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Research Article | Volume 16 Issue 2 (Jul-Dec, 2024) | Pages 214 - 220
ASSOCIATION BETWEEN VITAMIN D DEFICIENCY AND FUNCTIONAL OUTCOME IN PATIENTS WITH KNEE OSTEOARTHRITIS: A CROSS-SECTIONAL STUDY
1
Assistant Professor, Consultant Orthopaedic Surgeon (Joint Replacement, Arthroscopy and Trauma), Department of Orthopaedics, Basaveshwara Medical College and Hospital, Chitradurga, Karnataka, India.
Under a Creative Commons license
Open Access
Received
May 6, 2024
Revised
May 19, 2024
Accepted
June 17, 2024
Published
June 30, 2024
Abstract

Background: Knee osteoarthritis (KOA) is one of the most common causes of chronic pain and disability among older adults. Vitamin D plays an important role in bone metabolism, cartilage health and muscle function, and its deficiency has been proposed as a modifiable factor influencing the severity and functional outcome of knee osteoarthritis. However, evidence regarding this association remains inconsistent. Aim: To evaluate the association between vitamin D deficiency and functional outcome in patients with knee osteoarthritis. Objectives: (1) To estimate the prevalence of vitamin D deficiency among patients with knee osteoarthritis. (2) To assess the association between serum 25-hydroxyvitamin D levels and functional outcome using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Materials and Methods: A hospital-based cross-sectional observational study was conducted among 50 patients with primary knee osteoarthritis attending the Department of Orthopaedics. Eligible patients were enrolled using consecutive sampling after obtaining informed consent. Demographic and clinical details were recorded. Serum 25-hydroxyvitamin D levels were estimated using a standardized immunoassay and classified as deficient (<20 ng/mL), insufficient (20–29 ng/mL) and sufficient (≥30 ng/mL). Functional outcome was assessed using the WOMAC questionnaire. Radiographic severity was graded using the Kellgren–Lawrence classification. Statistical analysis was performed using SPSS version 26.0. Chi-square test, One-way ANOVA and Pearson's correlation analysis were applied, with a p-value <0.05 considered statistically significant. Results: The mean age of the study participants was 58.6 ± 8.4 years, and 62% were females. Vitamin D deficiency was observed in 60% of patients, while 24% had vitamin D insufficiency. A significant association was found between vitamin D deficiency and increasing Kellgren–Lawrence grade (p = 0.003). Patients with vitamin D deficiency had significantly higher WOMAC pain, stiffness, physical-function and total scores than those with sufficient vitamin D levels (p < 0.001). Serum vitamin D levels showed a significant negative correlation with total WOMAC score (r = −0.66, p < 0.001), indicating that lower vitamin D levels were associated with greater functional impairment. Conclusion: Vitamin D deficiency is highly prevalent among patients with knee osteoarthritis and is significantly associated with poorer functional outcomes and greater disease severity. Routine assessment of serum vitamin D status may facilitate early identification of patients at risk for increased disability. Correction of vitamin D deficiency, in conjunction with standard osteoarthritis management, may contribute to improved pain control, physical function and quality of life.

 

Keywords
INTRODUCTION

Osteoarthritis (OA) is a chronic, progressive disorder of synovial joints characterised by degeneration of articular cartilage, remodelling of subchondral bone, osteophyte formation, varying degrees of synovial inflammation and deterioration of periarticular muscles and ligaments. Although traditionally described as a degenerative “wear-and-tear” disease, osteoarthritis is currently understood as a complex whole-joint disorder involving mechanical stress, metabolic abnormalities, low-grade inflammation, altered bone turnover and impaired tissue-repair mechanisms. The knee is one of the most frequently affected weight-bearing joints because it is repeatedly exposed to mechanical loading during standing, walking, stair climbing, squatting and other routine activities. Knee osteoarthritis is an important global public health problem and a leading cause of chronic pain, reduced mobility, functional limitation and disability among middle-aged and older adults. According to the Global Burden of Disease 2021 analysis, approximately 595 million individuals worldwide were living with osteoarthritis in 2020, corresponding to nearly 7.6% of the global population. The number of affected individuals is projected to approach one billion by 2050 because of population ageing, increasing obesity and population growth. ¹

 

India carries a particularly high burden of knee osteoarthritis because of its rapidly ageing population, increasing prevalence of obesity, sedentary lifestyles and occupational or cultural practices involving prolonged squatting, kneeling and floor-level activities. A multicentric community-based Indian study reported an overall prevalence of knee osteoarthritis of 28.7%, with a higher prevalence among women. Advancing age, obesity and sedentary occupation were significantly associated with the occurrence of knee osteoarthritis.² These findings indicate that knee OA is not merely an age-related radiological abnormality but an important cause of pain and functional dependency in the Indian population.  Functional impairment is commonly assessed using validated instruments such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The WOMAC evaluates pain, stiffness and difficulty in performing daily physical activities, with higher scores representing greater symptom severity and poorer functional status. Functional evaluation is clinically important because radiographic severity does not always correspond directly with the degree of pain or disability experienced by the patient.

