Bisphosphonates Health Dictionary

Bisphosphonates: From 2 Different Sources


Bisphosphonates, of which disodium etidronate is one, are a group of drugs used mainly in the treatment of PAGET’S DISEASE OF BONE and in established vertebral osteoporosis (see BONE, DISORDERS OF). Their advantage over CALCITONIN (which has to be given by subcutaneous or intramuscular injection) is that they can be taken orally. They act by reducing the increased rate of bone turnover associated with the disease. Disodium etidronate is used with calcium carbonate in a 90-day cycle (duration of therapy up to three years) in the treatment of osteoporosis.
Health Source: Medical Dictionary
Author: Health Dictionary
pl. n. a class of drugs that inhibit the resorption of bone by blocking the action of *osteoclasts. This property makes them useful for treating certain bone disorders, such as Paget’s disease and osteoporosis, as well as malignant disease – both in terms of pain relief and in treating hypercalcaemia due to cancer. There is a risk of *osteonecrosis of the jaw in patients receiving bisphosphonates for cancer. This risk is increased by tooth extraction. Bisphosphonates include *alendronic acid, etidronate, *pamidronate disodium, risedronate, clodronate, and *zoledronic acid.
Health Source: Oxford | Concise Colour Medical Dictionary
Author: Jonathan Law, Elizabeth Martin

Bone, Disorders Of

Bone is not an inert sca?olding for the human body. It is a living, dynamic organ, being continuously remodelled in response to external mechanical and chemical in?uences and acting as a large reservoir for calcium and phosphate. It is as susceptible to disease as any other organ, but responds in a way rather di?erent from the rest of the body.

Bone fractures These occur when there is a break in the continuity of the bone. This happens either as a result of violence or because the bone is unhealthy and unable to withstand normal stresses.

SIMPLE FRACTURES Fractures where the skin remains intact or merely grazed. COMPOUND FRACTURES have at least one wound which is in communication with the fracture, meaning that bacteria can enter the fracture site and cause infection. A compound fracture is also more serious than a simple fracture because there is greater potential for blood loss. Compound fractures usually need hospital admission, antibiotics and careful reduction of the fracture. Debridement (cleaning and excising dead tissue) in a sterile theatre may also be necessary.

The type of fracture depends on the force which has caused it. Direct violence occurs when an object hits the bone, often causing a transverse break – which means the break runs horizontally across the bone. Indirect violence occurs when a twisting injury to the ankle, for example, breaks the calf-bone (the tibia) higher up. The break may be more oblique. A fall on the outstretched hand may cause a break at the wrist, in the humerus or at the collar-bone depending on the force of impact and age of the person. FATIGUE FRACTURES These occur after the bone has been under recurrent stress. A typical example is the march fracture of the second toe, from which army recruits suffer after long marches. PATHOLOGICAL FRACTURES These occur in bone which is already diseased – for example, by osteoporosis (see below) in post-menopausal women. Such fractures are typically crush fractures of the vertebrae, fractures of the neck of the femur, and COLLES’ FRACTURE (of the wrist). Pathological fractures also occur in bone which has secondary-tumour deposits. GREENSTICK FRACTURES These occur in young children whose bones are soft and bend, rather than break, in response to stress. The bone tends to buckle on the side opposite to the force. Greenstick fractures heal quickly but still need any deformity corrected and plaster of Paris to maintain the correction. COMPLICATED FRACTURES These involve damage to important soft tissue such as nerves, blood vessels or internal organs. In these cases the soft-tissue damage needs as much attention as the fracture site. COMMINUTED FRACTURES A fracture with more than two fragments. It usually means that the injury was more violent and that there is more risk of damage to vessels and nerves. These fractures are unstable and take longer to unite. Rehabilitation tends to be protracted. DEPRESSED FRACTURES Most commonly found in skull fractures. A fragment of bone is forced inwards so that it lies lower than the level of the bone surrounding it. It may damage the brain beneath it.

HAIR-LINE FRACTURES These occur when the bone is broken but the force has not been severe enough to cause visible displacement. These fractures may be easily missed. Symptoms and signs The fracture site is usually painful, swollen and deformed. There is asymmetry of contour between limbs. The limb is held uselessly. If the fracture is in the upper

limb, the arm is usually supported by the patient; if it is in the lower limb then the patient is not able to bear weight on it. The limb may appear short because of muscle spasm.

