None, D. P. K. R. & None, D. P. K. P. (2024). Association Between Vitamin D Deficiency and Severity of Knee Osteoarthritis in Adults: A Hospital-Based Cross-Sectional Study. Journal of Contemporary Clinical Practice, 10(1), 582-588.
MLA
None, Dr P. Kaliprasad Rao and Dr. Prashanth Kumar Patnaik . "Association Between Vitamin D Deficiency and Severity of Knee Osteoarthritis in Adults: A Hospital-Based Cross-Sectional Study." Journal of Contemporary Clinical Practice 10.1 (2024): 582-588.
Chicago
None, Dr P. Kaliprasad Rao and Dr. Prashanth Kumar Patnaik . "Association Between Vitamin D Deficiency and Severity of Knee Osteoarthritis in Adults: A Hospital-Based Cross-Sectional Study." Journal of Contemporary Clinical Practice 10, no. 1 (2024): 582-588.
Harvard
None, D. P. K. R. and None, D. P. K. P. (2024) 'Association Between Vitamin D Deficiency and Severity of Knee Osteoarthritis in Adults: A Hospital-Based Cross-Sectional Study' Journal of Contemporary Clinical Practice 10(1), pp. 582-588.
Vancouver
Dr P. Kaliprasad Rao DPKR, Dr. Prashanth Kumar Patnaik DPKP. Association Between Vitamin D Deficiency and Severity of Knee Osteoarthritis in Adults: A Hospital-Based Cross-Sectional Study. Journal of Contemporary Clinical Practice. 2024 Jan;10(1):582-588.
Background: Vitamin D plays an important role in musculoskeletal health; however, its association with the radiographic severity of knee osteoarthritis remains uncertain. Objectives: To assess serum vitamin D status and examine its association with radiographic severity among adults with knee osteoarthritis. Methods: This hospital-based cross-sectional study included 120 adults with knee osteoarthritis at RVM Institute of Medical Sciences and Research Center, Laxmakkapally, Mulugu, Siddipet, Telangana, India, from April to November 2023. Radiographic severity was assessed using the Kellgren–Lawrence grading system (grades II–IV). Serum 25-hydroxyvitamin D levels were classified as deficient (<20 ng/mL), insufficient (20–<30 ng/mL), or sufficient (≥30 ng/mL). Associations between vitamin D status and radiographic severity were analysed using Pearson’s chi-square test. Results: The mean age of participants was 58.40 ± 9.20 years, and 78 (65.0%) were women. Mean serum vitamin D concentration was 20.11 ± 9.31 ng/mL. Vitamin D deficiency was observed in 66 (55.0%) participants, insufficiency in 34 (28.3%), and sufficiency in 20 (16.7%). Kellgren–Lawrence grades II, III, and IV were recorded in 42 (35.0%), 48 (40.0%), and 30 (25.0%) participants, respectively. A statistically significant association was observed between vitamin D status and radiographic severity (χ² = 24.88; p < 0.001). Grade IV osteoarthritis was more frequent among participants with vitamin D deficiency than among those without deficiency (39.4% vs. 7.4%; χ² = 16.21; p < 0.001). Conclusion: Vitamin D deficiency was significantly associated with greater radiographic severity of knee osteoarthritis. These findings suggest a relationship between reduced serum vitamin D levels and advanced radiographic disease. However, the cross-sectional study design does not establish causality, and further prospective studies are required to clarify this association
Keywords
Knee osteoarthritis
Vitamin D deficiency
25-hydroxyvitamin D
Kellgren–Lawrence grade
Radiographic severity
Cross-sectional study
INTRODUCTION
Osteoarthritis (OA) is a chronic, progressive joint disorder characterised by degenerative changes involving articular cartilage, subchondral bone, synovium, and surrounding joint structures. Knee osteoarthritis is a major cause of pain, stiffness, functional limitation, and reduced quality of life, particularly among middle-aged and older adults. The severity of the disease varies considerably, and radiographic abnormalities may not always correlate with clinical symptoms. Therefore, assessment of structural changes is essential for evaluating disease severity and understanding factors associated with its progression.[1] The development and progression of knee osteoarthritis are influenced by several factors, including advancing age, obesity, previous joint injuries, mechanical stress, occupational activities, and metabolic disturbances.[2]
Vitamin D plays an important role in calcium homeostasis, bone mineralisation, skeletal muscle function, and maintenance of musculoskeletal health. Vitamin D deficiency may contribute to impaired bone metabolism, muscle weakness, and functional limitations, potentially influencing the clinical manifestations of osteoarthritis.[3] Serum 25-hydroxyvitamin D [25(OH)D] is widely used to assess vitamin D status. For the purpose of this study, serum concentrations below 20 ng/mL were classified as deficient, levels between 20 and <30 ng/mL as insufficient, and concentrations of 30 ng/mL or above as sufficient.[4] Although these categories are commonly used in clinical research, the optimal vitamin D concentration for preventing or slowing osteoarthritis progression remains uncertain.
