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).

As an organization accredited by the ACCME, MedscapeCME requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

MedscapeCME encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

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.

Accreditation Statements

For Physicians

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of MedscapeCME and Nature Publishing Group.

MedscapeCME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

MedscapeCME designates this educational activity for a maximum of 0.75 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

Read the target audience, learning objectives, and author disclosures.
Study the educational content online or printed out.
Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

processing....

Clinical Presentation

The clinical manifestations of Paget disease range from no symptoms in patients who are diagnosed accidentally to painful deformities of one or more bones in symptomatic patients. Symptoms and signs are more likely to occur in patients with polyostotic involvement than in those with monostotic involvement of the skeleton. In the latest large study of patients referred for evaluation of Paget disease, 34% had a monostotic lesion, with an overall average of 5.5 lesions per patient in the whole group.^[3]

An accidental discovery of Paget disease often occurs through the finding of elevated serum alkaline phosphatase activity on a screening chemistry panel followed by radiologic documentation of the disorder. Elevations of alkaline phosphatase activity reflect an increased number of osteoblasts in the sclerotic lesions of a patient with Paget disease. The activity of this enzyme reflects the rate of bone formation and the level of activity correlates directly with the extent of skeletal involvement.^[4] Normal levels are found in patients with small foci of active disease. Other indices of bone formation might also be increased, including levels of bonespecific alkaline phosphatase, procollagen type 1 N-propeptide or osteocalcin,^[5] but levels of these markers are not often tested for in clinical evaluations of patients who are not suspected of having bone disease. Biochemical markers of bone resorption are also increased in the serum or urine, or both, of most patients with Paget disease. Serum and urine levels of N-telopeptide and C-telopeptide, and urine pyridinoline levels might be increased,^[5] but in clinical practice serum alkaline phosphatase activity remains the most common metabolic parameter to reveal ‘silent Paget disease’. Paget disease is most likely to be noted in radiologic examinations intended to evaluate abdominal symptoms, back pain, pelvic pain or hip pain. In most of these cases, Paget disease is likely to be asymptomatic.

Bone pain in Paget disease is generally mild to moderate, is usually persistent, and might be slightly more severe in the weightbearing lower extremities. Pain in the lower extremity should be readily distinguished from arthritic pain, which is often much more severe during weight bearing and usually is absent or reduced in severity when the individual is sitting or lying. Skeletal deformities of Paget disease are most easily recognized in the skull and facial bones, and in the extremities. The skull enlarges asymmetrically over many years and would most readily be appreciated in an individual whose hat size has increased over time. Lateral or anterior bowing (or both) of the lower extremities can be seen in patients whose femur or tibia is completely or nearly completely affected by Paget disease.

« Back

Page 2 of 8

Clinical Course

CME Information

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: Clinical Presentation

Clinical Presentation

Table of Contents

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: Clinical Presentation

Clinical Presentation

Table of Contents