Key Topics

• • Overview of musculoskeletal disorders
• • Common drugs used in the management of musculoskeletal disorders and their pharmacology
• • Implications for dentistry

Learning Objectives

• • To describe the pharmacological management of musculoskeletal disorders
• • To understand the main drug categories and describe their mechanism of action, indications and adverse effects
• • To understand the implications of dentistry

Introduction

Musculoskeletal disorders include a wide range of diseases such as osteoarthritis and rheumatoid arthritis as well as the spondyloarthropathies and gout. Although the aetiology and presentations vary, they all result in inflammation that leads to tissue damage.

Acute inflammation describes the rapid response of the innate immune system to a challenge. It comprises of a cellular component (leucocytes, macrophages, mast cells, natural killer cells and endothelial cells), plasma proteins (including the complement, coagulation, fibrinolytic and kinin systems) and mediators (such as histamine, eicosanoids, cytokines, chemokines and nitric oxide).

Inflammation becomes chronic when the initiating trigger is not eradicated or the individual exhibits a susceptibility to prolonging the inflammatory process. Chronic inflammatory conditions such as rheumatoid arthritis involve interaction between the innate and adaptive immune response. The adaptive immune response involves both T and B lymphocytes. It is highly specific, resulting in the production of antibodies to an antigen. In chronic inflammatory diseases this process may become self-perpetuating.

This chapter will consider the aetiopathogenesis of these musculoskeletal disorders followed by a consideration of the relevant therapeutic agents used to treat them.

Musculoskeletal disorders

The most common of these disorders are: osteoarthritis, rheumatoid arthritis, the spondyloarthropathies and gout. These will be discussed in turn.

Osteoarthritis

Osteoarthritis (OA) is the most common disease of synovial joints leading to pain and disability. It is the result of aging and trauma on bone and cartilage within the joint. By the age of 60 years approximately half of the population will be affected by OA, with weight bearing joints such as the hips and knees most commonly involved. Treatment is directed towards pain management and preventing disease progression. This involves a combination of drugs, physical interventions (e.g. weight loss), exercises, aids (e.g. walking sticks) and surgery if necessary. Simple analgesics such as paracetamol are the first-line therapy followed by non-steroidal anti-inflammatory drugs (NSAIDs). However intra-articular corticosteroids many be required for inflammatory exacerbations.

Rheumatoid arthritis

Rheumatoid arthritis (RA) affects 2–3% of the population with three times as many women affected as men. It is a systemic disease characterized by a symmetrical inflammatory deforming polyarthropathy in addition to many extra-articular manifestations. The peak age of onset is between 30 and 40 years. However, it can present at any age. The aetiology is most likely autoimmune. There is often a strong family history and an association with HLA-DR4.

It often initially affects the small joints of the hands and feet before progressing to involve larger joints. The joints become stiff and swollen, eventually this may lead to subluxation and deformities. This is the result of erosion of bone, cartilage and tendons by an inflammatory pannus comprising of T lymphocytes and polymorphonuclear leucocytes leading to chronic synovitis.

RA management includes exercise and physiotherapy to maintain function and prevent deformities. Surgery may be required to correct deformities. Drug treatment aims to control symptoms and modify the underlying inflammatory process. Simple analgesics and NSAIDs are widely used in addition to disease-modifying anti-rheumatoid drugs (DMARDs) such as sulfasalazine, methotrexate and azathioprine. Patients with moderate to severe disease now often progress to the use of cytokine inhibitors such as infliximab and adalimumab or TNF α blockers such as etanercept.

The spondarthropathies

Spondyloarthropathies include a number of diseases such as ankylosing spondylitis, reactive arthritis, enteropathic arthropathies, psoriatic arthritis and juvenile chronic arthritis. There is often a strong family history as well as an association with HLA-B27.

Ankylosing spondylitis:

This typically affects young men. It presents with sacroiliitis causing pain in the buttocks which radiates down the back of the legs. This leads to spinal fusion with limitation of movement, low back pain and morning stiffness.

Psoriatic arthritis:

This occurs in 10% of patients with psoriasis affecting the small joints of the hands asymmetrically. Treatment includes analgesics and often immunosuppressant drugs.

Enteropathic arthropathy:

This occurs in patients with inflammatory bowel disease. It typically affects the knees and ankles as a monoarthritis or asymmetrical oligoarthritis. Management involves treating the underlying inflammatory bowel disease.

Gout

Gout is a crystal arthropathy arising from the deposition of sodium urate crystals in joints and soft tissue due to an abnormality of uric acid metabolism. There is either an overproduction or underexcretion of uric acid resulting in hyperuricaemia. There are many causes including idiopathic, drugs, renal impairment, hypertension and alcohol.

Acute attacks usually present as a red, hot, swollen and painful first toe although it can also affect the ankle, wrist or knee. This can lead to joint erosions and deformity and chronic tophaceous gout in which there is deposition of urate in the soft tissues and around joints.