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What are the characteristics of vitamin D metabolism in opioid dependence? An exploratory longitudinal study in Australian primary care
  1. Albert Stuart Reece1,
  2. Gary Kenneth Hulse2,3
  1. 1 Department of Psychiatry and Clinical Neurosciences, University of Western Australia, Brisbane, Queensland, Australia
  2. 2 Department of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Queensland, Australia
  3. 3 Psychiatry, Edith Cowan University at Joondalup, Western Australia, Australia
  1. Correspondence to Dr Albert Stuart Reece; sreece{at}


Objective Compare vitamin D levels in opioid dependence and control population and adjust for relevant confounding effects. Nuclear hormone receptors (including the vitamin D receptor) have been shown to be key transducers and regulators of intracellular metabolism and comprise an important site of pathophysiological immune and metabolic dysregulation potentially contributing towards pro-ageing changes observed in opioid-dependent patients (ODPs).

Design Longitudinal prospective comparing ODPs with general medical controls (GMCs).

Setting Primary care.

Participants Prospective review comparing 1168 ODP (72.5% men) and 415 GMC (51.6% men, p<0.0001). Mean ages were 33.92±0.31 (mean±SEM) and 41.22±1.32 years, respectively (p<0.0001). Opioid use in the ODP has been previously reported and shown to be typical.

Interventions Nil. Observational study only.

Primary and secondary outcomes Serum vitamin D levels and relevant biochemical parameters.

Results Vitamin D levels were higher in the ODP (70.35±1.16 and 57.06±1.81 nmol/L, p<0.0001). The difference in ages between the two groups was handled in an age-matched casecontrol subanalysis and also by multiple regression. Sexes were analysed separately. The age:status (or age:time:status) was significant in casecontrol, cross-sectional and longitudinal analyses in both sexes (p<0.05). Modelled vitamin D was 62.71 vs 57.81 nmol/L in the two groups. Time-dependent mixed-effects models quadratic in age outperformed linear-only models (p=0.0377). ODP vitamin D was shown to vary with age and to correlate with alanine aminotransferase establishing it as a biomarker of age in this group. Hepatitis C seronegativity was significant in regression models (from p=0.0015).

Conclusion Vitamin D was higher in ODP in both sexes in bivariate, cross-sectional, casecontrol and longitudinal analyses and was robust to the inclusion of metabolic and immune biomarkers. That Hepatitis C seronegativity was significant suggests opioid dependence has an effect beyond simply that of its associated hepatitides. This finding may relate to the accelerated ageing process previously described in opioid dependence.

  • vitamin D
  • biomarker
  • ageing
  • opioid dependence
  • heroin

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  • Contributors ASR: designed the study, performed the analysis, prepared the figures and wrote the first draft of the paper. GKH: wrote and the final draft and assisted with the statistical analysis.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was given ethical approval by the Human Research Ethics Committee of the Southcity Medical Centre which has been accredited by the National Health and Medical Research Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data for this paper may be obtained from the authors upon specific request.

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