Paget's disease of the bone; osteitis deformans
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Etiology
- genetic factors
- 'slow virus'
Epidemiology
- rare before age 20
- affects 3% of population > 45 years of age & 10% of population > 80 years of age
- slight predominance in men
Pathology
- focal monostotic or polyostotic bone disorder
- disorganized bone remodelling
- disordered osteoclast function
- acceleration of bone turnover
- disruption of normal bone architecture
- gross deformities of bone may occur
- local impingement of adjacent structures may occur
- disordered osteoclast function
- structural weakening of bone with tendency to fracture
- increased vascularity
- bone enlargement occurs in 3 phases:
- predilection for
- disease may be confined to 1 or several adjacent bones or involvement may be more generalized
Genetics
Clinical manifestations
- most patients are asymptomatic
- diagnosis is generally made fortuitously after noting isolated increase in serum alkaline phosphatase or incidental abnormal radiography
- clinical presentation depends upon bone involved
- skeletal pain (bone pain) may occur
- bone deformities may occur
- long bones
- skull (enlargement of skull)
- spine
- pelvis
- bone fractures
- degenerative arthritis from altered weight distribution
- impingement syndromes from disorganized bone remodelling
- cranial nerve impingement syndromes
- hearing loss may result from impingement on the inner ear & auditory nerve
- pain syndromes or neurologic dysfunction may result from impingement on the spinal cord & nerve roots (spinal stenosis)
- headaches occur secondary to enlargement of skull structures[5]
- high output heart failure
- angioid retinal streaks
Laboratory
- increased serum alkaline phosphatase
- isolated increase in serum alkaline phosphatase
- most useful marker for disease activity
- useful for evaluation of response to therapy[2]
- serum calcium (all patients) is generally normal, but may be increased during periods of immobility
- 25-OH vitamin D in serum (all patients)[2]
- parathyroid hormone (PTH) in serum may be increased
- urine N-telopeptide (OsteoMark) assay reflects osteoclast activity[4]
Radiology
- plain radiographs
- more specific than bone scan[5] to identify
- lytic areas
- focal osteolysis, coarse trabecular pattern[2]
- fissure fractures
- extent of deformities
- 'cotton wool' appearance of skull[2]
- thickening of bone cortex[2]
- lytic areas
- follow-up radiograph 1 year after diagnosis for patients with osteolytic lesions[9]
- more specific than bone scan[5] to identify
- pyrophosphate bone scan (all patients) shows focal areas of increased uptake[2]
- skull
- femur
- pelvis
* radiograph & bone scan images[11]
Complications
- fractures
- increased incidence of bone tumors (1% of cases)
- most commonly osteosarcomas
- pelvis
- femur
- humerus
- skull
- facial bones
- poor prognosis
- most commonly osteosarcomas
- neurologic complications
- impingement of nerves by enlarging bone
- especially cranial nerves II, V, VII, VIII
- compromise of vascular supply by enlarging bone
- impingement of nerves by enlarging bone
- high output congestive heart failure (rare) due to vascular shunts through involved skeleton
Differential diagnosis
- hypertrophic pulmonary osteoarthropathy[13]
- clubbing of fingers
- hemoptysis, blood-tinged sputum
- periostitis, periosteal thickening at long bones (femur, tibia)*
- arthritis*
- elevated erythrocyte sedimentation rate (ESR)
- elevated serum C-reactive protein
* also seen in primary hypertrophic osteoarthopathy
Management
- objectives
- relieve symptoms (bone pain, headache, back pain, radiculopathy)
- treat & prevent complications
- treat lytic involvement of vertebrae, skull, weight-bearing bones, areas adjacent to major joints[2]
- serum alkaline phosphatase is a useful marker for disease activity & response to therapy
- non-steroidal anti-inflammatory drugs (NSAIDs)
- no specific role in treatment of Paget's disease of the bone[14]
- antiresorptive drugs, bisphosphonates 1st line (IV for symptomatic disease)[12]
- zoledronate* IV[6]
- a single 5-mg dose of IV zoledronate for patients at high risk of complications[9]
- often reduces pain & normalizes serum alkaline phosphatase[2]
- pamidronate 60-90 mg IV over 4 hours
- sustained effect for 12-18 months
- reduction or normalization of alkaline phosphatase in 50-75% of patients
- repeat dose if necessary
- adverse effects reduced by supplementing calcium
- 1000 mg/day for 1 to 2 weeks after pamidronate
- alendronate*
- calcitonin
- etidronate less effective than zoledronate; risk of fracture[12]
- risedronate*
- zoledronate* IV[6]
- monitor response to therapy by measuring serum alkaline phosphatase
- surgery for impingement on nerves or blood supply
- elective - pretreat with pamidronate
- urgent - comcomittant pamidronate
More general terms
More specific terms
Additional terms
- extramammary Paget's disease
- osteoclast
- Paget's disease of the breast or nipple
- sequestosome-1; phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kD; ubiquitin-binding protein p62; EBI3-associated protein of 60 kD; p60; EBIAP (SQSTM1, ORCA, OSIL)
References
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 222
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Weiner S, In: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 4.0 4.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2266-69
- ↑ 5.0 5.1 5.2 5.3 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - ↑ 6.0 6.1 Reid IR et al, Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med 2005 Sep 1; 353:898-908 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16135834
- ↑ Josse RG, Hanley DA, Kendler D et al Diagnosis and treatment of Paget's disease of bone. Clin Invest Med. 2007;30(5):E210-23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17892763
- ↑ Ralston SH. Paget's disease of bone. N Engl J Med. 2013;368:644-650 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23406029
- ↑ 9.0 9.1 9.2 9.3 Singer FR et al Paget's Disease of Bone: An Endocrine Society Clinical Practice Guideline. J Clin Eocrinol Metab. Nov 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25406796 <Internet> http://press.endocrine.org/doi/pdf/10.1210/jc.2014-2910
- ↑ Goncalves MJ, Romao VC Images in clinical medicine. Saber tibia in Paget's disease of bone. N Engl J Med. 2014 Dec 18;371(25):2417 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25517708
- ↑ 11.0 11.1 Balani A, Marda SS IMAGES IN CLINICAL MEDICINE. Paget's Disease of Bone. N Engl J Med. 2016 Mar 31;374(13):1264. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27028916 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMicm1502815
- ↑ 12.0 12.1 12.2 NEJM Knowledge+ Question of the Week. Nov 3, 2020 https://knowledgeplus.nejm.org/question-of-week/763/
- ↑ 13.0 13.1 NEJM Knowledge+ Question of the Week. Oct 31, 2023 https://knowledgeplus.nejm.org/question-of-week/776/
- ↑ 14.0 14.1 Ralston SH, Corral-Gudino L, Cooper C et al Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline. J Bone Miner Res. 2019 Apr;34(4):579-604. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30803025 PMCID: PMC6522384 Free PMC article. Review.
- ↑ PubMed Health: Paget's disease of the bone: Osteitis deformans http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001451/
- ↑ National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Paget's Disease of Bone https://www.niams.nih.gov/health-topics/pagets-disease-bone
Patient information
Paget's disease of the bone patient information