Epidemiological differences between the sexes in adolescent patients with lumbar spondylolysis in Japan

doi:10.21203/rs.3.rs-2620569/v1

Background: Lumbar spondylolysis, a common identifiable cause of low back pain in young athletes, reportedly has a higher incidence rate in males. However, the reason for its higher incidence in males is not clear. This study aimed to investigate the epidemiological differences between the sexes in adolescent patients with lumbar spondylolysis.

Methods: A retrospective study was conducted in 197 males and 64 females diagnosed with lumbar spondylolysis. These patients visited our hospital from April 2014 to March 2020 with their main complaint being low back pain, and they were followed-up until the end of their treatment. We investigated associations between lumbar spondylosis, their background factors, and characteristics of the lesions and analyzed their treatment results.

Results: Males had a higher prevalence of spina bifida occulta (SBO) (p=0.0026), more lesions with bone marrow edema (p=0.0097), and more lesions in the L5 vertebrae (p=0.021) than females. The age at diagnosis, bone union rate, and treatment period were not significantly different between the sexes.

Conclusion: The higher prevalence of SBO in males may explain the sex differences in the incidence of lumbar spondylolysis. The progression of lumbar spondylolysis is however, more advanced in females, thus making a proper early diagnosis, especially in females, important.

lumbar spondylolysis

sex difference

adolescent

spina bifida occulta

bone marrow edema

L5

Lumbar spondylolysis is the most common identifiable cause of low back pain in young athletes [1], and the lower back is one of the most affected fatigue fracture sites [2]. The main symptom of lumbar spondylolysis is low back pain during exercise, but many cases are asymptomatic [3].Even when symptoms are present, they are often minor; therefore, many patients do not seek medical attention. However, if not properly treated, it can progress to spondylolisthesis and cause neurologic symptoms [4]; therefore, early detection and treatment of lumbar spondylolysis are very important.

The incidence of lumbar spondylolysis has been reported to differ between male and female athletes, with a male-to-female ratio of approximately 4:1 in Japan [5].An observational study of the Japanese general population using computed tomography (CT) scans also reported a higher incidence rate in males [6]. However, it is unclear why lumbar spondylolysis affects males more often.

In this study, we retrospectively analyzed the background factors, characteristics of the lesions, and treatment results of patients with lumbar spondylolysis to determine the differences between males and females.

Among patients of high school age or younger who visited our hospital with the chief complaint of low back pain from April 2014 to March 2020, lumbar spondylolysis cases diagnosed by both magnetic resonance imaging (MRI) and CT imaging who were followed up to the end of treatment were included in this study. Patients who did not follow the treatment protocol were excluded. Bilateral spondylolysis in one vertebral arch was counted as two lesions, lesions in multiple vertebrae were counted separately, and recurrent cases after bone union were counted as separate cases. Patients were divided into two groups, males and females, and the age at diagnosis and the presence of spina bifida occulta (SBO) in each patient were investigated. In addition, the presence of bone marrow edema, level of the affected vertebra, pathological stage, rate of bone fusion, and treatment period were analyzed for each lesion and statistically compared between the two groups.

Lumbar spondylolysis was defined as the presence of bone marrow edema in the pars interarticularis on MRI short tau inversion recovery (STIR) imaging, or the presence of a fracture line between the articular processes on CT. The treatment protocol was exercise prohibition and wearing a semi-rigid lumbosacral brace until the disappearance of bone marrow edema on MRI. In addition, physiotherapy was performed once a week from the beginning of the treatment until the patients returned to sports activities. SBO was defined as the presence of a bony defect in one of the vertebral arches of the lumbar or sacral vertebrae (S1, S2) on plain radiography, CT, or MRI. The pathological stages of the lesion were determined by axial slice classification using CT and MRI (as per Sairyo et al.) [7]. Bone union was defined as both the disappearance of bone marrow edema on MRI and bone union on CT. The treatment period was defined as the number of days from the date of diagnosis to the date of bone union. Pseudarthrosis lesions were excluded from the calculation of the rate of bone union, and lesions that achieved bone union were analyzed during the treatment period.

The Wilcoxon rank-sum test was used to analyze the age at diagnosis and treatment period, and the chi-square test was used for the other items. The affected vertebra was analyzed between L1–L4 vs. L5, and the pathological stage was analyzed between the pre-lysis and early stages vs. progressive stage. Statistical tests were performed at a significance level of p<0.05, using R software version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria), and the epitools package.

