Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives

Table 3

Summary of studies in the relationships between vitamin D levels and aspects of osteoarthritis.

Reference

Year

Country

Study design

Condition of samples

Samples

Age (years)^†

Females (%)

Controls

Age (yrs)

% female

Vitamin D assay

Follow-up

Results

Development and progression

Lane et al. [11]

1999

USA

Case-cohort longitudinal

Participants of the Study of Osteoporotic Fractures (SOF)

237

>65

100

N/A

—

—

Radioimmunoassay

8 yrs

Low 25(OH)D = 3x as likely to develop hip OA (JSN); Low 25(OH)D ≠ osteophyte growth defined hip OA; No association between 1,25(OH)2D3 and hip OA

McAlindon et al. [12]

1996

USA

Prospective observational study

Participants of the Framingham Study

556

70.3 ± 4.5

—

N/A

—

—

Competitive protein-binding assay

8 yrs

Low intake and serum Vit D ≠  ↑ risk for progression of knee OA; Vit D positively correlated with BMD, Vit D intake, and physical activity; Vit D inversely correlated with BMI; Low Vit D = increased risk of knee OA; Vit D levels predict osteophyte growth and cartilage loss (less so)

Konstari et al. [13]

2014

Finland

Longitudinal cohort

No hip or knee OA at baseline

5274

30–99

54.1

N/A

—

—

10 yrs

Low 25(OH)D ≠ development of hip or knee OA; Baseline 25(OH)D was associated with known risk factors of OA except for traumatic injury

Chaganti et al. [14]

2010

USA

Longitudinal cohort

Participants of the Osteoporotic Fractures in Men Study (MrOS)

1104

77.2 ± 5.3

0

N/A

—

—

MS

4.6 yrs

↑ 25(OH)D levels = ↓ prevalence of radiographic hip OA; Vit D insufficient men (levels of 25[OH]D 15.1–30 ng/mL) = 2-fold ↑ likelihood of prevalent radiographic hip OA compared with Vit D sufficient men

Abu El Maaty et al. [15]

2013

Egypt

Cross-sectional

Postmenopausal + clinically diagnosed knee OA

36

54.7 ± 3.2

100

10

25.8 ± 2

0

HPLC

N/A

↓ 25(OH)D levels are associated with newly diagnosed OA in postmenopausal Egyptian women

Heidari et al. [16]

2011

Iran

Cross-sectional

Knee OA (ACR Criteria)

148

60.2  ± 12.9

—

150

60.1  ± 10.2

—

ELISA

N/A

↓ 25(OH)D in OA than control (NS); High prevalence rate of serum 25-OHD deficiency; Significant positive association between serum 25(OH)D deficiency and knee OA in a subgroup of patients aged <60 years, greater association in younger patients

Bergink et al. [17]

2009

Netherlands

Prospective population-based cohort study

Participants of the Rotterdam Study

1248

66.2 ± 6.7

58.3

N/A

—

—

Radioimmunoassay

6.5 yrs

↓ Dietary intake of vitamin D = ↑ knee ROA; ↓ 25(OH)D = ↑ risk of progressive ROA, not in confounding factor adjusted results (including age, sex, BMD, smoking, JSN, fall tendency, health status, disability index, and caloric intake); ↓ Baseline BMD patients: ↓ 25(OH)D (serum and intake) = ↑ incidence of knee ROA

Ding et al. [18]

2009

Australia

Cohort study, cross-sectional and longitudinal

Participants of the Tasmanian Older Adult Cohort Study (TASOAC); did not have RA

1002

51–79

50

N/A

—

—

Radioimmunoassay

2.9 yrs

Baseline Vit D insuff. = ↓ knee cartilage (medial and lateral tibial sites), regardless of sex, ROA status, and knee pain; Baseline Vit D levels predicted changes in medial and lateral tibial cartilage volume; ↑ Serum 25(OH)D levels = ↑ knee tibial cartilage volume in older people, particularly in females, ROA patients, and those with knee pain; Vit D insuff. = moderate-to-severe JSN in older adults

