
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

71467
10.1038/s41598-024-71467-3
Article
Relationship between preoperative glucose level and all-cause mortality in patients with osteoporotic vertebral compression fracture who underwent percutaneous vertebroplasty
Lin Yu-Hsien 12
Lin Yu-Tsung 2
Wu Yun-Che 2
Wang Wen-Chien 2
Chen Kun-Hui 234
Pan Chien-Chou 25
Lee Cheng-Hung 237
Yang Shun-Fa 18
Wang Jun-Sing jswang@vghtc.gov.tw

369
1 https://ror.org/059ryjv25 grid.411641.7 0000 0004 0532 2041 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
2 https://ror.org/00e87hq62 grid.410764.0 0000 0004 0573 0731 Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
3 grid.260542.7 0000 0004 0532 3749 Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
4 https://ror.org/03fcpsq87 grid.412550.7 0000 0000 9012 9465 Department of Computer Science and Information Engineering, Providence University, Taichung, Taiwan
5 Department of Rehabilitation Science, Jenteh Junior College of Medicine, Nursing, and Management,, Miaoli, Taiwan
6 https://ror.org/00e87hq62 grid.410764.0 0000 0004 0573 0731 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
7 grid.411432.1 0000 0004 1770 3722 Department of Food Science and Technology, Hung Kuang University, Taichung, Taiwan
8 https://ror.org/01abtsn51 grid.411645.3 0000 0004 0638 9256 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
9 https://ror.org/00se2k293 grid.260539.b 0000 0001 2059 7017 Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
31 8 2024
31 8 2024
2024
14 202657 5 2024
28 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002–1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.

Keywords

Osteoporotic vertebral compression fracture
Percutaneous vertebroplasty
Blood glucose
DM
All-cause mortality
Subject terms

Health care
Medical research
Risk factors
issue-copyright-statement© Springer Nature Limited 2024
==== Body
pmcIntroduction

Osteoporotic vertebral compression fractures (OVCFs), the most common type of osteoporotic fractures, are common in older adults1,2. The incidence rate of OVCFs was reported to be 10.5% among patients in the 70- to 79-year-old age group and up to 18% among patients aged > 80 years3. OVCFs can cause considerable morbidities, such as back pain, disabilities, prolonged bed rest, decreased quality of life, poor mental health, and even mortality4. The pathology of OVCFs is limited to the anterior half of the vertebral body and does not involve the posterior osseous components or ligamentous complex. Therefore, for painful OVCFs with intractable pain, vertebroplasty (VP) is an effective procedure for decreasing pain and complications related to being bedridden and preventing further kyphotic deformities5–7.

However, the effect of VP on the overall long-term survival of patients with OVCFs remains unclear despite its demonstrated effectiveness in reducing fracture-related mortality8. These findings imply that there may be additional factors influencing the overall long-term survival of these patients. Diabetes mellitus (DM) and hyperglycemia are conditions characterized by impaired insulin secretion or peripheral-tissue insulin resistance, resulting in impaired oxygen delivery due to hemoglobin glycosylation and subsequent tissue ischemia. DM and hyperglycemia have been identified as independent risk factors for increased surgical complications9–11. However, their impact on long-term survival remains unclear. Therefore, this study aimed to investigate the association between preoperative glucose levels and all-cause mortality in patients with OVCFs receiving VP.

Methods

We hypothesized that glucose levels at admission may affect all-cause mortality in patients with OVCF receiving VP. This retrospective study at a single tertiary referral center included all adult patients diagnosed with single-level OVEF who underwent VP between 2013 and 2020. An OVCF was defined as a low-energy trauma mechanism, including a simple fall or no obvious trauma history. Participants with a history of high-energy trauma, including falls from a height, traffic accidents, initial presentation of multiple traumas, or diagnosis of burst fracture, were excluded. Patients with pathological fractures and those with no data on bone mineral density were also excluded. Preoperative admission glucose levels and baseline demographics, including age, sex, and comorbidities, were collected from the electronic medical records of the patients. The survival status of the patients was confirmed by the end of March 2021 using information from the Ministry of Health and Welfare, R.O.C. De-identified data were used for the analyses. This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Taichung Veterans General Hospital, Taichung, Taiwan (approval number: CE22167A). Informed consent was waived due to the retrospective nature of the study design.

