Box 1.

Indications for Bisphosphonate Treatment

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Strickberger, S. A., Schulman, S. P. & Hutchins, G. M. Association of Paget's disease of bone with calcific aortic valve disease. Am. J. Med. 82, 953–956 (1987).
Harrison, C. V. & Lennox, B. Heart block in osteitis deformans. Br. Heart J. 10, 167–176 (1948).
Reifenstein, E. C. Jr & Albright, F. Paget's disease: Its pathologic physiology and the importance of the complications arising from fracture and immobilization. N. Engl. J. Med. 231, 343–355 (1944).
Gutteridge, D. H., Gruber, H. E., Kermode, D. G. & Worth, G. K. Thirty cases of concurrent Paget's disease and primary hyperparathyroidism: sex distribution, histomorphometry, and prediction of the skeletal response to parathyroidectomy. Calcif. Tissue Int. 65, 427–435 (1999).
Nagant de Deuxchaisnes, C. N. & Krane, S. M. Paget's disease of bone: clinical and metabolic observations. Medicine (Baltimore) 43, 233–266 (1964).
Singer, F. R. & Krane, S. M. In Metabolic Bone Disease (eds Avioli, L. V. & Krane, S. M.) 552–553 (Academic Press, New York, 1978).
Ryan, W. G., Schwartz, T. B. & Perlia, C. P. Effects of mithramycin on Paget's disease of bone. Ann. Intern. Med. 70, 549–557 (1969).
Bockman, R. S. et al. A multicenter trial of low dose gallium nitrate in patients with advanced Paget's disease of bone. J. Clin. Endocrinol. Metab. 80, 595–602 (1995).
Sturtridge, W. C., Harrison, J. E. & Wilson, D. R. Long-term treatment of Paget's disease of bone with salmon calcitonin. Can. Med. Assoc. J. 117, 1031–1034 (1977).
El Sammaa, M., Linthicum, F. H. Jr. House, H. P. & House, J. W. Calcitonin as treatment for hearing loss in Paget's disease. Am. J. Otol. 7, 241–243 (1986).
Singer, F. R., Fredericks, R. S. & Minkin, C. Salmon calcitonin therapy for Paget's disease of bone. The problem of acquired clinical resistance. Arthritis Rheum. 23, 1148–1154 (1980).
Singer, F. R. Human calcitonin treatment of Paget's disease of bone. Clin. Orthop. Relat. Res. 127, 86–93 (1977).
Khairi, M. R. et al. Sodium Etidronate in the treatment of Paget's disease of bone. A study of long-term results. Ann. Intern. Med. 87, 656–663 (1977).
Nancollas, G. H. et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38, 617–627 (2006).
Russell, R. G. Bisphosphonates: From bench to bedside. Ann. N. Y. Acad. Sci. 1068, 367–401 (2006).
Delmas, P. D., Chapuy, M. C., Edouard, C. & Meunier, P. J. Beneficial effects of aminohexane diphosphonate in patients with Paget's disease of bone resistant to sodium etidronate. Am. J. Med. 83, 276–282 (1987).
Evans, R. A., Dunstan, C. R., Hills, E. & Wong, S. Y. Pathologic fracture due to severe osteomalacia following low-dose diphosphonate treatment of Paget's disease of bone. Aust. N. Z. J. Med. 13, 277–279 (1983).
Altman, R. D. Long-term follow-up of therapy with intermittent etidronate disodium in Paget's disease of bone. Am. J. Med. 79, 583–590 (1985).
Stone, M. D., Hawthorne, A. B., Kerr, D., Webster, G. & Hosking, D. J. Treatment of Paget's disease with intermittent low-dose infusions of disodium pamidronate (APD). J. Bone Miner. Res. 5, 1231–1235 (1990).
Thiebaud, D., Jaeger, P., Gobelet, C., Jacquet, A. F. & Burckhardt, P. A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget's disease of bone. Am. J. Med. 85, 207–212 (1988).
Cundy, T., Wattie, D. & King, A. R. High-dose pamidronate in the management of resistant Paget's disease. Calcif. Tissue Int. 58, 6–8 (1996).
Gutteridge, D. H. et al. Paget's disease: Acquired resistance to one aminobisphosphonate with retained response to another. J. Bone Miner. Res. 14 (Suppl. 2), 79–84 (1999).
Siris, E. et al. Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone. J. Clin. Endocrinol. Metab. 81, 961–967 (1996).
De Groen, P. C. et al. Esophagitis associated with the use of alendronate. N. Engl. J. Med. 335, 1016–1021 (1996).
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Perazella, M. A. & Markowitz, G. S. Bisphosphonate nephrotoxicity. Kidney Int. 74, 1385–1393 (2008).
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Roohi, F., Mann, D. & Kula, R. W. Surgical management of hydrocephalic dementia in Paget's disease of bone: the 6-year outcome of ventriculo-peritoneal shunting. Clin. Neurol. Neurosurg. 107, 325–328 (2005).
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Parvizi, J., Frankle, M. A., Tiegs, R. D. & sim, F. H. Corrective osteotomy for deformity in Paget disease. J. Bone Joint Surg. Am. 85-a, 697–702 (2003).
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Author(s)