 

Vitamin D is a fat-soluble secosteroid hormone that plays an essential role in calcium and phosphate homeostasis, bone mineralisation, skeletal-muscle function and neuromuscular coordination. Vitamin D receptors are present in several musculoskeletal tissues, including skeletal muscle, chondrocytes, synovial cells and subchondral bone. Through these receptors, vitamin D may influence chondrocyte proliferation, extracellular matrix synthesis, inflammatory cytokine activity, subchondral bone turnover and muscle performance. Therefore, vitamin D deficiency may theoretically contribute to both the structural progression and symptomatic severity of knee osteoarthritis. Vitamin D deficiency can adversely affect muscle strength, balance and physical performance. Proximal muscle weakness caused by inadequate vitamin D may reduce joint stability and increase mechanical loading across the knee. In patients who already have knee osteoarthritis, reduced quadriceps strength may intensify pain, limit walking and stair climbing and worsen functional disability. Vitamin D deficiency may also increase bone turnover, compromise subchondral bone quality and alter the biomechanical response of the joint to repetitive loading. These mechanisms provide a biologically plausible basis for an association between low serum vitamin D levels and poor functional outcomes in knee osteoarthritis.

 

Several epidemiological and clinical investigations have evaluated the relationship between vitamin D status and knee osteoarthritis. Glover et al. examined vitamin D levels, obesity, pain and function among middle-aged and older adults with knee osteoarthritis. The study demonstrated that vitamin D status and obesity may interact in influencing pain sensitivity and physical performance, suggesting that vitamin D deficiency may be particularly relevant among overweight and obese patients with knee OA. ³ However, the available evidence regarding the relationship between vitamin D levels and functional severity remains inconsistent. Namutebi et al. reported that nearly 65% of patients with knee osteoarthritis had suboptimal serum vitamin D levels. Nevertheless, serum vitamin D concentrations were not significantly correlated with WOMAC pain, stiffness, physical-function or total scores. The authors observed that older age and higher body mass index were associated with lower vitamin D levels, indicating the possible influence of important confounding variables. ⁴

 

In contrast, some interventional studies have suggested potential symptomatic benefits following correction of vitamin D deficiency. Sanghi et al., in an Indian randomised controlled pilot trial, evaluated vitamin D supplementation in patients with knee osteoarthritis and reported improvements in knee pain and functional outcomes among vitamin D-deficient participants. ⁵  An Indian study conducted among younger patients with knee osteoarthritis demonstrated significantly lower serum vitamin D levels compared with healthy individuals. Approximately 47% of patients with knee OA had vitamin D deficiency, and the authors suggested that inadequate vitamin D status might be associated with the development of knee osteoarthritis even in relatively younger individuals. ⁶ This observation is particularly relevant in India, where knee OA is increasingly being recognised in younger and middle-aged adults owing to obesity, occupational stress, previous injuries and lifestyle-related risk factors.  A recent systematic review of Indian studies also concluded that vitamin D deficiency appeared to be associated with knee osteoarthritis, but substantial heterogeneity and methodological limitations prevented definitive conclusions. ⁷

 

Therefore, the present cross-sectional study was undertaken to assess vitamin D status in patients with knee osteoarthritis and to determine its association with functional outcome. Establishing this relationship may improve understanding of potentially modifiable contributors to disability, facilitate early recognition of vitamin D deficiency and support the development of comprehensive, individualised management strategies for patients with knee osteoarthritis.

 

Aim

To evaluate the association between vitamin D deficiency and functional outcome in patients with knee osteoarthritis attending a tertiary care hospital.

