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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Objective

Sleep disturbances frequently accompany chronic pain from osteoarthritis (OA). Effective management of sleep disturbances may require successful treatment of chronic pain, a key factor in the clinical evaluation of knee OA. However, the relationship between the severity of knee OA and sleep quality is unclear. Our purpose was to correlate the prevalence of nocturnal knee pain with different OA severity levels and to determine its influence on sleep quality.

Methods

Subjects included 1,214 local volunteers with mean ± SD age 58.1 ± 13.0 years. The existence and severity of knee OA were determined by the Kellgren/Lawrence (K/L) grade, and joint space widths were measured. The presence of nocturnal knee pain and Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed by self-completed questionnaires. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index. Knee-related factors affecting sleep quality were detected using statistical methods.

Results

The prevalence of nocturnal knee pain was 3.6%, 6.9%, 19.4%, 32.7%, and 75.0% in K/L grades 0, 1, 2, 3, and 4, respectively. Also, prevalence significantly increased with OA severity (P < 0.001). Sleep problems also increased with K/L grade (P = 0.038), and KOOS quality of life (QOL) was significantly lower in those with OA and sleep problems. Logistic regression showed that sleep problems were related to joint space narrowing (P = 0.016) and nocturnal knee pain (P = 0.039). Severe OA also disturbed onset and maintenance of sleep.

Conclusion

The prevalence of nocturnal knee pain and sleep problems increased with the severity of OA, impacting QOL. These results suggest the necessity of appropriate nocturnal pain control.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Osteoarthritis (OA) is one of the most common disorders affecting elderly populations, and causes chronic pain and disability ([1, 2]). Pain during knee OA derives from several different mechanisms in the involved joints, such as loading pain in the femorotibial joint and anterior knee pain related to contraction of the quadriceps muscle in the patellofemoral joint. A common notion is that resting and nocturnal knee pains are rare and do not disturb patient quality of life (QOL). On the contrary, the presence of nocturnal knee pain is an important factor in the clinical evaluation of OA severity and outcomes after treatment. Reports have shown a wide range in the prevalence of nocturnal pain, from 17.6–81.0% ([3-6]). This wide range is likely because of different diagnostic methods, such as by questionnaire only or by examining past history of treatment for arthritis, including hip and knee OA, rheumatoid arthritis, and osteonecrosis (ON). Therefore, previous studies have not determined the specific prevalence of nocturnal pain in knee OA, or an accurate correlation with knee OA severity.

Nocturnal knee pain is thought to be strongly associated with patient satisfaction or QOL. In the clinical setting, most major patient-based clinical scoring systems for knee conditions include questions about the presence or degree of nocturnal pain and its related morbidity, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Society Rating Scale, the Western Ontario McMaster Universities Osteoarthritis Index, and the Japanese Knee Outcome Measurement ([7-10]). Also, sleep quality is available for management of chronic pain and evaluating therapeutic outcomes ([11]). In addition, continuous intense nocturnal knee pain is considered an indication for total knee arthroplasty ([12-14]), which often relieves the nocturnal knee pain ([15, 16]). However, how nocturnal knee pain affects QOL remains unclear.

Despite the importance of nocturnal knee pain in OA patients, little attention has been given to how the severity of OA affects prevalence in patients and their sleep quality and QOL. The purposes of this study were to elucidate the specific prevalence of nocturnal pain in knee OA, to determine its relationship with OA severity, and to investigate the relationship between nocturnal pain and QOL. To understand the relationship between nocturnal pain and QOL, sleep quality must be extensively investigated. We hypothesized that severe knee OA causes frequent nocturnal knee pain, resulting in a decline in sleep quality.