Examination may reveal crepitus – a bony grating – at the fracture site. The diagnosis is con?rmed by radiography.

Treatment Healing of fractures (union) begins with the bruise around the fracture being resorbed and new bone-producing cells and blood vessels migrating into the area. Within a couple of days they form a bridge of primitive bone across the fracture. This is called callus.

The callus is replaced by woven bone which gradually matures as the new bone remodels itself. Treatment of fractures is designed to ensure that this process occurs with minimal residual deformity to the bone involved.

Treatment is initially to relieve pain and may involve temporary splinting of the fracture site. Reducing the fracture means restoring the bones to their normal position; this is particularly important at the site of joints where any small displacement may limit movement considerably.

with plaster of Paris. If closed traction does not work, then open reduction of the fracture may

be needed. This may involve ?xing the fracture with internal-?xation methods, using metal plates, wires or screws to hold the fracture site in a rigid position with the two ends closely opposed. This allows early mobilisation after fractures and speeds return to normal use.

External ?xators are usually metal devices applied to the outside of the limb to support the fracture site. They are useful in compound fractures where internal ?xators are at risk of becoming infected.

Consolidation of a fracture means that repair is complete. The time taken for this depends on the age of the patient, the bone and the type of fracture. A wrist fracture may take six weeks, a femoral fracture three to six months in an adult.

Complications of fractures are fairly common. In non-union, the fracture does not unite

– usually because there has been too much mobility around the fracture site. Treatment may involve internal ?xation (see above). Malunion means that the bone has healed with a persistent deformity and the adjacent joint may then develop early osteoarthritis.

Myositis ossi?cans may occur at the elbow after a fracture. A big mass of calci?ed material develops around the fracture site which restricts elbow movements. Late surgical removal (after 6–12 months) is recommended.

Fractured neck of FEMUR typically affects elderly women after a trivial injury. The bone is usually osteoporotic. The leg appears short and is rotated outwards. Usually the patient is unable to put any weight on the affected leg and is in extreme pain. The fractures are classi?ed according to where they occur:

subcapital where the neck joins the head of the femur.

intertrochanteric through the trochanter.

subtrochanteric transversely through the upper end of the femur (rare). Most of these fractures of the neck of femur

need ?xing by metal plates or hip replacements, as immobility in this age group has a mortality of nearly 100 per cent. Fractures of the femur shaft are usually the result of severe trauma such as a road accident. Treatment may be conservative or operative.

In fractures of the SPINAL COLUMN, mere damage to the bone – as in the case of the so-called compression fracture, in which there is no damage to the spinal cord – is not necessarily serious. If, however, the spinal cord is damaged, as in the so-called fracture dislocation, the accident may be a very serious one, the usual result being paralysis of the parts of the body below the level of the injury. Therefore the higher up the spine is fractured, the more serious the consequences. The injured person should not be moved until skilled assistance is at hand; or, if he or she must be removed, this should be done on a rigid shutter or door, not on a canvas stretcher or rug, and there should be no lifting which necessitates bending of the back. In such an injury an operation designed to remove a displaced piece of bone and free the spinal cord from pressure is often necessary and successful in relieving the paralysis. DISLOCATIONS or SUBLUXATION of the spine are not uncommon in certain sports, particularly rugby. Anyone who has had such an injury in the cervical spine (i.e. in the neck) should be strongly advised not to return to any form of body-contact or vehicular sport.

Simple ?ssured fractures and depressed fractures of the skull often follow blows or falls on the head, and may not be serious, though there is always a risk of damage which is potentially serious to the brain at the same time.

Compound fractures may result in infection within the skull, and if the skull is extensively broken and depressed, surgery is usually required to check any intercranial bleeding or to relieve pressure on the brain.

The lower jaw is often fractured by a blow on the face. There is generally bleeding from the mouth, the gum being torn. Also there are pain and grating sensations on chewing, and unevenness in the line of the teeth. The treatment is simple, the line of teeth in the upper jaw forming a splint against which the lower jaw is bound, with the mouth closed.

Congenital diseases These are rare but may produce certain types of dwar?sm or a susceptibility to fractures (osteogenesis imperfecta).