In this study, the guidelines of the American Diabetes Association11 were followed, and the patients were divided into two groups based on preoperative glucose levels: < 110 mg/dl (normoglycemia) and ≥ 110 mg/dL (hyperglycemia). Subsequent analysis was conducted to investigate the influence of preoperative hyperglycemia and glucose level on long-term all-cause mortality. Confounding factors such as age, sex, body mass index, smoking, hypertension, cardiovascular disease, and osteoporosis were adjusted for before proceeding with further analysis.

Statistical analysis

Categorical and continuous variables were examined for statistically significant between-group differences using the chi-square test and independent t-test, respectively. Kaplan–Meier survival curves were plotted for the study population according to their preoperative glucose levels (normoglycemia [< 110 mg/dL] vs. hyperglycemia [≥ 110 mg/dL]). Cox proportional hazard models were used to examine the effects of hyperglycemia (< 110 mg/dL vs. ≥ 110 mg/dL), preoperative glucose levels (as a continuous variable), and history of diabetes on all-cause mortality with adjustments for age, sex, and concomitant chronic diseases. A cubic spline analysis of preoperative glucose levels vs. risk of all-cause mortality per a Cox proportional hazards model was conducted as a sensitivity test. All statistical analyses were performed using Statistical Package for the Social Sciences (IBM SPSS version 22.0; International Business Machines Corp., NY, USA). Statistical significance was set at p < 0.05.

Results

Overall, 131 patients were included in this study. The mean age of the patients was 75.8 ± 9.3 years, and 26.7% were male. Furthermore, 20.6% and 54.2% of the patients were diagnosed with diabetes and hypertension, respectively. A history of cardiovascular disease was noted in 8.4% of the participants, while 77.9% had osteoporosis.

Baseline characteristics categorized by preoperative fasting plasma glucose levels into two groups are presented in Table 1. Most baseline characteristics were not significantly different between the two groups. However, in the hyperglycemia group, there were fewer male patients (19.7% vs. 36.4%, p = 0.034), and the patients had higher body mass indexes (BMIs; 24.6 ± 4.5 vs. 23.1 ± 3.4, p = 0.032) and higher prevalence of diabetes (31.6% vs. 5.5%, p < 0.001).Table 1 Baseline characteristics of the study population.

	Admission fasting plasma glucose	P	
 < 110 mg/dL	 ≥ 110 mg/dL	
Number of patients	55	76		
Age, years	75.1 ± 9.6	76.4 ± 9.0	0.398	
Male sex, n (%)	20 (36.4)	15 (19.7)	0.034	
Body mass index, kg/m2	23.1 ± 3.4	24.6 ± 4.5	0.032	
Smoking, n (%)	4 (7.3)	5 (6.6)	0.877	
Diabetes, n (%)	3 (5.5)	24 (31.6)	 < 0.001	
Hypertension, n (%)	25 (45.5)	46 (60.5)	0.087	
Cardiovascular disease, n (%)	4 (7.3)	7 (9.2)	0.693	
Osteoporosis, n (%)	43 (78.2)	59 (77.6)	0.940	
Fasting plasma glucose, mg/dL	97.8 ± 7.0	159.6 ± 65.1	 < 0.001	
Level of vertebroplasty, n (%)			0.952	
 T-spine	22 (40.0)	30 (39.5)		
 L-spine	33 (60.0)	46 (60.5)		
Values are mean ± SD or n (%).

This study employed a Cox proportional hazard model to analyze the impact of hyperglycemia on admission (≥ 110 mg/dL) relative to that of normoglycemia (< 110 mg/dL) on all-cause mortality (Table 2). The analysis revealed a significant correlation between hyperglycemia on admission (≥ 110 mg/dL) and all-cause mortality (hazard ratio, 2.668; 95% CI 1.064–6.689; p = 0.036). This correlation remained significant even after adjusting for age and sex (Model 2), as well as other factors and comorbidities that may affect the outcome, such as BMI, smoking, hypertension, cardiovascular disease, and osteoporosis (Model 3). Kaplan–Meier survival curves for both groups show a significantly lower survival rate in the hyperglycemia group during median follow-up of 2.1 years (log-rank test: p = 0.029; Fig. 1).Table 2 Association of preoperative hyperglycemia, glucose levels, and history of diabetes with all-cause mortality.