Frederick R. Singer, MD

Director, Endocrine/Bone Disease Program, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California; Clinical Professor of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California

Disclosures

Disclosure: Frederick R. Singer, MD, has disclosed that he has acted as a consultant for Amgen Inc. Dr. Singer has also disclosed that he has acted as a consultant to, been involved in speaker's bureaus for (honoraria), and has received grant/research support (including for clinical trials) from Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Procter & Gamble.

CME Author(s)

Charles P. Vega, MD, FAAFP

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

Disclosures

Disclosure: Charles P. Vega, MD, FAAFP, has disclosed no relevant financial relationships.

Editor(s)

Jenny Buckland

Editor, Nature Reviews Rheumatology

Disclosures

Disclosure: Jenny Buckland has disclosed no relevant financial relationships.

CME

Paget Disease: When to Treat and When Not to Treat

Authors: Frederick R. Singer, MD
CME Released: 8/4/2009
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 8/4/2010

Start Activity

Target Audience and Goal Statement

This activity is intended for primary care physicians, orthopaedists, endocrinologists, rheumatologists, and other physicians who care for patients with Paget's disease.

The goal of this activity is to diagnose and treat Paget's disease effectively.

Upon completion of this activity, participants will be able to:

Identify elements of the clinical presentation of Paget's disease
Describe complications of Paget's disease
Specify the most potent bisphosphonate in the treatment of Paget's disease
Classify who should receive immediate treatment for Paget's disease

Disclosures

Author(s)

Frederick R. Singer, MD

Director, Endocrine/Bone Disease Program, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California; Clinical Professor of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California

Disclosures

Disclosure: Frederick R. Singer, MD, has disclosed that he has acted as a consultant for Amgen Inc. Dr. Singer has also disclosed that he has acted as a consultant to, been involved in speaker's bureaus for (honoraria), and has received grant/research support (including for clinical trials) from Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Procter & Gamble.

CME Author(s)

Charles P. Vega, MD, FAAFP

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

Disclosures

Disclosure: Charles P. Vega, MD, FAAFP, has disclosed no relevant financial relationships.

Editor(s)

Jenny Buckland

Editor, Nature Reviews Rheumatology

Disclosures

Disclosure: Jenny Buckland has disclosed no relevant financial relationships.

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Conclusions

Several potent agents in the bisphosphonate family are now available that are highly effective in suppressing disease activity in patients with Paget disease. Bone pain, when present, is reduced and progression of osteolytic lesions can be halted or even reversed. Further study is required to determine whether prevention of possible complications in asymptomatic patients is achievable with these agents. Future studies assessing whether the inhibitor of receptor activator for nuclear factorêB (RANK) ligand, denosumab, is also effective in treating Paget disease will be of great interest; the importance of the RANK ligand-RANK interaction in osteoclast biology predicts that this might be a promising future thera peutic approach for patients with this potentially painful and deforming skeletal disease.^[71]

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CME Information

Acknowledgments

The author appreciates the long-term support of the Edythe and Eli Broad Foundation, and of Lois Rosen. Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Reprint Address

John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA; Email: [email protected]

Box 1.

CME

Paget Disease: When to Treat and When Not to Treat

Target Audience and Goal Statement

Disclosures

Author(s)

Frederick R. Singer, MD

CME Author(s)

Charles P. Vega, MD, FAAFP

Editor(s)

Jenny Buckland

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Paget Disease: When to Treat and When Not to Treat: Conclusions

Conclusions

Table of Contents

Acknowledgments

Reprint Address

Box 1.

References

Faculty and Disclosures

Author(s)

Frederick R. Singer, MD

CME Author(s)

Charles P. Vega, MD, FAAFP

Editor(s)

Jenny Buckland

CME

Paget Disease: When to Treat and When Not to Treat

Target Audience and Goal Statement

Disclosures

Author(s)

Frederick R. Singer, MD

CME Author(s)

Charles P. Vega, MD, FAAFP

Editor(s)

Jenny Buckland

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Paget Disease: When to Treat and When Not to Treat: Conclusions

Conclusions

Table of Contents

Acknowledgments

Reprint Address