Box 1.

Indications for Bisphosphonate Treatment

Paget, J. On a form of chronic inflammation of bones (osteitis deformans). Medico-Chirurgical Transactions of London 60, 37–63 (1877).
Maldague, B. & Malghem, J. Dynamic radiologic patterns of Paget's disease of bone. Clin. Orthop. Relat. Res. 217, 126–151 (1987).
Haddaway, M. J., Davie, M. W., McCall, I. W. & Howdle, S. Effect of age and gender on the number and distribution of sites in Paget's disease of bone. Br. J. Radiol. 80, 532–536 (2007).
Franck, W. A., Bress, N. M., singer, F. R. & Krane, S. M. Rheumatic manifestations of Paget's disease of bone. Am. J. Med. 56, 592–603 (1974).
Shankar, S. & Hosking, D. J. Biochemical assessment of Paget's disease of bone. J. Bone Miner. Res. 21 (Suppl. 2), P22–P27 (2006).
Renier, J. C. & Audran, M. Progression in length and width of pagetic lesions, and estimation of age at disease onset. Rev. Rhum. Engl. Ed. 64, 35–43 (1997).
Daroszewska, A. & Ralston, S. H. Mechanisms of disease: genetics of Paget's disease of bone and related disorders. Nat. Clin. Pract. Rheumatol. 2, 270–277 (2006).
Wermers, R. A., Tiegs, R. D., Atkinson, E. J., Achenbach, S. J. & Melton, L. J. 3rd. Morbidity and mortality associated with Paget's disease of bone: a population-based study. J. Bone Miner. Res. 23, 819–825 (2008).
Mackenzie, I., Young, C. & Fraser, W. D. Tinnitus and Paget's disease of bone. J. Laryngol. Otol. 120, 899–902 (2006).
Smith, B. J. & Eveson, J. W. Paget's disease of bone with particular reference to dentistry. J. Oral Pathol. 10, 233–247 (1981).
Hadjipavlou, A. G., Gaitanis, L. N., Katonis, P. G. & Lander, P. Paget's disease of the spine and its management. Eur. Spine J. 10, 370–384 (2001).
Dove, J. Complete fractures of the femur in Paget's disease of bone. J. Bone Joint Surg. Br. 62-B, 12–17 (1980).
Allen, M. L. & John, R. L. Osteitis deformans (Paget's disease). Fissure fractures—their etiology and clinical significance. Am. J. Roentgenol. Rad. Ther. 38, 109–115 (1937).
Marr, D. S., Rosenthal, D. I., Cohen, G. L. & Tomford, W. W. Rapid postoperative osteolysis in Paget disease. A case report. J. Bone Joint Surg. Am. 76, 274–277 (1994).
Deyrup, A. T. et al. Sarcomas arising in Paget disease of bone: a clinicopathologic analysis of 70 cases. Arch. Pathol. Lab. Med. 131, 942–946 (2007).
Mangham, D. C., Davie, M. W. & Grimer, R. J. Sarcoma arising in Paget's disease of bone: declining incidence and increasing age at presentation. Bone 44, 431–436 (2009).
Singer, F. R. & Mills, B. G. Giant cell tumor arising in Paget's disease of bone. recurrences after 36 years. Clin. Orthop. Relat. Res. 293, 293–301 (1993).
Haworth S. Cardiac output in osteitis deformans. Clin. Sci. 12, 271–275 (1953).
Laroche, M. & Delmotte, A. Increased arterial calcification in Paget's disease of bone. Calcif. Tissue Int. 77, 129–133 (2005).
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).
Siris, E. S. et al. risedronate in the treatment of Paget's disease of bone: an open label, multicenter study. J. Bone Miner. Res. 13, 1032–1038 (1998).
Reid, I. R. et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N. Engl. J. Med. 353, 898–908 (2005).
Hosking, D. et al. Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. J. Bone Miner. Res. 22, 142–148 (2007).
Tziomalos, K. et al. Persistent effect of zoledronic acid in Paget's disease. Clin. Exp. Rheumatol. 25, 464–466 (2007).
Fraunfelder, F. W., Fraunfelder, F. T. & Jensvold, B. Scleritis and other ocular side effects associated with pamidronate disodium. Am. J. Ophthalmol. 135, 219–222 (2003).
Perazella, M. A. & Markowitz, G. S. Bisphosphonate nephrotoxicity. Kidney Int. 74, 1385–1393 (2008).
Shane, E. et al. Osteonecrosis of the jaw: more research needed. J. Bone Miner. Res. 21, 1503–1505 (2006).
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).
McDonald, D. J. & Sim, F. H. Total hip arthroplasty in Paget's disease. A follow-up note. J. Bone Joint Surg. Am. 69, 766–772 (1987).
Lusty, P. J., Walter, W. L., Walter, W. K. & Zicat, B. Cementless hip arthroplasty in Paget's disease at medium-term follow-up (average of 6.7 years). J. Arthroplasty 22, 692–696 (2007).
Gabel, G. T., Rand, J. A. & Sim, F. H. Total knee arthroplasty for osteoarthrosis in patients who have Paget disease of bone at the knee. J. Bone Joint Surg. Am. 73, 739–744 (1991).
Lee, G. C., Sanchez-Sotelo, J. & Berry, D. J. Total knee arthroplasty in patients with Paget's disease of bone at the knee. J. Arthroplasty 20, 689–693 (2005).
Meyers, M. H. & Singer, F. R. Osteotomy for tibia vara in Paget's disease under cover of calcitonin. J. Bone Joint Surg. Am. 60, 810–814 (1978).
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).
Shardlow, D. L., Giannoudis, P. V., Matthews, S. J. & Smith, R. M. Stabilisation of acute femoral fractures in Paget's disease. Int. Orthop. 23, 283–285 (1999).
Wootton, R., Reeve, J., Spellacy, E. & Tellez-Yudilevich, M. Skeletal blood flow in Paget's disease of bone and its response to calcitonin therapy. Clin. Sci. Mol. Med. 54, 69–74 (1978).
Eekhoff, M. E. et al. Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey-the rotterdam study. J. Bone Miner. Res. 19, 566–570 (2004).
Takata, S. et al. Guidelines for diagnosis and management of Paget's disease of bone in Japan. J. Bone Miner. Metab. 24, 359–367 (2006).
Selby, P. L. Guidelines for the diagnosis and management of Paget's disease: a UK perspective. J. Bone Miner. Res. 21 (Suppl. 2), P92–P93 (2006).
Siris, E. S., Lyles, K. W., Singer, F. R. & Meunier, P. J. Medical management of Paget's disease of bone: indications for treatment and review of current therapies. J. Bone Miner. Res. 21 (Suppl. 2), P94–P98 (2006).
Josse, R. G. et al. Diagnosis and treatment of Paget's disease of bone. Clin. Invest. Med. 30, e210–223 (2007).
Adami, S. et al. Italian guidelines for the diagnosis and treatment of Paget's disease of bone [italian]. Reumatismo 59, 153–168 (2007).
Devogelaer, J. P. et al. Management of patients with Paget's disease: a consensus document of the Belgian Bone Club. Osteoporos. Int. 19, 1109–1117 (2008).
Ralston, S. H. et al. Initial results from the PRISM study: a large randomized comparative trial of intensive versus symptomatic treatment for Paget's disease. J. Bone Miner. Res. 21 (Suppl. 1), LB1 (2006).
Nathan, A. W., Ludlam, H. A., Wilson, D. W. & Dandona, P. Hypercalcaemia due to immobilization of a patient with Paget's disease of bone. Postgrad. Med. J. 58, 714–715 (1982).
Meunier, P. J. & Vignot, E. Therapeutic strategy in Paget's disease of bone. Bone 17, s489–s491 (1995).
Whitson, H. E., Lobaugh, B. & Lyles, K. W. Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone. Bone 39, 954–958 (2006).
Boyce, B. F. & Xing, L. Functions of RANKL/ RANK/OPG in bone modeling and remodeling. Arch. Biochem. Biophys. 473, 139–146 (2008).

