Sir James Paget

Sir James Paget, 1st Baronet, FRS, FRCS (Eng), DCL (Oxon), LLD (Cantab & Edin) (January 11, 1814 – December 30, 1899) was a preeminent Victorian surgeon, master educator, and the universally acknowledged founder of modern surgical pathology. Celebrated internationally for his epochal 1877 clinical and pathological delineation of osteitis deformans—subsequently immortalized as Paget’s disease of bone—he bridged the historic divide between bedside operative surgery and cellular histopathology, transforming musculoskeletal medicine decades prior to the advent of diagnostic radiography. Serving as Surgeon and Lecturer at St Bartholomew’s Hospital, Hunterian Professor and President of the Royal College of Surgeons of England, Vice-Chancellor of the University of London, and Serjeant-Surgeon to Queen Victoria, Paget reshaped clinical science through meticulous longitudinal observation and microscopic correlative pathology. His vast legacy encompasses his landmark treatise Lectures on Surgical Pathology (1853), the discovery of the parasitic nematode Trichinella spiralis (1835), the original description of Paget’s disease of the nipple (1874) heralding underlying ductal breast carcinoma, and effort-induced thrombosis of the axillary-subclavian vein (Paget-Schroetter syndrome, 1875), establishing him as one of the foremost medical pioneers of the nineteenth century.

1. The Shoulders of Giants: Historical Context & Significance

Every modern orthopaedic surgeon evaluating an expanded, hypervascular osseous deformity, fixing an atypical transverse chalkstick fracture, navigating high-flow intraoperative hemorrhage during total hip arthroplasty, or appraising an elevated bone-specific alkaline phosphatase stands squarely upon the empirical and pathological foundations established by Sir James Paget. In the early nineteenth century, British surgery remained an empirical manual craft. Skeletal disorders were an undifferentiated diagnostic swamp, loosely labeled as “scrofula”, “rickets”, “mollities ossium”, “hyperostosis”, or “syphilitic caries”. Operating surgeons prided themselves on rapid amputations and manual speed rather than tissue biology, dismissing the microscope as an idle laboratory toy. Bone was widely viewed as a static, inert mineral scaffold rather than a dynamic, living metabolic organ constantly remodeled by specialized cellular machinery.

“If I have seen further, it is by standing on the shoulders of giants.”

Sir Isaac Newton (1675) / Bernard of Chartres

Paget shattered this stagnant orthodoxy by fusing tireless microscopic dissection with long-term clinical observation. Where others saw only grotesque deformities or hopeless terminal softening, Paget discerned distinct pathological processes governed by altered cellular physiology. He demonstrated that bone is capable of profound cellular hyperactivity, uncoupled remodeling, and structural architectural transformation. When Paget presented his nineteen-year longitudinal study of osteitis deformans before the Royal Medical and Chirurgical Society in 1876, he documented the life history of a chronic skeletal disease with unprecedented clinical, biomechanical, and histological fidelity. He proved that massive bone enlargement and bowing could arise in adult life without constitutional fever or joint ankylosis, and identified its potential for late malignant sarcomatous degeneration.

Paget’s legacy extends far beyond a single eponymous skeletal disorder. Through his masterwork Lectures on Surgical Pathology, Paget introduced cellular pathology into mainstream British surgical practice, providing generations of surgeons with the scientific language needed to understand inflammation, repair, hypertrophy, and neoplasia. His clinical deductions anticipated modern discoveries in osteoclast biology, the RANK/RANKL/osteoprotegerin regulatory axis, mutations in the SQSTM1 (p62) gene, and the development of targeted aminobisphosphonate pharmacotherapy. By establishing that operative craftsmanship must be guided by microscopic pathology, Paget elevated surgery from an empirical trade to an academically rigorous clinical science.

2. Early Life, Formative Education & Career Milestones

Education and Formative Surgical Training

James Paget was born on January 11, 1814, in Great Yarmouth, Norfolk, England. He was the fifth son of Samuel Paget, a prosperous brewer, merchant, and shipowner who served as mayor of the town, and Sarah Elizabeth Tolver, an accomplished and dedicated mother. Raised in a large, intellectually vibrant household of seventeen children, James developed an early appetite for natural history, self-discipline, and classical study. His elder brother, Sir George Edward Paget, preceded him into medicine, eventually becoming Regius Professor of Physic at Cambridge and President of the General Medical Council. Although the family experienced financial distress following the end of the Napoleonic Wars, the home instilled in Paget a lifelong work ethic and deep moral conviction.