	Hazard ratio (95% CI)	P	
Fasting plasma glucose (≥ 110 mg/dL vs. < 110 mg/dL)	
 Model 1	2.668 (1.064, 6.689)	0.036	
 Model 2	2.673 (1.047, 6.821)	0.040	
 Model 3	2.708 (1.047, 7.003)	0.040	
Fasting plasma glucose (mg/dL)	
 Model 1	1.007 (1.002, 1.012)	0.006	
 Model 2	1.008 (1.003, 1.013)	0.001	
 Model 3	1.007 (1.001, 1.013)	0.016	
History of diabetes (yes vs. no)	
 Model 1	1.579 (0.659, 3.783)	0.306	
 Model 2	1.596 (0.664, 3.834)	0.296	
 Model 3	2.781 (0.980, 7.890)	0.055	
Model 1, unadjusted. Model 2, adjusted for age and sex. Model 3 adjusted for variables in Model 2 plus body mass index, smoking, hypertension, cardiovascular disease, and osteoporosis.

Fig. 1 Kaplan–Meier survival curves of the study population per preoperative glucose levels. Normoglycemia (< 110 mg/dL) vs. Hyperglycemia (≥ 110 mg/dL).

We further analyzed the impact of preoperative fasting glucose levels (as a continuous variable) on all-cause mortality using a Cox proportional hazard model (Table 2). The analysis revealed a significant correlation between preoperative fasting glucose level and all-cause mortality (hazard ratio, 1.007; 95% CI 1.002–1.012; p = 0.006). This correlation remained significant even after adjusting for age and sex (Model 2), as well as other factors and comorbidities that may affect the outcome, such as BMI, smoking, hypertension, cardiovascular disease, and osteoporosis (Model 3). A cubic spline plot analysis (Fig. 2) showed that the hazard ratio of all-cause mortality began to increase when the glucose levels on admission exceeded 130–150 mg/dL.Fig. 2 Cubic spline analysis of preoperative glucose levels versus the risk of postoperative long-term all-cause mortality. Adjustments for age, sex, body mass index, smoking, diabetes, hypertension, cardiovascular disease, and osteoporosis (p = 0.034).

Finally, to investigate the impact of DM on all-cause mortality, a Cox proportional hazard model was employed for analysis (Table 2). Although the hazard ratio was 1.579, the 95% confidence interval and p-value did not reach statistical significance, indicating that the presence of DM was not a significant factor influencing long-term all-cause mortality.

To validate our findings, we examined the association of fasting plasma glucose with all-cause mortality in another cohort of 266 patients (mean age 76.0 ± 9.4 years, male 22.9%, mean body mass index 24.6 ± 4.0 kg/m2) who underwent VP for compression fractures between 2013 and 2020 in our hospital. These patients did not have data on bone mineral density, and were not included in our initial analyses. After median follow-up of 4.2 years, we found a significant association between fasting plasma glucose (≥ 110 vs. < 110 mg/dl) and all-cause mortality after adjustment of age, sex, and body mass index (hazard ratio 1.625; 95% CI 1.038–2.545; p = 0.034; Table 3). Similar association was noted when fasting plasma glucose was examined as a continuous variable (mg/dl) (hazard ratio 1.625; 95% CI 1.038–2.545; p = 0.034).Table 3 Associations of fasting plasma glucose with all-cause mortality in another cohort of 266 patients who underwent vertebroplasty.

	Hazard Ratio (95% CI)	P	
Fasting plasma glucose (≥ 110 mg/dL vs. < 110 mg/dL)	
 Model 1	1.649 (1.056, 2.577)	0.028	
 Model 2	1.625 (1.038, 2.545)	0.034	
Fasting plasma glucose (mg/dL)	
 Model 1	1.005 (1.001, 1.010)	0.026	
 Model 2	1.005 (1.000, 1.009)	0.046	
Model 1, unadjusted. Model 2, adjusted for age, sex, and body mass index.

Discussion

In this study, higher preoperative glucose levels were found to be associated with increased long-term all-cause mortality, with a median follow-up period of > 2 years among patients with OVCFs who underwent VP. This correlation remained significant even after adjusting for other confounding factors using Cox proportional hazard models. Additionally, the presence of DM did not affect long-term all-cause mortality. These findings underscored the role of preoperative hyperglycemia as a risk factor for increased long-term mortality in patients with OVCFs undergoing VP.

