Magnesium Oral Supplementation for Acute Non-specific Low Back Pain
Magnesium Oral Supplementation for Acute Non-specific Low Back Pain
Acute non-specific low back pain (LBP) is one of the most common complaints at the emergency
 department. It is more prevalent in countries with high-income economies, where 60-80% of the
 population report back pain at some point in their life. Numerous medication options are
 available for acute LBP relief such as non-steroid anti-inflammatory drugs (NSAIDs),
 myorelaxant drugs, opioids, and benzodiazepines. Magnesium is a physiological
 voltage-dependent blocker of N-methyl-D-aspartate NMDA)-coupled channels that can influence
 inflammatory pain and neuropathic pain through several different mechanisms. In this study
 the investigators aimed to investigate the effect of magnesium oral supplementation for acute
 low back pain.
This study was conducted at our emergency department between June 2018 and March 2020 after
 receiving approval from our institutions' ethics committee (2018/1330). This study was
 registered as a randomized controlled trial with the US National Institute of Health
 (clinical trials.gov). We conducted a three-arm, prospective randomized open label clinical
 trial to compare isolated NSAID group, NSAID with paracetamol group and NSAID with oral
 magnesium supplementation group (described below) for treatment of acute LBP. Patients were
 included after providing informed consent predicated on their understanding of expected
 complications and treatment outcomes. Consolidate Standards of Reporting Trials (CONSORT)
 guidelines were followed reporting the results of the study Patients from a single university
 hospital were recruited for this study between June 2018 and March 2020. Inclusion criteria
 were defined as (1) age>18 years old, (2) duration of symptoms <2 weeks and (3) functionally
 impairing LBP which we defined as a score of > 5 on Roland-Morris Disability Questionnaire
 (RMDQ).

 Exclusion criteria included (1) age>65 years old, (2) history of trauma, (3) presence of
 radicular pain physical examination which was defined as pain radiating below the gluteal
 folds, (4) history of primary vertebral tumor or metastasis, (4) patients who were pregnant
 or lactating, (5) presence of any contraindication or allergy to investigational medications,
 (6) history of chronic analgesic use, (7) history of autoimmune diseases or inflammatory
 rheumatic disorders, (8) history of cardiopulmonary restrictions, severe kidney or liver
 function disorders and (9) history of prior surgery of lumbar spine.

 We based our sample size calculation assumptions on a recently published clinical trial [11]
 and widely accepted minimum clinically important improvement of 5 points on the RMDQ.(14)
 With alpha and beta values were set at 0.05 and 0.20 respectively, sample size calculation
 revealed that 50 patients were needed in each study group. To account for protocol
 violations, lost-to-follow-up and to ensure sufficient power for the intention to treat
 analysis (in previous work, up to 1/3 of enrolled patients did not use the investigational
 medication), we enrolled 80 patients for each group.

 A computer generated random list was established with an online sequencer
 (www.random.org/sequences) according to which participants were randomly assigned to one of
 three study groups with 1:1:1 allocation ratio. Group A included isolated NSAID treatment and
 received 400 mg etodolac twice a day. Group B included NSAID and magnesium treatment and
 received a combination of 400 mg etodolac twice a day with 365 mg oral magnesium
 supplementation once a day. Group C included NSAID and paracetamol treatment and combination
 of 400 mg etodolac twice a day with 500 mg paracetamol twice a day was administered to the
 participants of this group (Figure-1). We effort to prevent the placebo effect by comparing
 the NSAID + magnesium therapy with both a NSAID plus paracetamol therapy and an isolated
 NSAID therapy. Treatment was performed by two authors (S.B and K.Ş) and patients were
 followed-up by same authors throughout the study. External medication was not allowed with
 the exception of topical analgesics. Patients who received any intravenous or intramuscular
 analgesia during the treatment period were excluded from study. Co-medications for any
 accompanying chronic condition (diabetes, hypertension etc.) were unchanged.

 Clinical evaluation of participants was performed at first admission to emergency department,
 at 4th and 10th days after the initiation of designated treatment. Outcome measures included
 pain, mobility of lumbar spine and functional outcome. Pain intensity was assessed using a
 visual analogue scale (VAS). Lumbar spine mobility was assessed using the "finger to floor"
 test. Participants were asked to stand on erect posture with knees extended and then to bend
 forward in an attempt to reach for the floor with their fingertips without losing knee
 extension. Distance between patient's fingertips and the floor was then measured with a
 measuring tape. Functional outcome was evaluated with Roland-Morris Disability Questionnaire
 (RMDQ) score. RMDQ is a 24-item LBP functional scale and is recommended for research
 purposes. Higher scores signify greater low back-related functional impairment. An
 improvement of 5 points was considered clinically significant.
Inclusion Criteria:

 -  patients aged>18 years old,

 -  initiation of acute low back pain in the 10 days prior to study entry and functionally
 impairing low back pain, which we defined as a score of > 5 on the Roland-Morris
 Disability Questionnaire (RMDQ).

 Exclusion Criteria:

 -  aged>65 years old,

 -  history of trauma,

 -  radicular pain, which we defined as pain radiating below the gluteal folds,

 -  history of vertebral tumor or metastasis,

 -  patients who were pregnant or lactating,

 -  unavailable for follow-up,

 -  with allergy or contraindication to the investigational medications,

 -  chronic analgesic use,

 -  autoimmune diseases or inflammatory rheumatic disorders,

 -  cardiopulmonary restrictions,

 -  severe kidney or liver function disorders and prior surgery on the lumbar spine.