Vertebral Augmentation: The Comprehensive Guide to Vertebroplasty, Kyphoplasty, and Implant Augmentation

22 Effect of Vertebral Augmentation on Morbidity and Mortality

Jae Hun Kim and Yong-Chul Kim

Summary

Vertebral compression fractures (VCFs) are common and are typically managed with either nonsurgical management (NSM) or vertebral augmentation including vertebroplasty and kyphoplasty. The different treatment types will also have different outcomes in regard to patient morbidity and mortality. The presence of a painful VCF will cause a significant increase in mortality due to complications such as pneumonia and pulmonary embolism caused by the patient’s deconditioned status. Many studies from many countries have shown a consistent mortality benefit of vertebroplasty over NSM and of kyphoplasty over vertebroplasty. As a result of the downward trend in treating VCFs resulting from the negative vertebroplasty versus sham articles published in 2009 patient mortality rates associated with VCFs have increased. Many review articles and meta-analyses have reported the safety of vertebral augmentation and have reported a very similar amount of pain relief with both vertebroplasty and kyphoplasty but better vertebral height restoration and lower cement extravasation rates with kyphoplasty. Patients with moderate to severe pain who undergo NSM rather than vertebral augmentation tend to have persistent and severe pain, functional impairments, and increased rates of mortality. This increased mortality rate can be reduced by vertebral augmentation which not only reduces the risk of death for the patient but can demonstrably prolong their life expectancy as well. The presence of a VCF is an important marker for the increased risk of another VCF and should be looked upon as a possible indication to treat the patient. In general, vertebral augmentation will provide optimal clinical outcomes in improving patients’ pain, function and quality of life and has been shown to significantly decrease morbidity and mortality.

Keywords: morbidity, mortality, vertebral compression fracture, pneumonia, pulmonary embolism, nonsurgical management

22.1 Introduction

The VCF is the most common type of osteoporotic fracture and occurs in approximately 20% of the individuals older than 70 years and in 40% of women over the age of 80.¹^,² Despite being common, only about one-third of the VCF patients present with pain. A VCF may cause acute pain, disability, and increased mortality, especially in elderly patients.¹ There are various treatments for VCF and the goals of these treatments are reducing pain, restoring mobility, and stabilizing the vertebra.² NSM includes medications such as NSAIDs or opioids, bed rest, or external bracing. These treatments, however, can give rise to undesirable adverse effects or fail in preventing kyphotic deformity and alleviating pain.³^,⁴ Vertebral augmentation including vertebroplasty and kyphoplasty is an effective treatment for pain related to VCFs. Vertebral augmentation procedures are minimally invasive surgical treatments that contribute to the objectives of decreasing pain, restoring vertebral height, and improving mobility.⁵

22.2 Nonsurgical Management vs. Vertebral Augmentation

There are several treatment modalities for VCFs. In general, two sets of treatments are identified, the surgical and the NSM treatments. Some patients undergo vertebroplasty or kyphoplasty and other patients are prescribed medications and/or use orthostatic braces for the treatment of their VCFs. In this chapter, a review and the description of the effect of morbidity and mortality of vertebral augmentation versus the NSM of VCFs will be discussed.

Although the etiology of increased mortality is not directly tied to the pathophysiology of the acute VCF itself, several studies report that painful VCF increases the mortality of the affected patients.⁶^–¹¹ This high incidence of the mortality is not the direct consequence of the fracture but is related to deconditioning and the elderly patient’s poor health status, weight loss, and physical frailty. Additionally, the patients undergoing NSM for a compression fracture have increased pulmonary impairment.⁶^–⁸ Moreover, the risk of death related to pulmonary problems is higher in patients who have severe thoracic kyphosis, and the risk of pneumonia is significantly higher in patients not undergoing vertebroplasty.⁶^,⁹ In a cohort study, when comparing nonvertebroplasty patients to vertebroplasty patients, a hazard ratio of 1.39 related to death after 1 year was observed.⁶ The results showed that aged patients who did not receive vertebroplasty within 3 months had higher risks of death and respiratory failure than those patients who received vertebroplasty within the first 3 months. The increased risk of death and respiratory failure in nonvertebroplasty patients remained even after 12 years.⁶ According to these results, vertebroplasty was recommended for older (≥ 70 years old) patients with severe pain.

