Paget’s disease of bone is common, affecting up to 4% of Australians over the age of 55 years. The incidence of the disease and the severity of newly diagnosed cases appear to be falling, for unknown reasons.
The cause of Paget’s disease is unknown, but there is a strong genetic influence. Recently, mutations in the sequestosome 1/p62 gene have been identified as a cause of familial Paget’s disease and of some apparently sporadic cases of the disease.
The disease is often asymptomatic, but can cause bone pain, deformity, fracture and other complications.
Paget’s disease is eminently treatable. Potent bisphosphonates such as pamidronate, alendronate and risedronate relieve symptoms and may reduce the risk of complications.
The Pharmaceutical Benefits Scheme subsidises treatment only for patients with symptomatic disease. A strong case be made for also treating asymptomatic patients with involvement of long bones, vertebrae or base of skull, patients with significant osteolytic lesions, and perhaps all younger patients.
- 1. Paget J. On a form of chronic inflammation of bones. Medico-chirurgical Transactions 1877; 65: 37-63.
- 2. Lyles KW, Siris ES, Singer FR, Meunier PJ. A clinical approach to diagnosis and management of Paget’s disease of bone. J Bone Miner Res 2001; 16: 1379-1387.
- 3. Selby PL, Davie MW, Ralston SH, Stone MD. Guidelines on the management of Paget’s disease of bone. Bone 2002; 31: 366-373.
- 4. Cooper C, Dennison E, Schafheutle K, et al. Epidemiology of Paget’s disease of bone. Bone 1999; 24: 3S-5S.
- 5. Gardner MJ, Guyer PB, Barker DJP. Radiological prevalence of Paget’s disease of bone in British migrants to Australia. BMJ 1978; 1: 1655-1657.
- 6. Cooper C, Schafheutle K, Dennison E, et al. The epidemiology of Paget’s disease in Britain: is the prevalence decreasing? J Bone Miner Res 1999; 14: 192-197.
- 7. Doyle T, Gunn J, Anderson G, et al. Paget’s disease in New Zealand: evidence for declining prevalence. Bone 2002; 31: 616-619.
- 8. Siris ES, Ottman R, Flaster E, Kelsey JL. Familial aggregation of Paget’s disease of bone. J Bone Miner Res 1991; 6: 495-500.
- 9. Seton M, Choi HK, Hansen MF, et al. Analysis of environmental factors in familial versus sporadic Paget’s disease of bone — the New England Registry for Paget’s Disease of Bone. J Bone Miner Res 2003; 18: 1519-1524.
- 10. Laurin N, Brown JP, Morissette J, Raymond V. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet 2002; 70: 1582-1588.
- 11. Hocking LJ, Lucas GJ, Daroszewska A, et al. Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget’s disease. Hum Mol Genet 2002; 11: 2735-2739.
- 12. Hocking LJ, Lucas GJA, Daroszewska A, et al. UBA domain mutations of SQSTM1 in Paget’s disease of bone: genotype phenotype correlation, functional analysis and structural consequences. J Bone Miner Res 2004; 19: 1122-1127.
- 13. Duran A, Serrano M, Leitges M, et al. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Dev Cell 2004; 6: 303-309.
- 14. Suda T, Takahashi N, Udagawa N, et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999; 20: 345-357.
- 15. Helfrich MH, Hobson RP, Grabowski PS, et al. A negative search for a paramyxoviral etiology of Paget’s disease of bone: molecular, immunological, and ultrastructural studies in UK patients. J Bone Miner Res 2000; 15: 2315-2329.
- 16. Walton KR, Green JR, Reeve J, Wootton R. Reduction of skeletal blood flow in Paget’s disease with disodium etidronate therapy. Bone 1985; 6: 29-31.
- 17. Walsh JP, Ward LC, Stewart GO, et al. A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget’s disease of bone. Bone 2004: 34: 747-754.
- 18. Siris E, Weinstein RS, Altman R, et al. Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab 1996; 81: 961-967.
- 19. Reid IR, Nicholson GC, Weinstein RS, et al. Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate: a randomized, placebo-controlled trial. Am J Med 1996; 101: 341-348.
- 20. Khan SA, Vasikaran S, McCloskey EV, et al. Alendronate in the treatment of Paget’s disease of bone. Bone 1997; 20: 263-271.
- 21. Stewart GO, Gutteridge DH, Price RI, et al. Prevention of appendicular bone loss in Paget’s disease following treatment with intravenous pamidronate disodium. Bone 1999; 24: 139-144.
- 22. Altman RD. Long-term follow-up of therapy with intermittent disodium etidronate in Paget’s disease of bone. Am J Med 1985; 79: 583-590.
- 23. Gutteridge DH, Ward LC, Stewart GO, et al. Paget’s disease: acquired resistance to one aminobisphosphonate with retained response to another. J Bone Miner Res 1999; 14 Suppl 2: 79-84.
- 24. Trombetti A, Arlot M, Thevenon J, et al. Effect of multiple intravenous pamidronate courses in Paget’s disease of bone. Rev Rhum Engl Ed 1999; 66: 467-476.
Publication of your online response is subject to the Medical Journal of Australia's editorial discretion. You will be notified by email within five working days should your response be accepted.