Several observational studies have investigated the association between vitamin D status and knee osteoarthritis, with conflicting findings. The Framingham Study reported that lower dietary vitamin D intake and serum vitamin D concentrations were associated with progression of established knee osteoarthritis.[5] The Rotterdam Study examined the relationship between vitamin D status, bone mineral density, and radiographic knee osteoarthritis, highlighting the potential involvement of skeletal and metabolic factors.[6] Similarly, Ding et al. observed an association between lower serum vitamin D concentrations and increased knee cartilage loss among older adults.[7] However, Felson et al., in two longitudinal studies, found no significant association between low vitamin D levels and worsening knee osteoarthritis.[8] These inconsistencies indicate that the relationship between vitamin D deficiency and structural disease severity requires further investigation.
Randomised controlled trials have also evaluated the effectiveness of vitamin D supplementation in patients with knee osteoarthritis. McAlindon et al. reported that vitamin D supplementation did not significantly reduce knee pain or cartilage volume loss over two years.[9] Similarly, Jin et al. found no significant improvement in their primary outcomes of knee pain and tibial cartilage volume following supplementation.[10] The VIDEO trial also failed to demonstrate a significant reduction in radiographic joint-space narrowing.[11] These findings suggest that although vitamin D deficiency may be associated with osteoarthritis severity, supplementation has not consistently demonstrated disease-modifying benefits. Furthermore, factors such as reduced sunlight exposure, limited physical activity, obesity, and comorbid conditions may influence both vitamin D status and osteoarthritis severity.Considering the conflicting evidence and the clinical importance of vitamin D in musculoskeletal health, further evaluation of its association with radiographic knee osteoarthritis is warranted.
The present hospital-based cross-sectional study was undertaken to assess serum vitamin D status among 120 adults with knee osteoarthritis and examine its association with radiographic severity using the Kellgren–Lawrence grading system. The study also aimed to determine the distribution of radiographic grades II–IV and compare the prevalence of severe (grade IV) osteoarthritis between participants with and without vitamin D deficiency. These findings may contribute to a better understanding of the relationship between vitamin D status and the structural severity of knee osteoarthritis in the hospital-based study population.
MATERIALS AND METHODS
Study Design and Setting
This hospital-based cross-sectional observational study was conducted at RVM Institute of Medical Sciences and Research Center, Laxmakkapally, Mulugu, Siddipet, Telangana, India, from April 2023 to November 2023. The study aimed to assess serum vitamin D status and its association with radiographic severity among adults diagnosed with knee osteoarthritis. Each participant was considered an individual unit of analysis, with one index knee selected for radiographic severity assessment.
Participants and Sample Size
The study included 120 adults aged 40–78 years with symptomatic and radiographically confirmed knee osteoarthritis, classified according to the American Rheumatism Association criteria.[12] Patients with Kellgren–Lawrence grades II–IV were included in the analysis. The sample size comprised 120 participants enrolled during the study period.
Clinical Assessment
Demographic and clinical characteristics, including age, sex, body mass index (BMI), duration of symptoms, knee involvement, hypertension, diabetes mellitus, and knee pain severity, were considered for analysis. BMI was expressed in kg/m², while symptom duration was recorded in years. Knee pain intensity was evaluated using a 0–10 numerical scale. In participants with bilateral knee osteoarthritis, the knee exhibiting the higher radiographic grade was considered the index knee for severity assessment.
Vitamin D Assessment
Serum 25-hydroxyvitamin D [25(OH)D] concentration was used to determine vitamin D status. Participants were classified into three categories: vitamin D deficiency (<20 ng/mL), insufficiency (20–<30 ng/mL), and sufficiency (≥30 ng/mL), based on established research thresholds.[4] Vitamin D status was evaluated in relation to the radiographic severity of knee osteoarthritis. Serum concentrations were expressed in ng/mL and summarised using descriptive statistics.
