Paget’s Disease of Bone

Paget’s disease of bone (PDB), also known historically as osteitis deformans, is a focal disorder of bone metabolism Bone metabolism Bone is the primary storage site of calcium in the body; thus, bone metabolism plays a critical role in maintaining normal calcium levels. Bone metabolism (and thus calcium levels) are primarily regulated by 3 hormones, namely, calcitonin, parathyroid hormone (PTH), and vitamin D. Bone Metabolism that affects about 2%–9% of people. Commonly affected areas include the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull, spine, pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis, and long bones of the lower extremity. The 2 main clinical manifestations of Paget’s disease are bone pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and the consequences of bone deformities, such as fractures, osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis, or nerve impingement. The management includes bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates, calcitonin, and surgery for the management of fractures, deformities, and complications. The prognosis for PDB is good, especially if treatment is started before major changes have occurred in the bones.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Paget’s disease of bone (PDB, also known as osteitis deformans) is a disorder of bone metabolism Bone metabolism Bone is the primary storage site of calcium in the body; thus, bone metabolism plays a critical role in maintaining normal calcium levels. Bone metabolism (and thus calcium levels) are primarily regulated by 3 hormones, namely, calcitonin, parathyroid hormone (PTH), and vitamin D. Bone Metabolism affecting the aging skeleton.

Epidemiology

  • 2nd most common metabolic bone disorder, after osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Most common after 55 years of age
  • 3:2 male predominance
  • Geographic variations in prevalence:
    • United States: 1% of population > 40 years old
    • Most common in Europe (except Scandinavia), Australia, and New Zealand, with an average of 3%–4%, and ranges from 2%–9%
    • Rare in Asia
  • Positive family history: in 12%–40% of patients 
  • Asymptomatic in 70% of cases
  • Overall, the incidence is declining.

Etiology

  • Uncertain: genetic and infectious etiologies implicated and likely additive
  • Genetic:
    • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inheritance with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables penetrance
    • Mutations of genes SQSTM1, RANK, and regions of chromosomes 5 and 6 are all involved in bone metabolism Bone metabolism Bone is the primary storage site of calcium in the body; thus, bone metabolism plays a critical role in maintaining normal calcium levels. Bone metabolism (and thus calcium levels) are primarily regulated by 3 hormones, namely, calcitonin, parathyroid hormone (PTH), and vitamin D. Bone Metabolism.
    • Germline mutations in SQSTM1:
      • Approximately 40% of the PDB familial cases
      • Approximately 10% of sporadic cases
  • Viral infections:
    • Less well established than genetic etiologies
    • Substantial evidence for possible measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus infection of osteoclasts
    • Measle vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination may explain the declining incidence of PBD.

Pathophysiology

Pathogenesis

  • A disease of osteoclasts
  • Osteoclast activity accelerates the rate of bone remodeling Bone remodeling Bone, while seemingly inert, is an active, growing, and changing part of the human body, in addition to being the body's primary calcium reservoir. In the correct homeostatic conditions, bone can remodel in response to damage, stress, or hormonal signaling (parathyroid hormone and calcitonin). Bone Remodeling and Healing, causing overgrowth and impaired structural integrity of affected bone.
  • This is followed by increased osteoblast activity.
  • Result is enlarged and thickened, but deformed and weakened, bone.
  • Only some areas of bone are affected, for unknown reasons.
  • 3 sequential phases of PDB:
    1. Initial osteolytic stage: predominant osteoclast activity
    2. Mixed osteoclastic-osteoblastic stage
    3. Burned-out quiescent osteosclerotic stage: Osteoblast activity predominates. 

PDB osteoclasts

  • Have unique characteristics:
    • Markedly increased number during the active osteolytic phase
    • Atypical/bizarre appearance, with numerous nuclei (up to 100 compared with 10–12 normally)
    • Intranuclear inclusions present in some
    • Hypersensitivity to vitamin D
  • 2 essential cytokines required for osteoclast differentiation: 
    • Macrophage colony-stimulating factor Macrophage colony-stimulating factor A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a mw of 70 kda. It binds to a specific high affinity receptor. White Myeloid Cells ( M-CSF M-CSF A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a mw of 70 kda. It binds to a specific high affinity receptor. White Myeloid Cells)
    • Receptor activator of nuclear factor-κB ligand (RANKL)
  • Differentiation is inhibited by osteoprotegerin (OPG; a soluble decoy receptor for RANKL) and modulated by other cytokines and hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview.
  • Abnormalities of these pathways form the basis for the genetic etiology of PDB.