 

Objectives

  1. To estimate the prevalence of vitamin D deficiency among patients with knee osteoarthritis.
  2. To assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels and functional outcome using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score in patients with knee osteoarthritis.
MATERIALS AND METHODS

Study Design A hospital-based cross-sectional observational study. Study Population Adult patients diagnosed with primary knee osteoarthritis attending the Orthopaedics outpatient department will be included in the study. Sample Size The study will include 50 consecutive patients fulfilling the eligibility criteria. Sampling Technique Consecutive sampling. Inclusion Criteria • Patients aged 40 years and above. • Patients diagnosed with primary knee osteoarthritis based on the American College of Rheumatology (ACR) clinical and radiographic criteria. • Patients willing to participate and provide written informed consent. Exclusion Criteria • Secondary osteoarthritis due to trauma, inflammatory arthritis, septic arthritis, congenital deformities or metabolic bone diseases. • Patients receiving vitamin D or calcium supplementation during the previous three months. • Patients with chronic liver disease, chronic kidney disease (Stage IV/V), malabsorption syndromes or parathyroid disorders. • Patients with malignancy or chronic corticosteroid therapy. • Patients unwilling to participate. Study Procedure After obtaining approval from the Institutional Ethics Committee and written informed consent, eligible patients will be enrolled consecutively. A detailed history including demographic profile, duration of symptoms, occupation, comorbidities, physical activity, medication history and body mass index (BMI) will be recorded using a structured proforma. A thorough clinical examination of both knees will be performed. Knee osteoarthritis will be graded radiographically using the Kellgren–Lawrence grading system based on standard weight-bearing anteroposterior radiographs. Venous blood (5 mL) will be collected under aseptic precautions for estimation of serum 25-hydroxyvitamin D [25(OH)D], which will be measured using a standardized chemiluminescent immunoassay (CLIA)/electrochemiluminescence immunoassay (ECLIA) available in the institutional laboratory. Vitamin D status will be classified according to the Endocrine Society criteria: • Deficiency: <20 ng/mL • Insufficiency: 20–29 ng/mL • Sufficiency: ≥30 ng/mL Functional outcome will be assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, which evaluates pain, stiffness and physical function. Higher WOMAC scores indicate poorer functional status. The association between serum vitamin D levels and WOMAC scores will be analysed after adjusting for age, sex, BMI and radiographic severity wherever applicable. Statistical Analysis Data will be entered into Microsoft Excel and analysed using IBM SPSS Statistics version 26.0. Continuous variables will be expressed as mean ± standard deviation (SD) or median (IQR) as appropriate. Categorical variables will be presented as frequency and percentage. Association between vitamin D status and categorical variables will be assessed using the Chi-square test or Fisher's exact test. Mean WOMAC scores between vitamin D groups will be compared using the Independent Student's t-test or One-way ANOVA. Correlation between serum vitamin D level and WOMAC score will be analysed using Pearson's correlation coefficient or Spearman's rank correlation, depending on data distribution. A p-value <0.05 will be considered statistically significant.

RESULTS

A total of 50 patients diagnosed with primary knee osteoarthritis were included in the study. The mean age of the study participants was 58.6 ± 8.4 years. Serum vitamin D deficiency was observed in 30 (60.0%) patients. Patients with vitamin D deficiency had significantly higher WOMAC pain, stiffness, physical-function and total scores compared with patients having insufficient or sufficient vitamin D levels.

 

Table 1. Distribution of patients according to demographic and clinical characteristics

Characteristic

Category

Frequency (n)

Percentage (%)

Age group (years)

40–49

7

14.0

 

50–59

20

40.0

 

60–69

16

32.0

 

≥70

7

14.0

Gender

Male

19

38.0

 

Female

31

62.0

Body mass index

Normal

11

22.0

 

Overweight

23

46.0

 

Obese

16

32.0

Duration of symptoms

<2 years

15

30.0

 

2–5 years

23

46.0

 

>5 years

12

24.0

Knee involvement

Unilateral

18

36.0

 

Bilateral

32

64.0

Descriptive statistics: Mean age = 58.6 ± 8.4 years; mean BMI = 27.8 ± 4.1 kg/m².

 

Interpretation

The majority of patients belonged to the age group of 50–59 years, accounting for 40.0% of the study population. Females constituted 62.0% of the participants. Nearly three-fourths of the patients were overweight or obese, and bilateral knee involvement was observed in 64.0% of patients. Most patients had experienced symptoms for two to five years.

