OBJECTIVE: Osteoporosis represents the most common metabolic disease of the bone, with an estimated 10% of adults aged 50 years or older affected in the United States. This patient population is at increased risk for spine fracture and instrumentation-related complications after spine surgery. Surgeon knowledge of the available treatments for patients with low bone mineral density (BMD) and how they impact biology of fusion may help mitigate negative effects in the postoperative period. Recombinant parathyroid hormone, which is sold under the name teriparatide, is the most extensively studied bone-protecting agent in humans. Additionally, the success of the monoclonal antibody denosumab has led to further clinical investigations of human patients undergoing spine surgery. Another monoclonal antibody, romosozumab, was recently approved by the US FDA for human use in patients with osteoporosis. Although studies of romosozumab in patients undergoing spine surgery have not been conducted, this is a promising potential therapeutic agent based on its early success in preclinical and clinical trials. Here, the authors aimed to review the mechanisms of action and evidence of use of antiresorptive and anabolic agents in patients with osteoporosis undergoing spine surgery. METHODS: In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted to explore the antiresorptive and anabolic agents used in the perioperative period in patients with osteoporosis undergoing spinal surgery. The search was performed by using the PubMed, Embase, and Cochrane Library databases. Titles and abstracts were screened and subsequently selected for full review. RESULTS: The initial search returned 330 articles. Of these articles, 23 final articles were included and reviewed. Many of these articles reported that use of adjuvant agents in the perioperative period improved radiographic evidence of bony fusion and bone fusion rates. These agents tended to improve BMD postoperatively. CONCLUSIONS: Although antiosteoporosis agents are effective to varying degrees as treatments of patients with low BMD, teriparatide and bisphosphonates have been the most extensively studied with respect to spinal instrumentation. The advent of newer agents represents an area for further exploration, especially due to the current paucity of controlled investigations. It is imperative for spine surgeons to understand the mechanisms of action of these drugs and their effects on biology of fusion.

Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system, and dysregulation of its cellular functions is associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radiosensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Furthermore, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.

Hypothyroidism has been independently associated with the development of several comorbidities and is known to increase complication rates in non-spinal surgeries. However, there are limited data regarding the effects of hypothyroidism in major spine surgery. Therefore, we present the largest retrospective analysis evaluating outcomes in hypothyroid patients undergoing spinal fusion. A retrospective review of the National Inpatient Sample (NIS) from 2004-2014 was performed. Patients with an International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) procedure code indicating spinal fusion (81.04-81.08, 81.34-81.38, 81.0x, 81.3x) were included. Patients with an ICD-9-CM diagnosis code indicating hypothyroidism (244.x) were compared to those without. Cervical and lumbar fusions were evaluated independently. Significant covariates in univariable logistic regression were utilized to construct multivariable models to analyze the effect of hypothyroidism on perioperative morbidity and mortality. A total of 4,149,125 patients were identified, of which 9.4% were hypothyroid. Although, hypothyroid patients had a higher risk of hematologic complications (lumbar - odds ratio [OR] 1.176, p < 0.0001; cervical - OR 1.162, p < 0.0001), they exhibited decreased in-hospital mortality (lumbar - OR .643, p < 0.0001; cervical - OR .606, p < 0.0001). Hypothyroid lumbar fusion patients also demonstrated decreased rates of perioperative myocardial infarction (MI) (OR .851, p < 0.0001). All these results were independent of patient gender. Hypothyroid patients undergoing spinal fusion demonstrated lower rates of inpatient mortality and, in lumbar fusions, also had lower rates of acute MI when compared to their euthyroid counterparts. This suggests that hypothyroidism may offer protection against all-cause mortality and may be cardioprotective in the postoperative period for lumbar spinal fusions independent of patient gender.

Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system and dysregulation of its cellular functions are associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radio-sensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Further, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.