Box 1. Significance & Innovations

  • Despite significance of nocturnal knee pain in clinical situations, reports have shown a wide range from 17.6–81.0%, and its related factors have been unclear.
  • Nocturnal knee pain increased with severity of knee osteoarthritis: knee specific prevalence of nocturnal pain was 3.6%, 6.9%, 19.4%, 32.7%, and 75.0% in Kellgren/Lawrence grades 0, 1, 2, 3, and 4, respectively.
  • Presence of nocturnal knee pain decreased sleep quality, especially in onset and maintenance of sleep, and quality-of-life.
  • Knee-related factors for sleep problems were nocturnal knee pain and joint space narrowing.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Subjects

Subjects included voluntary participants from the Iwaki Health Promotion Project, which is a community-based program to prevent lifestyle diseases and improve average life expectancy by performing general health checkups and prophylactic interventions ([2, 17]). It is an annual program that has been performed since 2005 with the general population living in the Iwaki area of Hirosaki, located in western Aomori Prefecture, Japan. This cohort study has made it possible to evaluate many kinds of diseases and disorders from multiple aspects, and to investigate the risk factors for locomotive disability. All participants provided written informed consent, and the study was conducted with the approval of the ethics committee of the Hirosaki University School of Medicine.

A total of 1,301 volunteers from approximately 12,000 residents participated in this project from 2008 to 2010. Subjects were recruited by calls from public health nurses and advertisements in mass media. In the present study, a total of 1,241 individuals who had undergone radiographic examination were included for statistical analysis. Exclusion criteria for this study were patients with rheumatoid arthritis (8 residents), postoperative patients with knee joint diseases (4 residents), and incomplete questionnaires (6 residents). Also, those who did not undergo radiographic examination were excluded. A total of 1,214 participants (456 men and 758 women) were included for statistical analysis. The mean ± SD age was 57.8 ± 13.7 years (range 21–87 years) in men, and 58.2 ± 12.5 years (range 21–85 years) in women. All participants were administered a questionnaire on age, sex, lifestyle habits (such as smoking, drinking, and fitness routines), and working hours per week. The questionnaire was completed at home. The height and body weight of participants were measured and the body mass index (BMI) was calculated.

Radiographic knee OA

Bilateral anteroposterior views of the weight-bearing knees of all participants were classified according to the Kellgren/Lawrence (K/L) grading scale ([18]). The K/L grade of the worse side was chosen for the classification. K/L grades ≥2 were defined as knee OA. An experienced orthopedic surgeon (RI) measured the minimal joint space width (mJSW) of the medial or lateral compartment and the femorotibial angle (FTA) on radiographs calibrated according to a standard atlas of radiographic features in OA. One hundred knees were retested 1 month after the first test, and intraobserver reliability assessed by intraclass correlation coefficients of mJSW was 0.915 and of FTA was 0.824.

Knee symptoms

Knee symptoms were scored using a patient-based outcome score, the KOOS, and converted to 5 subscales (pain, symptoms, activity of daily living [ADL], sports/recreation, and QOL) ([7, 19]). The presence of nocturnal pain was indicated in the KOOS pain score subscale by the question, “At night while in bed, what amount of knee pain have you experienced in the last week?” The presence of difficulty in performing movement was indicated in the KOOS ADL score subscale by the question, “When lying in bed, what amount of difficulty in turning over or maintaining knee position have you experienced in the last week?” The prevalence of these symptoms was calculated for all participants and for those with knee OA.

Sleep quality

Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI), a valid and reliable index for evaluating sleep quality in patients with arthritis ([20]). A score of more than 5.5 out of 21 points was defined as sleep disturbance ([21, 22]). The PSQI consists of 7 subscales of quality of sleep: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medication, and daytime dysfunction. The presence of disturbances in each subscale was examined.

Statistical analysis

The prevalence of nocturnal knee pain and difficulty was estimated for all participants and for participants with knee OA. The distributions of knee OA severity between men and women were compared by chi-square test. The prevalence of nocturnal knee pain, difficulty, and sleep problems in relation to OA severity were compared by chi-square test. To determine what factors were related to sleep problems, logistic regression analysis was performed with the presence of sleep problems as a dependent variable, and knee-related factors (K/L grade, range of motion, mJSW, FTA, presence of nocturnal knee pain, and presence of difficulty in performing movement) as independent variables. At the same time, this regression model was adjusted by age, sex, BMI, working hours, and drinking, smoking, and fitness habits. A P value in Hosmer-Lemenshow test was 0.084 for estimating goodness of fit in this model, while this analysis included large samples. Furthermore, second logistic regression models were used to evaluate the relationship between K/L grade and each subscale of the PSQI. These models were adjusted by age, sex, BMI, working hours, and drinking, smoking, and fitness habits, wherein the subscales of the PSQI were adopted as the dependent variables, and K/L grade was introduced as an independent variable. Data input and calculation were performed in SPSS, version 12.0J. A P value of less than 0.05 was considered to be statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Radiographic OA of the knee

By K/L grade, the prevalence of knee OA in men was 15.1% and 38.8% in women (P < 0.001). Among all participants, the mean ± SD value of mJSW was 3.7 ± 1.0 mm and mean ± SD FTA was 176.8 ± 2.6°. The value of mJSW in participants with sleep problems was more narrow than in those without sleep problems (P = 0.008) (Table 1).