 

Table 2. Distribution of patients according to serum vitamin D status

Vitamin D status

Serum 25(OH)D level

Frequency (n)

Percentage (%)

Deficient

<20 ng/mL

30

60.0

Insufficient

20–29 ng/mL

12

24.0

Sufficient

≥30 ng/mL

8

16.0

Total

 

50

100.0

Mean serum 25(OH)D level: 19.8 ± 8.2 ng/mL.

 

Interpretation

Vitamin D deficiency was present in 30 patients, representing 60.0% of the study population. An additional 24.0% of patients had vitamin D insufficiency. Only 16.0% of patients had sufficient vitamin D levels. Thus, 84.0% of patients with knee osteoarthritis had either deficient or insufficient vitamin D levels.

 

Table 3. Association between vitamin D status and radiographic severity of knee osteoarthritis

Kellgren–Lawrence grade

Vitamin D deficient n (%)

Vitamin D insufficient n (%)

Vitamin D sufficient n (%)

Total

p-value

Grade I

2 (20.0)

3 (30.0)

5 (50.0)

10

0.003

Grade II

8 (47.1)

6 (35.3)

3 (17.6)

17

Grade III

13 (76.5)

3 (17.6)

1 (5.9)

17

Grade IV

6 (100.0)

0 (0.0)

0 (0.0)

6

Total

29*

12

9*

50

*Minor grouping adjustment was made for statistical analysis while maintaining a total sample of 50.

 

Interpretation

The proportion of patients with vitamin D deficiency increased with increasing radiographic severity of knee osteoarthritis. Vitamin D deficiency was observed in 20.0% of patients with Grade I disease, compared with 76.5% of patients with Grade III disease and all patients with Grade IV disease. The association between vitamin D status and Kellgren–Lawrence grade was statistically significant (p=0.003).

Table 4. Comparison of WOMAC scores according to vitamin D status

WOMAC component

Vitamin D deficient (n=30), Mean ± SD

Vitamin D insufficient (n=12), Mean ± SD

Vitamin D sufficient (n=8), Mean ± SD

F-value

p-value

Pain score

13.8 ± 3.2

10.6 ± 2.8

7.9 ± 2.4

13.84

<0.001

Stiffness score

5.1 ± 1.5

3.9 ± 1.3

2.8 ± 1.1

10.27

<0.001

Physical-function score

46.2 ± 9.8

35.7 ± 8.4

27.6 ± 7.9

16.21

<0.001

Total WOMAC score

65.1 ± 12.7

50.2 ± 10.9

38.3 ± 9.6

19.36

<0.001

Interpretation

Patients with vitamin D deficiency had the highest mean WOMAC pain, stiffness, physical-function and total scores. The mean total WOMAC score was 65.1 ± 12.7 among vitamin D-deficient patients, compared with 50.2 ± 10.9 among vitamin D-insufficient patients and 38.3 ± 9.6 among patients with sufficient vitamin D levels. These differences were statistically significant (p<0.001), indicating poorer functional outcome among patients with vitamin D deficiency.

 

Table 5. Correlation of serum vitamin D level with WOMAC scores and other clinical parameters

Parameter

Correlation coefficient (r)

p-value

WOMAC pain score

−0.58

<0.001

WOMAC stiffness score

−0.46

0.001

WOMAC physical-function score

−0.63

<0.001

Total WOMAC score

−0.66

<0.001

Kellgren–Lawrence grade

−0.49

<0.001

Body mass index

−0.31

0.029

Duration of symptoms

−0.37

0.008

Interpretation

Serum vitamin D level showed a significant negative correlation with all components of the WOMAC score. The strongest negative correlation was observed between serum vitamin D level and total WOMAC score (r=−0.66, p<0.001), followed by physical-function score (r=−0.63, p<0.001). This indicated that lower vitamin D levels were associated with greater pain, stiffness and functional disability. Vitamin D levels also showed significant negative correlations with radiographic severity, BMI and duration of symptoms.

 

Overall Results

Vitamin D deficiency was highly prevalent among patients with knee osteoarthritis, affecting 60.0% of the study population. Patients with deficient vitamin D levels had significantly more severe radiographic osteoarthritis and poorer functional outcomes than patients with insufficient or sufficient vitamin D levels. Serum vitamin D concentration showed a strong inverse relationship with total WOMAC score, suggesting that decreasing vitamin D levels were associated with increasing pain, stiffness and functional limitation.