Radiographic Assessment
Radiographic severity of knee osteoarthritis was assessed using the Kellgren–Lawrence grading system.[13] Participants were categorised into grade II (definite osteophytes with possible joint-space narrowing), grade III (multiple osteophytes, definite joint-space narrowing, and possible bony deformity), and grade IV (marked joint-space narrowing, severe sclerosis, and definite bony deformity). Grade IV osteoarthritis was considered severe radiographic disease. The distribution of radiographic grades was compared across vitamin D categories to evaluate the association between vitamin D status and structural disease severity.
Statistical Analysis
Data were summarised using descriptive and inferential statistics. Continuous variables were expressed as mean ± standard deviation or median with interquartile range, as appropriate. Categorical variables were presented as frequencies and percentages. Pearson’s chi-square test was used to assess the association between vitamin D status and Kellgren–Lawrence radiographic grades. An additional comparison was performed between participants with vitamin D deficiency and those without deficiency to evaluate the prevalence of grade IV osteoarthritis. All statistical tests were two-sided, and a p-value <0.05 was considered statistically significant. The analysis focused on unadjusted associations without multivariable adjustment. Reporting was guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations.[14]
Ethical Considerations
The study was approved by the Institutional Ethics Committee, RVM Institute of Medical Sciences and Research Center, Siddipet, Telangana, India. Participant confidentiality and privacy were maintained throughout the study. All collected information was used exclusively for research purposes, and personal identifiers were excluded from data analysis and reporting. The study was conducted in accordance with institutional ethical guidelines and the principles of the Declaration of Helsinki.
RESULTS
Demographic and Clinical Characteristics
A total of 120 adults with knee osteoarthritis were included in the study. The mean age was 58.40 ± 9.20 years (range: 40–78 years), and 78 participants (65.0%) were women. Mean body mass index was 28.10 ± 4.30 kg/m². Median symptom duration was 4.0 years (IQR: 2.0–7.0 years). Bilateral knee involvement was recorded in 84 participants (70.0%). Hypertension and diabetes mellitus were present in 48 (40.0%) and 32 (26.7%) participants, respectively. The mean knee pain score was 6.20 ± 1.70 (Table 1).
Table 1 Demographic and Clinical Characteristics of Participants (N = 120)
Characteristic Value
Age, years, M ± SD 58.40 ± 9.20
Age group, n (%)
40–49 years 22 (18.3)
50–59 years 43 (35.8)
60–69 years 39 (32.5)
≥70 years 16 (13.3)
Sex, n (%)
Male 42 (35.0)
Female 78 (65.0)
Body mass index, kg/m², M ± SD 28.10 ± 4.30
Symptom duration, years, median (IQR) 4.0 (2.0–7.0)
Bilateral knee involvement, n (%) 84 (70.0)
Hypertension, n (%) 48 (40.0)
Diabetes mellitus, n (%) 32 (26.7)
Knee pain score (0–10), M ± SD 6.20 ± 1.70
Note.N = total sample size; n = frequency; M = mean; SD = standard deviation; IQR = interquartile range. Percentages may differ slightly from 100% due to rounding.
Vitamin D Status
The mean serum 25-hydroxyvitamin D concentration was 20.11 ± 9.31 ng/mL. Vitamin D deficiency was identified in 66 participants (55.0%), insufficiency in 34 (28.3%), and sufficiency in 20 (16.7%). The mean concentrations for these categories were 13.20 ± 3.80, 24.30 ± 2.70, and 35.80 ± 4.90 ng/mL, respectively (Table 2).
Table 2 Distribution of Participants According to Serum Vitamin D Status (N = 120)
Vitamin D status 25(OH)D threshold n (%) 25(OH)D, M ± SD (ng/mL)
Deficient <20 ng/mL 66 (55.0) 13.20 ± 3.80
Insufficient 20–<30 ng/mL 34 (28.3) 24.30 ± 2.70
Sufficient ≥30 ng/mL 20 (16.7) 35.80 ± 4.90
Total — 120 (100.0) 20.11 ± 9.31
Note.25(OH)D = 25-hydroxyvitamin D; M = mean; SD = standard deviation; n = frequency. Percentages are based on N = 120.
Radiographic Severity of Knee Osteoarthritis
Kellgren–Lawrence grade III was the most frequent radiographic category (48 participants; 40.0%). Grade II occurred in 42 participants (35.0%), and grade IV in 30 (25.0%) (Table 3).
Table 3 Distribution of Radiographic Severity of Knee Osteoarthritis (N = 120)
Kellgren–Lawrence grade n %
Grade II 42 35.0
Grade III 48 40.0
Grade IV 30 25.0
Total 120 100.0
Note.n = number of participants. Grade IV indicates severe radiographic osteoarthritis.
