International Journal of Endocrinology / 2015 / Article / Tab 3

Review Article

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.

ReferenceYearCountryStudy designCondition of samplesSamplesAge (years)Females (%)ControlsAge (yrs)% femaleVitamin D assayFollow-upResults

Development and progression Lane et al. [11]1999USACase-cohort longitudinalParticipants of the Study of Osteoporotic Fractures (SOF)237>65100N/ARadioimmunoassay8 yrsLow 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]1996USAProspective observational studyParticipants of the Framingham Study55670.3 ± 4.5N/ACompetitive protein-binding assay8 yrsLow 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]2014FinlandLongitudinal cohortNo hip or knee OA at baseline527430–9954.1N/A10 yrsLow 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]2010USALongitudinal cohortParticipants of the Osteoporotic Fractures in Men Study (MrOS)110477.2 ± 5.30N/AMS4.6 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]2013EgyptCross-sectionalPostmenopausal + clinically diagnosed knee OA3654.7 ± 3.21001025.8 ± 20HPLCN/A↓ 25(OH)D levels are associated with newly diagnosed OA in postmenopausal Egyptian women
Heidari et al. [16]2011IranCross-sectionalKnee OA (ACR Criteria)14860.2  ± 12.915060.1  ± 10.2ELISAN/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]2009NetherlandsProspective population-based cohort studyParticipants of the Rotterdam Study124866.2 ± 6.758.3N/ARadioimmunoassay6.5 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]2009AustraliaCohort study, cross-sectional and longitudinalParticipants of the Tasmanian Older Adult Cohort Study (TASOAC); did not have RA100251–7950N/ARadioimmunoassay2.9 yrsBaseline 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]2007USA2 longitudinal cohort studiesParticipants of the Framingham Study715Framingham: 53.1 ± 8.753.1N/ARadioimmunoassay9.5 yrsBaseline 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
277BOKS: 41.4N/ARadioimmunoassay30 moBaseline 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 functionMuraki et al. [20]2011UKCross-sectional, cohort studyParticipants of the Hertfordshire Cohort Study78765.6 ± 2.749.5Chemiluminescent25(OH)D ≠ knee ROA
↑ Vit D = ↑ knee pain
Fok1 VDR polymorphism = knee ROA and pain
Laslett et al. [21]2014AustraliaLongitudinal population-based cohort study76962.1 ± 7.050.5N/ARadioimmunoassay5 yrsVit 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]2013TurkeyProspective cohortKnee OA (ACR Criteria)7448.70 ± 7.1467.67037HPLC~6 moNo correlation between Vit D status and WOMAC or VAS
Al-Jarallah et al. [23] 2011KuwaitCross-sectionalPrimary knee OA9956.49 ± 9.1291N/ARadioimmunoassayN/AMost knee OA patients were Vit D def.
25(OH)D ≠ OA severity (radiographic) or functional assessment

BMD and body compositionBischoff-Ferrari et al. [24]2005USAPopulation-based cohortPrimary knee OA (Framingham Study)22874.4 ± 11.164N/ARadioimmunoassay 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]2012DenmarkProspective cohort studyKnee OA + obese (BMI >30 kg/m2)17562.6 ± 6.381N/AMicroparticle chemiluminescence immunoassay16 weKnee OA patients on a formula diet had ↑ Vit D levels and BMD
Hunter et al. [26]2003UKCross-sectional twin studyParticipants of St. Thomas’ UK Adult Twin Registry164424–79100N/ARadioimmunoassayN/AKnee OA patients have ↓ Vit D levels
Vit D levels ≠ osteophytes
Barker et al. [27]2014USACross-sectionalKnee OA5648 ± 155N/AChemiluminescent immunoassayN/AVit 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.

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