In 1830, at the age of sixteen, Paget was apprenticed to Charles Costerton, an active local general practitioner and surgeon in Great Yarmouth. Over four and a half years of rigorous apprenticeship, Paget learned the fundamentals of wound dressing, dispensing medicines, minor surgical interventions, and anatomical dissection. During these formative years, Paget pursued botanical studies along the Norfolk coastline with his brother Charles, culminating in the 1834 publication of Sketch of the Natural History of Yarmouth and its Neighbourhood. This meticulous catalogue of over seven hundred species revealed his early capacity for systematic classification and scientific precision.

In October 1834, at the age of twenty, Paget moved to London to enter the Medical College of St Bartholomew’s Hospital. Living in frugal lodgings and enduring significant financial hardship, he devoted himself entirely to the dissection rooms, hospital wards, and post-mortem theater. During his first winter session in February 1835, while dissecting the rectus abdominis and pectoral muscles of a forty-year-old Italian laborer who had died of tuberculosis, Paget noticed thousands of tiny, gritty, whitish specks distributed throughout the voluntary muscle fibers that repeatedly dulled the edge of his scalpel. While senior anatomists had previously dismissed such specks as incidental calcareous concretions, Paget carefully excised several fragments for microscopic evaluation.

Securing access to a compound microscope at the British Museum through the renowned botanist Robert Brown, Paget observed that each minute cyst enclosed a microscopic, coiled, living parasitic worm. On March 3, 1835, Paget presented his discovery and detailed drawings before the Abernethian Society, the student scientific body of St Bartholomew’s Hospital. Although Richard Owen, the Hunterian Professor at the Royal College of Surgeons, subsequently obtained specimens and formally named the nematode Trichinella spiralis before the Zoological Society of London, Owen’s communication rested upon the primary microscopic discovery made by the first-year medical student. This initial breakthrough earned Paget early recognition among London’s leading scientific figures. Paget completed his medical examinations and was admitted as a Member of the Royal College of Surgeons (MRCS) in May 1836.

Academic Appointments and Clinical Leadership

Following his qualification in 1836, Paget spent seven years in austere poverty, as London hospital appointments were unpaid and private practice was inaccessible without established family patronage. To support himself and assist in repaying debts from his father’s business failure, Paget engaged in demanding medical journalism and scientific cataloguing. He served as sub-editor of The London Medical Gazette from 1837 to 1842, contributed critical reviews, prepared English abstracts of French and German scientific literature, and catalogued the pathological museum collections of the Royal College of Surgeons and St Bartholomew’s Hospital.

In 1837, Paget was appointed Curator of the Anatomical and Pathological Museum at St Bartholomew’s Hospital, followed by his appointment as Demonstrator of Morbid Anatomy in 1839. In 1843, following the establishment of a residential college for medical students within St Bartholomew’s, Paget was chosen as its first Warden. For eight years, Paget and his wife Lydia lived within the hospital gates, providing pastoral guidance, academic mentorship, and moral leadership to generations of medical students, creating a standard of collegiate medical education that was emulated throughout Great Britain.

In 1843, Paget was elected Lecturer in General Anatomy and Physiology at St Bartholomew’s Hospital, a post he held with distinction until 1865. In 1847, he was appointed Assistant Surgeon to St Bartholomew’s Hospital and was elected Hunterian Professor of Anatomy and Surgery at the Royal College of Surgeons of England. Between 1847 and 1852, he delivered his historic Hunterian lectures, systematically presenting the principles of surgical pathology. Published in 1853 as Lectures on Surgical Pathology, this two-volume treatise established histopathology as an indispensable discipline for operative surgery and remained the preeminent surgical textbook in the English language for decades.

Paget was elected a Fellow of the Royal Society (FRS) in 1851, later serving as its Vice-President. In 1861, he became Full Surgeon to St Bartholomew’s Hospital, where his operative clinics attracted surgeons from across the world. However, in 1871, at the height of his surgical career, Paget sustained an accidental puncture wound during a post-mortem dissection of a patient who had died of pyemia. He suffered severe dissection-wound septicaemia, developing diffuse lymphangitis, metastatic abscesses, and acute pleurisy that brought him to the verge of death. Although he recovered after months of convalescence, the illness diminished the fine tactile sensitivity of his hands. Recognizing the physical demands of major operative surgery, Paget resigned his post as Full Surgeon in 1871, accepting the role of Consulting Surgeon to St Bartholomew’s Hospital, while channeling his energy into private consultations, university leadership, and clinical research.

