Vitamin D Supplementation for Nonspecific Musculoskeletal Pain in Non-Western Immigrants: A Randomized Controlled Trial

The use of vitamin D in non-Western vitamin D-deficient immigrants with non-specific musculoskeletal pain is a topical issue for research. We are pleased, therefore, to read the interesting study by Schreuder and colleagues (Schreuder et al., 2012). Study participants with vitamin D deficiency were appropriately chosen as their baseline pain scores were high, giving sensitivity to detect a clinically meaningful pain relief.

Schreuder et al. state that "Patients in the vitamin D group were significantly more likely than their counterparts in the placebo group to report pain relief 6 weeks after treatment (34.9% vs 19.5%, P = .04)." and conclude "There is a small positive effect 6 weeks after high-dose vitamin D3 on persistent nonspecific musculoskeletal pain".

There are several reasons to be cautious about this result. The conclusion is based on small numbers, using an outcome of 'any improvement'. Small studies are highly susceptible to the random play of chance, and large studies are needed to be confident in small treatment effects (Moore et al., 2010). Schreuder and colleagues "defined treatment success as any improvement in reported pain (either "much less pain" or "less pain")" over 6 weeks. Using this outcome, especially over a comparatively short duration, may be problematic. In fibromyalgia, shorter study duration and the use of 'any improvement' as an outcome overestimated the treatment effect compared with longer duration and using higher levels of response (Straube et al., 2010). We think this may be generally applicable to chronic pain trials. We and others have recently argued for the clinically meaningful, but more difficult to achieve, responder outcomes of 'at least 30% pain relief' and, especially, 'at least 50% pain relief' over baseline (Moore et al., 2010; Dworkin et al., 2008).

Indeed, when improvement is defined as "much less pain" in the data presented by Schreuder and colleagues, few patients achieved it (2/44 with vitamin D and 1/40 with placebo, over 6 weeks; see Table 3 in Schreuder et al., 2012). It is difficult to see a clinically relevant benefit of vitamin D treatment based on these data. A meaningful benefit with vitamin D supplementation is further questioned by the absence of a statistically significant improvement in pain scores when these were measured on the visual analogue scale.

Schreuder and colleagues conclude that "future investigation should involve greater numbers of participants and focus on longer follow-up, higher supplementation doses, and mental health." We would like to add the use of responder outcomes such as 'at least 50% pain relief'. This will ensure that the benefit measured is clinically meaningful.

References

1. Schreuder F, Bernsen RM, van der Wouden JC. Vitamin D supplementation for nonspecific musculoskeletal pain in non-Western immigrants: a randomized controlled trial. Ann Fam Med. 2012;10(6):547- 555.

2. Moore RA, Eccleston C, Derry S, Wiffen P, Bell RF, Straube S, McQuay H; ACTINPAIN Writing Group of the IASP Special Interest Group on Systematic Reviews in Pain Relief; Cochrane Pain, Palliative and Supportive Care Systematic Review Group Editors. "Evidence" in chronic pain-establishing best practice in the reporting of systematic reviews. Pain. 2010;150(3):386-389.

3. Straube S, Derry S, Moore RA, Paine J, McQuay HJ. Pregabalin in fibromyalgia-responder analysis from individual patient data. BMC Musculoskelet Disord. 2010;11:150.

4. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105-121.

Competing interests:   None declared