Infection of bone (osteomyelitis) may occur after an open fracture, or in newborn babies with SEPTICAEMIA. Once established it is very di?cult to eradicate. The bacteria appear capable of lying dormant in the bone and are not easily destroyed with antibiotics so that prolonged treatment is required, as might be surgical drainage, exploration or removal of dead bone. The infection may become chronic or recur.

Osteomalacia (rickets) is the loss of mineralisation of the bone rather than simple loss of bone mass. It is caused by vitamin D de?ciency and is probably the most important bone disease in the developing world. In sunlight the skin can synthesise vitamin D (see APPENDIX 5: VITAMINS), but normally rickets is caused by a poor diet, or by a failure to absorb food normally (malabsorbtion). In rare cases vitamin D cannot be converted to its active state due to the congenital lack of the speci?c enzymes and the rickets will fail to respond to treatment with vitamin D. Malfunction of the parathyroid gland or of the kidneys can disturb the dynamic equilibrium of calcium and phosphate in the body and severely deplete the bone of its stores of both calcium and phosphate.

Osteoporosis A metabolic bone disease resulting from low bone mass (osteopenia) due to excessive bone resorption. Su?erers are prone to bone fractures from relatively minor trauma. With bone densitometry it is now possible to determine individuals’ risk of osteoporosis and monitor their response to treatment.

By the age of 90 one in two women and one in six men are likely to sustain an osteoporosis-related fracture. The incidence of fractures is increasing more than would be expected from the ageing of the population, which may re?ect changing patterns of exercise or diet.

Osteoporosis may be classi?ed as primary or secondary. Primary consists of type 1 osteoporosis, due to accelerated trabecular bone loss, probably as a result of OESTROGENS de?ciency. This typically leads to crush fractures of vertebral bodies and fractures of the distal forearm in women in their 60s and 70s. Type 2 osteoporosis, by contrast, results from the slower age-related cortical and travecular bone loss that occurs in both sexes. It typically leads to fractures of the proximal femur in elderly people.

Secondary osteoporosis accounts for about 20 per cent of cases in women and 40 per cent of cases in men. Subgroups include endocrine (thyrotoxicosis – see under THYROID GLAND, DISEASES OF, primary HYPERPARATHYROIDISM, CUSHING’S SYNDROME and HYPOGONADISM); gastrointestinal (malabsorption syndrome, e.g. COELIAC DISEASE, or liver disease, e.g. primary biliary CIRRHOSIS); rheumatological (RHEUMATOID ARTHRITIS or ANKYLOSING SPONDYLITIS); malignancy (multiple MYELOMA or metastatic CARCINOMA); and drugs (CORTICOSTEROIDS, HEPARIN). Additional risk factors for osteoporosis include smoking, high alcohol intake, physical inactivity, thin body-type and heredity.

Individuals at risk of osteopenia, or with an osteoporosis-related fracture, need investigation with spinal radiography and bone densitometry. A small fall in bone density results in a large increase in the risk of fracture, which has important implications for preventing and treating osteoporosis.

Treatment Antiresorptive drugs: hormone replacement therapy – also valuable in treating menopausal symptoms; treatment for at least ?ve years is necessary, and prolonged use may increase risk of breast cancer. Cyclical oral administration of disodium etidronate – one of the bisphosphonate group of drugs – with calcium carbonate is also used (poor absorption means the etidronate must be taken on an empty stomach). Calcitonin – currently available as a subcutaneous injection; a nasal preparation with better tolerance is being developed. Calcium (1,000 mg daily) seems useful in older patients, although probably ine?ective in perimenopausal women, and it is a safe preparation. Vitamin D and calcium – recent evidence suggests value for elderly patients. Anabolic steroids, though androgenic side-effects (masculinisation) make these unacceptable for most women.

With established osteoporosis, the aim of treatment is to relieve pain (with analgesics and physical measures, e.g. lumbar support) and reduce the risk of further fractures: improvement of bone mass, the prevention of falls, and general physiotherapy, encouraging a healthier lifestyle with more daily exercise.

Further information is available from the National Osteoporosis Society.

Paget’s disease (see also separate entry) is a common disease of bone in the elderly, caused by overactivity of the osteoclasts (cells concerned with removal of old bone, before new bone is laid down by osteoblasts). The bone affected thickens and bows and may become painful. Treatment with calcitonin and bisphosphonates may slow down the osteoclasts, and so hinder the course of the disease, but there is no cure.