In 1871, Queen Victoria created him a Baronet (Sir James Paget of Harewood Place) in recognition of his service to medicine and his role in treating HRH The Prince of Wales (later King Edward VII) during a life-threatening episode of typhoid fever. Paget had been appointed Surgeon-Extraordinary to Queen Victoria in 1858 and was elevated to Serjeant-Surgeon in 1877 upon the death of Sir William Fergusson. He served as President of the Clinical Society of London in 1869, President of the Royal College of Surgeons of England in 1875, President of the Royal Medical and Chirurgical Society from 1875 to 1877, and President of the Pathological Society of London in 1887. From 1883 to 1895, he served as Vice-Chancellor of the University of London. In 1881, Paget presided over the 7th International Medical Congress in London, welcoming over three thousand international delegates, including Louis Pasteur, Rudolf Virchow, Robert Koch, and Jean-Martin Charcot. Paget died in London on December 30, 1899, at the age of eighty-five; his funeral service was conducted in Westminster Abbey before he was laid to rest at Finchley Cemetery.

3. Core Orthopaedic Breakthroughs, Eponymous Signs & Innovations

Sir James Paget’s scientific breakthroughs transformed multiple surgical disciplines, laying the foundation for modern orthopaedic pathology, metabolic bone disease management, surgical oncology, and vascular surgery. His rigorous methodology paired precise clinical phenomenology with morbid anatomy and microscopic analysis, establishing diagnostic signs and pathological concepts that remain essential to contemporary clinical practice.

Hallmark Anatomical, Diagnostic and Operative Contributions

• Paget’s Disease of Bone (Osteitis Deformans, 1877): A chronic, non-malignant metabolic disorder of bone remodeling characterized by focal, uncoupled, hyperactive osteoclastic resorption followed by chaotic osteoblastic bone deposition, leading to marked osseous expansion, cortical thickening, sabre shin tibial bowing, progressive skull enlargement, severe hypervascularity, elevated serum alkaline phosphatase, and risk of malignant transformation into secondary osteosarcoma.
• Paget’s Disease of the Nipple / Areola (1874): A chronic, unilateral eczematous and ulcerating condition of the nipple-areolar complex with intraepithelial neoplastic cells (Paget cells), signaling the presence of an underlying ductal carcinoma in situ (DCIS) or invasive ductal adenocarcinoma of the breast.
• Paget-Schroetter Syndrome (Effort Thrombosis, 1875): Primary spontaneous thrombosis of the axillary-subclavian vein following repetitive or strenuous upper extremity exertion, resulting in sudden upper limb edema, cyanosis, and dilated subcutaneous collateral veins across the shoulder and anterior chest wall.
• Lectures on Surgical Pathology (1853): The foundational two-volume masterwork that introduced microscopic histopathology into British operative surgery, systematically establishing the cellular pathology of inflammation, tissue repair, atrophy, hypertrophy, and oncologic neoplasms.
• Discovery of Trichinella spiralis (1835): First microscopic identification and description of encysted nematode larvae within human skeletal muscle tissue, discovering the causative agent of human trichinosis.
• Paget’s Abscess: A chronic or recurrent dormant abscess appearing at the anatomical site of a long-healed inflammatory, infectious, or tuberculous process years or decades after apparent clinical recovery.

The landmark breakthrough of Paget’s career was his presentation of “On a Form of Chronic Inflammation of Bones (Osteitis Deformans)” before the Royal Medical and Chirurgical Society on November 14, 1876, published in the society’s Transactions in 1877. Paget detailed five clinical cases followed longitudinally over decades, beginning with Thomas Holmes, a coachman first examined by Paget in 1856 at age forty-six and monitored until his death in 1876. Paget described how the disease began with persistent, deep aching pain in the lower extremities, followed by progressive anterolateral bowing of the left femur, gradual bowing of the right lower limb, and a marked enlargement of the cranium that forced the patient to buy progressively larger hats (the head circumference expanded from 22.5 to 27.25 inches). As the spine underwent kyphotic collapse, the trunk shortened and the patient assumed an ape-like posture with hands dangling below the knees. Paget emphasized that despite profound skeletal distortion, the patient’s cognitive functions remained intact, and adjacent joint articulations remained mobile.

