Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Paget Disease

  • Author: Mujahed M Alikhan, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Dec 17, 2015
 

Background

Paget disease is a localized disorder of bone remodeling that typically begins with excessive bone resorption followed by an increase in bone formation. This osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.

The English surgeon Sir James Paget first described chronic inflammation of bone as osteitis deformans in 1877.[1] Paget disease, as the condition came to be known, is the second most common bone disorder (after osteoporosis) in elderly persons.

Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:

  • Bone pain (the most common symptom)
  • Secondary osteoarthritis (when Paget disease occurs around a joint)
  • Bony deformity (most commonly bowing of an extremity)
  • Excessive warmth (due to hypervascularity)
  • Neurologic complications (caused by the compression of neural tissues)

Paget disease may involve a single bone but is more frequently multifocal. It has a predilection for the axial skeleton (ie, spine, pelvis, femur, sacrum, and skull, in descending order of frequency), but any bone may be affected. After onset, Paget disease does not spread from bone to bone, but it may become progressively worse at preexisting sites.

Sarcomatous degeneration of pagetic bone is an uncommon but often deadly complication. Pagetic sarcoma is malignant, and the course usually is rapid and fatal

Although the etiology of Paget disease is unknown, both genetic and environmental contributors have been suggested. Ethnic and geographic clustering of Paget disease is well described. Paget disease is common in Europe (particularly Lancashire, England), North America, Australia, and New Zealand. It is rare in Asia and Africa. In the United States, most, although not all, individuals with Paget disease are white. (See Epidemiology.)

A familial link for Paget disease was first reported by Pick in 1883, who described a father-daughter pair with Paget disease. This was followed shortly thereafter with a sibling case of Paget disease described by Lunn in 1885. Approximately 40% of persons with Paget disease report a family history of the disease, although the true prevalence of the disease is likely higher.

Some studies suggest a genetic linkage for Paget disease located on chromosome arm 18q. This has not been demonstrated in most families with Paget disease, however, which suggests genetic heterogeneity.

An environmental trigger for Paget disease has long been considered but never proven. Bone biopsies in patients with Paget disease have demonstrated antigens from several different Paramyxoviridae viruses, including measles virus and respiratory syncytial virus, located within osteoclasts. However, the putative antigen or antigens remain unknown.

Measurement of serum alkaline phosphatase—in some cases, bone-specific alkaline phosphatase (BSAP)—along with several urinary markers, can be useful in the diagnosis of Paget disease. Plain radiographs and bone scanning should be performed upon initial diagnosis. (See Workup.) Medical therapy is principally with bisphosphonates; surgical therapy may be indicated. (See Treatment.)

A 2014 Endocrine Society Clinical Practice Guideline on Paget disease recommends the following[2] :

  • Plain radiographs of the pertinent regions of the skeleton in patients with suspected Paget disease
  • A radionucleotide bone scan to determine the extent of the disease if the diagnosis is confirmed
  • Measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients
  • Consider treatment with a bisphosphonate for most patients with active Paget disease who are at risk for future complications
  • Consider a single 5-mg dose of intravenous zoledronate as the treatment of choice in patients who have no contraindication
  • Consider measurement of a specific marker of bone formation and bone resorption in patients with monostotic disease who have a normal serum total alkaline phosphatase
  • Consider serial radionuclide bone scans to determine the response to treatment if the markers are normal
  • Bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget disease and may reverse paraplegia associated with spinal Paget disease
  • Consider treatment with a bisphosphonate before surgery on pagetic bone
Next

Pathophysiology

Three phases of Paget disease have been described: lytic, mixed lytic and blastic, and sclerotic. In an individual patient, different skeletal lesions may progress at different rates. Thus, at any one time, multiple stages of the disease may be demonstrated in different skeletal regions.

Paget disease begins with the lytic phase, in which normal bone is resorbed by osteoclasts that are more numerous, are larger, and have many more nuclei (up to 100) than normal osteoclasts (5-10 nuclei). Bone turnover rates increase to as much as 20 times normal.