Edidin et al¹² investigated the morbidity and mortality after VCFs in a US Medicare population (a total 1,038,956 VCF patients). According to this study, the NSM cohort had a 55% higher adjusted risk of mortality than kyphoplasty cohort and 25% higher adjusted risk of mortality than the vertebroplasty cohort. The kyphoplasty cohort had a 19% lower adjusted risk of mortality than the vertebroplasty cohort. Additionally, the kyphoplasty cohort had significantly lower risks of morbidity than the NSM cohort, with those patients undergoing NSM having increased risks for deep venous thrombosis, infection, myocardial infarction, and cardiac complications.¹²

In the United States, the number of vertebral augmentation procedures began decreasing after 2009, probably related to the publications in the New England Journal of Medicine that reported no significant difference between vertebroplasty and a sham procedure.¹³^,¹⁴ The majority of the medical societies continued to recommend vertebroplasty as a safe and effective procedure for treating VCFs but there was opposition from some societies and some health technology assessments.¹⁵^–¹⁷ The reduction in vertebroplasty procedures amounted to a 10% decrease, from 24% of patients with painful VCFs receiving vertebral augmentation in 2008 to 10% in 2014.¹⁸ This reduction was calculated from an analysis of the Medicare population of over two million VCF patients. The authors reported that in the 5-year time period following the publication of these articles an increased mortality rate was found in patients who presented with VCFs, presumably related to under-treatment of the fractures.¹⁸ This increased mortality rate of patient treated with NSM was 55% more at 1 year and 24% more at 10 years than those patients treated with vertebral augmentation kyphoplasty.¹⁸

There are several comparative studies on the effectiveness and safety of NSM versus vertebroplasty, and kyphoplasty. These studies have collected various data, such as pain scores, short-form-36, EQ-5D, Roland Morris Disability Questionnaire (RDQ), QUALEFFO, Dallas Pain Questionnaire (DPQ), Oswestry Disability Index (ODI), Barthel scale, modified mini-mental state examination (MMSE), vertebral body height, kyphotic wedge angle, incidence of new fractures, cost-effectiveness, restricted activity days, and bed rest days. According to a recent meta-analysis, vertebroplasty was the more effective treatment for pain relief, quality of life, and daily function when compared to NSM.² Both vertebroplasty and kyphoplasty were more effective for improving quality of life and daily function than NSM. There were also no significant differences in the incidence of new fracture among the three treatments. They also analyzed the ranking probability and concluded that vertebroplasty was the most effective treatment for pain relief and kyphoplasty had the most beneficial effect on quality of life, daily function, and incidence of new fractures.²

Mattie et al¹⁹ in a meta-analysis comparing vertebroplasty and NSM concluded that the pain reduction effect of vertebroplasty exceeded any pain relief obtained with NSM up to 1 year postoperatively. In other meta-analyses, there were controversies in the comparison between vertebroplasty and kyphoplasty about pain relief.²⁰^–²² According to Zhao et al,²¹ kyphoplasty was better than vertebroplasty in ODI and long-term pain relief but there were no significant differences in short-term visual analog scale (VAS), posterior vertebral body height, and adjacent level fractures. Ma et al²⁰ reported that kyphoplasty was superior to vertebroplasty in patients with a large kyphosis angle, vertebral fissures, fractures in the posterior edge of the vertebral body, or significant height loss in the fractured vertebrae. Finally, Xing et al²² concluded that kyphoplasty had better outcomes than vertebroplasty in long-term kyphosis angle stability, improved the height of the vertebral body and reduced incidence of bone cement leakage. In these meta-analyses, vertebroplasty and kyphoplasty were safe and very effective surgical procedures for the treatment of painful VCFs.