Modern cellular biology has confirmed Paget’s pathological intuition. The primary abnormality in Paget’s disease resides within the osteoclast lineage. Pagetic osteoclasts are pathologically enlarged, multinucleated cells containing up to one hundred nuclei (compared to three to five nuclei in normal physiological osteoclasts). These giant osteoclasts demonstrate hyper-responsiveness to osteoclastogenic factors, particularly receptor activator of nuclear factor-κB ligand (RANKL), interleukin-6 (IL-6), and 1,25-dihydroxyvitamin D3. The unrestrained, intense osteoclastic resorption triggers an uncoupled, chaotic compensatory osteoblastic response. Because osteoid is deposited with frantic speed, it cannot undergo organized lamellar remodeling. The resulting bone is primitive woven bone, producing the pathognomonic microscopic appearance: a disordered mosaic or “jigsaw puzzle” pattern of irregular cement lines joining randomly oriented bone packets with complete loss of normal Haversian osteon architecture.

Genetic investigations have demonstrated that 40 to 50 percent of patients with familial Paget’s disease and 5 to 10 percent of sporadic cases harbor germline mutations in the SQSTM1 gene on chromosome 5q35. The gene encodes sequestosome-1 (p62), an essential scaffold protein in the RANK/NF-κB signaling pathway. Mutations in the ubiquitin-associated (UBA) domain of p62 impair ubiquitin binding, leading to constitutive hyperactivation of downstream NF-κB signaling and promoting osteoclast proliferation and survival. Furthermore, electron microscopy has identified paracrystalline nucleocapsid-like viral inclusions within pagetic osteoclast nuclei that cross-react with antibodies to paramyxoviruses (measles virus, canine distemper virus, and respiratory syncytial virus), supporting a two-hit etiology wherein viral infection triggers disease in a genetically primed host.

Paget’s disease progresses through three classic radiographic and histological phases:

• 1. Osteolytic (Incipient Active) Phase: Dominated by intense osteoclastic resorption. In long bones, this manifests radiographically as a sharp, V-shaped or wedge-shaped radiolucent front advancing along the cortex, designated the “blade of grass” sign or “candle flame” sign. In the skull, it presents as circumscribed radiolucency, most prominent in the frontal and occipital regions, termed osteoporosis circumscripta cranii.
• 2. Mixed (Active) Phase: Characterized by simultaneous, aggressive osteoclastic bone resorption and chaotic osteoblastic bone deposition. The bone expands in volume and diameter, while cortices thicken and show coarsened, disorganized trabeculae. In the vertebral column, endplate thickening creates the classic “picture frame” vertebra. In the calvarium, interspersed areas of resorption and irregular sclerotic deposition produce the pathognomonic “cotton wool” skull appearance.
• 3. Osteosclerotic (Inactive / Burnt-Out) Phase: Marked by osteoclast and osteoblast exhaustion. The bone becomes uniformly dense, sclerotic, and expanded, with complete loss of normal corticomedullary demarcation. In the spine, this produces the homogeneously radiodense “ivory vertebra”. Despite its radiographic density and increased thickness, this sclerotic bone is disorganized, brittle, and biomechanically fragile.

The biomechanical consequences of this disordered remodeling are profound. Pagetic bone exhibits decreased tensile and compressive strength, leading to progressive bowing under physiological loads. The femur develops severe anterolateral bowing, while the tibia develops marked anterior bowing (“sabre shin”). Transverse microfractures (Looser’s zones or pseudo-fractures) frequently develop along the convex tensile cortex of bowed long bones. Under minimal low-energy trauma, these tensile fissures can propagate completely across the brittle bone, causing classic transverse “chalkstick” or “banana” fractures that run perpendicular to the long axis without comminution. Neural structures are also vulnerable: skull base remodeling can cause platybasia and basilar invagination, compressing the brainstem and cranial nerves (producing sensorineural hearing loss, facial nerve palsy, or visual loss). In the spine, vertebral expansion causes severe spinal canal stenosis and cauda equina syndrome. Furthermore, the extreme osseous hypervascularity characterized by dilated sinusoids and microvascular arteriovenous shunts can double cardiac output in patients with polyostotic disease involving more than 15 percent of the skeleton, precipitating high-output congestive heart failure.

Diagnostic evaluation relies on a combination of plain radiographs, bone scintigraphy, and biochemical profiling. Plain radiographs demonstrate the characteristic signs: “cotton wool” skull, “picture frame” vertebra, “ivory vertebra”, “blade of grass” lytic wedge, pelvic iliopectineal line thickening (“brim sign”), and curved sabre tibia. Technetium-99m methylene diphosphonate (Tc-99m MDP) bone scintigraphy is the most sensitive modality for mapping skeletal involvement, revealing intense focal tracer uptake (“hot spots”) at sites of active turnover. Laboratory evaluation reveals marked elevations in serum total and bone-specific alkaline phosphatase (bALP), reflecting osteoid formation, along with elevated urinary N-telopeptide (NTx) or serum C-telopeptide (CTx), reflecting bone resorption. Serum calcium, phosphate, and parathyroid hormone levels remain characteristically normal in uncomplicated disease; however, acute skeletal immobilization following a fracture or bed rest can uncouple osteoclasis from mechanical stimulation, triggering severe, life-threatening immobilization hypercalcemia and hypercalciuria.