A total of 261 patients with 450 lumbar spondylolysis lesions were analyzed, including 197 males with 336 lumbar spondylolysis and 64 females with 114 lumbar spondylolysis. The proportion of unilateral cases, bilateral cases, multiple vertebrae cases, and recurrent cases are described in Table 1.

Table 1 Characteristics of cases

	Males	Females
Total cases	197	64
Unilateral cases	73 (37%)	19 (30%)
Bilateral cases	110 (56%)	41 (64%)
Multiple vertebrae cases	14 (7%)	4 (6%)
Recurrent cases	17 (9%)	2 (3%)
Total lesions	336	114

The median age at diagnosis was 14 years (interquartile range [IQR], 13–16 years) in both males and females, with no statistically significant difference (p=0.66, Fig. 1, Table 2). The number of patients with SBO was 128/197 (65%) in males and 28/64 (44%) in females, and the prevalence of SBO was significantly higher in males than in females (p=0.0026, Fig. 2, Table 2).

Table 2 Age and SBO prevalence of cases

	Males (n =197)	Females (n =64)	p-value
Age, median (IQR)	14 (13–16)	14 (13–16)	0.66
SBO	128 (65%)	28 (44%)	0.0026

Abbreviations: IQR, interquartile range; SBO, spina bifida occulta. Statistical significance level p<0.05.

There was a statistically significant difference in the presence of bone marrow edema with 200/336 lesions (60%) in males and 52/114 (46%) lesions in females (p = 0.0097). The affected vertebral levels were 1 L1, 5 L2, 15 L3, 52 L4, and 263 L5 in males and 17 L3, 20 L4, and 77 L5 in females (Table 3). The prevalence of L5 lesions was significantly higher in males than in females (78% vs. 68%, p = 0.021). The pathological stages of the lesions were 47 pre-lysis, 101 early, 52 progressive, and 136 terminal stages in males, and 16 pre-lysis, 24 early, 12 progressive, and 62 terminal stages in females (Table 3). The ratio of pre-lysis and early stages vs. progressive stage did not differ between males and females (p = 0.67).

Table 3 Characteristics of lesions

	Males (n = 336)	Females (n = 114)	p-value
Bone marrow edema	200 (60%)	52 (46%)	0.0097
Affected vertebral levels			0.021
L1	1 (0%)	0 (0%)
L2	5 (1%)	0 (0%)
L3	15 (4%)	17 (15%)
L4	52 (15%)	20 (18%)
L5	263 (78%)	77 (68%)
Pathological stage			0.67
Pre-lysis	47 (14%)	16 (14%)
Early	101 (30%)	24 (21%)
Progressive	52 (15%)	12 (11%)

Statistical significance level p<0.05.

The bone union rate was 145/200 (73%) in males and 40/52 (77%) in females, with no statistically significant difference (p=0.52). The median treatment period was 96 days (IQR, 66–129 days) in males and 91.5 days (IQR, 71.5–111 days) in females, which also showed no statistical difference (p=0.18, Fig. 3, Table 4).

Table 4. Bone union rate and treatment period

	Males	Females	p-value
Bone union	145 (73%)	40 (77%)	0.52
	(n = 200)	(n = 52)
Treatment period, median (IQR)	96 (66–129)	91.5 (71.5–111)	0.18
	(n = 145)	(n = 40)

Abbreviations: IQR, interquartile range. Statistical significance level p<0.05.

Lumbar spondylolysis is more common in athletes during the growth period. One of the reasons for this is the increase in exercise intensity during this period. In addition, muscle weakness and stiffness are common during this period when bone growth outpaces musculotendinous growth. Although there is no significant difference in bone growth between males and females until puberty, bone metabolism in females increases in early puberty and reaches its peak at mid-puberty. In contrast, bone metabolism increases slowly after puberty in males [8]; therefore, females are expected to have a lower age at diagnosis. However, in our study, there was no significant difference between the ages at diagnosis of the males and females. The proportion of males diagnosed was higher than that of females, which is consistent with previous studies [5, 6, 9]. Fig. 1 shows a decrease in the number of cases of males and females aged 15 years. This is likely due to the fact that third-grade junior high school students in Japan, aged 14 to 15, often take time off from sports activities to focus on their studies for high school entrance examinations.

