Arthritis / Joint and Bone

What is gout?

Gout is caused by an excess of uric acid in the blood (hyperuricaemia) which forms crystals and these uric acid crystals are then deposited in the joints and tissues. Uric acid is a produced as a result of metabolism of purines, which are found in high protein foods like meat and fish. Excess uric acid is normally removed by the kidneys, however, if too much is produced or the kidneys cannot dispose of it sufficiently uric acid build up in the blood.
Deposition of uric acid crystals in joints causes painful swelling of the joints and loss of joint mobility and affects mainly the big toe but can affect other joints, including joints of the hands, feet, knee and elbow. There are several risk factors for gout including genetic predisposition, obesity, excess alcohol intake and high meat consumption.

Uricosuric treatments for gout

There are specific medications for treating gout, which are known as a uricosuric drug that helps the removal of uric acid from the blood and this reduces the risk of uric acid crystals being deposited in the joints. Uricosuric drugs like probenecid work by acting directly on the kidneys to increase excretion of uric acid by the kidneys and this limits the amount of uric acid in the blood. Less uric acid reduces crystal formation, which allows the crystals already in the joints to dissolve and the pain and swelling to be reduced.

Other gout treatments

Allopurinol blocks an enzyme involved in uric acid synthesis and this reduces the amount of uric acid production and reduces levels of uric acid in the blood. Allopurinol is also used for prevention of kidney stone formation and uric acid crystals under the skin called skin tophi.

Colchicine blocks the action of inflammatory cells and is used to treat gout to help reduce inflammation associated with uric acid crystals in the joints.

What is inflammation?

Inflammation is a normal reaction to protect the body from harmful pathogens or irritants, such as chemicals, and to promote healing of damaged tissues, as in arthritis. It is a complex process of cellular interactions of the immune system that is mediated by chemicals produced at the site of tissue damage, infection or trauma.

The process of inflammation includes the widening and increased permeability of small blood vessels, exudation of fluid into and migration of immune cells like macrophages and neutrophils into the tissues where damage, infection or irritation has occurred. The fluid causes swelling and the cells produce inflammatory chemicals like prostaglandins, interleukins and leukotrienes. These chemicals attract more inflammatory cells to help with wound healing and disposing of harmful pathogens but they also magnify the inflammatory response. In doing their job, some of these inflammatory mediators can also cause pain, swelling, fever and redness. If the inflammatory process continues beyond protecting and healing, it becomes chronic and can end up damaging normal tissues.

Inflammation and prostaglandins

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX), an enzyme involved in the synthesis of prostaglandins like PGE2, which have important functions throughout the body but are also potent inflammatory mediators and cause pain, swelling and other symptoms of inflammation. They are called nonsteroidal as corticosteroids are also used to treat inflammation but target a different enzyme in the pathway of prostaglandin synthesis.

There are two known COX enzymes, COX-1, COX-2 and there is also a variant of COX-1, known as COX-3, which is found mainly in the brain. COX-1 is present in most cells and plays an important role in many normal cell functions, including aggregation of blood platelets, which controls bleeding; protection of the stomach lining or mucosa by promoting cell growth; also in maintaining normal kidney function by regulating blood flow. COX-2 is only produced by inflammatory cells, and is induced during the inflammatory process, although it is also found in very small amounts in some tissues.

Oral anti- inflammatory drugs

Oral nonsteroidal anti-inflammatory drugs (NSAID) target inflammation systemically, wherever it occurs throughout the body and can be used for short-term or long-term treatment of inflammatory joint diseases like arthritis, to help relieve pain and improve mobility in affected joints.

Meloxicam and celecoxib are specific COX-2 inhibitors and have no inhibitory action against COX-1, which makes them more effective for pain and inflammation, without the gastrointestinal or kidney side effects associated with COX-1 inhibition.

Topical anti-inflammatory drugs

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits primarily COX-2 but also has some inhibitory effect on COX-1 and is, therefore, more specific as an anti-inflammatory than other non-specific NSAIDs like Ibuprofen. As a topical treatment for arthritis, diclofenac is absorbed through the skin and acts directly on the soft tissues surrounding joints to relieve pain and inflammation due to sprains and strains. It also acts within superficial arthritic joints, such as the hands, wrists, elbows, knees, ankles or feet, to reduce inflammation due to osteoarthritis and relieve symptoms like pain and swelling in the joints.