The occurrence of OVCFs increased significantly with age12. Older age also led to higher morbidity and mortality rates13,14. VP is a common procedure for treating painful OVCFs, which can lower fracture-related mortality8, pain scores determined using the visual analog scale, opioid and non-steroidal anti-inflammatory drug use, and complications related to prolonged immobilization5–7. However, its impact in reducing long-term all-cause mortality rates remains unclear15–18. Identifying risk factors for mortality in elderly patients is therefore crucial.

Diabetes and hyperglycemia impair oxygen delivery to peripheral tissues through hemoglobin glycosylation, resulting in tissue ischemia and other downstream consequences. DM is a major risk factor for complications following various surgical procedures. Approximately 25% of patients who underwent spinal surgery had a history of diabetes19–21. Extensive research has demonstrated that diabetes and hyperglycemia are independent risk factors associated with increased surgical complications, such as surgical site infection and adverse cardiovascular events, following spine surgery9,10. Previous studies have also shown that long-term poor blood glucose control can lead to the accumulation of advanced glycation end products, which can inhibit osteoblast differentiation, promote osteoblast apoptosis and osteoclast formation, reduce bone mass, and worsen osteoporosis22,23. Additionally, patients with diabetes may have other comorbidities that influence their medical outcomes9,24. There is plenty of literature to support the notion that high preoperative glucose levels and DM lead to poorer outcomes and higher complication rates.

However, to our knowledge, there is no available literature examining the impact of preoperative blood glucose levels on the long-term survival of patients who underwent VP for OVCFs. Our study found that among patients who underwent VP for OVCFs, preoperative hyperglycemia emerged as an independent risk factor for long-term all-cause mortality. Conversely, DM was not associated with long-term all-cause mortality. Such results underscore the greater impact of hyperglycemia on long-term survival compared with DM, although this is not the first study with such findings.

Umpierrez et al.25 analyzed 2030 consecutive adult patients admitted to the general ward. After adjusting for other relevant risk factors, newly discovered hyperglycemia was found to be associated with an 18.3-fold increased mortality rate compared with that in patients with normoglycemia, whereas in the known diabetes group, the increase was only 2.7-fold. Additionally, patients with newly discovered hyperglycemia during admission, compared with those having a history of DM or normoglycemia during admission, had longer hospital stays, higher admission rates to intensive care units, and were less likely to be discharged home.

Although the underlying mechanisms remain unclear, the study by Umpierrez et al. suggests that newly diagnosed hyperglycemia may be a marker of more severe illness rather than the primary cause of increased morbidity and mortality25. This is because the blood glucose levels of patients with newly diagnosed hyperglycemia were lower than those of the patients with known DM. Stress hyperglycemia, caused by physiological illness, results in a temporary increase in blood glucose levels and typically occurs in individuals with undiagnosed DM or impaired glucose intolerance or owing to severe stress leading to increased counterregulatory hormone levels25.

Stress hyperglycemia may involve several potential mechanisms, including increased secretion of counterregulatory hormones (catecholamines, cortisol, and glucagon), leading to increased gluconeogenesis and decreased glycogenolysis26,27; lactate serving as a substrate for gluconeogenesis, with increased lactate resulting in increased gluconeogenesis28,29; and peripheral insulin resistance25. Conversely, hyperglycemia itself can create a toxic cellular milieu30,31, leading to intracellular and extracellular dehydration, electrolyte abnormalities, and suppression of immune function25.

In another recent study32, an analysis of 174,671 hospitalized patients found that inpatient hyperglycemia was associated with a 2.18-fold increased risk of mortality compared with normoglycemia (odds ratio [OR]: 95% CI 2.08, 2.31). Furthermore, this study categorized baseline glycemic status into four groups: non-type 2 DM, pre-DM, unscreened status, and type 2 DM. The study found that compared to baseline type 2 DM status, the ORs for 30‐day mortality were 1.41 (1.25–1.60), 1.32 (1.16–1.51), and 1.30 (1.04–1.62) in non‐type 2 DM, pre‐DM, and unscreened status groups, respectively. This study also confirmed the impact of hyperglycemia at the time of admission on mortality, which was even greater in patients without pre-existing DM than in those with DM. The study suggests that this could be because individuals in the type 2 DM or pre-DM status groups may have already undergone relevant lifestyle changes and received medications in a community setting, which could have a protective effect33. This finding is similar to those of our study, in which we found no association between isolated DM and all-cause mortality; instead, preoperative hyperglycemia remained associated with all-cause mortality even after eliminating other interfering factors.