Gross pathology

  • Most common sites: 
    • Skull
    • Thoracolumbar spine
    • Pelvis 
    • Long bones of the lower extremities
    • Axial skeleton or proximal femur is involved in 80% of cases.
  • Monostotic in 15% of cases; polyostotic in 85%
  • Focally enlarged and deformed bone 
  • Irregular thickening of both cortical and cancellous bone

Microscopic pathology

  • Osteolytic phase:
    • Numerous resorption pits
    • Osteoclasts increased in number and aberrant
  • Mixed phase: 
    • Many bone surfaces lined by plump osteoblasts
    • Loose connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue, osteoprogenitor cells, and numerous blood vessels adjacent to new bone
    • Woven bone becomes lamellar with a mosaic pattern.
    • Porous cortex
    • Thickened, but structurally unsound, trabecular structure
    • Evolves into an osteosclerotic phase, with some osteoblasts and few osteoclasts remaining in mosaic-patterned bone.
  • Sclerotic phase (pathognomonic of PDB):
    • Mosaic pattern of lamellar bone
    • Looks like a jigsaw puzzle
    • Prominent cement lines joining randomly oriented units of lamellar bone 

Clinical Presentation

Over 70% of cases are asymptomatic.

Pain

  • Transmitted by periosteal nerves and is due to:
    •   Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones overgrowth
    •  Hyperemia
    •  Microfractures
  • Dull, aching type of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Constant, day and night 
  • Worse in weight-bearing bones

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones deformities and fractures

Sites involved rarely change over a patient’s lifetime.

  • Head:
    • Enlarged skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull with frontal bossing
    • Dilated scalp veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins
    • Basilar invagination (i.e., the tip of the odontoid process is above the foramen magnum) 
    • Jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint deformity, malocclusion, and periodontal disease 
    • Angioid streaks (cracks in Bruch’s membranes of the eyes, can cause choroidal neovascularization)
  • Spine and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis:
    • Compression fractures
    • Pelvis: 
      • Pain
      • Arthritis 
      • Protrusio acetabuli (femoral head projects medial to the ilioischial line)
  • Long bones: 
    • Bowing deformities, with arthritis of adjacent joints
    • Fractures:
      • Transverse fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures at the lesser trochanter of femur the most common
      • The most common complication in long bones
      • Blood loss increased due to increased vascularity
      • Casting or immobility can cause severe osteopenia. 
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin overlying bones: warm due to increased vascularity in bone

Complications of bone overgrowth

  • Neurologic:
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss and dizziness (due to vestibulocochlear nerve and cochlear involvement)
    • Hydrocephalus
    • Instability of gait
    • Dementia from vascular steal due to bone vascularity 
    • Spinal stenosis Spinal stenosis Spinal stenosis is the progressive narrowing of the central spinal canal, intervertebral foramen, and lateral recess, leading to compression of the nerve root. Spinal stenosis can occur in the cervical, thoracic, and lumbar spine and is commonly caused by degenerative bone disease (mostly affecting the elderly). Spinal Stenosis
    • Spinal cord ischemia: due to vascular steal 
    • Radiculopathies (nerve compression)
  • Metabolic:
    • More common in untreated patients with polyostotic disease
    • High-output heart failure
    • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia during immobilization or fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures:
      • Hypercalciuria 
      • Increased risk of kidney stones  
  • Neoplastic:
    • Occur in < 1% of PDB
    • Risk is higher in polyostotic and long-standing disease.
    • Osteosarcoma Osteosarcoma Osteosarcoma is a primary malignant tumor of the bone characterized by the production of osteoid or immature bone by the tumor cells. The disease is most common in children and young adults and most frequently affects growth plates of the long bones, although it can involve any bone. Osteosarcoma the most common
    • Fibrosarcoma
    • Giant cell tumors: 
      • Mostly benign
      • Cause local destruction
      • Rarely metastasize

Diagnosis

History

  • Elderly patients 
  • Pathologic fractures
  • Hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia after bedrest

Laboratory findings

  • Serum alkaline phosphatase:
    • Often elevated, with normal gamma-glutamyl-transpeptidase (unlike liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease)
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones-specific alkaline phosphatase (bSAP) elevation
  • Other markers of bone turnover:
    • Urinary N-telopeptide crosslink (NTX) 
    • Serum C-telopeptide crosslink (CTX)
    • Amino-terminal propeptide of type I procollagen (PINP)
  • Serum calcium and phosphorus:
    • Normal in most patients
    • May be elevated in cases of fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures or immobility
    • If elevated in an ambulatory patient without fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures, may indicate other pathology (i.e., primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism)

Imaging

  • Most important diagnostic tool
  • Plain radiographs: 
    • Osteolytic lesions in early PDB: “ osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis circumscripta” in the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull
    • Thickened, denser, and enlarged bone as osteoblast activity increases
    • Mixed lytic/sclerotic lesions, with flame-shaped lytic lesion progressing ahead of thickened cortex and trabecular bone
    • Deformation of bone shape
    • Pseudofractures (Looser’s lines): small fissures on the convex surface of long bones
    • Protrusio acetabuli and iliopectineal line involvement
    • “Ivory spine”: thickened and enlarged vertebrae 
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones scintigraphy:
    • Obtain a baseline scan in all cases.
    • Increased uptake at the sites of active lesions
    • May be the earliest imaging change
  • Other modalities:
    • Computed tomography (CT) or magnetic resonance imaging (MRI)
    • May be helpful if malignancy is suspected
    • Evaluate fractures in selected cases.

