Osteoporosis and low bone mineral density (BMD) pose significant challenges in adult spinal deformity surgery, increasing the risks of complications such as vertebral compression fractures, hardware failure, proximal junctional kyphosis/failure, and pseudoarthrosis. This narrative review examines the current evidence on bone health optimization strategies for spinal deformity patients. Preoperative screening and medical optimization are crucial, with vitamin D supplementation showing particular benefit. Among the pharmacologic agents, bisphosphonates demonstrate efficacy in improving fusion rates and reducing hardware-related complications, though the effects may be delayed. Teriparatide, a parathyroid hormone analog, shows promise in accelerating fusion and enhancing pedicle screw fixation. Newer anabolic agents like abaloparatide and romosozumab require further study but show potential. Romosozumab, in particular, has demonstrated significant improvements in lumbar spine BMD over a shorter duration compared to other treatments. Surgical techniques like cement augmentation and the use of larger interbody cages can mitigate the risks in osteoporotic patients. Overall, a multifaceted approach incorporating medical optimization, appropriate pharmacologic treatment, and tailored surgical techniques is recommended to improve outcomes in adult spinal deformity patients with compromised bone quality. Future research should focus on optimizing the treatment protocols, assessing the long-term outcomes of newer agents in the spine surgery population, and developing cost-effective strategies to improve access to these promising therapies.

Study Design: Systematic Review and Meta-analysis. Objectives: To evaluate the impact of race on post-operative outcomes and complications following elective spine surgery in the United States. Methods: PUBMED, MEDLINE(R), ERIC, EMBASE, and SCOPUS were searched for studies documenting peri-operative events for White and African American (AA) patients following elective spine surgery. Pooled odds ratios were calculated for each 90-day outcome and meta-analyses were performed for 4 peri-operative events and 7 complication categories. Sub-analyses were performed for each outcome on single institution (SI) studies and works that included 100,000 patients. AA patients had increased rates of 90-day readmission (OR 1.33, P = .0001), non-routine discharge (OR 1.71, P = .0001), and mortality (OR 1.66, P = .0003), but not re-operation (OR 1.16, P = .1354). AA patients were more likely to have wound-related complications (OR 1.47, P = .0001) or medical complications (OR 1.35, P = .0006), specifically cardiovascular (OR 1.33, P = .0126), deep vein thrombosis/pulmonary embolism (DVT/PE) (OR 2.22, P = .0188) and genitourinary events (OR 1.17, P = .0343). SI studies could only detect racial differences in re-admissions and non-routine discharges. Studies with <100,000 patients replicated the above findings but found no differences in cardiovascular complications. Disparities in mortality were only detected when all studies were included. Conclusions: AA patients faced a greater risk of morbidity across several distinct categories of peri-operative events. SI studies can be underpowered to detect more granular complication types (genitourinary, DVT/PE). Rare events, such as mortality, require larger sample sizes to identify significant racial disparities.

Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery in the nervous system. AAVs are widely used in research and are the basis of multiple FDA-approved gene therapies. Here, we find that the immune response to AAV’s genome reduces dendritic complexity in mammalian cortex. Dendritic loss associated with AAV-mediated gene delivery occurs at experimentally-relevant titers, cannot be explained by responses to transgene expression or surgery, and is not restricted to a particular capsid serotype, encoded transgene, promoter, or production facility. AAV-associated dendritic loss is accompanied by a decrease in the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and upregulation of immune molecules that can limit dendritic complexity and synaptic transmission. Blocking detection of unmethylated CpG-rich DNA via Toll-like receptor 9 (TLR9) protects dendritic complexity, suggesting that immunodetection of a core feature of the AAV genome triggers dendritic loss. These results reveal previously unsuspected impacts of AAV on neuronal structure and function and identify TLR9 inhibitors as important tools to improve the safety and efficacy of AAV-mediated gene delivery in the nervous system.

Frailty is a known predictor of poor outcomes following spine surgery. While both mFI-11 and mFI-5 are used to assess frailty, no pooled analysis has independently evaluated their prognostic performance across multiple outcomes. This study examines how mFI-11 and mFI-5 stratify frailty and how consistently each index predicts postoperative outcomes in elective spine surgery. A systematic literature search was conducted using PubMed, Scopus, and Web of Science databases to identify cohort studies reporting associations of mFI-11 or mFI-5 with postoperative outcomes in elective spine surgery. Meta-analyses using random-effects models calculated pooled odds ratios (ORs) and p-values for key outcomes including any adverse event, medical complication, surgical complication, mortality, reoperation, and non-routine discharge. A total of 22 studies were included in the meta-analysis. mFI-11 was associated with increased odds of medical complications (OR 2.09, p=0.0014) and surgical complications (OR 2.03, p=0.0390), but not reoperation (OR 0.95, p=0.8822). These findings were inconsistently significant across sub-analyses comparing higher mFI-11 scores to mFI-11=0. mFI-5 predicted a broader range of outcomes, including any complication (OR 1.7, p<0.0001), non-routine discharge (OR 3.29, p<0.0001), and mortality (OR 2.29, p=0.0133). These significant results persisted across sub-analyses comparing higher mFI-5 scores to mFI-5=0. mFI-5 showed more consistent associations with postoperative outcomes than mFI-11. MFI-5 demonstrates greater consistency in predicting adverse outcomes in elective spine surgery than mFI-11. mFI-5 may serve as a practical tool for frailty stratification in surgical patients. Further studies are needed to validate these results and optimize frailty assessment in spine surgery.