The second phase, the mixed phase, is characterized by rapid increases in bone formation from numerous osteoblasts. Although increased in number, the osteoblasts remain morphologically normal. The newly made bone is abnormal, however, with collagen fibers deposited in a haphazard fashion rather than linearly, as with normal bone formation. As the osteoclastic and osteoblastic activities of bone destruction and formation repeat, a high degree of bone turnover occurs.

In the final phase of Paget disease, the sclerotic phase, bone formation dominates and the bone that is formed has a disorganized pattern (woven bone) and is weaker than normal adult bone. This woven bone pattern allows the bone marrow to be infiltrated by excessive fibrous connective tissue and blood vessels, leading to a hypervascular bone state.

After a variable amount of time, osteoclastic activity may decrease, but abnormal bone formation continues. Some pockets of normal-appearing lamellar bone may replace immature woven bone. Eventually, osteoblastic activity also declines, and the condition becomes quiescent. This is the sclerotic, or burned-out, phase. Continued bone resorption and formation are minimal or absent.

Paget disease can affect every bone in the skeleton, but it has an affinity for the axial skeleton, long bones, and the skull. The skeletal sites primarily affected include the pelvis, lumbar spine, femur, thoracic spine, sacrum, skull, tibia, and humerus. The hands and feet are very rarely involved.

Complications of Paget disease depend on the site affected and the activity of the disease. When Paget disease occurs around a joint, secondary osteoarthritis may ensue. Skull involvement may lead to the following:

  • Deafness
  • Vertigo
  • Tinnitus
  • Dental malocclusion
  • Basilar invagination
  • Cranial nerve disorders

Frequently, erythema is present over the affected bone area, which is due to the increased hypervascularity. In patients with Paget disease who have extensive bony involvement, this increased bone vascularity may cause high-output cardiac failure and an increased likelihood of bleeding complications following surgery.

Vertebral involvement of Paget disease may be associated with serious complications, including nerve root compressions and cauda equina syndrome. Fractures, which are the most common complication of Paget disease, may occur and may have potentially devastating consequences. Rarely, pagetic bone may undergo a sarcomatous transformation.

Standard serum chemistry values, including serum calcium, phosphorus, and parathyroid hormone levels, are normal in persons with Paget disease. However, hypercalcemia may complicate the course of Paget disease, most frequently in the setting of immobilization. Elevated levels of uric acid and an increased prevalence of gout have been reported in patients with Paget disease.

Levels of bone turnover markers (including markers of bone formation and resorption) are elevated in patients with active Paget disease and may be used to monitor the course of disease. The degree of elevation of these biomarkers helps identify the extent and severity of bone turnover.

Markers of bone turnover that are useful to monitor in persons with Paget disease include the following:

  • Bone-specific alkaline phosphatase (marker of bone formation)
  • Deoxypyridinoline (marker of bone resorption)
  • N -Telopeptide of type I collagen (marker of bone resorption)
  • Alpha-alpha type I C -telopeptide fragments

Alpha-alpha type I C-telopeptide fragments are sensitive markers of bone resorption for assessing disease activity and monitoring treatment efficacy in persons with Paget disease.[3] Serum osteocalcin, a marker of bone formation, is not a useful parameter to assess in persons with Paget disease. Upon successful treatment of Paget disease, the level of these bone markers is expected to decrease.

The juvenile form of Paget disease differs greatly from the adult version. Juvenile Paget disease is characterized by widespread skeletal involvement and has distinctly different histologic and radiologic features.

Previous
Next

Etiology

The cause of Paget disease is unknown. Both genetic and environmental factors have been implicated.

Genetic predisposition

The geographic distribution of the disease may be explained by genetic transmission and dissemination by population migration. Studies have found a positive family history in 12.3% of 788 patients in the United States, 13.8% of 407 patients in Great Britain, and 22.8% of 658 patients in Australia. In the former 2 studies, a 7- to 10-fold increase in the incidence of Paget disease was observed in relatives of patients diagnosed with the condition, compared with control groups.

In one study, 15-40% of affected patients had a first-degree relative with Paget disease. Numerous other studies have described families exhibiting autosomal dominant inheritance.