Fig. 2 shows that males had a higher prevalence of SBO than females at most ages. Moreover, younger patients had a higher prevalence in both the males and females. SBO is a spinal deformity associated with the increased incidence of spondylolysis [6]. The prevalence of SBO among children in the general population has been reported to be higher in males and at younger ages. Among children aged 4–15 years, 51.4 % of males and 32.2% of females had SBO [10]. Considering that the patients were older in this study, aged 8–18 years, the present results indicate that the same trend is observed in cases of lumbar spondylolysis, but with a much higher prevalence. The difference in SBO prevalence between males and females with lumbar spondylolysis has never been reported before, and this study is the first to show this difference. Moreover, this study indicates that the higher prevalence of SBO in males may be responsible for the higher incidence of lumbar spondylolysis in males.

The ratio of the presence of bone marrow edema in the lesions was higher in males, which is equal to the higher ratio of terminal stage lesions in females. Although the number of cases is smaller in females, the progression of lumbar spondylolysis is more advanced. Lumbar spondylolysis has been reported to be the most common cause of low back pain without neurological symptoms in males, while in females, other diseases such as undiagnosed mechanical low back pain (UMLBP) are often involved [9]. Since lumbar spondylolysis in females may include many advanced cases, it is important to make a proper early diagnosis, especially in females.

L5 was the most affected vertebral level in both males and females, but was significantly more prevalent in males. The angle of lumbar spine lordosis has been reported to be greater in patients with L5 spondylolysis [11]. In general, as females reach puberty, their subcutaneous fat increases and body composition changes [9]. As a result, females are reported to have a greater lumbar lordosis than males[12]. Based on these reports, females are expected to suffer more L5 spondylolysis, but our data showed the opposite result. This indicates that spinal alignment alone does not determine the vertebral level of spondylolysis. Regarding the pathological stages, there was no tendency for females to have a higher incidence of progressive-stage lesions, although females had a higher incidence of terminal-stage lesions.

The bone union rate and treatment period did not differ between males and females. However, some males required a significantly longer treatment period of approximately 8 months (Fig. 3). Although the bone union rate and treatment period are similar for males and females, we should keep in mind that some males may require an extremely long treatment period.

One of the limitations of this study is that we were not able to evaluate the incidence of lumbar spondylolysis in the general population. Because there may be a difference in the time between the onset of lumbar spondylolysis and the visit to the hospital for males and females, it is desirable to evaluate the status of lumbar spondylolysis in the general population. However, the present study was conducted on patients who visited our hospital because MRI evaluation was necessary. In the future, it will be necessary to conduct a prospective study that includes items related to bone metabolism, such as bone age, bone mineral density, and blood vitamin D, and items related to the psychological aspects of patients, such as satisfaction with treatment, so that other new findings can be obtained.

Lumbar spondylolysis was more common in males than in females. Males had a higher prevalence of SBO, which may explain the higher incidence of lumbar spondylolysis in males. The higher ratio of terminal stage lesions in females indicates that the progression of lumbar spondylolysis is more advanced in females. Therefore, proper early diagnosis, especially in females, is important. L5 was the most affected vertebral level but was more common in males. The age at diagnosis, bone union rate, and treatment period did not differ between males and females. However, we need to consider that some male patients may require an extremely long treatment period.

CT computed tomography

MRI magnetic resonance imaging

STIR short tau inversion recovery

SBO spina bifida occulta

IQR interquartile range

UMLBP undiagnosed mechanical low back pain

Ethics approval and consent to participate

This research was approved by the Institutional Review Board of Tsukuba University Hospital Mito Clinical Education and Training Center/ Mito Kyodo General Hospital (IRB No. 21-11), and the methods in this study were performed in line with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patients’ parents or legal guardians.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors' contributions

RA wrote the main manuscript text and prepared the figures and tables. MT designed the study. MT, HG, SO, FE, KN, YT, TF, TM, and AH treated the patients. MT and MY critically revised the manuscript. All authors reviewed and approved the final manuscript.

Acknowledgements

We are grateful to Miki Omori, the medical clerk at the Mito Clinical Education and Training Center, University of Tsukuba Hospital, and Mito Kyodo General Hospital, for her contributions to data analysis.

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No competing interests reported.

Epidemiological differences between the sexes in adolescent patients with lumbar spondylolysis in Japan

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