{"id":4422546,"date":"2025-01-11T23:18:04","date_gmt":"2025-01-12T05:18:04","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/paget-disease\/"},"modified":"2025-01-13T06:23:07","modified_gmt":"2025-01-13T12:23:07","slug":"paget-disease","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/paget-disease\/","title":{"rendered":"Paget Disease"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">PAGET DISEASE OF THE BONE<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definition and Pathology<\/strong>\n<ul class=\"wp-block-list\">\n<li>Also called <strong>osteitis deformans<\/strong>.<\/li>\n\n\n\n<li>Characterized by uncontrolled, highly active, <strong>large osteoclasts<\/strong> \u2192 <strong>increased bone resorption<\/strong>.<\/li>\n\n\n\n<li>Marked <strong>compensatory osteoblastic activity<\/strong> causes new bone that is <strong>disorganized<\/strong> (lacking normal lamellar structure).<\/li>\n\n\n\n<li>Increased local bone blood flow and <strong>fibrous tissue<\/strong> in the adjacent marrow.<\/li>\n\n\n\n<li><strong>Prevalence<\/strong> ~3% in adults >40 years; often asymptomatic, evolves slowly.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Epidemiology<\/strong>\n<ul class=\"wp-block-list\">\n<li>Same prevalence in men and women, but <strong>more commonly symptomatic in men<\/strong>.<\/li>\n\n\n\n<li>Typically detected in the <strong>sixth decade<\/strong> of life.<\/li>\n\n\n\n<li>Often found incidentally (e.g., <strong>elevated alkaline phosphatase<\/strong> on labs or suspicious findings on radiographs).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">CLINICAL MANIFESTATIONS<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Symptoms<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Bone pain<\/strong> due to periosteal stretching or microfractures; worse with weight bearing.<\/li>\n\n\n\n<li><strong>Warmth<\/strong> over the affected bone from increased local blood flow.<\/li>\n\n\n\n<li>Can be <strong>monostotic<\/strong> (one bone) or <strong>polyostotic<\/strong> (multiple).<\/li>\n\n\n\n<li>Most commonly involves <strong>pelvis, spine, femur, skull, tibia<\/strong>.\n<ul class=\"wp-block-list\">\n<li><strong>Femur\/tibia<\/strong>: Bowing of legs, gait changes.<\/li>\n\n\n\n<li><strong>Spine<\/strong>: Kyphosis, possible spinal cord compression.<\/li>\n\n\n\n<li><strong>Skull<\/strong>: Hearing loss (<a href=\"https:\/\/myendoconsult.com\/learn\/mnemonic-cranial-nerves-dirty-surprise\/\"  data-wpil-monitor-id=\"269\">cranial nerve<\/a> VIII compression), skull deformities (frontal\/occipital), rare facial nerve palsy.<\/li>\n\n\n\n<li><strong>Others<\/strong>: Visual disturbances (optic nerve), platybasia, hydrocephalus (skull base involvement).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Complications<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Fractures<\/strong> (transverse; low threshold because of bone architecture).<\/li>\n\n\n\n<li><strong>Bony neoplasia<\/strong>: Increased frequency of giant cell tumor, fibrosarcoma, chondrosarcoma, osteosarcoma.<\/li>\n\n\n\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/topics\/primary-hyperparathyroidism\/\"  data-wpil-monitor-id=\"270\">Primary hyperparathyroidism<\/a><\/strong> more frequent.<\/li>\n\n\n\n<li><strong>High-output cardiac failure<\/strong> when >20% of skeleton is involved (increased vascularity).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">EVALUATION<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>History &amp; Examination<\/strong>\n<ul class=\"wp-block-list\">\n<li>Evaluate for bone pain, skeletal deformities, hearing changes, possible nerve compressions.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Imaging<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Radionuclide bone scan<\/strong>: Focal areas of increased uptake in pagetic bone.<\/li>\n\n\n\n<li><strong>Plain radiographs<\/strong>: Confirm Paget disease, assess extent (e.g., lytic, mixed, or sclerotic lesions).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Serum alkaline phosphatase<\/strong>: Typically elevated in active disease.<\/li>\n\n\n\n<li><strong>Calcium<\/strong>: Normal unless immobilization or coexisting hyperparathyroidism.