Studies of potential genetic markers for Paget disease have found an association between human leukocyte antigen–A (HLA-A), HLA-B, and HLA-C (class I) and clinical evidence of disease. Two studies reported an increased frequency of DQW1 and DR2 antigens (class II HLA). The studies on HLA have not been conclusive, however; variation among families tested suggests that genetic heterogeneity is likely.[4]

Subsequent genome linkage studies identified several loci associated with Paget disease. Mutations in the sequestosome SQSTM1/p62 gene were identified in 30% of familial Paget cases. The SQSTM1/p62 protein is a selective activator of NFB (nuclear factor kappa-B) transcription factor, which is involved in osteoclast differentiation and activation in response to the cytokines interleukin-1 (IL-1) and RANKL (receptor activator of nuclear factor kappa-B ligand). How germline DNA mutations can cause bone disease that is focal in nature remains unclear.

Alterations in cytokine expression have been found in persons with Paget disease[5] : elevated interleukin-6 (IL-6) levels are found in bone marrow plasma and peripheral blood in patients with Paget disease but not in healthy controls. One hypothesis is that some unidentified viral infection up-regulates IL-6 and the IL-6 receptor genes; however, this has not been shown conclusively.[6, 7]

Osteoclast precursors in patients with Paget disease also appear to be hyperresponsive to vitamin D (specifically, 1,25(OH)2 D3, the active form of vitamin D3[8] ) and calcitonin and have up-regulation of the c-fos proto-oncogene[9] and BC12, the antiapoptosis gene. Treatment efficacy of bisphosphonates in Paget disease may be due to suppression of RANKL-induced bone resorption, with decreases in RANKL and increased osteoprotegerin production.

Macrophage-colony stimulating factor (M-CSF) may play a role in Paget disease. M-CSF is a growth factor produced by many cells, including osteoblasts and marrow fibroblasts. Significantly high levels of M-CSF have been found in patients with untreated Paget disease; however, its exact role remains to be determined.

The development of Paget disease of bone may be related to a deregulation of autophagy, a catabolic process responsible for the degradation of damaged organelles, cytoplasmic proteins, and protein aggregates. Structures observed in the cytoplasm of many osteoclasts in Paget disease may be protein aggregates that would normally be degraded via autophagy.[10]

Variants of several genes involved in the process of autophagy, such as SQSTM1, VCP, and OPTN have been linked with Paget disease. For example, 20–40% of patients with a positive family history of Paget disease and 5–10% of patients with sporadic Paget disease are carriers of a mutation in SQSTM1.[10]

A study of ATG genes, which code for proteins involved in autophagy, found that persons who are carriers of the C allele of the ATG16L1 rs2241880 and the G allele of ATG5 rs2245214 polymorphisms were associated with an increased risk of developing Paget disease, whereas carrier sof the T allele of ATG10 rs1864183 polymorphism were at decreased risk.[10]

Environmental factors

Environmental factors also may contribute to the pathogenesis of Paget disease. Supporting observations include the variable penetrance of Paget disease within families with a genetic predisposition; the fact that the disease remains highly localized to a particular bone or bones rather than affecting the entire skeleton; and data that reveal a declining incidence and severity of the disease over the past 20-25 years.

Viral infection

The leading hypothesis for an infectious etiology in Paget disease is the slow virus theory. According to this hypothesis, bone marrow cells (the progenitors of osteoclasts) are infected by a virus, causing an abnormal increase in osteoclast formation. Clinical expression of these viral infections may take years, which may account for the advanced age of most people diagnosed with Paget disease. Familial and geographic clustering also may support the theory of a viral process.

Suspected viruses are paramyxoviruses, such as measles or canine distemper viruses. Respiratory syncytial virus also is suspected; however, no virus has been cultured from pagetic tissue, and extracted ribonucleic acid (RNA) has not confirmed a viral presence.

Some studies have found viral inclusion particles in pagetic osteoclasts.[11] Measles virus messenger RNA sequences have been found in osteoclasts and other mononuclear cells of pagetic bones. Canine distemper virus nucleocapsid antigens have also been found in osteoclasts from patients with Paget disease. However, the presence of these paramyxovirus-like nuclear inclusions does not prove that these are responsible for the development of pagetic lesions; rather, these inclusions may be markers of the disease itself.