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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, 11:59 PM EST

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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For Physicians

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Abstract and Introduction

Abstract

Paget disease of bone is a focal disorder of the skeleton that can affect one or more bones. Many patients are discovered accidentally because of elevated serum alkaline phosphatase activity or an abnormal skeletal radiograph intended to evaluate an unrelated condition. Patients are often asymptomatic, but a subset experience considerable morbidity that can include bone pain and skeletal deformity, as well as a variety of regional complications, such as hearing loss associated with cranial involvement, degenerative arthritis of the hip or knee, fractures of the lower extremities and, rarely, sarcoma or giant cell tumors. Bisphosphonates have proven to be effective in controlling disease activity because they inhibit osteoclast function. Administration of these agents can relieve bone pain, decrease biochemical markers of bone resorption and bone formation, and retard or reverse the early osteolytic phase of the disease. Future studies are needed to determine whether these drugs, if used in an early stage of the disease, can prevent complications in asymptomatic patients.

Introduction

In 1877 sir James Paget published his classic study of patients he had seen with focal enlargement and de formity of the skeleton.^[1] Later, with the advent of radiologic evaluation of the skeleton,^[2] it was appreciated that the earliest phase of Paget disease was characterized by one or more focal osteolytic lesions, which developed over many years into sclerotic lesions that could then be detected on physical examination (Figure 1).

Figure 1.

Enlarge

Cortical changes in an untreated patient with Paget disease. Evolution of cortical changes in the left tibia on the lateral view of an untreated woman with Paget disease from age 45 to 68 years, as assessed by radiography. The arrows indicate the area of marked cortical thickening. The distal tibia appeared normal in 1964, but sclerotic changes progressively increased by 1987. Anterior bowing, which was mild in 1964, became progressively worse by 1987. Reproduced with permission from the American society for Bone and Mineral research © J. Bone Miner. Res. 12, 691–692 (1997).

Page 1 of 8

Clinical Presentation

CME Information

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

Abstract and Introduction

Abstract

Introduction

Figure 1.

Table of Contents