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Additional Tests<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Serum calcium<\/strong> to assess for hyperparathyroidism.<\/li>\n\n\n\n<li><strong>Audiogram<\/strong> if skull involvement.<\/li>\n\n\n\n<li><strong>Bone biopsy<\/strong> if suspicion of malignancy or if imaging is inconclusive.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Markers of Bone Turnover<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Bone formation markers<\/strong>: Bone-specific alkaline phosphatase, osteocalcin, propeptides of type I collagen (PINP).<\/li>\n\n\n\n<li><strong>Bone resorption markers<\/strong>: Urinary hydroxyproline, collagen crosslinks (N-telopeptide, C-telopeptide).<\/li>\n\n\n\n<li>In Paget disease, both formation and resorption markers increase and <strong>normalize with successful treatment<\/strong>.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">PATHOGENESIS AND TREATMENT<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Potential Cause<\/strong>\n<ul class=\"wp-block-list\">\n<li>Believed to be <strong>viral<\/strong> (paramyxovirus) trigger + <strong>genetic predisposition<\/strong>.<\/li>\n\n\n\n<li>Viral inclusions found in pagetic osteoclasts.<\/li>\n\n\n\n<li>~30% have <strong>family history<\/strong> of Paget disease; <strong>SQSTM1 (sequestosome 1) mutations<\/strong> implicated.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>When to Treat<\/strong>\n<ul class=\"wp-block-list\">\n<li>Many patients asymptomatic \u2192 no treatment needed if minimal disease.<\/li>\n\n\n\n<li><strong>Indications<\/strong>: Pain, risk of bone or nerve complications, moderate-high disease activity, extensive skull involvement, major weight-bearing bones, or younger patients.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Main Goal<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Suppress osteoclast activity<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Bisphosphonates<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong> to inhibit osteoclasts.<\/li>\n\n\n\n<li>Examples: etidronate, pamidronate, alendronate, tiludronate, risedronate, zoledronic acid.<\/li>\n\n\n\n<li>Routes: High-dose oral or IV.<\/li>\n\n\n\n<li>Effective for remission >1 year in many cases.<\/li>\n\n\n\n<li><strong>Side effects<\/strong>:\n<ul class=\"wp-block-list\">\n<li>IV forms \u2192 ~20% get transient \u2018flu-like\u2019 symptoms 1\u20132 days after infusion.<\/li>\n\n\n\n<li>Oral forms \u2192 esophageal irritation; must take upright, fasting, with water.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Monitoring<\/strong>: Discontinue once <a href=\"https:\/\/myendoconsult.com\/learn\/bone-turnover-markers-in-osteoporosis\/\"  data-wpil-monitor-id=\"271\">bone turnover markers<\/a> normalize; retreat if\/when they rise again.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Other Therapies<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Calcitonin<\/strong>: Historically used but less potent than bisphosphonates.<\/li>\n\n\n\n<li><strong>Plicamycin (mithramycin)<\/strong>: Rarely used (toxicity).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Supportive<\/strong>\n<ul class=\"wp-block-list\">\n<li>Adequate <strong>calcium<\/strong> and <strong>vitamin D<\/strong> supplementation.<\/li>\n\n\n\n<li>Monitor 25-hydroxyvitamin D levels to ensure repletion.<\/li>\n\n\n\n<li>Physical therapy, analgesics for pain control.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>PAGET DISEASE OF THE BONE CLINICAL MANIFESTATIONS EVALUATION PATHOGENESIS AND TREATMENT<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[687],"class_list":["post-4422546","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-parathyroid-gland","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422546","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":3,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422546\/revisions"}],"predecessor-version":[{"id":4422549,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422546\/revisions\/4422549"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422546"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422546"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}