Other suggested etiologies

The possibility of an inflammatory cause of Paget disease is supported by evidence of clinical improvement after treatment with anti-inflammatory medications. Elevated parathyroid hormone in Paget disease also has been observed, but no firm evidence links the 2 disorders, and one case of Paget disease was diagnosed in a patient with idiopathic hypoparathyroidism. An osteogenic mechanism also has been proposed. Autoimmune, connective tissue, and vascular disorders are proposed as other possible etiologies.

Previous
Next

Epidemiology

United States statistics

Paget disease is estimated to affect 1 to 3 million people in the United States. Epidemiologic studies are inherently imprecise, however, because many individuals with Paget disease are asymptomatic.

According to a 2000 study by Altman et al, the prevalence of pelvic Paget disease in the United States was 0.71% ± 0.18%, based on data from the National Health and Nutrition Examination Survey I (NHANES I, 1971-1975). The male-to-female ratio was 1.2:1, and the prevalence of pelvic Paget disease was the same in white persons and black persons.

The prevalence of pelvic Paget disease increases with age, with the highest prevalence in persons older than 65 years. A survey study suggested that the prevalence in the United States is 2.3% of the population between ages 65 and 74 years.[12] Paget disease is estimated to occur in 1-3% of individuals older than 45-55 years and in up to 10% of persons older than 80 years. Geographically, pelvic Paget disease was least common in the southern United States and most common in the northeastern United States.[12]

International statistics

The prevalence of Paget disease varies greatly in different areas of the world. The highest prevalence is in Europe (predominantly England, France, and Germany).[13] The United States, Australia, and New Zealand have high prevalence rates because of significant populations with northern European ancestry and a large population of British immigrants.[14] The disease is rare in Asian countries, especially China, India, and Malaysia, and in the Middle East and Africa.

Prevalence may vary even within the same country.[15] A prevalence of 2% in certain British cities can be contrasted with rates in Lancaster, England, which had a prevalence of 8.3%.[16]

In Europe, the prevalence rates of Paget disease appear to decrease from north to south, with the exception of Norway and Sweden, which both have very low rates (0.3%). The highest prevalence in Europe is found in England (4.6%) and France (2.4%) in hospitalized patients older than 55 years. Other European countries, such as Ireland, Spain, Germany, Italy, and Greece, report prevalence rates of Paget disease that range from 0.5% to approximately 2%. The prevalence rates of Paget disease in Australia and New Zealand range from 3-4%.

The prevalence of Paget disease in sub-Saharan Africa is 0.01-0.02%. In Israel, Paget disease is predominantly found in Jews; however, cases have recently been reported in Israeli Arabs.

In South America, the incidence of Paget disease is relatively high in Argentina (around Buenos Aires), which was settled by Spanish and Italian immigrants, and lower in Chile and Venezuela.

Research from Europe and New Zealand indicates that the prevalence of Paget disease has decreased since the 1980s but that increased incidence with age has been maintained.[17] The estimated prevalence of Paget's disease in patients aged 55 years or older has decreased to approximately 2%.

Race-, sex-, and age-related differences in incidence

Paget disease is not known to demonstrate a predilection for any race. Nevertheless, unusual patterns of prevalence have been noted. Paget disease is more common in males than females. The male-to-female ratio is approximately 1.8:1.

Paget disease is distinctly rare in persons younger than 25 years and increases in frequency with increasing age. Paget disease is believed to develop in persons in the fifth decade of life and is most commonly diagnosed in the sixth decade. The incidence of Paget disease in persons older than 80 years is approximately 10%. There is a juvenile form of Paget disease, but it is very different from the adult form.

Previous
Next

Prognosis

The general outlook for patients with Paget disease is good, especially if treatment is administered before major changes have occurred in the bones. Treatment does not cure Paget disease, but it can control it. Patients with severe polyostotic Paget disease have a less favorable prognosis than those with monostotic disease. Patients with polyostotic disease are at higher risk for complications.