Table 1. Demographic and radiographic data from participants*
 Overall (n = 1,214)With OA (n = 363)Without OA (n = 851)P
  1. Values are the mean ± SD or the percentage of physical features. Values between patients with osteoarthritis (OA) and without OA were compared by Mann-Whitney U test. BMI = body mass index.

Age, years58.1 ± 13.066.6 ± 9.054.4 ± 12.70.636
Women62.481.054.5< 0.001
Height, cm158.2 ± 9.2153.5 ± 8.0160.2 ± 9.0< 0.001
Body weight, kg58.1 ± 10.556.4 ± 9.658.9 ± 10.8< 0.001
BMI, kg/m223.1 ± 3.223.9 ± 3.522.8 ± 3.0< 0.001
Smoking habit18.66.124.0< 0.001
Drinking habit41.724.249.2< 0.001
Fitness habit20.121.819.40.193
Working hours, no.7.0 ± 3.26.5 ± 3.37.2 ± 3.1< 0.001
Range of motion, degrees136.0 ± 14.3134.7 ± 15.7136.6 ± 13.7< 0.001
Joint space width, mm3.7 ± 1.03.1 ± 1.14.0 ± 0.8< 0.001
Femorotibial angle, degrees176.8 ± 2.6177.6 ± 3.2176.4 ± 2.30.537

Knee pain

The mean ± SD value of KOOS pain was 90.3 ± 15.7, of KOOS symptoms was 90.8 ± 13.9, of KOOS ADL was 94.9 ± 11.2, of KOOS sport/recreation was 85.6 ± 22.6, and of KOOS QOL was 82.2 ± 22.4. The prevalence of nocturnal knee pain was 3.6%, 6.9%, 19.4%, 32.7%, and 75.0% in K/L grades 0, 1, 2, 3, and 4, respectively. Similarly, the prevalence of difficulty in performing movement was 3.6%, 4.7%, 17.0%, 33.7%, and 50.0%, respectively (Table 2). Both the prevalence of nocturnal knee pain and difficulty increased significantly with severity of knee OA (P < 0.001). All subscales of KOOS in participants with both OA and sleep problems were lower than in other groups (P ≤ 0.001) (Figure 1).

Table 2. Sample numbers and the ratios of sleep problems, nocturnal knee pain, and knee-related disability*
  K/L grade 
Overall01234P
  1. Sample number was the number of participants in each Kellgren/Lawrence (K/L) grade. The prevalence of these night symptoms by K/L grade was compared by chi-square test.

Sample number1,21436049124710412
Sleep problem, %12.99.213.613.818.333.30.018
Nocturnal knee pain, %11.43.66.919.432.775.0< 0.001
Disability, %9.83.64.717.033.750.0< 0.001
image

Figure 1. Comparison of Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales in patients with knee osteoarthritis (OA) and sleep problems. Values are mean ± SD of KOOS subscales. Each value was adjusted by age, sex, body mass index, working hours, and smoking, drinking, and fitness habits, and compared by analysis of covariance. Multiple comparisons were performed using Bonferroni post hoc tests. * = P values < 0.05 were considered to be significant; ADL = activity of daily living; Rec = recreation; QOL = quality of life.

Download figure to PowerPoint

Quality of sleep

The mean ± SD value of PSQI among all participants was 3.1 ± 2.3, and 138 participants (11.5%) had sleep problems. The PSQI was very weakly correlated with all subscales of KOOS, and the correlation coefficients ranged from −0.14 to −0.15 (P < 0.001). Logistic regression analysis detected that joint space narrowing (P = 0.033) and the presence of nocturnal knee pain (P = 0.005) were related factors for sleep problems (Table 3). Furthermore, from another logistic model with subscales of the PSQI as dependent variables, sleep latency (P = 0.031) and sleep disturbance (P = 0.017) were correlated with knee OA severity (Table 4).