When the preoperative glucose level was above 150 mg/dL, the hazard ratio for long-term mortality increased significantly (Fig. 2). This result indicates that maintaining a preoperative glucose level below 150 mg/dL is beneficial for elderly patients with OVCFs. Lastly, the current study emphasizes the association between preoperative glucose levels and long-term all-cause mortality after VP.

Despite the novelty of this study, it has some limitations. First, the retrospective nature of this study introduced a potential risk of selection bias, and the sample size of our patient cohort was relatively small. Second, although other related comorbidities and risk factors were controlled for, the severity of comorbidities (such as blood pressure control status, glycosylated hemoglobin [HbA1c] levels in patients with DM, severity of cardiovascular disease, and T-score for osteoporosis) was not accounted for, which could have influenced the results. Finally, HbA1c, which reflects the 3-month control status of diabetes, has been shown to be associated with infection rate and postoperative outcomes of elective spine surgery34; however, there was no data regarding its association with long-term mortality after an orthopedic surgery. Given that this study focused on patients who required VP for painful OVCFs, which is often an urgent or emergent surgery rather than an elective one, the modifiable variable of interest was the preoperative glucose level instead of HbA1c. However, as mentioned earlier, long-term blood glucose control also affects postoperative outcomes; therefore, including HbA1c levels in the analysis could be considered in a larger prospective study in the future.

Conclusion

Preoperative hyperglycemia was independently associated with survival outcomes in patients with OVCFs who underwent VP. Conversely, DM was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in an aging surgical population.

Acknowledgements

We would like to convey our special thanks to the professional statistician affiliated to the Biostatistics Task Force of Taichung Veterans General Hospital.

Author contributions

Y-HL and J-SW designed and conducted the research. Y-HL, Y-TL, W-CW, Y-CW, K-HC, C-CP, C-HL and S-FY contributed acquisition of data, analysis, and interpretation of data. Y-HL and J-SW wrote the first draft of the manuscript. Y-HL, Y-TL, W-CW, Y-CW, K-HC, C-CP, C-HL and S-FY revised the manuscript critically for important intellectual content. All authors approved the final draft of the manuscript.