Morbidity from Paget disease can be extensive. The excessive remodeling of bone associated with Paget disease may result in pain, fractures, and bone deformities. Complications associated with fractures, such as articular and neurologic problems, may increase mortality in patients with Paget disease. The hypervascularity of bone that may result from Paget disease may cause excessive bleeding following fractures or surgery.

The prognosis is extremely unfavorable if the patient has any type of sarcomatous degeneration, especially if there is multicentricity. The 5-year survival rate for a patient with Paget disease and sarcoma is 5-7.5%; however, it may be as high as 50% for those who undergo operative tumor ablation and chemotherapy before metastases occur. The 5-year survival rate for elderly patients with primary nonpagetic sarcoma is 37%.

Higher doses of radiation may be delivered if the neoplasm is located on the limb. Consequently, a more central lesion carries a less favorable prognosis.

Previous
Next

Patient Education

Patient education about the pathophysiology of Paget disease and its complications is essential. The patient needs to understand the importance of proper posture, body mechanics, and avoidance of trauma. Precautions against falling should be reinforced. At the same time, the hazards of immobility increase greatly with Paget disease. The patient should understand the necessity of staying active.

Knowledge of the signs and symptoms of complications is important. For instance, increased local pain with soft tissue mass should be reported to a physician immediately, as this may represent a sarcoma.

Understanding the potential side effects of medications is helpful and reassuring to the patient. For example, patients taking bisphosphonates should be aware of the potential for osteonecrosis of the jaw.

Patient education about delayed bone healing and the long rehabilitation process is important in situations of fracture and postsurgery. Reinforcement about the importance of careful, prolonged, protected weight bearing is crucial because the pagetic bone is abnormal and weak. Nonunion and refracture rates are high among patients with Paget disease.

Family members should be informed of the increased incidence of Paget disease in families. Proper patient education on the nature of Paget disease is essential. The Paget Foundation for Paget's Disease of Bone and Related Disorders (telephone: 800-237-2438) can provide useful information for patients.

Previous
 
 
Contributor Information and Disclosures
Author

Mujahed M Alikhan, MD Rheumatologist

Mujahed M Alikhan, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Karen Driver, MS Medical Writer, Procter and Gamble Company

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Laura D Carbone, MD, MS Professor of Medicine, Division of Connective Health Diseases, Director, Memphis Metabolic Bone Center, Department of Medicine, University of Tennessee Health Science Center College of Medicine

Laura D Carbone, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Rheumatology, American Medical Women’s Association, American Society for Bone and Mineral Research; and International Society for Clinical Densitometry

Disclosure: Novartis Honoraria Consulting, Speaking and teaching; P&G Honoraria Consulting, Speaking and teaching

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Marlon J Navarro, MD Fellow, Department of Rheumatology, University of Tennessee at Memphis

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Paget J. On a form of chronic inflammation of bones. Medico-chirurgical Transactions. 1877;65:37-63:

  2. [Guideline] Singer FR, Bone HG 3rd, Hosking DJ, Lyles KW, Murad MH, Reid IR, et al. Paget's Disease of Bone: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014 Dec. 99(12):4408-22. [Medline].

  3. Alexandersen P, Peris P, Guañabens N, Byrjalsen I, Alvarez L, Solberg H, et al. Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone. J Bone Miner Res. 2005 Apr. 20(4):588-95. [Medline].

  4. Hughes AE, Shearman AM, Weber JL, Barr RJ, Wallace RG, Osterberg PH, et al. Genetic linkage of familial expansile osteolysis to chromosome 18q. Hum Mol Genet. 1994 Feb. 3(2):359-61. [Medline].

  5. Neale SD, Schulze E, Smith R, Athanasou NA. The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease. QJM. 2002 Apr. 95(4):233-40. [Medline].

  6. Hoyland JA, Freemont AJ, Sharpe PT. Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget's disease. J Bone Miner Res. 1994 Jan. 9(1):75-80. [Medline].

  7. Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Löwik CW, Papapoulos SE. Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate. J Bone Miner Res. 1995 Jun. 10(6):956-62. [Medline].