Modern medical management is founded on nitrogen-containing aminobisphosphonates, most notably intravenous zoledronic acid (a single 5 mg infusion) or oral risedronate (30 mg daily for two months). These agents inhibit the enzyme farnesyl pyrophosphate (FPP) synthase in the mevalonate pathway, disrupting the post-translational prenylation of small GTPases (Rho, Rac, Cdc42) required for osteoclast cytoskeleton integrity and ruffled border survival, thereby inducing osteoclast apoptosis and normalizing bone turnover. Preoperative bisphosphonate suppression for three to six months prior to elective orthopaedic reconstruction is mandatory to diminish bone hypervascularity and prevent catastrophic intraoperative hemorrhage. In joint arthroplasty, sclerotic bone requires careful reaming to avoid eccentric cortical perforation and thermal necrosis, while severe deformities may necessitate concomitant corrective osteotomies. Intramedullary fixation of chalkstick fractures presents unique technical challenges, as narrow or obliterated medullary canals and bowed cortices require flexible reamers and biplanar imaging to prevent cortical shattering.

The most devastating complication of Paget’s disease is secondary malignant transformation (Paget’s sarcoma), which occurs in approximately 1 percent of patients with long-standing disease (rising to 5 to 10 percent in severe polyostotic involvement). Secondary osteosarcoma accounts for over half of these cases, followed by fibrosarcoma, undifferentiated pleomorphic sarcoma, and chondrosarcoma. Patients typically present with sudden, severe, unremitting bone pain, rapid swelling, or an enlarging, warm soft tissue mass in a previously quiescent bone, or with a pathological fracture through a ragged lytic cortical lesion. The prognosis is dismal, with a median survival of less than twelve months and a five-year overall survival rate below 10 percent, due to advanced patient age, aggressive biology, chemoresistance, and early hematogenous pulmonary metastasis.

In addition to his skeletal work, Paget’s 1874 paper in St Bartholomew’s Hospital Reports documented fifteen cases of chronic, weeping, eczematous erosion of the nipple and areola that invariably preceded underlying ductal carcinoma of the breast. Histopathologically, this condition is characterized by large, vacuolated, intraepithelial adenocarcinoma cells (Paget cells) infiltrating the squamous epidermis via epidermotropic spread from ductal carcinoma in situ or invasive ductal cancer. In 1875, Paget described acute spontaneous axillary-subclavian vein thrombosis following strenuous upper limb exertion, an entity later corroborated by Leopold von Schrötter in 1884 and known today as Paget-Schroetter syndrome. Furthermore, his classic textbook Lectures on Surgical Pathology (1853) established cellular pathology as the foundation of operative decision-making, while his identification of encysted Trichinella spiralis in 1835 initiated the study of human trichinosis.

4. Master Class Pro-Tip

1. Perioperative Management & Vascular Hemorrhage Control: In patients with active Paget disease of bone undergoing elective orthopaedic reconstruction (such as total hip or total knee arthroplasty, or deformity osteotomy), preoperative medical suppression is non-negotiable. Active pagetic bone is permeated by dilated sinusoids and high-flow microvascular arteriovenous shunts; operating during an unsuppressed active phase risks torrential, intractable cancellous bleeding from reamed canals and osteotomy surfaces that resists standard electrocautery and topical hemostatic agents. Obtain baseline serum bone-specific alkaline phosphatase (bALP) or total alkaline phosphatase and administer a potent nitrogen-containing aminobisphosphonate—ideally intravenous zoledronic acid (5 mg) at least 6 to 12 weeks preoperatively, or oral risedronate (30 mg daily for 2 months). Normalize or dramatically suppress alkaline phosphatase prior to making the incision. Ensure adequate hydration and verify normal serum 25-hydroxyvitamin D and calcium levels prior to bisphosphonate administration to avoid acute hypocalcemia. Intraoperatively, maintain meticulous hemostasis, utilize tranexamic acid (TXA) aggressively (both intravenous and topical), have cell-salvage systems ready, and prepare for rapid cement pressurization, which acts as an effective tamponade against cancellous vascular oozing.

