoagulation. Functional outcomes and complications were recorded. Overall, 16 (17.2%) of 93 patients who were initially treated with 1 of the adjuvants had pathologically confirmed recurrences. No additional recurrences were noted after retreatment, leading to an overall recurrence rate of 17.1% with phenol and 14.8% with argon beam photocoagulation (P=.726). While avoiding the toxic effects of phenol, argon beam photocoagulation provides for statistically equivalent recurrence rates, functional outcomes, and complication rates in the treatment of benign-aggressive bone tumors.