  8. Menaa C, Barsony J, Reddy SV, Cornish J, Cundy T, Roodman GD. 1,25-Dihydroxyvitamin D3 hypersensitivity of osteoclast precursors from patients with Paget's disease. J Bone Miner Res. 2000 Feb. 15(2):228-36. [Medline].

  9. Hoyland J, Sharpe PT. Upregulation of c-fos protooncogene expression in pagetic osteoclasts. J Bone Miner Res. 1994 Aug. 9(8):1191-4. [Medline].

  10. Usategui-Martín R, García-Aparicio J, Corral-Gudino L, Calero-Paniagua I, Del Pino-Montes J, González Sarmiento R. Polymorphisms in autophagy genes are associated with paget disease of bone. PLoS One. 2015. 10 (6):e0128984. [Medline].

  11. Rebel A, Basle M, Pouplard A, Malkani K, Filmon R, Lepatezour A. Towards a viral etiology for Paget's disease of bone. Metab Bone Dis Relat Res. 1981. 3(4-5):235-8. [Medline].

  12. Altman RD, Bloch DA, Hochberg MC, Murphy WA. Prevalence of pelvic Paget's disease of bone in the United States. J Bone Miner Res. 2000 Mar. 15(3):461-5. [Medline].

  13. Poór G, Donáth J, Fornet B, Cooper C. Epidemiology of Paget's disease in Europe: the prevalence is decreasing. J Bone Miner Res. 2006 Oct. 21(10):1545-9. [Medline].

  14. Cooper C, Dennison E, Schafheutle K, Kellingray S, Guyer P, Barker D. Epidemiology of Paget's disease of bone. Bone. 1999 May. 24(5 Suppl):3S-5S. [Medline].

  15. Guañabens N, Garrido J, Gobbo M, Piga AM, del Pino J, Torrijos A, et al. Prevalence of Paget's disease of bone in Spain. Bone. 2008 Dec. 43(6):1006-9. [Medline].

  16. Barker DJ, Chamberlain AT, Guyer PB, Gardner MJ. Paget's disease of bone: the Lancashire focus. Br Med J. 1980 Apr 26. 280(6222):1105-7. [Medline]. [Full Text].

  17. Doyle T, Gunn J, Anderson G, Gill M, Cundy T. Paget's disease in New Zealand: evidence for declining prevalence. Bone. 2002 Nov. 31(5):616-9. [Medline].

  18. Dove J. Complete fractures of the femur in Paget's disease of bone. J Bone Joint Surg Br. 1980 Feb. 62-B(1):12-7. [Medline].

  19. Mangham DC, Davie MW, Grimer RJ. Sarcoma arising in Paget's disease of bone: declining incidence and increasing age at presentation. Bone. 2009 Mar. 44(3):431-6. [Medline].

  20. Goldman AB, Bullough P, Kammerman S, Ambos M. Osteitis deformans of the hip joint. AJR Am J Roentgenol. 1977 Apr. 128(4):601-6. [Medline].

  21. Lluberas-Acosta G, Hansell JR, Schumacher HR Jr. Paget's disease of bone in patients with gout. Arch Intern Med. 1986 Dec. 146(12):2389-92. [Medline].

  22. Alvarez L, Guañabens N, Peris P, Monegal A, Bedini JL, Deulofeu R, et al. Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. J Bone Miner Res. 1995 Mar. 10(3):458-65. [Medline].

  23. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008 Sep. 83(9):1032-45. [Medline]. [Full Text].

  24. Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics. 2002 Sep-Oct. 22(5):1191-216. [Medline].

  25. Seitz S, Priemel M, Zustin J, Beil FT, Semler J, Minne H, et al. Paget's disease of bone: histologic analysis of 754 patients. J Bone Miner Res. 2009 Jan. 24(1):62-9. [Medline].

  26. 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 Aug. 16(8):1379-87. [Medline].

  27. Silverman SL. Paget disease of bone: therapeutic options. J Clin Rheumatol. 2008 Oct. 14(5):299-305. [Medline].

  28. Abelson A. A review of Paget's disease of bone with a focus on the efficacy and safety of zoledronic acid 5 mg. Curr Med Res Opin. 2008 Mar. 24(3):695-705. [Medline].

