Paracetamol Is Ineffective In The Treatment Of Low Back Pain

Paracetamol Is Ineffective In The Treatment Of Low Back Pain

Introduction:

Low back and neck pain (spinal pain) are leading causes of disability worldwide, and osteoarthritis of the hip or knee is the 11th highest contributor to global disability. Moreover, the point prevalence of spinal pain is 9.4%, and osteoarthritis affects nearly 4% of the global population.

Doctors prescribe NSAIDs

Prescription of drugs usually painkillers such as Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is the most common approach to treatment used by doctors for spinal pain and osteoarthritis. Guidelines consistently recommend the prescription of paracetamol (acetaminophen) as the first line analgesic for these conditions. Paracetamol is used to treat inflammatory pain and it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity (it is a weak COX inhibitor).

Paracetamol effects liver functioning

For paracetamol to shows its optimal effect one might require regular doses of up to 4000 mg/day. The amount is highly debated by the researchers, as it exposes the body to some serious side-effects, primarily in the liver functioning. Supratherapeutic doses of paracetamol can overwhelm the normal metabolic pathways and protective mechanisms in the liver and produce dangerous amounts of a toxic metabolite, N-acetyl-p-benzoquinoneimine. Moreover, working out a schedule for such a dosage will be a pain in itself. The metabolism of the body will never be able to flush paracetamol completely, adding more serious side-effects which might not even exist in literature.

Paracetamol

The National Institute for Health and Care Excellence (NICE), currently recommends paracetamol for both lower back pain and for osteoarthritis. Their decision to favour paracetamol is based on various previous clinical studies which report small effects of paracetamol compared with placebo.

Why this study?

As researchers correctly pointed out with a single word "uncertainty" in role of paracetamol in low back and neck pain, with various findings and recommendations, it was decided to review the efficacy and safety of paracetamol in patients with spinal pain or osteoarthritis of the hip or knee by including data from placebo controlled trials only, as these represent the highest standard of evidence to inform the optimal use of drugs.

Methodology:

A systematic electronic search in Medline, Embase, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials from inception to 8 December 2014, yielded 5498 records, and after excluding duplicates, researchers screened 4037 titles and abstracts. Two reviewers independently assessed the risk of bias of the included studies using the Cochrane Collaboration’s tool. Consensus and a third reviewer was used to resolve any disagreement.

Results:

Researchers found that here is “high quality” evidence suggesting paracetamol has a significant but small effect in patients with hip or knee osteoarthritis compared with placebo in the short term. The small effects, less than 4 points on a 0-100 point scale, are not likely to be meaningful for clinicians or patients. “High quality” evidence shows that paracetamol is ineffective for low back pain, but researchers found no trials investigating neck pain. In case of osteoarthritis, the value was found to be -3.7 points on a 0-100 pain scale. These results therefore provide an argument to reconsider the endorsement of paracetamol in clinical practice guidelines for low back pain and hip or knee osteoarthritis.

Exercise is better way to handle such pains

One more interesting finding that exercises (such as strengthening exercise) compared with no exercise control result in large treatment effects for pain reduction on lower limb osteoarthritis.

Article citation: Machado, G. C.; et. al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ 2015, 350, h1225. DOI: http://dx.doi.org/10.1136/bmj.h1225

Biomarkers of Early Stage Osteoarthritis, Rheumatoid Arthritis

Biomarkers of Early Stage Osteoarthritis, Rheumatoid Arthritis 

Musculoskeletal disease including osteoarthritis (OA) and rheumatoid arthritis (RA) is the most common cause of chronic disability worldwide and is increasingly important in current ageing populations. Severe life impairment may be prevented if decline in musculoskeletal health and development of OA and RA are identified and treated in the early stages.

An inexpensive, minimally invasive biochemical test which preferably detects and distinguishes common types of arthritis at the early stage is required. Magnetic resonance imaging (MRI) techniques have been developed for early-stage evaluation of cartilage damage in OA. MRI is an expensive technique and also not favoured by all. Early biochemical tests for detection of established RA were based on measurement of rheumatoid factor (RF) which in current form have reported sensitivity and specificity of 63% and 94% respectively for established or advanced disease. RF is often negative with eRA. The anti-cyclic citrullinated peptide (CCP) antibody test is used for early-stage detection of RA and has sensitivity of 61%. 

There is currently no simple biochemical test to detect early-stage osteoarthritis (eOA) and to discriminate different types of early-stage arthritis.

Tests for early-stage rheumatoid arthritis (eRA) such as RF and CCP antibodies require refinement to improve clinical utility. Researchers have developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline (Hyp) in body fluids. On correlating CP in the plasma of healthy subjects it was surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA.

A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.

        

The clinical presence of anti-CCP antibodies, antibodies which bind to synthetic cyclic citrullinated peptide, are considered to reflect immunogenicity of endogenous citrullinated proteins (CPs) but the diagnostic utility of CPs has hitherto been little explored. 

The researchers hypothesized that changes in plasma CP and Hyp, combined with anti-CCP antibody test, would provide improved diagnostic power over current standard techniques for diagnosis of early-stage arthritis.

The surprising and remarkable biochemical finding of this study is increased levels of plasma CP in eOA. Increased CP was found in serum of eRA but this was suspected with regard to the high prevalence of anti-CCP antibody positivity in eRA. Also remarkable was the higher CP concentration in plasma than in synovial fluid of patients with eOA and reversal of this in patients with aOA. Autoimmunity to CP is important in the pathogenesis of RA and underlies the diagnostic utility of anti-CCP antibody measurement for eRA5. We found high levels of serum CP in patients with eRA and association of this with anti-CCP antibodies, consistent with formation and immunogenicity of CPs.

Article citation: Ahmed, U.; et. al. Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health. Scientific Reports, 2015, 5, Article number: 9259 doi:10.1038/srep09259