Bone Disorders

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Questions Received:

  1. What can you tell me about osteosarcoma? (risk factors, aetiology, epidemiology, pathogenesis, and information regarding support groups)

  2. My son has a hereditary bone disorder that I think is called "Dyaphesal Aclasis". It manifests itself by the growth of extra bone nodules at the end of the bones. What I'm looking for is information on how the disease develops.

  3. I have a bone disorder called ostiocondritius. I am unsure if I have spelt this correctly. I have had this disorder since I was 13 years old. All the doctors I have seen cannot give me a cure or what is causing this disorder. This bone disorder has affected both of my arms, crumbling of my joints, and is very painful. I have had two operations on both arms to remove loose bodies, but still have not been able to find a cure. Please can u help me or point me in the right direction?

Responses:

What can you tell me about osteosarcoma? (risk factors, aetiology, epidemiology, pathogenesis, and information regarding support groups)

30th September 1999

Osteosarcoma (also known as osteogenic sarcoma) is a malignant primary neoplasm of bone. The tumour usually arises in the metaphysis (shaft) of a long bone, particularly those adjacent to the knee.

Risk Factors & Aetiology

Some patients with osteosarcoma have deletions and mutations of the retinoblastoma gene on chromosome 13, although this change is also seen in other tumour types. The risk of osteosarcoma is increased in patients with inherited retinoblastoma and the Li Fraumeni syndrome. Osteosarcomas may arise after exposure to radiation and also in adults with Paget's disease. Some relatively benign conditions such as fibrous dysplasia, skeletal infarction, or chronic osteomyelitis may transform into osteosarcoma, but the mechanisms of these transformations are not yet known.

Epidemiology

Osteosarcoma is rare, and affects only 2 or 3 people in every 1 million. However, it is the most common primary bone tumour. Slightly more males are affected than females. It most commonly develops during adolescence, slightly earlier in females than males.

Pathogenesis

The World Health Organization distinguishes "central" (medullary) and "surface" forms of osteosarcoma (Schajowicz et al, 1995). The tumour may be osteolytic, in which bone is destroyed and neighbouring soft tissues are invaded by tumour cells, or osteoblastic resulting in the formation of new bone.

Diagnosis

There is generally a mild and discontinuous pain in the early stages, but the pain becomes more continuous with time and is typically made worse with exercise. After a few weeks a swelling becomes apparent and increases rapidly, interfering with movement. The affected area feels warmer because of the increased blood supply. In about half of osteosarcoma patients the serum alkaline phosphatase level is increased. The radiographic features are variable, depending on the age of the patient, the site of the lesion, and the amount of neoplastic bone production, but usually enable early diagnosis (Kricun, 1993). A biopsy is recommended before starting treatment. Depending on the stage of tumour development, it may be necessary to look for metastases. A CT scan of the lungs is the best technique to search for occult lung metastases.

Treatment

Chemotherapy is now widely used in the treatment of osteosarcoma before surgery and after. The surgical approach is reasonably standardised for most types of presentation, and in many cases consists of the resection of a segment of the affected bone. If tumour cells have spread more widely within the limb an amputation may be required.

Prognosis

Before the introduction of chemotherapy, the majority of patients survived for only a few months. Now with the use of chemotherapy survival is greatly improved (Davis et al, 1994). Survival is best if there are no distant metastases. Follow-up is required to ensure the early detection of any recurrence. The risk is higher in the first 2 or 3 years after treatment and becomes very low after 5 years.

Support Groups

An Internet search will reveal a variety of support agencies for osteosarcoma. For example, visit American Cancer Society (http://www.cancer.org) and more specifically the section on osteosarcoma. (This will open a new browser window.)

References

My son has a hereditary bone disorder that I think is called "Dyaphesal Aclasis". It manifests itself by the growth of extra bone nodules at the end of the bones. What I'm looking for is information on how the disease develops.

29th March 2000

The disorder is called diaphyseal aclasis or hereditary multiple exostosis. The main clinical feature is the growth of one or several abnormal bony protuberances, usually from long bones in the limbs such as the femur, tibia or fibula, but occasionally from other bones such as the vertebrae (Labram and Mohan, 1996). The nodules arise from displaced portions of the cartilagenous growth plates of developing bones during childhood and adolescence. Usually the growth of the nodules ceases when the growth of the adjacent bone ceases at the end of adolescence. Often the nodules produce no symptoms, but occasionally they might interfere with the movement of joints or tendons (especially in the forearm, knee and ankle regions) or put pressure on adjacent nerves. There may be some lessening of the overall growth of the skeleton. There is a small risk (less than 3%) that malignant changes may occur in the abnormal bony tissue (Wicklund et al, 1995). The over-all prevalence of this condition was found to be at least one in 50,000 (Schmale, Conrad, and Raskind, 1994), and of those affected about 90% had a family history of the condition.

