Effective Doses of Recombinant Human Bone Morphogenetic Protein-2 in Experimental Spinal Fusion

Study Design Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives To characterize the dose-response relationship of recombinant human bone morphogenetic protein-2 in a spinal fusion model. Summary of Background Data Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein-2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results As in the study using 2300 μg of recombinant human bone morphogenetic protein-2, implantation of 58–920 μg of recombinant human bone morphogenetic protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. Conclusions No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human bone morphogenetic protein-2

Preoperative Vitamin D Repletion in Total Knee Arthroplasty: A Cost-Effectiveness Model.

BackgroundRecent studies have identified vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/L) as a potentially modifiable risk factor for prosthetic joint infection (PJI) in arthroplasty. The purpose of this study is to determine whether implementation of preoperative 25(OH)D repletion is cost-effective for reducing PJI following total knee arthroplasty (TKA).MethodsA cost estimation predictive model was generated to determine the utility of both selective and nonselective 25(OH)D repletion in primary TKA to prevent PJI. Input data on the incidence of 25(OH)D deficiency, relative complication rates, and costs of serum 25(OH)D repletion and 2-stage revision for PJI were derived from previously published literature identified using systematic review and publicly available data from Medicare reimbursement schedules. Mean, lower, and upper bounds of 1-year cost savings were computed for nonselective and selective repletion relative to no repletion.ResultsSelective preoperative 25(OH)D screening and repletion were projected to result in $1,504,857 (range,$215,084-$4,256,388) in cost savings per 10,000 cases. Nonselective 25(OH)D repletion was projected to result in$1,906,077 (range, $616,304-$4,657,608) in cost savings per 10,000 cases. With univariate adjustment, nonselective repletion is projected to be cost-effective in scenarios where revision for PJI costs ≥$10,636, incidence of deficiency is ≥1.1%, and when repletion has a relative risk reduction ≥4.2%.ConclusionThis predictive model supports the potential role of 25(OH)D repletion as a cost-effective mechanism of reducing PJI risk in TKA. Given the low cost of 25(OH)D repletion relative to serum laboratory testing, nonselective repletion appears to be more cost-effective than selective repletion. Further prospective investigation to assess this modifiable risk factor is warranted

Survivorship analysis of 141 modular metallic endoprostheses at early followup

Although our institution historically has been known for its use of osteoarticular allografts in limb salvage surgery for tumors, during the last 8 years there has been an increase in the use of metallic modular endoprostheses. A retrospective review of 141 patients in whom a modular endoprosthesis was implanted in the past 8 years was done, and survival data were compiled using Kaplan-Meier survival analysis, clinical score was determined using a previously described system, and a multivariate regression analysis was done to identify independent risk factors. There were 13 failures (defined as need for revision of the majority of the prosthetic components, excluding cases of local recurrence) yielding an overall implant survival of 91%. Based on Kaplan-Meier estimates, the endoprosthetic survival rate was 88% at 3 years and 76% at 5 years; per location, it was 100% for the proximal humerus, 100% for the proximal femur, 87% for modular knees, and 53% for total femoral implants at 3 years. The clinical scores were good to excellent in 74% of the patients. Multivariate analysis showed that only location and infection were independent risk factors for prosthesis failure. Loosening, infection, and dislocation were independently predictive of a fair or poor clinical score. Age, gender, diagnosis, length of implant, dislocation, nor failed prior allograft had an independent effect on implant survival or clinical outcome. The proximal humeral and proximal femoral implants had greater survival rates than modular knee and total femoral implants. Conversion of failed allografts to modular endoprostheses had a trend for a higher failure rate, but after a multivariate analysis, did not prove to be an independent risk factor for failure. We think that our experience is similar to other endoprosthesis survivorship reports in the literature with short-term followup

Leiomyosarcoma of somatic soft tissues

Leiomyosarcoma is a rare, aggressively malignant connective tissue tumor of mature adults, which arises from smooth muscle. It occurs most frequently in the uterus, bowel, vascular tissues, and less commonly in somatic soft tissue or bone. The tumor when it arises in soft tissue has distinctive histologic features which somewhat resemble malignant fibrous histiocytoma (otherwise known as myxofibrosarcoma). The Orthopaedic Oncology Service at our institution has treated 66 patients with these lesions and thus far, 1/2 of the patients have died of disease at a mean of 3 years after discovery. Factors that increase the death rate include size of the tumor, Musculoskeletal Tumor Society Stage of disease, and to a lesser extent particularly in the lower extremities, anatomic site. Radiation and chemotherapy had little direct effect on the outcome but patients treated with surgery and adjunctive agents seemed to live longer than their cohorts treated with surgery alone. The purpose of this study is a general review of the clinical and prognostic features of this cancer

Preoperative Vitamin D Deficiency Is Associated With Higher Postoperative Complication Rates in Total Knee Arthroplasty.

The purpose of this study was to determine the relative incidence of postoperative complications in 25-hydroxyvitamin D (25D)-deficient and -sufficient patients undergoing total knee arthroplasty (TKA). Patients who were either serum 25D deficient (25D <20 ng/mL) or 25D sufficient (25D ≥20 ng/mL) 90 days prior to primary TKA from 2007 to 2016 were identified using the Humana administrative claims registry. The incidence of postoperative medical and surgical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Risk-adjusted odds ratios (ORs) were calculated using multivariate logistic regression with age, sex, and Charlson Comorbidity Index as covariates. In total, 868 of 6593 patients who underwent TKA from 2007 to 2016 were 25D deficient, corresponding to a 13.2% prevalence rate. On adjustment for age, sex, and Charlson Comorbidity Index, 25D-deficient patients had a higher incidence of postoperative stiffness requiring manipulation under anesthesia (OR, 1.69; 95% confidence interval [CI], 1.39-2.04; P<.001), surgical site infection requiring irrigation and debridement (OR, 1.76; 95% CI, 1.25-2.48; P=.001), and prosthesis explantation (OR, 2.97; 95% CI, 2.04-4.31; P<.001) at 1 year. Patients who were 25D deficient also had higher rates of postoperative deep venous thrombosis (OR, 1.80; 95% CI, 1.36-2.38; P<.001), myocardial infarction (OR, 2.11; 95% CI, 1.41-3.15; P<.001), and cerebrovascular accident (OR, 1.73; 95% CI, 1.17-2.57; P=.006). Thus, serum 25D levels below 20 ng/mL are associated with a higher incidence of postoperative complications and may be a perioperative modifiable risk factor in TKA. [Orthopedics. 2018; 41(4):e489-e495.]