Endocrine Abstracts

Paget’s disease of bone (PDB) is the second commonest bone disease. The original disease description in 1876 by Sir James Paget remains an incisive, accurate report of the pathophysiology of PDB, which is characterised by focal regions of increased bone remodelling with initial excessive bone resorption and osteolytic lesions followed by long term increased bone formation and sclerosis. The majority of patients are elderly, many are asymptomatic. Those that are referred to hospital are usually symptomatic with bone pain, skeletal deformity, pathological fractures, neurological symptoms and deafness¹.

There is marked geographical variation in PDB with the highest prevalence/incidence in the UK, particular North West England. Recent studies in the UK and New Zealand have suggested that there is a decline in the prevalence and severity of PDB and a gradual decrease in concentration of total ALP at presentation^1–3.

Measurement of new biochemical markers of bone metabolism have failed to establish an obvious successor to total ALP in terms of the cost-benefit for the information gained either for diagnosis or follow-up. The modest benefit of bone specific ALP is seen in patients with monostotic (single bone involvement) PDB.

The bisphosphonate drugs are the treatment of choice for PDB. IV zoledronate has been assessed compared to oral risedronate in 176 patients with PDB. A single 5 mg infusion of zoledronate produced a more rapid, more complete, and more sustained response in PDB than 2 months treatment with 30 mg risedronate daily^4,5.

However questions have been raised regarding the optimal way to treat and assess patients with PDB. A prospective randomised trial of intensive vs symptomatic management (PRISM) of PDB has been performed to investigate how patients should be treated and subsequently extended to include treatment with zoledronate (PRISM-EZ). 1324 entered PRISM with one half receiving increasing analgesia or mild bisphosphonate treatment (symptomatic) and the other group receiving potent bisphosphonates to maintain their total ALP within the reference range (intensive). The primary endpoint was fracture, with secondary endpoints of progression of deafness, requirement for orthopaedic surgery and quality of life⁶. No significant difference was observed between the treatments after an average of 32 months treatment.

There is some suggestion from these recent trials that the previous apparent close association between total ALP and disease activity/symptomatology, especially following treatment, no longer holds true and patients should always be assessed clinically including radiological assessment rather than basing treatment purely on biochemical measurements⁶.

References: 1. Davie M, et al. Paget’s disease of bone: a review of 889 patients. Bone 1999 24 11S–12S.

2. Cooper C, et al. The epidemiology of Paget’s disease in Britain: is the prevalence decreasing? JBMR 1999 14 192–197.

3. Cundy T, et al. Evidence for secular change in Paget’s disease. Bone 1997 20 69–71.

4. Reid I, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. NEJM 2005 353 898–908.

5. Hosking, et al. Long term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. JBMR 2007 22 142–148.

6. Langston A, et al. Clinical determinants of quality of life in Paget’s disease of bone. CTI 2007 80 1–9.