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The treatment of Paget’s: Objective and treatment threshold

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 (8-10). 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.

According to recent recommendations on the management of Paget’s disease, the presence of asymptomatic but active disease (i.e., above normal serum alkaline phosphatase – bALP -) constitutes an indication for treatment aimed at preventing later complications. Others argue that the evidence does not yet support such use, because it has not been shown in clinical tri­als that suppression of the disease reduces progression of the deformity. The need for treatment might be considered more pressing when the involved skeletal sites are potentially more likely to give rise to severe problems or complications (e.g., weight-bearing bones, areas near major joints, vertebral bodies, extensive involvement of the skull). In this setting, treatment is also more warranted in younger patients, who may have to live with the disease for years. However, even in the elderly, med­ical treatment is justified in the presence of bone involvement very close to joints or nerve roots that might quickly (within the space of a few years) give rise to problems. Treatment might also be indicated in some cases with normal bALP activity but with focal symptoms. We have observed a few cases presenting small (a phalange, the clavicle, part of the parietal bone) but very active monostotic lesions, in whom a first course of treatment relieved symptoms and fully sup­pressed bALP (even taking it to the lower end of the normal range). Although the symptoms returned within a few months (in spite of the bALP value still being well within the normal range), it was found that they could rapidly be relieved again with further courses of treatment (Figure 1). One of the most scarring complications of surgery at the site of a pagetic lesion is severe blood loss. Although controlled stud­ies are not available, an intense course of treatment is recom­mended in this situation, the aim being to reduce as much as possible the vascularity of the lesion.
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F i g u r e 1 - Changes in pain scoreFigure 1 – Changes in pain score (Visual analogue scale, VAS) and in serum alkaline phosphatase (bALP) after single i.v. infusions of 100 mg neridronate (arrows) in a patient with focal pagetic lesion of the left parietal bone of the skull. Pain resumed despite persistent normal levels of bALP and was relieved by each neridronate infusion.

Category: Disease

Tags: bisphosphonate, bone turnover, Paget

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