A meta-analysis performed by Chen et al²³ regarding the efficacy and tolerability of NSM versus vertebroplasty and kyphoplasty found that the latter two significantly decreased pain compared with conservative treatment. In their ranking probabilities, vertebroplasty was the most effective treatment for pain relief but only kyphoplasty had a significantly lower risk of all-cause discontinuation compared with NSM. In this meta-analysis, there were no significant differences in the incidence of new fractures among the three different treatments,²³ and other meta-analyses have also showed no significant differences of new fractures between vertebroplasty and kyphoplasty²⁰^–²² and between vertebroplasty and NSM.²⁴^,²⁵

There are also several studies on the superiority of vertebroplasty over NSM in improving the daily function and quality of life.²⁴^,²⁵ Blasco et al²⁶ reported that vertebroplasty had higher QUALEFFO scores compared with NSM up to 6 months. The differences were mainly associated with difference in physical activity seen as the result of each treatment. Wardlaw et al²⁷ reported that kyphoplasty patients had a better quality of life (SF-36 PCS and EQ-5D) and RDQ scores than the NSM patients. Additionally, kyphoplasty decreased restricted activity days and bed rest about 2.9 days per 2 weeks at 1 month. However, after 12 months, there was no significant difference among NSM and kyphoplasty. Yang et al²⁸ reported that vertebroplasty yielded faster and better pain relief and improved function for up to 1 year. The results also showed fewer complications after vertebroplasty than NSM. Liu et al²⁹ found that kyphoplasty increased vertebral body height and decreased kyphotic wedge angle as compared with vertebroplasty.

According to a prospective multicenter international study, vertebroplasty produces rapid pain reduction at 1 day after treatment along with improvement in mobility and function.³⁰ Colangelo et al³¹ reported that kyphoplasty allowed faster recovery and avoided the deformity in kyphosis related to VCFs compared with NSM. Interestingly, the risk of having a subsequent vertebral fracture was higher after kyphoplasty than NSM in this retrospective study, but, according to another meta-analysis, there were no differences in the incidence of secondary fractures between vertebral augmentation and NSM in the treatment of osteoporotic compression fractures.³² A recent meta-analysis showed that there was no evidence of an increased risk of new fracture of vertebral bodies, especially those adjacent to the treated vertebrae following vertebral augmentation compared to conservative management.³³ Yi et al³⁴ in a prospective study containing 290 consecutive patients with 363 fractures found no increased risk of VCF for those patients treated with vertebral augmentation as compared to those patients treated with NSM, but they did find that the additional fractures occurred sooner in patients treated with vertebral augmentation. This differing temporal relationship of the appearance of subsequent VCFs may serve to explain why some analyses show differences in subsequent fractures while others don’t. Finally, Masoudi et al³⁵ investigated the effect of kyphoplasty compared with conservative management in stable thoracolumbar fractures in parachute jumpers, and concluded that kyphoplasty in stable thoracolumbar fractures is related to decreased pain, better functional recovery, fewer days of absence from work, and a shorter duration in returning to parachuting. The outcomes of conservative management and vertebral augmentation have been discussed in ▶Table 22.1.

22.3 Outcome of Patients with Vertebral Fractures Not Treated with Vertebral Augmentation

Many patients with VCFs are treated with NSM. Approximately two-thirds of all vertebral fractures are asymptomatic and the other one-third of vertebral fractures are symptomatic and painful. In most fractures the pain gradually decreases over time and patients return to activity or their work in about 6 to 8 weeks. Some patients, however, have persistent pain and their VCF never heals or inadequately heals. Clinical VCFs have been related to pain but disability, and functional impairment can persist even though the pain resolves.³⁶^,³⁷ John A. Kanis et al³⁸ investigated the relationship between VCF and deaths in 16,051 menand women aged 50 years or more who required hospitalization. The results showed 28% of all deaths were considered causally related to the VCF.