If bone loses its blood supply (avascular necrosis) it eventually fractures or collapses. If the blood supply does not return, bone’s normal capacity for healing is severely impaired.

For the following diseases see separate articles: RICKETS; ACROMEGALY; OSTEOMALACIA; OSTEOGENESIS IMPERFECTA.

Tumours of bone These can be benign (non-cancerous) or malignant (cancerous). Primary bone tumours are rare, but secondaries from carcinoma of the breast, prostate and kidneys are relatively common. They may form cavities in a bone, weakening it until it breaks under normal load (a pathological fracture). The bone eroded away by the tumour may also cause problems by causing high levels of calcium in the plasma.

EWING’S TUMOUR is a malignant growth affecting long bones, particularly the tibia (calfbone). The presenting symptoms are a throbbing pain in the limb and a high temperature. Treatment is combined surgery, radiotherapy and chemotherapy.

MYELOMA is a generalised malignant disease of blood cells which produces tumours in bones which have red bone marrow, such as the skull and trunk bones. These tumours can cause pathological fractures.

OSTEOID OSTEOMA is a harmless small growth which can occur in any bone. Its pain is typically removed by aspirin.

OSTEOSARCOMA is a malignant tumour of bone with a peak incidence between the ages of ten and 20. It typically involves the knees, causing a warm tender swelling. Removal of the growth with bone conservation techniques can often replace amputation as the de?nitive treatment. Chemotherapy can improve long-term survival.... bone, disorders of

Paget’s Disease Of Bone

Also called osteitis deformans, this is a chronic disease in which the bones (see BONE) – especially those of the skull, limbs, and spine – gradually become thick and also soft, causing them to bend. It is said to be the most common form of bone disease in the world, and it is estimated that some 600,000 people in England may suffer from it. It seldom occurs under the age of 40. Pain is its most unpleasant manifestation. The cause is not known, and there is no known cure, but satisfactory results are being obtained from the use of CALCITONIN and a group of drugs known as BISPHOSPHONATES

(e.g. etidronate). Those with the disease can obtain help and advice from the National Association for the Relief of Paget’s Disease.... paget’s disease of bone

Bisphosphonate Drugs

Drugs used to slow bone metabolism (for example in Paget’s disease) and to reduce the high calcium levels in the blood associated with destruction of bone by secondary cancer growths.

Bisphosphonates are also used in the prevention or treatment of osteoporosis.... bisphosphonate drugs

Etidronate

(disodium etidronate) n. see bisphosphonates.... etidronate

Osteoporosis

n. a bone disease characterized by a decrease in bone mineral density and bone mass, resulting in bones that are liable to fracture. Infection, injury, and *synovitis can cause localized osteoporosis of adjacent bone. Generalized osteoporosis is common in older people, and in women it often follows the menopause. It is also a feature of *Cushing’s syndrome and prolonged steroid therapy. Osteoporosis can be detected by *quantitative digital radiography, ultrasound, and *DEXA scans. A diet with adequate calcium, together with exercise, are preventative, and several drugs, including *bisphosphonates, parathyroid hormone (PTH), and *denosumab, can be used to reduce the risk of fracture.... osteoporosis

Paget’s Disease

1. a chronic disease of bones, occurring in the elderly and most frequently affecting the skull, backbone, pelvis, and long bones. Affected bones become thickened and their structure disorganized: X-rays reveal patchy *sclerosis. There are often no symptoms, but pain, deformity, and fracture can occur; when the skull is affected, blindness and deafness can occur due to nerve compression. There is a very small (1%) risk of malignant change (*osteosarcoma). Treatment is with *bisphosphonates. Medical name: osteitis deformans. 2. a malignant condition of the nipple, resembling eczema in appearance, associated with underlying infiltrating cancer of the breast. See also breast cancer. 3. an uncommon condition of the vulva characterized by an epithelial lesion that histologically resembles the lesion of Paget’s disease of the nipple. It may be associated with locally invasive *adenocarcinomas of the surrounding skin, as well as tumours at other sites. [Sir J. Paget (1814–99), British surgeon]... paget’s disease



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