Felson et al. [19]

2007

USA

2 longitudinal cohort studies

Participants of the Framingham Study

715

Framingham: 53.1 ± 8.7

53.1

N/A

—

—

Radioimmunoassay

9.5 yrs

Baseline Vit D ≠ radiographic worsening; ↑ Vit D = slightly ↑ rates of worsening (NS after adjustment for risk factors); Vit D def. = slight ↑ in risk of JSN (NS after adjustment for risk factors); ↓ Vit D = slight ↓ risk of osteophyte growth

277

BOKS:

41.4

N/A

—

—

Radioimmunoassay

30 mo

Baseline Vit D ≠ radiographic worsening; ↑ Vit D = ↑ risk of worsening; No Vit D def. = slight ↑ risk of JSN (NS after adjustment for risk factors); ↓ Vit D ≠ osteophyte growth; Vit D def. appears slightly protective against cartilage loss

Pain and function

Muraki et al. [20]

2011

UK

Cross-sectional, cohort study

Participants of the Hertfordshire Cohort Study

787

65.6 ± 2.7

49.5

—

—

—

Chemiluminescent

—

25(OH)D ≠ knee ROA; ↑ Vit D = ↑ knee pain; Fok1 VDR polymorphism = knee ROA and pain

Laslett et al. [21]

2014

Australia

Longitudinal population-based cohort study

769

62.1 ± 7.0

50.5

N/A

—

—

Radioimmunoassay

5 yrs

Vit D def. predicts knee pain over a 5-year period; Vit D def. may predict hip pain over 2.4 yrs

Yazmalar et al. [22]

2013

Turkey

Prospective cohort

Knee OA (ACR Criteria)

74

48.70 ± 7.14

67.6

70

37

HPLC

~6 mo

No correlation between Vit D status and WOMAC or VAS

Al-Jarallah et al. [23]

2011

Kuwait

Cross-sectional

Primary knee OA

99

56.49 ± 9.12

91

N/A

—

—

Radioimmunoassay

N/A

Most knee OA patients were Vit D def.; 25(OH)D ≠ OA severity (radiographic) or functional assessment

BMD and body composition

Bischoff-Ferrari et al. [24]

2005

USA

Population-based cohort

Primary knee OA (Framingham Study)

228

74.4 ± 11.1

64

N/A

—

—

Radioimmunoassay and competitive protein-binding assay

↑ Vit D status = ↑ BMD (femoral neck) in primary knee ROA independent of sex, age, BMI, physical activity, knee pain, and disease severity

Christensen et al. [25]

2012

Denmark

Prospective cohort study

Knee OA + obese (BMI >30 kg/m^2)

175

62.6 ± 6.3

81

N/A

—

—

Microparticle chemiluminescence immunoassay

16 we

Knee OA patients on a formula diet had ↑ Vit D levels and BMD

Hunter et al. [26]

2003

UK

Cross-sectional twin study

Participants of St. Thomas’ UK Adult Twin Registry

1644

24–79

100

N/A

—

—

Radioimmunoassay

N/A

Knee OA patients have ↓ Vit D levels; Vit D levels ≠ osteophytes

Barker et al. [27]

2014

USA

Cross-sectional

Knee OA

56

48 ± 1

55

N/A

—

—

Chemiluminescent immunoassay

N/A

Vit D def. = quadriceps dysfunction but ≠ inflammatory cytokines

† means at baseline in longitudinal studies. Vit D: vitamin D; ROA: radiographic osteoarthritis; ACR: American College of Rheumatology; NS: not statistically significant; BMI: body mass index; BMD: bone mineral density; HPLC: high performance liquid chromatography; ELISA: enzyme-linked immunosorbent assay; MS: mass spectrometry; Insuff.: insufficient; Def.: deficient; ↓: lower/decreased; ↑: higher/increased; ≠: no association; =: association; yrs: years; mo: months; we: weeks; JSN: joints space narrowing; N/A: not applicable.