  29. Woitge HW, Oberwittler H, Heichel S, Grauer A, Ziegler R, Seibel MJ. Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone. Clin Chem. 2000 May. 46(5):684-90. [Medline].

  30. González DC, Mautalen CA. Short-term therapy with oral olpadronate in active Paget's disease of bone. J Bone Miner Res. 1999 Dec. 14(12):2042-7. [Medline].

  31. Miller PD, Brown JP, Siris ES, Hoseyni MS, Axelrod DW, Bekker PJ. A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget's disease of bone. Paget's Risedronate/Etidronate Study Group. Am J Med. 1999 May. 106(5):513-20. [Medline].

  32. Roux C, Gennari C, Farrerons J, Devogelaer JP, Mulder H, Kruse HP, et al. Comparative prospective, double-blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget's disease of bone. Arthritis Rheum. 1995 Jun. 38(6):851-8. [Medline].

  33. Siris E, Weinstein RS, Altman R, Conte JM, Favus M, Lombardi A, et al. Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone. J Clin Endocrinol Metab. 1996 Mar. 81(3):961-7. [Medline].

  34. Al-Rashid M, Ramkumar DB, Raskin K, Schwab J, Hornicek FJ, Lozano-Calderón SA. Paget Disease of Bone. Orthop Clin North Am. 2015 Oct. 46 (4):577-85. [Medline].

  35. Walsh JP, Ward LC, Stewart GO, Will RK, Criddle RA, Prince RL. A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone. Bone. 2004 Apr. 34(4):747-54. [Medline].

  36. Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med. 2005 Sep 1. 353(9):898-908. [Medline].

  37. Langston AL, Campbell MK, Fraser WD, MacLennan GS, Selby PL, Ralston SH. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone. J Bone Miner Res. 2010 Jan. 25(1):20-31. [Medline].

  38. Merlotti D, Gennari L, Martini G, Valleggi F, De Paola V, Avanzati A, et al. Comparison of different intravenous bisphosphonate regimens for Paget's disease of bone. J Bone Miner Res. 2007 Oct. 22(10):1510-7. [Medline].

  39. Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD. Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. J Bone Miner Res. 2007 Jan. 22(1):142-8. [Medline].

  40. Reid IR, Lyles K, Su G, Brown JP, Walsh JP, del Pino-Montes J. A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res. 2011 Sep. 26(9):2261-70. [Medline].

  41. Devogelaer JP, Geusens P, Daci E, Gielen E, Denhaerynck K, Macdonald K, et al. Remission over 3 years in patients with Paget disease of bone treated with a single intravenous infusion of 5 mg zoledronic acid. Calcif Tissue Int. 2014 Mar. 94(3):311-8. [Medline].

  42. Parvizi J, Klein GR, Sim FH. Surgical management of Paget's disease of bone. J Bone Miner Res. 2006 Dec. 21 Suppl 2:P75-82. [Medline].

  43. Jorge-Mora A, Amhaz-Escanlar S, Lois-Iglesias A, Leborans-Eiris S, Pino-Minguez J. Surgical treatment in spine Paget's disease: a systematic review. Eur J Orthop Surg Traumatol. 2015 Jul 1. [Medline].

  44. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004 May. 62(5):527-34. [Medline].

  45. Drake WM, Kendler DL, Brown JP. Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000. Clin Ther. 2001 Apr. 23(4):620-6. [Medline].

  46. Siris ES, Lyles KW, Singer FR, Meunier PJ. Medical management of Paget's disease of bone: indications for treatment and review of current therapies. J Bone Miner Res. 2006 Dec. 21 Suppl 2:P94-8. [Medline].

 
Previous
Next
 
Radiograph showing a 44-year-old African American man with characteristic changes of Paget disease in the left hemipelvis.
Radiograph showing a 72-year-old white woman with Paget disease of the lower leg and typical bowing.
Dual-energy x-ray absorptiometry scan of a 72-year-old white woman with Paget disease of the lower leg and typical bowing (same patient as in Image 2).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.