Data availability

The data that support the findings of this study are available from Dr. Jun-Sing Wang but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Dr. Jun-Sing Wang.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Delmas PD Underdiagnosis of vertebral fractures is a worldwide problem: The Impact study J. Bone Miner. Res. 2005 20 557 563 10.1359/JBMR.041214 15765173
Delmas, P. D. et al. Underdiagnosis of vertebral fractures is a worldwide problem: The Impact study. J. Bone Miner. Res. 20, 557–563 (2005).15765173 10.1359/JBMR.041214
2. Majumdar SR Incidental vertebral fractures discovered with chest radiography in the emergency department: Prevalence, recognition, and osteoporosis management in a cohort of elderly patients Arch. Intern. Med. 2005 165 905 909 10.1001/archinte.165.8.905 15851642
Majumdar, S. R. et al. Incidental vertebral fractures discovered with chest radiography in the emergency department: Prevalence, recognition, and osteoporosis management in a cohort of elderly patients. Arch. Intern. Med. 165, 905–909 (2005).15851642 10.1001/archinte.165.8.905
3. Cosman F Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: Results from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 Osteoporos. Int. 2017 28 1857 1866 10.1007/s00198-017-3948-9 28175980
Cosman, F. et al. Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: Results from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. Osteoporos. Int. 28, 1857–1866 (2017).28175980 10.1007/s00198-017-3948-9
4. Ensrud KE Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. Fracture intervention trial research group J. Am. Geriatr. Soc. 2000 48 241 249 10.1111/j.1532-5415.2000.tb02641.x 10733048
Ensrud, K. E. et al. Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. Fracture intervention trial research group. J. Am. Geriatr. Soc. 48, 241–249 (2000).10733048 10.1111/j.1532-5415.2000.tb02641.x
5. Wardlaw D Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (Free): A randomised controlled trial Lancet 2009 373 1016 1024 10.1016/S0140-6736(09)60010-6 19246088
Wardlaw, D. et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (Free): A randomised controlled trial. Lancet 373, 1016–1024 (2009).19246088 10.1016/S0140-6736(09)60010-6
6. Klazen CA Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): An open-label randomised trial Lancet 2010 376 1085 1092 10.1016/S0140-6736(10)60954-3 20701962
Klazen, C. A. et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): An open-label randomised trial. Lancet 376, 1085–1092 (2010).20701962 10.1016/S0140-6736(10)60954-3
7. Clark W Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): A multicentre, randomised, double-blind, placebo-controlled trial Lancet 2016 388 1408 1416 10.1016/S0140-6736(16)31341-1 27544377
Clark, W. et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet 388, 1408–1416 (2016).27544377 10.1016/S0140-6736(16)31341-1
8. Gerling MC Cement augmentation of refractory osteoporotic vertebral compression fractures: Survivorship analysis Spine (Phila Pa 1976) 2011 36 E1266 E1269 10.1097/BRS.0b013e31820a0b3f 21358465
Gerling, M. C. et al. Cement augmentation of refractory osteoporotic vertebral compression fractures: Survivorship analysis. Spine (Phila Pa 1976) 36, E1266–E1269 (2011).21358465 10.1097/BRS.0b013e31820a0b3f
9. Olsen MA Risk factors for surgical site infection following orthopaedic spinal operations J. Bone Jt. Surg. Am. 2008 90 62 69 10.2106/JBJS.F.01515
Olsen, M. A. et al. Risk factors for surgical site infection following orthopaedic spinal operations. J. Bone Jt. Surg. Am. 90, 62–69 (2008).10.2106/JBJS.F.01515
10. Pull ter gunne AF A methodological systematic review on surgical site infections following spinal surgery: Part 1: Risk factors Spine (Phila Pa 1976) 2012 37 2017 2033 10.1097/BRS.0b013e31825bfca8 22565388
Pull ter gunne, A. F. et al. A methodological systematic review on surgical site infections following spinal surgery: Part 1: Risk factors. Spine (Phila Pa 1976) 37, 2017–2033 (2012).22565388 10.1097/BRS.0b013e31825bfca8
11. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the expert committee on the diagnosis and classification of diabetes mellitus Diabetes Care 2003 26 S5 S20 10.2337/diacare.26.2007.S5 12502614
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26, S5–S20 (2003).12502614 10.2337/diacare.26.2007.S5
12. Lau E Ong K Kurtz S Schmier J Edidin A Mortality following the diagnosis of a vertebral compression fracture in the medicare population J. Bone Jt. Surg. Am. 2008 90 1479 1486 10.2106/JBJS.G.00675
