Definition

Pagets disease is a disease of the actual localized modelling of the bone architecture.

Aetiology

Bone is a living structure, and has many cells, but the main two, are the osteoclast which resorbs bone and the osteoblast which lays down new quality bone. These work in cycles - causing a process of new bone replacing old bone. The calcification process - laying down of mineral calcium thereafter proceeds and the bone hardens.
This cycle is called - remodelling. In pagets disease, this process is disordered, with large abnormal osteoclasts working at a much greater turnover than normal, followed by the irregular laying down of bone, in a whorled, disorganised manner - instead of in smooth parallel layers. The region becomes very vascular, and the bone circulation locally is greater - resulting in local heat at the bone surface. The boone thickens abnormally, as well as becoming irregular.
This turnover can occur at 40 X normal, and there is inadequate time for the mineralisation process of calcium deposition. The bone therefore becomes brittle at times and softer at other times. The thickening is called sclerosis.

The fundamental cause of this process is not known, but some evidence of a post viral phenomenon exists. Genetic components and family factors are also apparent.

Epidemiology

The disease was described by Sir James Paget in the 20th century, but is recognised in archeological specimens. The disease is more common as one gets older and is more common in males compared to females. It is unusual in black people compared to white people and is more commoner in the northern hemisphere (except Scandinavia). It occurs in 4-5% of most western countries after age 40, but in the 80's may be found in about 10% of people screened for Pagets - of whom the majority are not complaining of symptoms.

Clinical

The patient is frequently entirely assymptomatic and the condition can be discovered after routine Xrays, requested for other reasons. However of those people who become symptomatic, the commonest features are:

Pain
Deformity of bone
Manifestations of complications.

The sites of involvement are most frequently, the lower limbs - tibia and femur, as well as pelvis, skull, and spine. However - any bone can be involved. The site of the process potentially causes aggravating circumstances and complications. Involvement in the skull and spine can cause nerve entrapment. ie deafness, or paralysis. Involvement around joints can result in a secondary arthritis, and may result in cartilage damage. Involvement of long bones causes deformity - with bending of the bones - bowing. Deformity of the skull can occur with bony prominence - called bossing. The circulation in the bone can be so extensive in some extreme cases, that blood can be diverted from other organs or tissues - called "steel" syndrome. Heart failure from increase in circulation, or stroke or paralysis are rare such complications of this process.
Fractures can also occur as the bone is brittle.

Transition of the process to a cancerous form is also well described. This is called sarcomatous transformation. This is associated with a change of symptoms and increase in pain. Vigilance may be required

Pagets of the tibia - lower leg - bowing - clinical and Xray

Detail of the thickened and irregular bone structure

Pelvic involvement

Hip involvement - pre-post joint replacement

Investigations

The condition is not an inflammatory one, but one of bone turnover and increased circulation. Therefore blood tests can be done to assess the state of bone turnover. The best single blood test is the alkaline phosphatase enzyme, which can also be used to follow the disease process and response to treatment.

Xrays are also fairly classical in their appearence, although other conditions can mimic this. Various stges are seen..from an early lytic phase of bone washout ..to a mixed picture of bone disorganisation..to a later thickened and sclerotic picture with bone cysts.

Technetium bone scan is very useful in assessing the whole body for distribution of the process.

Differential diagnosis

The biggest problem is differentiation from malignancy, or spread from malignancy or change to malignancy. Malignancy that can look like this include, lymphoma or prostate malignancy. Since the problem of Pagets is common especially in the elderly, co-existence of Pagets and malignancy may occur, coincidently, making the clinical assessment even more complicated. The transition to sarcoma, may be associated with a "sunburst" appearence on the Xray.
Inflammatory blood markers such as the ESR and CRP are more likely to be elevated if there is a malignant process present.

Treatment

The disease is now treatable. Gone are the days where pain killers and antiinflammatories were the only approach. The mainstay of therapy at the current state of the art is that of bisphosphonates, either oral or intravenous pulse. Such preperations include - alendronate(oral), risedronate (oral) and pamidronate (intravenous). My personal preference is pamidronate, given as infusions of 30-60mg IV . Such therapy results in a reduction in the alkaline phosphatase, and reduction in pain. The infusion may last 12-18 months, but more frequent infusions can be given and dose increaded depending on response.

Who should be treated

Asymptomatic elderly people do not require therapy, unless there are risks of complication - especially if the disease interferes with adjacent joints. Symptomatic disease should be treated.
Disease with complications should be treated.
All young people should be treated.

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