What is osteoporosis?

Osteoporosis is the thinning of the bones which results in increased risk of fracture particularly in the hip, spine, wrist and upper arm. Multiple fractures of the vertebrae can cause stooped posture and loss of height which is very common in the elderly. Fractures cause chronic and acute pain and can cause disability and loss of mobility. Bone loss is gradual and is usually symptom free until it is advanced.

Osteoporosis affects both men and women and is a common problem associated with aging. It is also associated with lack of oestrogen in postmenopausal women; or following treatment with corticosteroids, an anti-inflammatory steroid that can cause bone loss. Risk factors for osteoporosis include, family history, smoking, excessive alcohol intake, thin build, lack of physical activity, lack of dietary calcium and low levels of Vitamin D.

Bone turnover and osteoporosis

Bone turnover is the normal mechanism for bone remodelling, which is a dynamic process that allows bones to grow and repair. Bone resorption and formation takes place constantly on the surface of bones. Resorption is carried out by osteoclast cells and is the process by which bone is broken down and minerals like calcium and phosphate released into the blood. Bone formation is carried out by osteoblast cells and is the process by which new bone is formed, with a build-up of bone matrix containing proteins, calcium, phosphate and other minerals, which form the scaffolding that gives bone its strength.

When the process of bone turnover is out of balance and bone loss is greater than bone formation this results is a loss of bone mass making bones brittle and likely to fracture more easily. Bone density is the amount of bone tissue in a certain volume of bone and when this falls below a certain level, this is defined as osteoporosis.

Treatments for osteoporosis

Treatments for osteoporosis are based on increasing bone mineral density and reducing bone turnover, thereby restoring the balance between bone resorption and formation, to prevent loss of bone density in people with or at risk of osteoporosis.

Bisphosphonates like alendronate and risedronate are an effective treatment for osteoporosis. They are synthetic chemicals similar to the naturally occurring pyrophosphates that are formed form as a product of normal phosphate metabolism. Like pyrophosphates, biphosphonates binds strongly to hydroxyapatite, the mineralised bone scaffolding, at the site of bone resorption. This inhibits the action of osteoclasts in resorbing bone reducing the amount of bone remodelling and loss of calcium from bone. Biphosponates can also be used in combination with cholecalciferol or Vitamin D3, which is converted to its active form, calcitriol, a hormone that regulates calcium metabolism. Calcitriol regulates calcium absorption in the intestine and excretion in the kidneys. If there is a lack of Vitamin D3 then calcium levels may become low and this contributes to brittle bones and to osteoporosis. Calcitriol also regulates bone remodelling. Combining cholecalciferol with bisphosphonates adds another dimension to combatting osteoporosis.

Another treatment for osteoporosis is raloxifene, a selective oestrogen receptor modulator. Loss of oestrogen at menopause is associated with increased bone remodelling. Raloxifene mimics the actions of oestrogen and binds to the oestrogen receptor in bone, where it inhibits the actions of osteoclasts.

Oral anti- inflammatory drugs

Oral nonsteroidal anti-inflammatory drugs (NSAID) target inflammation systemically, wherever it occurs throughout the body. They work by inhibiting the action of the enzyme cyclooxygenase (COX) that is involved in the synthesis of prostaglandins. Some NSAIDs, including celecoxib and meloxicam, are more specific and inhibit only the COX 2 enzyme that produces the inflammatory mediator prostaglandin E2, and not COX1 enzyme that is needed for normal cellular processes. These NSAIDs can be used for short-term or long-term treatment, depending on the condition, and they may help improve mobility in affected joints.

Gout uricosuric drug

Gout and gouty arthritis are caused by excess uric acid in the blood being deposited in joints as crystals and causing inflammation with its associated pain and swelling. Uricosuric drugs work by acting directly on the kidneys to limit the amount of uric acid in the blood and reduce crystal formation, which allows the crystals already in the joints to dissolve and the pain and swelling to be reduced.