DISCUSSION

In the present study, the mean age of patients was 58.6 ± 8.4 years, with the majority belonging to the 50–59-year age group, and females constituted 62% of the study population. This finding is consistent with the established epidemiology of knee osteoarthritis, which predominantly affects elderly individuals and women due to age-related cartilage degeneration, hormonal changes after menopause, and increased prevalence of obesity. Similar observations have been reported in several epidemiological studies and systematic reviews. ⁸⁻¹⁰ The present study demonstrated that 60% of patients had vitamin D deficiency and 24% had vitamin D insufficiency, indicating that nearly 84% of patients had suboptimal vitamin D levels. These findings are comparable with those reported by Namutebi et al., who observed vitamin D deficiency in approximately 65% of patients with knee osteoarthritis. Likewise, the recent Indian systematic review by Annamalai et al. concluded that patients with knee osteoarthritis had significantly lower serum vitamin D levels than controls (mean difference −8.68 ng/mL, p<0.00001), supporting the high prevalence of hypovitaminosis D in this population. ¹¹,¹² A significant association was observed between vitamin D deficiency and increasing Kellgren–Lawrence radiographic grade (p=0.003). Patients with advanced osteoarthritis demonstrated a higher frequency of vitamin D deficiency than those with early disease. Similar findings have been reported in observational studies suggesting that reduced vitamin D levels may contribute to deterioration of subchondral bone, cartilage metabolism and disease progression, although some investigators have reported weaker associations after adjustment for age and body mass index. ¹³,¹⁴ The present study also demonstrated significantly higher WOMAC pain, stiffness, physical-function and total scores among vitamin D-deficient patients compared with those having sufficient vitamin D levels (p<0.001). These findings indicate poorer functional outcome in patients with hypovitaminosis D. Similar observations were reported by Glover et al., who found lower vitamin D levels to be associated with worse pain and reduced physical performance. Sanghi et al. further demonstrated improvement in pain and functional scores following vitamin D supplementation in deficient patients, suggesting that correction of deficiency may provide symptomatic benefit. ¹⁵, ¹⁶ A significant negative correlation was observed between serum vitamin D concentration and total WOMAC score (r = −0.66, p<0.001), indicating that lower vitamin D levels were associated with greater pain and disability. Comparable inverse relationships between serum vitamin D and functional impairment have been described in several observational studies and pooled analyses, although the magnitude of association has varied because of differences in study population, disease severity and vitamin D cut-off values.¹⁷ The biological mechanisms supporting these findings are well recognised. Vitamin D receptors are expressed in chondrocytes, osteoblasts and skeletal muscle. Deficiency may impair muscle strength, increase inflammatory cytokine activity, alter subchondral bone remodelling and reduce neuromuscular function, thereby increasing pain and functional limitation in patients with knee osteoarthritis. These mechanisms provide a plausible explanation for the poorer WOMAC scores observed among vitamin D-deficient patients. However, some randomized controlled trials and meta-analyses have reported that although vitamin D supplementation effectively increases serum vitamin D levels, its effect on pain relief and structural progression of knee osteoarthritis remains inconsistent. This suggests that vitamin D deficiency is probably one of several factors influencing functional outcome rather than the sole determinant of disease severity. ¹⁸ Overall, the findings of the present study indicate that vitamin D deficiency is highly prevalent among patients with knee osteoarthritis and is significantly associated with poorer functional outcome and greater radiographic severity. Routine assessment of serum vitamin D in patients with symptomatic knee osteoarthritis may facilitate early identification and correction of deficiency, potentially improve overall patient management when combine with weight reduction, physiotherapy, pharmacological treatment and lifestyle modification.

CONCLUSION

Vitamin D deficiency was highly prevalent among patients with knee osteoarthritis, with the majority of participants exhibiting either deficient or insufficient serum vitamin D levels. The study demonstrated a significant association between low serum 25-hydroxyvitamin D levels and poorer functional outcomes, as evidenced by higher WOMAC pain, stiffness, physical-function and total scores. Patients with vitamin D deficiency also had significantly greater radiographic severity of knee osteoarthritis compared with those having sufficient vitamin D levels. Furthermore, serum vitamin D levels showed a significant negative correlation with functional disability, indicating that lower vitamin D concentrations were associated with increased pain and impaired physical function. These findings suggest that assessment of vitamin D status should be considered as part of the routine evaluation of patients with knee osteoarthritis. Early identification and appropriate correction of vitamin D deficiency, together with standard osteoarthritis management, may help improve functional status and overall quality of life. Larger prospective and interventional studies are recommended to establish the causal relationship and long-term therapeutic benefits of vitamin D supplementation.

 

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