Guideline sources The following summarized guidelines for the evaluation and management of Paget's disease are prepared by our editorial team based on guidelines from the Paget's Association (PA 2019) and the Endocrine Society (ES 2014). 1 2 3 3 4 5 6 Definition Paget's disease is a chronic non-inflammatory skeletal disorder characterized by excessive and abnormal bone remodeling, resulting in deformed, enlarged, and biomechanically unstable bone. 3 Epidemiology Paget's disease is caused by osteoclastic abnormalities due to genetic mutations (sequestosome 1 gene), with some evidence suggesting a role for chronic paramyxovirus infection. 3 Pathophysiology In the United States, the estimated prevalence of Paget's disease ranges from 0.9% to 3.9%. 4 Disease course In patients with Paget's disease, hyperosteoclastosis with associated fibrosis and disorganized bone deposition results in a mosaic of woven bone that is mechanically weak, and increases the https://web.pathway.md/diseases/recjAqGdB1x4jFkD9 1/5 6/29/23, 10:51 PM Paget's disease Pathway risk of fracture and deformity. Platybasia, leontiasis, cranial neuropathy, radiculopathies, osteosarcomas, chondrosarcomas, and fibrosarcoma may develop as a consequence. 5 Prognosis and risk of recurrence Progression to osteosarcoma is associated with poor prognosis, even with aggressive operative management. 6 Guidelines 1. Diagnostic investigations Laboratory evaluation: As per PA 2019 guidelines, obtain serum total ALP (in conjunction with liver biochemical tests) as part of the initial laboratory evaluation for the presence of metabolically active Paget's disease. B Show 2 more As per ES 2014 guidelines, obtain serum total ALP (or a more specific marker of bone formation, when appropriate), as part of the initial biochemical evaluation of a patient with Paget's disease. A Plain radiographs: As per PA 2019 guidelines, obtain radiographs of the abdomen, tibiae, skull, and facial bones as part of the initial diagnostic evaluation in patients suspected to have Paget's disease on biochemical or clinical grounds. B As per ES 2014 guidelines, obtain plain radiographs of any regions of the skeleton where bone disease may be present in patients with suspected Paget's disease. A Radionuclide bone scan: As per PA 2019 guidelines, obtain a radionuclide bone scan, in addition to targeted radiographs, to fully and accurately define the extent of the metabolically active disease in patients with Paget's disease. B As per ES 2014 guidelines, consider obtaining a radionuclide bone scan in patients with Paget's disease, in order to determine the extent of the disease and identify possible asymptomatic sites. C Magnetic resonance imaging and computed tomography: insufficient evidence to recommend MRI or CT for the diagnosis of Paget's disease. Consider using these imaging techniques for the assessment of disease complications. 2. Medical management Bisphosphonates: As per PA 2019 guidelines, initiate bisphosphonate therapy for the treatment of bone pain associated with Paget's disease. Use zoledronic acid as the bisphosphonate most likely to give a favorable pain response. B Show 6 more https://web.pathway.md/diseases/recjAqGdB1x4jFkD9 2/5 6/29/23, 10:51 PM Paget's disease Pathway As per ES 2014 guidelines: Initiate bisphosphonate therapy in most patients with active Paget's disease who are at risk of future complications. B Consider using zoledronic acid (5 mg IV, for one dose) as the treatment of choice in patients without contraindications. C Calcitonin: Consider administering calcitonin for the short-term treatment of bone pain in patients with Paget's disease in whom bisphosphonates are contraindicated. C Consider administering calcitonin as adjunctive treatment in patients with Paget's disease who have evidence of neurological dysfunction. C Denosumab: Consider using denosumab for the treatment of giant cell tumor complicating Paget's disease, when the tumor is non-resectable. C Insufficient evidence to recommend denosumab for the routine treatment of Paget's disease. I Treatment targets: As per PA 2019 guidelines: Target an improvement in symptoms, rather than targeting a normal total ALP, in patients with Paget's disease. B Avoid measuring biochemical markers of bone turnover as a means of predicting the response of bone pain to osteoclast inhibitors in Paget's disease. D As per ES 2014 guidelines, target bone turnover marker levels below the midpoint of the reference range to maximize the duration of remission. B Management of spinal cord dysfunction: As per PA 2019 guidelines, consider administering a trial of calcitonin as adjunctive therapy in patients with Paget's disease who have evidence of neurological