VCFs can have a prominent and persistent effect on quality of life. Additionally, patients without vertebral augmentation can have mobilization difficulty and various complications such as deep vein thrombosis, pulmonary embolism, pressure ulcers, progressive vertebral body collapse, kyphotic deformity, back pain, neurologic compression, sleep disturbances, depression, and worsening osteoporosis. Bed rest can exacerbate the osteoporosis because of loss of body mass and bone density. Conversely, asymptomatic vertebral fractures are not necessarily related to the impairment of quality of life as long as a new vertebral fracture does not develop.³⁷^,³⁹ In the case of a new VCF in a patient with an underlying asymptomatic vertebral fracture, the disability and functional impairment may be significantly increased.³⁹

As mentioned above, VCFs can yield higher risks of morbidity and mortality, and vertebral augmentation may decrease these risks.⁸^,¹²^,⁴⁰^,⁴¹ Mortality in the VCF patients is rarely caused directly by vertebral fracture but mostly related to cancer (in neoplastic fractures) or to pulmonary causes such as pneumonia or pulmonary embolism.⁴²^–⁴⁴ The adverse outcomes related to pulmonary causes are associated with impaired pulmonary function including a decrease in vital capacity and inspiratory time resulting from the VCF.⁴⁵^–⁴⁷ Therefore, the decreased risks of mortality after vertebral augmentation are very likely related to improved pulmonary function.⁶^,⁹^,⁴²^,⁴⁷ According to a population-based study, VCF is an independent risk factor for the future development of pneumonia, especially if the VCF is located in the thoracic region.⁴⁸ An investigation of the US Medicare population showed a higher mortality risk in the patients that did not undergo vertebral augmentation.¹² The NSM cohort had a 55% higher adjusted risk of mortality than kyphoplasty cohort and 25% higher adjusted risk of mortality than vertebroplasty cohort. Previously, Chen et al⁴⁹ reported that vertebroplasty improved adjusted survivorship by 15% and kyphoplasty by 32% compared with the NSM patients at 3 years of follow-up. The patients with VCFs not treated with vertebral augmentation had higher adjusted risks of pneumonia, myocardial infarction, cardiac complications, deep vein thrombosis, and urinary tract infections. Conclusively, the results of the US Medicare population asserted that the patients without spinal augmentation had a significantly higher adjusted risk of death most often associated with pneumonia and significantly higher rates of morbidities.¹² In an investigation outside the United States⁶ a Taiwanese analysis of data from National Health Insurance Research Database after hospital admission of 10,785 painful VCF patients showed the risk of death was 39% higher in patients who received medical management (HR: 1.39, 95% CI: 1.09–1.78, p = 0.008) compared to those patients who underwent vertebroplasty.

The presence of a VCF along with increased age and low bone mineral density (BMD) is a known risk factor for the development of additional VCFs.⁵⁰^,⁵¹ Therefore, previous vertebral fractures in combination with old age and low BMD are associated with a prominent increased vertebral fracture risk. Additionally, a recent vertebral fracture can increase the risk of a future fracture within 2 years, especially in year 1 after the initial fracture.⁵²^,⁵³ According to the investigation of Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, prior vertebral fracture and vertebral fracture in the first year were independent predictors of subsequent vertebral fractures in years 2 and 3 (adjusted OR: 2.8, 95% CI 1.9–4.0 and 3.1, 95% CI 1.9–5.0, respectively).⁵¹ In the long-term follow-up over 15 years, one prevalent fracture resulted in a 2.5-fold increased risk of incident fractures (95% CI: 1.8–3.4) and more than two prevalent vertebral fractures resulted in a 5.2-fold increased risk of fracture (95% CI: 3.5–7.8).⁵⁴

Even though two-thirds of VCFs may be asymptomatic and not associated with functional impairment, the symptomatic VCF can increase the patient’s risk of subsequent fractures and their associated risk of morbidity and mortality. Vertebral augmentation including vertebroplasty and kyphoplasty decreases the risks of morbidity and mortality and improves the patient’s pain, mobilization, kyphotic angulation, and quality of life.