**1. Introduction**

Vertebral fractures are the most common osteoporotic fracture [1]. When osteoporotic vertebral body fractures occur, the symptoms improve approximately 3 months after the injury in most cases [2]. However, in some cases, the symptoms persist chronically. A study found that patients with new vertebral fractures had significantly more back pain and poorer physical function at all time points up to 12 months after fracture than those without fractures [2]. In addition, if there is a history of vertebral fractures, recovery after a new vertebral fracture is even worse. In a study comparing the post-vertebral fracture course, patients with a history of vertebral fracture had significantly lower physical motor function, activities of daily living, and quality of life (QOL) up to 12 months after injury than patients without a history of vertebral fracture [3]. However, it is still unclear how fresh vertebral fractures affect the patient's QOL and low back pain during a follow-up period of more than 1 year. Thus, this study aimed to describe the course of acute vertebral

**Citation:** Inose, H.; Kato, T.; Shirasawa, S.; Takahashi, S.; Hoshino, M.; Yamato, Y.; Matsukura, Y.; Hirai, T.; Yoshii, T.; Okawa, A. Time Course of Acute Vertebral Fractures: A Prospective Multicenter Cohort Study. *J. Clin. Med.* **2021**, *10*, 5961. https:// doi.org/10.3390/jcm10245961

Academic Editor: Emmanuel Andrès

Received: 2 November 2021 Accepted: 17 December 2021 Published: 19 December 2021

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fractures in terms of pain and QOL and to characterize patients with residual low back pain long after a vertebral fracture.

#### **2. Materials and Methods**

This study was a follow-up study of women involved in the previous prospective randomized study (UMIN000014876) that compared the effectiveness of rigid and soft braces for acute thoracolumbar OVFs [4]. Briefly, the original trial enrolled 284 patients aged between 65 and 85 years who were diagnosed with one fresh OVF between T10 and L2 within four weeks of injury; 141 of these patients were randomly assigned to wear rigid braces and 143 were assigned to wear soft braces. Patients wore ready-made braces until a custom-made thoracolumbar sacral rigid or soft brace was applied. Patients in the rigid-brace group received a rigid thoracolumbosacral orthosis. Patients in the soft-brace group received a soft thoracolumbosacral orthosis. In both the rigid and flexible bracing groups, the patients were instructed to always wear the braces, when possible. All the participants were instructed to wear the brace for a total of 12 weeks. Detailed inclusion and exclusion criteria of the study have been described previously [4].

Among the patients who completed the previous brace trial, patients from hospitals that agreed to participate in this study were included in this study. Accordingly, a total of 73 patients were enrolled. Of the 73, 3 died, 2 refused to cooperate, and 28 could not be contacted. Finally, 40 patients with mean 5.3 years of follow-up were included in this study. With regard to the use of anti-osteoporosis treatments during the 48-week brace treatment prospective randomized study, the patients were allowed to use only the medications that were used prior to the injury or newly prescribed active vitamin D [4]. During the subsequent follow-up period, prescription of any anti-osteoporosis medication was allowed.

This study was approved by each hospital's institutional review board, and informed consent was obtained from all the participants included in the study.

#### *2.1. Patient-Reported Outcome Measures*

Regarding the patient-reported outcome measures (PROMs), scores on the European Quality of Life-5 Dimensions (EQ-5D; range, −0.111 to 1, with higher scores indicating a better QOL) [5] and the visual analog scale (VAS) for low back pain (range, 0–10, with higher scores indicating more severe pain) [6] were used. These questionnaires were provided at a regular hospital visit (0, 12, and 48 weeks after brace application) but were completed without assistance from the surgeon or any other person involved in this study. After 48 weeks, since regular visits to the hospital were not mandatory, outcome assessment at the last follow-up was completed by mailing a questionnaire. To maximize participant retention, we decided to mail the questionnaires. This is because, according to previous research, comparing three different methods of administering a brief screening questionnaire to the elderly, response rates were higher for the postal questionnaire than the interview method [7].

#### *2.2. Radiographic Assessment*

Lateral radiography was performed at 0, 12, and 48 weeks. MRI was performed at enrollment. In the radiographic analysis, the anterior vertebral body compression percentage [4,8], which is defined as the ratio between the vertical height of the compressed anterior section of the injured vertebral body and the posterior vertebral body height at the same level, was measured independently at 0, 12, and 48 weeks after brace application by two radiologists. The mean values of the two evaluators were used. In this study, a previous vertebral fracture was defined as a decrease of at least 20% in the height of any vertebral body at Week 0 [9]. To investigate the presence of degenerative spinal diseases that can cause low back pain, we investigated lumbar spinal canal stenosis and lumbar disc herniation by MRI at enrollment. Lumbar spinal canal stenosis was diagnosed as C or higher in Schizas' classification [10].

#### *2.3. Data Analysis*

All data were collected by a clinical research assistant. An analysis of variance with repeated measures was used to analyze the data over time. When there was a significant main effect of time, Tukey's HSD analysis was performed to identify the differences among time points.

In this study, "residual low back pain" was defined as VAS for low back pain ≥3.5 at the final follow-up; VAS score <3.5 is used to describe mild pain, and VAS score ≥ 3.5 is used to describe moderate or severe pain [11]. We performed outcome and risk factor analyses by comparing patients with VAS scores <3.5 and ≥3.5 for low back pain. We analyzed the differences between the two groups using the Mann–Whitney U test for continuous variables and Fisher's exact test or chi-squared test for nominal variables. To identify the most significant risk factors for residual low back pain at the final follow-up, we performed risk factor analysis using multivariable logistic regression analysis with a forward-backward stepwise procedure (*p* < 0.1 for entry). We then calculated the odds ratios (ORs) and their approximate 95% confidence intervals (CIs) for residual low back pain. For continuous variables, the OR reflects the incremental risk associated with a one-unit change in that variable. JMP version 12 (SAS Institute, Cary, NC, USA) was used for all statistical analyses. All tests were two-sided, and *p*-values < 0.05 were considered significant.