Association Between Vitamin D Status and Radiographic Severity
Serum vitamin D status was significantly associated with radiographic severity (χ²(4) = 24.88, p < .001). Grade IV disease occurred in 26 of 66 deficient participants (39.4%), compared with 2 of 34 insufficient participants (5.9%) and 2 of 20 sufficient participants (10.0%). Grade II disease occurred in 18.2%, 52.9%, and 60.0% of these groups, respectively. (Table 4).
Table 4 Association Between Serum Vitamin D Status and Radiographic Severity of Knee Osteoarthritis (N = 120)
Vitamin D status Grade II, n (%) Grade III, n (%) Grade IV, n (%) Total, n
Deficient 12 (18.2) 28 (42.4) 26 (39.4) 66
Insufficient 18 (52.9) 14 (41.2) 2 (5.9) 34
Sufficient 12 (60.0) 6 (30.0) 2 (10.0) 20
Total 42 (35.0) 48 (40.0) 30 (25.0) 120
Note.Individual category percentages are calculated within rows; total-row percentages use N = 120. Pearson’s χ²(4, N = 120) = 24.88, p < .001.
Association Between Vitamin D Deficiency and Grade IV Knee Osteoarthritis
When participants with vitamin D insufficiency and sufficiency were combined, grade IV disease occurred in 26 of 66 participants with deficiency (39.4%) and 4 of 54 without deficiency (7.4%). The absolute prevalence difference was 32.0 percentage points. This unadjusted association was statistically significant (χ²(1) = 16.21, p < .001; Table 5).
Table 5 Association Between Vitamin D Deficiency and Grade IV Knee Osteoarthritis (N = 120)
Vitamin D category Grade IV, n (%) Grades II–III, n (%) Total, n
Deficiency present 26 (39.4) 40 (60.6) 66
Deficiency absent 4 (7.4) 50 (92.6) 54
Total 30 (25.0) 90 (75.0) 120
Note.Percentages are calculated within rows. Deficiency was defined as serum 25(OH)D <20 ng/mL. Grade IV indicates severe radiographic disease. Pearson’s χ²(1, N = 120) = 16.21, p < .001.
DISCUSSION
The present study examined the association between serum vitamin D status and radiographic severity of knee osteoarthritis among 120 adults. Vitamin D deficiency was observed in 55.0% of participants and was significantly associated with greater radiographic severity. Grade IV osteoarthritis was present in 39.4% of participants with vitamin D deficiency compared with 7.4% of those without deficiency. The association between vitamin D status and Kellgren–Lawrence grading was statistically significant (χ² = 24.88; p < 0.001). These findings suggest that reduced serum vitamin D concentrations are associated with more advanced radiographic changes in knee osteoarthritis. However, the cross-sectional nature of the study limits conclusions regarding causality or disease progression.
The findings are consistent with several observational studies investigating the relationship between vitamin D deficiency and knee osteoarthritis. McAlindon et al., in the Framingham Study, reported that lower serum vitamin D concentrations and reduced dietary vitamin D intake were associated with progression of established knee osteoarthritis.[5] Similarly, the Rotterdam Study investigated the relationship between vitamin D status, bone mineral density, and radiographic knee osteoarthritis, highlighting the potential involvement of skeletal and metabolic factors in disease development.[6] Ding et al. also reported an association between lower serum vitamin D levels and increased knee cartilage loss among older adults.[7] These observations support the biological relevance of vitamin D in joint health. However, unlike these longitudinal investigations, the present study evaluated radiographic severity at a single point in time and therefore cannot determine whether vitamin D deficiency preceded structural joint changes.
Despite these findings, the relationship between vitamin D status and knee osteoarthritis remains controversial. Felson et al., in two longitudinal studies, found no significant association between low vitamin D concentrations and worsening knee osteoarthritis.[8] Differences in study populations, baseline disease characteristics, vitamin D assessment methods, and radiographic outcome measures may explain variations across studies. In the present study, grade IV osteoarthritis was more frequent among participants with vitamin D deficiency than among those with insufficient or sufficient vitamin D levels. However, the prevalence of grade IV disease was slightly higher in the vitamin D-sufficient group (10.0%) than in the insufficient group (5.9%), indicating the absence of a consistent dose–response relationship across all vitamin D categories. The relatively small number of participants in the sufficient group also limits interpretation of these differences.