Lau, E., Ong, K., Kurtz, S., Schmier, J. & Edidin, A. Mortality following the diagnosis of a vertebral compression fracture in the medicare population. J. Bone Jt. Surg. Am. 90, 1479–1486 (2008).10.2106/JBJS.G.00675
13. Cauley JA Thompson DE Ensrud KC Scott JC Black D Risk of mortality following clinical fractures Osteoporos. Int. 2000 11 556 561 10.1007/s001980070075 11069188
Cauley, J. A., Thompson, D. E., Ensrud, K. C., Scott, J. C. & Black, D. Risk of mortality following clinical fractures. Osteoporos. Int. 11, 556–561 (2000).11069188 10.1007/s001980070075
14. Jalava T Association between vertebral fracture and increased mortality in osteoporotic patients J. Bone Miner. Res. 2003 18 1254 1260 10.1359/jbmr.2003.18.7.1254 12854835
Jalava, T. et al. Association between vertebral fracture and increased mortality in osteoporotic patients. J. Bone Miner. Res. 18, 1254–1260 (2003).12854835 10.1359/jbmr.2003.18.7.1254
15. Levy H Seydafkan S Rice JD Easley KA Tangpricha V Comparative efficacy of vertebroplasty, kyphoplasty, and medical therapy for vertebral fractures on survival and prevention of recurrent fractures Endocr. Pract. 2012 18 499 507 10.4158/EP11349.OR 22440996
Levy, H., Seydafkan, S., Rice, J. D., Easley, K. A. & Tangpricha, V. Comparative efficacy of vertebroplasty, kyphoplasty, and medical therapy for vertebral fractures on survival and prevention of recurrent fractures. Endocr. Pract. 18, 499–507 (2012).22440996 10.4158/EP11349.OR
16. McCullough BJ Comstock BA Deyo RA Kreuter W Jarvik JG Major medical outcomes with spinal augmentation vs conservative therapy JAMA Intern. Med. 2013 173 1514 1521 10.1001/jamainternmed.2013.8725 23836009
McCullough, B. J., Comstock, B. A., Deyo, R. A., Kreuter, W. & Jarvik, J. G. Major medical outcomes with spinal augmentation vs conservative therapy. JAMA Intern. Med. 173, 1514–1521 (2013).23836009 10.1001/jamainternmed.2013.8725
17. Kurra S Metkar U Lieberman IH Lavelle WF The effect of kyphoplasty on mortality in symptomatic vertebral compression fractures: A review Int. J. Spine Surg. 2018 12 543 548 10.14444/5066 30364815
Kurra, S., Metkar, U., Lieberman, I. H. & Lavelle, W. F. The effect of kyphoplasty on mortality in symptomatic vertebral compression fractures: A review. Int. J. Spine Surg. 12, 543–548 (2018).30364815 10.14444/5066
18. Ong KL Beall DP Frohbergh M Lau E Hirsch JA Were VCF patients at higher risk of mortality following the 2009 publication of the vertebroplasty "sham" trials? Osteoporos. Int. 2018 29 375 383 10.1007/s00198-017-4281-z 29063215
Ong, K. L., Beall, D. P., Frohbergh, M., Lau, E. & Hirsch, J. A. Were VCF patients at higher risk of mortality following the 2009 publication of the vertebroplasty “sham” trials?. Osteoporos. Int. 29, 375–383 (2018).29063215 10.1007/s00198-017-4281-z
19. Guzman JZ The impact of diabetes mellitus on patients undergoing degenerative cervical spine surgery Spine (Phila Pa 1976) 2014 39 1656 1665 10.1097/BRS.0000000000000498 24983933
Guzman, J. Z. et al. The impact of diabetes mellitus on patients undergoing degenerative cervical spine surgery. Spine (Phila Pa 1976) 39, 1656–1665 (2014).24983933 10.1097/BRS.0000000000000498
20. Liow MHL Poorer fusion outcomes in diabetic cervical spondylotic myelopathy patients undergoing single-level anterior cervical discectomy and fusion does not compromise functional outcomes and quality of life Spine (Phila Pa 1976) 2018 43 477 483 10.1097/BRS.0000000000002395 28858183
Liow, M. H. L. et al. Poorer fusion outcomes in diabetic cervical spondylotic myelopathy patients undergoing single-level anterior cervical discectomy and fusion does not compromise functional outcomes and quality of life. Spine (Phila Pa 1976) 43, 477–483 (2018).28858183 10.1097/BRS.0000000000002395
21. Phan K Kim JS Lee N Kothari P Cho SK Impact of insulin dependence on perioperative outcomes following anterior cervical discectomy and fusion Spine (Phila Pa 1976) 2017 42 456 64 10.1097/BRS.0000000000001829 27488292
Phan, K., Kim, J. S., Lee, N., Kothari, P. & Cho, S. K. Impact of insulin dependence on perioperative outcomes following anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 42, 456–64 (2017).27488292 10.1097/BRS.0000000000001829
22. Paschou SA Dede AD Anagnostis PG Vryonidou A Morganstein D Goulis DG Type 2 diabetes and osteoporosis: A guide to optimal management J. Clin. Endocrinol. Metab. 2017 102 3621 3634 10.1210/jc.2017-00042 28938433
