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

The Relationship Between Serum 25 Hydroxy Vitamin D Levels and Musculoskeletal Adverse Effects in Patients With Acne Vulgaris Using Isotretinoin: A Cross-sectional Controlled Study

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.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Isotretinoin Adverse Reaction; Musculoskeletal Disease Other
• Intervention / Treatment: Drug: Isotretinoin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06230
    • Ankara Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isotretinoin-induced adverse effect group; Patients receiving isotretinoin with dose of 0.5-1 mg/kg/day and had musculoskeletal adverse effects	Drug: Isotretinoin; ISO; Other Names: Isotretinoin capsules
Active Comparator: Control group; Pateients receiving isotretinoin with dose of 0.5-1 mg/kg/day had no musculoskeletal adverse effects	Drug: Isotretinoin; ISO; Other Names: Isotretinoin capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Musculoskeletal adverse effects in isotretinoin receiving patients	Locomotor system examination of the participants will perform by the same clinician.The participants were assessed in aspect of musculoskeletal symptoms such as arthralgia, low back pain, calcification of tendon and ligaments, polyneuropathy, hyperostoses of the spine (DISH syndrome), myalgia, cramps and sacroiliitis	2 days
Serum 25 hydroxy vitamin D level	serum vitamin d levels will measure in two groups.	7 days

Collaborators and Investigators

• Sponsor: Ankara Training and Research Hospital
• Investigators: Principal Investigator: Cevriye Mülkoğlu, Ankara Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): August 15, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: D014807; D02.455.326.271.665.202.495.325; C17.800.030.150
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Musculoskeletal Diseases; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: AnkaraTRH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No