Medical Inspection – Health Blog

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DXA densitometers have undergone remarkable technological improvements both in the process of x-ray emission and x-ray absorption.

These facts have allowed a shorter scan time, increased diag­nostic accuracy (accuracy of density measurements) and a re­duction of the dose to the patient.

In first generation DXA densitometers the x-ray beam is ex­tremely thin (pencil beam), as it is obtained by means of a nar­row collimation.

Given the dot-like morphology of the beam, the scans of the x- ray source are characterized by repeated passages separated by few millimeters over different positions of the longitudinal axis of the patient.

The detection system is usually represented by a phosphor crystal.

A further generation of densitometers (second generation ma­chines) is represented by the use of a fan beam rather than pencil beam technology.

Fan beam machines employ wider beams that permit more rapid scanning and a spatial resolution of 0,5-0,7 mm. There have also been employed new detection devices made of ar­rays of solid detectors.

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Introduction

Dual x-ray absorpiometry (DXA) was introduced in 1987 and, to date, it still represents the most widely used technique for the diagnosis of osteoporosis in the clinical practice. The World Health Organization (WHO) has defined the threshold levels for the diagnosis of osteopenia and osteoporosis using DXA technique.

DXA machines consist of a mobile source of X-rays, a patient couch, a detection system on which fall the radiations emerged from the bones under examination. The x-ray source is under the couch and moves together with the detection system which is located opposite to it over the body of the patient. The main characteristic of DXA lies in the fact that it uses an x- ray beam composed of two different photon energies. The method used to produce the two photon energies may be either constant or pulsed. In the first case it is produced a beam which is constant in intensity and voltage and is filtered by a filter made of cerium or samarium (rare earth) in order to obtain two distinct beams with different energies. The pulsed method produces an alternant emission of beams with different energies with a frequency of 60 Hz/sec. The energy used (70-140 kV Hologic; 40-70 kV Lunar; 45-80 kV Norland) is conveniently chosen to compensate the differ­ent attenuation coefficients of mineralized bone and soft tissue. Practically, the intensity of high energy photons and low energy photons is analyzed separately after they have passed through bones and soft tissues.

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Bisphosphonates are currently regarded as the treatment of choice and the only realistic therapeutic option, but in the near future other therapies (for example, anti-RANKL agents) may become available. Here we discuss the individual compounds, considering the evidence of their efficacy and the most com­monly used therapeutic regimens. With the sole exception of etidronate, the bisphosphonates appear to provide equivalent benefits. The degree of suppression of disease activity and the proportion of patients in whom the normalisation of bALP is achieved depends not on the potency of the individual com­pounds but rather on the dose administered and the duration of the treatment. Attempts to show that patients responding poor­ly to one compound can respond better to another have been unconvincing.

E t i d r o n a t e . Etidronate was the first bisphosphonate used for the clinical treatment of Paget’s disease. It is still available in most countries, but is gradually being abandoned in favour of the new bisphosphonates. Etidronate is commer­cially available in a 200- or 400-mg tablet. The recommended regimen is 5 mg/kg/day (i.e., a daily dose of 400 mg in most patients, taken at any time of day on an empty stomach) for a period of 6 months. The main problem associated with etidronate therapy is the development of mineralisation de­fects. All bisphosphonates have the capacity, at high enough doses, to impair mineralisation of newly forming bone. In the case of etidronate, the doses that most effectively reduce the increased bone resorption can also impair mineralisation, thus making it necessary to administer the compound at sub- optimal doses, and for no longer than 6 months at a time. Thus, in the most severe cases, etidronate therapy is able neither to suppress disease activity adequately nor to relieve symptoms.

Tiludronate. Tiludronate is about 10 times more potent than etidronate, and its use at effective doses is not associated with mineralisation problems. In most countries it has been regis­tered for treatment of Paget’s disease as Skelid in a 200-mg tablet. The recommended dose is 400 mg daily for 3 months, followed by a 3-month post-treatment observation period, after which the bALP is likely to have reached its nadir. This ap­proach led to a normal serum bALP at the 6-month point in a quarter of moderately affected subjects. The drug should be taken with a large glass of water in fasting conditions (at least 4 h after food) and the patient should avoid lying down for 30 minutes after ingesting it.

Pamidronate. Pamidronate has been available in the Nether­lands for several decades and worldwide (in an i.v. formulation) only since the early ’90s. The greater potency of pamidronate provided a number of advantages over etidronate and tilu- dronate, which are shared by all the newer, amino-bisphospho- nates:

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The primary objective of Paget’s disease treatment is the relief of symptoms, and the new bisphosphonates are the agents most likely to relieve the aches and pain, excessive warmth over affected bone, headache due to skull involvement, low- back pain secondary to pagetic vertebral changes, and effects of nerve compression associated with the condition. Even though filling in of osteolytic blade-of-grass lesions in weight- bearing bones has been reported in some treated cases, bone deformities and secondary osteoarthritic lesions usually remain unchanged, and loss of hearing is unlikely to improve. The question of whether or not to institute medical treatment to prevent the development of late complications in patients deemed to be at risk is still debated. In the past, medical intervention in patients with evidence of active disease (elevat­ed levels of bone turnover markers) but who were totally asymptomatic was not considered strictly necessary. This atti­tude is now changing, for three reasons:

1. Biopsy sample studies have reported restoration of normal patterns of new bone deposition following suppression of pagetic activity. This might imply that prolonged suppression of overactivity can allow full restoration of normal lamellar bone and eventually a partial resolution of the deformities.

2. Untreated disease, in which abnormal bone turnover persists for decades, may be associated with the appearance or worsening of irreversible bone deformities, and then sympto­matic disease. This has never been proven, although incom­plete suppression of elevated indices of bone turnover, on older therapies, has been associated with disease progres­sion. In this regard, it should be mentioned that pro­longed treatment with the new bisphosphonates is followed by a normalisation of indices in most patients.

3. The safety profile, the general acceptability, and the costs of treatment with the newer bisphosphonates, especially when administered intravenously are, in Europe at least, excellent. This very low cost/benefit ratio has encouraged a less con­servative attitude to definition of the treatment threshold.

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