2. Arthroplasty Mechanics & Deformity Correction: Total joint reconstruction in pagetic bone demands thorough anticipation of distorted anatomy and altered osseous mechanics. Sclerotic, eburnated pagetic bone creates extreme resistance to reaming, predisposing to thermal necrosis, drill bit breakage, and catastrophic eccentric cortical perforation. Conversely, adjacent bone in the mixed phase may be abnormally soft and hypomineralized. In total hip arthroplasty, evaluate for acetabular protrusio and severe anterolateral femoral bowing. In cases with mild bowing, choose a shorter, cemented polished tapered femoral stem or an anatomically curved modular cementless stem to avoid impaction against the anterior or lateral cortex. If femoral bowing exceeds 15 to 20 degrees, standard femoral preparation is impossible without causing fracture; perform a staged or single-stage corrective osteotomy stabilized with a long diaphyseal-engaging fluted revision stem or locked plate. In total knee arthroplasty, anterior tibial bowing alters the sagittal mechanical axis, often requiring an increased posterior tibial slope cut and extensive soft tissue releases to overcome severe extra-articular deformity and flexion contracture. Sclerotic cancellous bone requires pulsed lavage and thorough drying prior to cement pressurization to ensure a robust PMMA cement mantle.

3. Vigilance for Malignant Transformation (Paget Sarcoma): Maintain an unyielding index of clinical suspicion for secondary sarcomatous degeneration (Paget sarcoma) in any patient with established Paget disease who presents with sudden, relentless worsening of localized bone pain (especially nocturnal pain unresponsive to bisphosphonates), rapid localized swelling, a warm palpable soft tissue mass, or an atypical pathological fracture. Secondary osteosarcoma occurs in approximately 1% of patients with long-standing Paget disease and carries an extraordinarily poor prognosis (median survival under 12 months). Immediate advanced cross-sectional imaging with contrast-enhanced MRI and thin-slice CT is mandatory to identify cortical destruction, non-concentric osteolysis, and soft tissue extension. Never attempt closed manipulation, unguided intramedullary nailing, or primary arthroplasty for an acute fracture through a suspicious pagetic lytic lesion. Perform an urgent, meticulously placed core needle or open biopsy within an oncologic surgical corridor under musculoskeletal oncology guidance. Early radical resection with wide oncologic margins remains the only potential pathway to disease control.

Master Class Surgical Pearl: Paget Disease of Bone – Perioperative Hemorrhage, Arthroplasty Mechanics, and Sarcomatous Transformation

5. Primary Landmark Publications & Bibliography

The foundational contributions of Sir James Paget are preserved in these original landmark monographs, classical treatises, and peer-reviewed surgical literature:

• Paget J. On a Form of Chronic Inflammation of Bones (Osteitis Deformans). Medico-Chirurgical Transactions. 1877;60:169–204. DOI
• Paget J. Additional Cases of Osteitis Deformans. Medico-Chirurgical Transactions. 1882;65:125–136. DOI
• Paget J. On Disease of the Mammary Areola Preceding Cancer of the Mammary Gland. St Bartholomew’s Hospital Reports. 1874;10:87–89. (Reprinted in: CA: A Cancer Journal for Clinicians. 1971;21(5):303–304. DOI)
• Ralston SH, Layfield R. Pathogenesis of Paget Disease of Bone. Calcified Tissue International. 2012;91(2):97–113. DOI
• Roodman GD, Windle JJ. Paget disease of bone. Journal of Clinical Investigation. 2005;115(2):200–208. DOI
• Bossaert L, Kluyskens Y, Snoeck J. Thrombosis of the Axillary and Subclavian Veins Following Muscular Effort (Paget-Von Schroetter syndrome). Acta Clinica Belgica. 1976;31(4):185–194. DOI
• Mostofi SB. Sir James Paget 1814–1899. In: Mostofi SB, ed. Who’s Who in Orthopedics. London: Springer-Verlag; 2005:256.

6. Biographical Provenance & Acknowledgments

This historical biography was synthesized for the OrthopaedicsOne Knowledge Network as part of A Who’s Who of Orthopaedics, adapted and expanded from the foundational biographical directory Who’s Who in Orthopedics (Springer-Verlag London) edited by Seyed B. Mostofi, BSc, MBBS, FRCS (Ed), commemorating the enduring clinical and pathological legacy of Sir James Paget documented on page 256 of Mostofi’s compendium.