Evidence from randomised controlled trials further highlights the complexity of this association. McAlindon et al. reported that vitamin D supplementation did not significantly improve knee pain or reduce cartilage volume loss over a two-year follow-up period.[9] Similarly, Jin et al. found no significant benefit of vitamin D supplementation on tibial cartilage volume or knee pain among patients with symptomatic knee osteoarthritis.[10] The VIDEO trial also reported no significant reduction in radiographic joint-space narrowing following vitamin D supplementation.[11] These findings indicate that an association between vitamin D deficiency and radiographic severity does not necessarily establish a therapeutic benefit of supplementation in modifying osteoarthritis progression. Nevertheless, identifying and appropriately managing vitamin D deficiency remains relevant to overall musculoskeletal health.
Several factors may influence the relationship between vitamin D status and radiographic severity. Advancing age, obesity, reduced physical activity, limited sunlight exposure, and associated metabolic disorders may contribute to lower vitamin D concentrations and greater osteoarthritis severity. Patients with advanced knee osteoarthritis may also experience restricted mobility and reduced outdoor activity, potentially contributing to lower vitamin D levels. Consequently, reverse causation and residual confounding cannot be excluded. Furthermore, radiographic severity does not always correspond directly with pain intensity or functional impairment, emphasising the importance of evaluating both structural and clinical outcomes. [1,2]
The present study contributes to the understanding of the association between serum vitamin D status and radiographic knee osteoarthritis in a hospital-based population. The significantly higher proportion of grade IV disease among vitamin D-deficient participants highlights the importance of further investigating metabolic and nutritional factors in osteoarthritis. However, the observed associations were unadjusted, and the potential influence of age, sex, obesity, comorbidities, and lifestyle factors should be considered when interpreting the findings. Future prospective studies with larger sample sizes, standardised biochemical and radiographic assessments, and appropriate multivariable analyses are warranted to clarify the temporal relationship between vitamin D deficiency and osteoarthritis severity.[14]
LIMITATIONS
The present study has certain limitations. Its single-centre, hospital-based design and relatively small sample size of 120 participants may limit the generalisability of the findings. The cross-sectional design prevents determination of causal or temporal relationships between vitamin D deficiency and radiographic severity. Potential confounding factors, including sunlight exposure, dietary vitamin D intake, supplementation, seasonal variations, and physical activity, were not evaluated in detail. Furthermore, the absence of multivariable adjustment for age, sex, body mass index, and associated comorbidities limits interpretation of vitamin D deficiency as an independent factor associated with disease severity. Larger multicentre prospective studies are recommended to confirm these findings.
CONCLUSION
The present study found a statistically significant association between vitamin D deficiency and greater radiographic severity of knee osteoarthritis among 120 adults. Vitamin D deficiency was observed in 55.0% of participants, while grade IV osteoarthritis was more frequent among vitamin D-deficient participants (39.4%) than among those without deficiency (7.4%). These findings suggest that reduced serum vitamin D levels are associated with advanced radiographic changes in knee osteoarthritis. However, the cross-sectional design does not establish a causal relationship or demonstrate that vitamin D supplementation can prevent disease progression. Further large-scale prospective studies are required to clarify the clinical significance of this association and evaluate the potential role of vitamin D status in osteoarthritis management.
REFERENCES
1. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745-59. PMID: 31034380.
2. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185-99. PMID: 23337796.
3. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81. PMID: 17634462.
4. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30. PMID: 21646368.
5. McAlindon TE, Felson DT, Zhang Y, Hannan MT, Aliabadi P, Weissman B, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. 1996;125(5):353-9. PMID: 8702085.
6. Bergink AP, Uitterlinden AG, Van Leeuwen JP, Buurman CJ, Hofman A, Verhaar JA, et al. Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: the Rotterdam Study. J Clin Rheumatol. 2009;15(5):230-7. PMID: 19654490.
7. Ding C, Cicuttini F, Parameswaran V, Burgess J, Quinn S, Jones G. Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study. Arthritis Rheum. 2009;60(5):1381-9. PMID: 19404958.
8. Felson DT, Niu J, Clancy M, Aliabadi P, Sack B, Guermazi A, et al. Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies. Arthritis Rheum. 2007;56(1):129-36. PMID: 17195215.
9. McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. 2013;309(2):155-62. PMID: 23299607.
10. Jin X, Jones G, Cicuttini F, Wluka A, Zhu Z, Han W, et al. Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis: a randomized clinical trial. JAMA. 2016;315(10):1005-13. PMID: 26954409.
11. Arden NK, Cro S, Sheard S, Doré CJ, Bara A, Tebbs SA, et al. The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. Osteoarthritis Cartilage. 2016;24(11):1858-66. PMID: 27264058.
12. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29(8):1039-49. PMID: 3741515.
13. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494-502. PMID: 13498604.
14. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296. PMID: 17941714.
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