dysfunction. Consider bisphosphonate treatment, although few studies support the use of bisphosphonates in this situation. C As per ES 2014 guidelines, consider immediate treatment with a potent intravenous bisphosphonate as well as neurosurgical consultation in patients with paraplegia associated with Paget's disease of the spine. Surgical intervention may not be necessary after effective medical treatment, unless there is severe structural damage. C 3. Surgical interventions Management of bone fractures: Perform surgery for fixation of fractures through affected bone in patients with Paget's disease, recognizing that the clinical outcome in femoral neck and subtrochanteric fractures is poor. B Insufficient evidence to recommend one type of surgical treatment over another. I Management of osteoarthritis: https://web.pathway.md/diseases/recjAqGdB1x4jFkD9 3/5 6/29/23, 10:51 PM Paget's disease Pathway Perform total hip or knee replacements for patients with Paget's disease who develop OA for which medical treatment is inadequate. B Consider performing an osteotomy in patients with Paget' s disease who develop OA for which medical treatment is inadequate. C Management of spinal stenosis: consider performing spine surgery in patients with Paget' s disease who develop spinal stenosis and spinal cord compression. C 4. Specific circumstances Patients with hearing loss: As per PA 2019 guidelines, insufficient evidence to recommend bisphosphonate therapy to prevent progression of hearing loss in patients with Paget's disease. As per ES 2014 guidelines, consider initiating a potent bisphosphonate in patients with Paget's disease and hearing loss, to prevent worsening of a hearing deficit. C Patients with osteoarthritis: As per PA 2019 guidelines, insufficient evidence to recommend bisphosphonate therapy to prevent progression of OA in patients with Paget's disease. As per ES 2014 guidelines, consider initiating treatment with a potent bisphosphonate preoperatively in patients who require an osteotomy to correct severe bowing of the lower extremity associated with impaired ambulation and/or severe joint pain. C Patients undergoing orthopedic or spinal surgery: As per PA 2019 guidelines, insufficient evidence to recommend bisphosphonate therapy as a means to reduce perioperative blood loss during elective orthopedic surgery. As per ES 2014 guidelines, consider initiating bisphosphonate therapy preoperatively in patients with Paget's disease who are scheduled to undergo elective total joint replacement for severe OA adjacent to Paget's disease, in order to prevent intraoperative hemorrhaging and postoperative loosening of the prosthesis. C Patients with osteosarcoma: Consider evaluation by an orthopedic surgeon for patients with osteosarcoma or a giant cell tumor. Consider pretreatment with a potent bisphosphonate to reduce bleeding from adjacent pagetic bone if surgery is planned. C Patients with congestive heart failure: consider initiating a bisphosphonate in patients with Paget's disease and congestive HF. C 5. Patient education Counseling on bisphosphonates: inform patients undergoing treatment with bisphosphonates for Paget's disease that this class of medication has a favorable adverse event profile. Advise patients that a transient flu-like illness occurs commonly with intravenous zoledronic acid. B https://web.pathway.md/diseases/recjAqGdB1x4jFkD9 4/5 6/29/23, 10:51 PM Paget's disease Pathway 6. Follow-up and surveillance Post-treatment follow-up: use biochemical markers as a more objective indicator of relapse than symptoms in patients with increased bone turnover. B Show 3 more Clinical findings Symptoms Past medical history Bone pain Bone cancer Diffuse aches Lab findings Hearing loss Joint pain serum ALP Joint swelling serum calcium Numbness Shooting pain that travels along or across the body Stiffness Tingling Neurological exam Median nerve neuropathy Imaging findings Thickened cortical bone References 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. Open 2. Singer FR, Bone HG rd, Hosking DJ et al. Paget's disease of bone: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Dec;99 12 4408 22. Open 3. Nebot Valenzuela E, Pietschmann P. Epidemiology and pathology of Paget's disease of bone - a review. Wien Med Wochenschr. 2017 Feb;167 1 2 2 8. Open 4. Merashli M, Jawad A. Paget's Disease of Bone among Various Ethnic Groups. Sultan Qaboos Univ Med J. 2015 Feb;15 1):e22 6. Open 5. Sabharwal R, Gupta S, Sepolia S et al. An Insight in to Paget's Disease of Bone. Niger J Surg. 2014 Jan;20 1 9 15. Open 6. Ralston SH. Clinical practice. Paget's disease of bone. N Engl J Med. 2013 Feb 14;368 7 644 50. Open https://web.pathway.md/diseases/recjAqGdB1x4jFkD9 5/5