Paschou, S. A. et al. Type 2 diabetes and osteoporosis: A guide to optimal management. J. Clin. Endocrinol. Metab. 102, 3621–3634 (2017).28938433 10.1210/jc.2017-00042
23. Lecka-Czernik B Diabetes, bone and glucose-lowering agents: Basic biology Diabetologia 2017 60 1163 1169 10.1007/s00125-017-4269-4 28434032
Lecka-Czernik, B. Diabetes, bone and glucose-lowering agents: Basic biology. Diabetologia 60, 1163–1169 (2017).28434032 10.1007/s00125-017-4269-4
24. Browne JA Cook C Pietrobon R Bethel MA Richardson WJ Diabetes and early postoperative outcomes following lumbar fusion Spine (Phila Pa 1976) 2007 32 2214 2219 10.1097/BRS.0b013e31814b1bc0 17873813
Browne, J. A., Cook, C., Pietrobon, R., Bethel, M. A. & Richardson, W. J. Diabetes and early postoperative outcomes following lumbar fusion. Spine (Phila Pa 1976) 32, 2214–2219 (2007).17873813 10.1097/BRS.0b013e31814b1bc0
25. Umpierrez GE Isaacs SD Bazargan N You X Thaler LM Kitabchi AE Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes J. Clin. Endocrinol. Metab. 2002 87 978 982 10.1210/jcem.87.3.8341 11889147
Umpierrez, G. E. et al. Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes. J. Clin. Endocrinol. Metab. 87, 978–982 (2002).11889147 10.1210/jcem.87.3.8341
26. O'Neill PA Davies I Fullerton KJ Bennett D Stress hormone and blood glucose response following acute stroke in the elderly Stroke 1991 22 842 847 10.1161/01.STR.22.7.842 1853403
O’Neill, P. A., Davies, I., Fullerton, K. J. & Bennett, D. Stress hormone and blood glucose response following acute stroke in the elderly. Stroke 22, 842–847 (1991).1853403 10.1161/01.STR.22.7.842
27. Gallagher JM Erich RA Gattermeyer R Beam KK Postoperative hyperglycemia can be safely and effectively controlled in both diabetic and nondiabetic patients with use of a subcutaneous insulin protocol JB JS Open Access 2017 2 e0008 10.2106/JBJS.OA.16.00008 30229209
Gallagher, J. M., Erich, R. A., Gattermeyer, R. & Beam, K. K. Postoperative hyperglycemia can be safely and effectively controlled in both diabetic and nondiabetic patients with use of a subcutaneous insulin protocol. JB JS Open Access 2, e0008 (2017).30229209 10.2106/JBJS.OA.16.00008
28. Woo E Ma JT Robinson JD Yu YL Hyperglycemia is a stress response in acute stroke Stroke 1988 19 1359 1364 10.1161/01.STR.19.11.1359 3188121
Woo, E., Ma, J. T., Robinson, J. D. & Yu, Y. L. Hyperglycemia is a stress response in acute stroke. Stroke 19, 1359–1364 (1988).3188121 10.1161/01.STR.19.11.1359
29. Wass CT Lanier WL Glucose modulation of ischemic brain injury: Review and clinical recommendations Mayo Clin. Proc. 1996 71 801 812 10.1016/S0025-6196(11)64847-7 8691903
Wass, C. T. & Lanier, W. L. Glucose modulation of ischemic brain injury: Review and clinical recommendations. Mayo Clin. Proc. 71, 801–812 (1996).8691903 10.1016/S0025-6196(11)64847-7
30. Mizock BA Alterations in carbohydrate metabolism during stress: A review of the literature Am. J. Med. 1995 98 75 84 10.1016/S0002-9343(99)80083-7 7825623
Mizock, B. A. Alterations in carbohydrate metabolism during stress: A review of the literature. Am. J. Med. 98, 75–84 (1995).7825623 10.1016/S0002-9343(99)80083-7
31. Rodrigues B McNeill JH The diabetic heart: Metabolic causes for the development of a cardiomyopathy Cardiovasc. Res. 1992 26 913 922 10.1093/cvr/26.10.913 1486584
Rodrigues, B. & McNeill, J. H. The diabetic heart: Metabolic causes for the development of a cardiomyopathy. Cardiovasc. Res. 26, 913–922 (1992).1486584 10.1093/cvr/26.10.913
32. Rayyan-Assi H Feldman B Leventer-Roberts M Akriv A Raz I The relationship between inpatient hyperglycaemia and mortality is modified by baseline glycaemic status Diabetes Metab. Res. Rev. 2021 37 e3420 10.1002/dmrr.3420 33137237
Rayyan-Assi, H., Feldman, B., Leventer-Roberts, M., Akriv, A. & Raz, I. The relationship between inpatient hyperglycaemia and mortality is modified by baseline glycaemic status. Diabetes Metab. Res. Rev. 37, e3420 (2021).33137237 10.1002/dmrr.3420
33. Plummer MP Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality Intensive Care Med. 2014 40 973 980 10.1007/s00134-014-3287-7 24760120
Plummer, M. P. et al. Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality. Intensive Care Med. 40, 973–980 (2014).24760120 10.1007/s00134-014-3287-7
34. Maitra S Mikhail C Cho SK Daubs MD Preoperative maximization to reduce complications in spinal surgery Glob. Spine J. 2020 10 45s 52s 10.1177/2192568219882349
Maitra, S., Mikhail, C., Cho, S. K. & Daubs, M. D. Preoperative maximization to reduce complications in spinal surgery. Glob. Spine J. 10, 45s–52s (2020).10.1177/2192568219882349
