Relationship Between Serum Vitamin D Levels and Musculoskeletal Adverse Effects in Patients Using Isotretinoin

Isotretinoin (ISO) has been used in the treatment of patients with severe acne vulgaris (AV) that is resistant to standard therapy with systemic antibiotics and topical agents, over the last few decades. There are various side effects of ISO in the skeletal system.

This study investigate the relationship between ISO-induced musculoskeletal adverse effects and serum 25 hydroxy (OH) vitamin D levels in patients with acne vulgaris.

The rheumatic side effects are the most common one which are musculoskeletal pains and arthralgia, seen over of the 16% patients receiving ISO. Mild, transient myalgias and arthralgias are very common and do not require cessation of the drug. The other musculoskeletal side effects of ISO are calcification of tendon and ligaments, hyperostosis of the spine (DISH syndrome), elevated creatine phosphokinase and cramps. There are many case reports related with ISO-induced sacroiliitis in the literature, mostly recent years.

The association between ISO and vitamin D levels has been evaluated with several studies in the literature17,18,19. However, the relationship between ISO-induced musculoskeletal side effects in AV patients and serum vitamin D levels has not been investigated until now. To the best our knowledge, this is the first study to evaluate the relationship between the serum vitamin D levels and the musculoskeletal side effects related with ISO in AV patients.

In this study, 87 patients receiving ISO for AV and had ISO-induced musculoskeletal side effects, were enrolled as adverse effect (AE) group. The control (C) group was consisted of age- and sex-matched 90 consecutive patients using ISO but had no musculoskeletal symptoms.

The participants was assessed in aspect of musculoskeletal symptoms such as arthralgia, low back pain, calsification of tendon and ligaments, polyneuropathy, hyperostoses of the spine (DISH syndrome), myalgia, cramps and sacroiliitis. It was queried that whether myalgia, arthralgia, low back pain or sacroiliitis has occurred after ISO treatment. Serum 25 (OH) vitamin D levels were measured in all participants. According to these results, patients in AE group were divided into three subgroups in aspect of the serum vitamin D levels. Patients with serum 25 (OH) vitamin D level is lower than 10 ng/ml, was recruited as Group I, between 10-20 ng/ml, as Group II, higher than 20 ng/ml as Group III.

Eligibility Criteria:
Inclusion Criteria:

* ISO at a dose of 0.5-1 mg/kg/day for at least 3 months,
* not to use vitamin D and/or calcium supplements for the last three months
* to be older than 18 years.

Exclusion Criteria:

* Patients who had renal, gastroenteritis, skeletal, psychiatric, hematological, endocrine disorders related with thyroid and bone metabolism
* Patients receiving drugs such as diuretics, multivitamins, anticonvulsants, glucocorticoids, erythromycin, estrogen compound pills, alcohol, vitamin D and/or calcium preparats in the last three months,
* Malignancy,
* Chronic liver and kidney failure,
* History of psoralen and ultraviolet A (PUVA)
* Women waiting pregnancy.