Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 26-20: Paget Disease of Bone (Osteitis Deformans) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Often asymptomatic Bone pain may be first symptom Kyphosis, bowed tibias, large head, deafness Frequent fractures Serum calcium and phosphate normal; elevated alkaline phosphatase and urinary hydroxyproline Dense, expanded bones on radiograph +++ General Considerations ++ Common condition manifested by one or more bony lesions having high bone turnover and disorganized osteoid formation Involved bones Have increased osteoclast activity, causing lytic lesions in bone that may progress at about 1 cm/yr Increased osteoblastic activity follows, producing a high rate of disorganized bone formation Become vascular, weak, and deformed Eventually, there appears to be a final burned-out phase with markedly reduced bone cell activity and abnormal bones that may be enlarged with skeletal deformity Most often discovered incidentally during radiographic imaging or evaluation of serum alkaline phosphatase elevation Cause is unknown; about 20% of cases are familial and transmitted as an autosomal dominant trait with incomplete penetrance +++ Demographics ++ Most common in the United Kingdom and in areas of European migration Rare in Africa, India, Asia, and Scandinavia In the United States, Paget disease is usually diagnosed in patients over age 40 years Affects about 1% of whites over age 55 years; prevalence increasing with age + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Often mild and asymptomatic; only 27% symptomatic at diagnosis Involves multiple bones (polyostotic) in 72% and only a single bone (monostotic) in 28%, occurring most commonly in the pelvis, vertebrae, femur, humerus, and skull Pain is usual first symptom Usually described as aching and deep Often worse at night Bones become soft, leading to bowed tibias, kyphosis, and frequent fractures with slight trauma If skull is involved, patient may report headaches, increased hat size, and deafness Increased vascularity over involved bones causes increased warmth Sarcomatous change suggested by marked increase in bone pain +++ Differential Diagnosis ++ Bone tumor, eg, osteosarcoma Plasma cell myeloma (formerly multiple myeloma) Metastatic cancer Fibrous dysplasia Osteitis fibrosa cystica Fibrogenesis imperfecta ossium Myelofibrosis Intramedullary osteosclerosis Erdheim-Chester disease Langerhans cell histiocytosis Sickle cell disease + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Serum alkaline phosphatase markedly elevated Other markers of bone turnover are also usually elevated, particularly Serum procollagen type-I N-terminal propeptide (PINP) Urine N-telopeptide of type 1I collagen cross-links (NTx) Serum calcium may be elevated, particularly if patient is at bed rest A serum 25-OH vitamin D should be obtained to screen for vitamin D deficiency, which Can present with an increased serum alkaline phosphatase and bone pain Should be corrected before prescribing a bisphosphonate Sarcomatous change is suggested by sudden rise in serum alkaline phosphatase +++ Imaging Studies ++ Bone radiographs show involved bones as expanded and denser than normal Multiple fissure fractures in long bones Initial lesion may be destructive and radiolucent, especially in skull ("osteoporosis circumscripta") Sarcomatous change suggested by appearance of new lytic lesion Technetium pyrophosphate bone scans helpful in delineating activity of bone lesions even before radiographic changes are apparent +++ Diagnostic Procedures ++ Bone biopsy in suspected sarcomatous change + Treatment Download Section PDF Listen +++ ++ Asymptomatic patients may require only clinical surveillance and no treatment However, treatment should be considered for asymptomatic patients who have extensive involvement of the skull, long bones, or vertebrae +++ Medications ++ Zoledronic acid Treatment of choice Administered intravenously as a single 5-mg dose Normalizes serum alkaline phosphatase in 89% of patients by 6 months and in 98% by 2 years Oral bisphosphonates Inferior to intravenous zoledronic acid Patients who do take bisphosphonates should drink 8 oz of plain water and must remain upright afterward to prevent esophageal complications Relative contraindications: history of Esophagitis Esophageal stricture Dysphagia Hiatal hernia Achalasia Patients who cannot tolerate bisphosphonates may be treated with calcitonin + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Monitor alkaline phosphatase +++ Complications ++ Fractures frequently occur with minimal trauma If patient is immobilized and has excessive calcium intake, hypercalcemia and kidney stones may develop Vertebral collapse may lead to spinal cord compression Osteosarcoma may develop in long-standing lesions (rare) Increased vascularity may cause high-output heart failure Arthritis frequently develops in joints adjacent to involved bone Extensive skull involvement may cause cranial nerve palsies Ischemic neurologic events may result from vascular "steal" phenomenon In severe forms, marked deformity, intractable pain, and heart failure occur Paradoxical increase in pain at sites of disease soon after starting therapy; pain usually subsides with further treatment Flu-like symptoms occur fairly frequently Following intravenous zoledronate, patients frequently experience fever, fatigue, myalgia, bone pain, and ocular problems Serious side effects are rare but include Seizures Uveitis Other potential side effects Acute kidney injury Hypocalcemia is common and may be severe; administering calcium and vitamin D supplements, especially during the first 2 weeks following treatment, is advisable Asthma may occur in aspirin-sensitive patients Esophageal complications of oral bisphosphonates may be prevented by taking oral bisphosphonates with 8 oz of plain water only +++ Prognosis ++ Prognosis is good but worse the earlier in life the disease starts Most patients treated with bisphosphonates have normalization of serum alkaline phosphatase within 6 months, most maintaining this biochemical remission for several years Fractures usually heal well +++ Prevention ++ Prompt bisphosphonate treatment markedly reduces occurrence of complications of severe Paget disease + References Download Section PDF Listen +++ + +Appleman-Dijkstra NM et al. Paget disease of bone. Est Pract Res Clin Endocrinol Metab. 2018 Oct;32(5):657–68. [PubMed: 30449547] + +Corral-Gudino L et al. Bisphosphonates for Paget's disease of bone in adults. Cochrane Database Syst Rev. 2017 Dec 1;12:CD004956. [PubMed: 29192423] + +Cundy T. Paget's disease of bone. Metabolism. 2018 Mar;80:5–14. [PubMed: 28780255] + +Kravets I. Paget's disease of bone: diagnosis and treatment. Am J Med. 2018 Nov;131(11):1298–303. [PubMed: 29752905] + +Ralston SH 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. [PubMed: 30803025]