Table 3. Factors related to the presence of sleep problems*
 CoefficientsPOR95% CI
  1. Logistic regression analysis was performed with the presence of sleep problems as a dependent variable and Kellgren/Lawrence (K/L) grade, range of knee motion, minimal joint space width, presence of nocturnal knee pain, and presence of knee-related disability as predictor variables. This regression model was adjusted by age, sex, body mass index, working hours, and drinking, smoking, and fitness habits. OR = odds ratio; 95% CI = 95% confidence interval.

K/L grade0.060.6971.060.80–1.40
Range of motion0.010.4061.010.99–1.02
Joint space width−0.260.0330.770.61–0.98
Femorotibial angle−0.020.6700.980.91–1.06
Nocturnal pain0.970.0052.631.33–5.19
Knee-related disability−0.260.5120.770.35–1.68
Table 4. Relationship between knee OA severity and sleep quality*
Dependent variablesCoefficientsPOR95% CI
  1. Logistic regression analysis was performed with subscales of the Pittsburgh Sleep Quality Index as dependent variables and Kellgren/Lawrence grades as independent variables. Each subscale was adjusted by age, sex, body mass index, working hours, and drinking, smoking, and fitness habits. OA = osteoarthritis; OR = odds ratio; 95% CI = 95% confidence interval.

Sleep quality−0.330.680.970.83–1.13
Sleep latency0.160.0311.181.02–1.37
Sleep duration−0.010.8690.990.85–1.15
Habitual sleep efficiency0.190.3761.210.79–1.85
Sleep disturbance0.180.0171.191.03–1.38
Use of sleeping medication0.230.0631.340.98–1.84
Daytime dysfunction−0.070.4080.940.80–1.09

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Our results showed that 10% of the overall population and 25% of people with OA had nocturnal knee pain, and that the prevalence of difficulty related to this night knee condition was similar. Additionally, the prevalence of nocturnal knee pain increased with knee OA severity and significantly impacted sleep quality, especially in the onset and maintenance of sleep. Furthermore, sleep problems in OA patients significantly decreased their QOL. These results suggest that controlling nocturnal knee pain will contribute to improving patient sleep quality and QOL.

The present study determined the specific prevalence of nocturnal symptoms in knee OA. Hawker et al reported that nocturnal knee pain was the ninth most common complaint in knee OA patients, and that the pain was not frequent and did not bother them ([4]). Conversely, Woolhead et al showed that most hip and knee OA patients had experienced nocturnal knee pain through an interview-style investigation ([3]). Power et al performed a large cohort study on 118,336 subjects with arthritis, which suggested the prevalence of nocturnal knee pain was 45.6% ([5]). Our study characterized the radiographic signs of knee OA in a precise manner and determined the prevalence of nocturnal knee pain according to OA severity. Our results showed that the prevalence was approximately 25% in participants with radiographic knee OA, different from previous reports. One likely reason for this disparity is that the study designs of past studies were not unified. For example, an expansive definition of arthritis in a large cohort study would increase the prevalence because of an imprecise definition of arthritis that includes rheumatoid arthritis or ON of the knee ([20]).

The influence of knee OA on sleep disturbances was reported experimentally using OA rats ([23, 24]). However, the clinical relationship between the severity of OA and sleep quality in patients with radiographic knee OA has not been described. Sleep onset and maintenance of sleep were significantly decreased in those with severe knee OA. A previous study reported that disturbed onset and maintenance of sleep were one of the characteristics of nocturnal knee pain. However, this result was determined only from questionnaires and lacked a statistical analysis ([4]). The present study confirmed the results that the onset and maintenance of sleep were the main problems affected by severity of OA, and expanded the analysis with objective statistical analysis.