The growth of abnormal bone nodules is thought to be due to defects in genes belonging to the EXT family. These genes are present on the autosomes, the gene EXT2 for example being located on the short arm of chromosome 11 (Potocki and Shaffer, 1996). Two of the genes, EXT1 and EXT2, encode enzymes that help in the synthesis of heparan sulphate, an important component of the extracellular matrix (McCormick, Duncan, and Tufaro, 1999).

The most common treatment of this condition is surgical removal of the nodules, and the results are generally good.

References

I have a bone disorder called ostiocondritius. I am unsure if I have spelt this correctly. I have had this disorder since I was 13 years old. All the doctors I have seen cannot give me a cure or what is causing this disorder. This bone disorder has affected both of my arms, crumbling of my joints, and is very painful. I have had two operations on both arms to remove loose bodies, but still have not been able to find a cure. Please can u help me or point me in the right direction?

11th April 2001

Osteochondritis - It seems likely that you have been diagnosed with osteochondritis dissecans – this is the most common cause of loose bodies in joint spaces in young people (Obedian and Grelsamer, 1997). It is quite a rare disorder, and seems to begin when localised regions of bone are damaged just beneath the articular cartilage of a joint. Although the cartilage receives nourishment from the synovial fluid that bathes its surface, there is a risk that it will lose its support and break free, giving rise to a loose fragment of cartilage and perhaps bone within the joint cavity. Loose fragments can interfere with normal joint function, giving rise to ‘catching’ and pain during movements.

Osteochondritis tends to occur in young, athletic people. Although it tended to affect mostly young men, in recent years young, active women are also showing the condition in increasing numbers (Williamson and Albright, 1996). This seems to be linked with the increasingly competitive participation of young people in sport and training. The most commonly affected parts of the skeleton include the femoral condyles (which contribute to the knee joint), the talar region of the ankle, and the capitulum of the humerus (where it contributes to the elbow joint). Less frequent locations include the patella (knee cap), femoral head (hip joint), glenoid cavity of the scapula (shoulder joint), tibial plateau (knee joint), and vertebrae. In most people, a joint on only one side of the body is affected, while in 20 to 30 percent of individuals the corresponding joints on both sides are affected. In your case it is both your arms that are affected - have you taken part in a sport or activity involving a lot of use of your arms? It has been found, for example, that lesions of the humerus are common in adolescent baseball pitchers and gymnasts (Saperstein and Nicholas, 1996).

Osteochondritis is diagnosed radiologically. Plain X-ray films can detect circumscribed areas of degenerating bone but are less reliable for assessing the condition of articular cartilage. Magnetic resonance imaging (MRI) gives a more precise indication of the stage of progression of the problem according to the following characteristics:

The first two stages are stable in the sense that the cartilage remains attached to the underlying bone. Stages III and IV are unstable because synovial fluid exists between the fragment and underlying bone, leading to the possibility of the fragment breaking free into the joint cavity (Obedian and Grelsamer, 1997).

Opinions are divided about what might be the cause or causes of osteochondritis. It has been proposed that there may be a genetic predisposition to the condition, but this would seem to apply in only a small proportion of cases. There may be a loss of blood supply to part of the developing bone resulting in its degeneration. Generally, though, the conclusion is being reached that repetitive shear and compressive stresses experienced by bones and joints during exercise might trigger the condition. During childhood and adolescence the bones are still forming, and they seem more vulnerable to the effects of stress than bones which have completed ossification. Until recently, studies trying to identify the earliest changes in osteochondritis focused on the articular cartilage, but now it is being suggested that changes begin first in the underlying bone, resulting in consequent changes in the cartilage (Koch, Kampen, and Laprell, 1997; Imhof et al, 1997). Subchondral bone is an important shock absorber, and its rich blood supply is probably important for the provision of glucose, oxygen, and water to the overlying cartilage (Imhof et al, 2000).

The treatment of this condition will depend on a number of factors, including the age of the affected person (and thus the stage of skeletal maturity), and the degree to which the condition has progressed. In the early stages, conservative measures such as avoidance of competitive sports for six to eight weeks can restore symptom-free activity (Obedian and Grelsamer, 1997). Physiotherapy can be helpful, particularly stretching, range-of-motion exercises, and muscle conditioning. Complete immobilization is no longer considered to be beneficial since it leads to muscle weakness and the subsequent risk of joint instability. Girls younger than 11 years of age and boys younger than 13 years of age have an excellent chance of resolution, while patients over 20 years of age tend to have poorer outcomes.

Persistent symptoms in a conservatively treated patient, or the onset of joint catching or grinding suggest detachment of a fragment within the joint and are an indication for arthroscopic evaluation and surgery. A loose body may be removed and modifications made to the lesion site. Following surgery, range-of-motion exercises and muscle conditioning are initiated early to achieve the best results.

References

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