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones biopsy

  • Rarely required 
  • To rule out malignancy 
  • Unusual clinical situation (young adult, Asian ethnicity)

Management

Indications for treatment

  • Symptomatic disease
  • Significant radiologic abnormalities
  • Significant biochemical abnormalities

Goals

  • Reduce pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain.
  • Reduce the rate of bone remodeling Bone remodeling Bone, while seemingly inert, is an active, growing, and changing part of the human body, in addition to being the body's primary calcium reservoir. In the correct homeostatic conditions, bone can remodel in response to damage, stress, or hormonal signaling (parathyroid hormone and calcitonin). Bone Remodeling and Healing.

Pharmacologic treatment

  • Bisphosphonates (first choice—zoledronic acid):
    • Inhibit osteoclast activity
    • Adverse effects: 
      • Gastrointestinal (GI) upset
      • Flu-like symptoms
      • Musculoskeletal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Osteonecrosis of the jaw (especially if invasive dental work done in the prior 6 months)
      • Hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia
  • Calcitonin (if bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates are not tolerated)

Surgical interventions

  • Fracture fixation 
  • Resection of bone tumors
  • Non-emergent correction of bone deformity
  • Joint arthroplasty
  • Spinal decompression: after treatment with bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates

Adjunctive measures

  • Walking aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
  • Analgesics
  • Physical therapy
  • Hearing aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS (if associated with hearing loss)

Differential Diagnosis

  • Metastatic disease: The 5 most common malignancies that metastasize to the bone are thyroid, lung, breast, kidney, and prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands. Diagnosis is established by history, CT, MRI, and biopsy.
  • Osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets: marked softening and weakening of bones due to impaired mineralization and most often caused by severe vitamin D deficiency; similar to PDB because of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and elevated alkaline phosphatase, but typical PDB X-ray patterns are not seen. Pseudofractures (Looser’s lines) of osteomalacia occur on the concave, not convex, side of the bone. 
  • Osteosarcoma Osteosarcoma Osteosarcoma is a primary malignant tumor of the bone characterized by the production of osteoid or immature bone by the tumor cells. The disease is most common in children and young adults and most frequently affects growth plates of the long bones, although it can involve any bone. Osteosarcoma: a primary bone malignancy. Occasionally associated with PDB; pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and soft tissue swelling should prompt an MRI to help in diagnosis. Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones biopsy for confirmation. 
  • Giant cell tumor of bone: benign bone tumors Benign bone tumors Benign bone lesions are a group of noncancerous, slow-growing neoplasms that arise from cartilage or bone. These lesions have distinct features, such as endosteal reactions with intraosseous calcification and bone formation. Benign Bone Tumors that can be locally aggressive. Associated with increased pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and swelling. Can occur in association with PDB (usually in the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull or pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis of patients with polyostotic disease); can also arise in non-osseous tissues. Diagnosis is confirmed with MRI and biopsy.

References

  1. Charles, J.F. (2020). Clinical manifestations and diagnosis of Paget disease of bone. Uptodate. Retrieved December 29, 2020, from   https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-paget-disease-of-bone#H22844044
  2. Paget Disease. (2020). In Kumar, V., Abbas, A. K., Aster, J.C., (Eds.). Robbins & Cotran Pathologic Basis of Disease. (10 ed. pp. 1182-1183).
  3. Charles, J.F. (2019). Paget’s Disease of Bone; Osteitis Deformans. MSD Manual Professional Edition. Retrieved December 29, 2020, from https://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/paget-disease-of-bone/paget-disease-of-bone
  4. Alonso, N., Calero-Paniagua, I., & del Pino-Montes, J. (2017). Clinical and genetic advances in Paget’s disease of bone: A review. Clinical Reviews in Bone and Mineral Metabolism, 15(1), 37–48. https://doi.org/10.1007/s12018-016-9226-0
  5. Oiseth, S. J. (2017). Beethoven’s autopsy revisited: A pathologist sounds a final note. Journal of medical biography, 25(3), 139–147. https://doi.org/10.1177/096777201557588

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