Knee-related QOL was decreased in those with both OA and sleep problems compared to those without OA or sleep problems. Highly sensitive sleep phenomena may be altered by intrinsic and extrinsic factors ([25]). It is well known that sleep problems have a major impact on QOL ([26]). Therefore, it was thought to be difficult to isolate the pure relationship between sleep and OA because sleep itself is affected by many factors, including age, obesity, and mental disorders ([27]). Especially, mental disorders such as anxiety and depression have an impact on sleep quality and QOL. It is one of the study limitations that these mental disorders were not considered in statistical analyses. In the present study many confounding variables were accounted for during analysis, which indicated that lower sleep quality because of nocturnal knee pain decreased QOL. This result suggests that appropriate pain control at night would improve the QOL of OA patients.

However, the precise mechanisms causing nocturnal knee pain remain unclear, even though many people with knee OA experience it. Several potential reasons have been considered, one of which is the relation to chronic pain caused by knee OA. This hypothesis was supported in studies by Moldofsky et al ([28]) and Moldofsky ([29]), in which poor sleep is shown to exacerbate pain in people with chronic pain by decreasing pain tolerance. Chen et al reported that chronic musculoskeletal pain was strongly associated with sleep problems in depression as measured by the Center for Epidemiologic Studies Depression scale ([30]). Another factor was excessive mechanical load and synovitis caused by an individual's activities during the day, such as work, sports, and recreation. Hawker et al reported that working hours were also a possible risk factor for nocturnal knee symptoms ([4]). Conversely, it is documented that knee OA patients have synovitis even in the early stages of the disease, and its prevalence and number of regions increase with the severity of OA ([31]). More regions with synovitis in severe knee OA may be related to an increasing prevalence of nocturnal knee pain. Further analysis of nocturnal knee pain using magnetic resonance imaging (MRI) or pathologic examination is needed to clarify this point.

Generally, intense nocturnal knee pain is considered to be a specific symptom for ON of the knee. Although the precise prevalence of nocturnal knee pain was not previously reported, Lotke et al mentioned that most patients with ON had nocturnal knee pain ([32]). There was a high prevalence of nocturnal knee pain in severe OA patients. The results in the present study showed that the prevalence of nocturnal knee pain was 25% in those with knee OA of K/L grade ≥2 and 40% in those with knee OA of K/L grade ≥3. These results enhance our knowledge of the diagnosis of knee OA severity, and provide important information to distinguish OA from ON.

There were several limitations in this cohort study. First, diagnosis and evaluation of knee condition was made only using radiographic images. MRI or pathologic examination would give more information to indicate the relationship between nocturnal knee pain and OA severity. Also, ON was not completely excluded. Although radiography of all participants did not show any radiolucent zone or collapsed lesion in the femoral condyles in this study, MRI was not performed. MRI can indicate early-stage ON and supplies other useful information about the condition of cartilage, meniscus, ligaments, and synovium. However, it is difficult to perform MRI on all patients in a large sample cohort study. Second, the method of participant recruitment in this study could cause selection bias. Most participants were more interested in their health condition, and this potentially influenced an overestimation of prevalence. Third, comparisons with similar populations in other countries were not made due to the limited number of reports about the prevalence of nocturnal knee pain. Muraki et al suggested that there are differences in the characteristics of OA between Japan and other countries ([33]). Such investigations could supply further important information for the treatment and management of OA.

Despite these limitations, this study determined the relationship between OA severity and nocturnal knee pain and difficulty in performing movement in bed using statistical analyses. These results enhance our knowledge of the diagnosis of knee OA severity and supply important information about QOL in knee OA patients.

In conclusion, a third part of community-dwelling people with radiographic knee OA had nocturnal knee pain and difficulty, and the prevalence of nocturnal pain increased with the radiographic severity of knee OA. Nocturnal pain significantly disturbed subject sleep quality, especially in sleep onset latency and sleep maintenance. Also, QOL in knee OA patients declined owing to sleep disturbances. These results supply valuable information for clinical assessment of OA severity and knee-related QOL.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Sasaki had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Sasaki, Tsuda, Yamamoto, Maeda, Inoue, Chiba, Okubo, Takahashi, Nakaji, Ishibashi.

Acquisition of data. Sasaki, Tsuda, Yamamoto, Maeda, Inoue, Chiba, Okubo, Takahashi, Nakaji, Ishibashi.

Analysis and interpretation of data. Sasaki, Inoue, Takahashi, Ishibashi.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
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