Paget disease of bone

Paget disease of bone is no longer considered a primary inflammatory disorder. It is a focal disorder of bone remodelling driven by abnormal osteoclast activity. Increased bone resorption is followed by accelerated but disorganised osteoblastic repair, resulting in enlarged, vascular and mechanically weak bone.

Aetiology:

Familial clustering and genetic associations, especially involving pathways regulating osteoclast formation and activity, support an inherited component. Viral hypotheses, particularly involving paramyxoviruses, have been proposed but remain unproven.

Clinical features:

Most newly diagnosed cases are asymptomatic and are discovered incidentally through X-rays or raised alkaline phosphatase.

Symptomatic disease may present with deep bone pain, warmth over affected bone, progressive bowing of long bones, spinal deformity, secondary osteoarthritis of adjacent joints, pathological fracture or neurological compression syndromes.

Skull enlargement may be associated with headache, hearing loss, tinnitus or cranial nerve compression. Sarcomatous transformation is rare but remains an important historical and clinical complication.

Investigations:

Plain radiographs show characteristic lytic and sclerotic changes. X-ray may show osteolytic, mixed lytic-sclerotic or osteosclerotic change, cortical thickening, bone expansion and deformity.

Bone scintigraphy can define the extent of skeletal involvement. CT or MRI is used to define complications such as fracture, spinal stenosis, and malignant transformation

Serum alkaline phosphatase is commonly elevated in active disease and is useful for monitoring treatment response, although monostotic disease may have normal biochemistry.

Bone histology can demonstrate increased and abnormal osteoclast activity, followed by disorganised osteoblastic bone formation and the characteristic mosaic pattern of lamellar bone.

Management

Treatment has been transformed by bisphosphonates, particularly zoledronic acid, which suppress excessive bone turnover and improve disease-related bone pain.

---

History of Paget disease

1873 – Vincenz Czerny (1842-1916) used the term Ostitis deformans in a report Eine locale Malacie des Unterschenkels. His patient was a 22-year-old man with gradually progressive deformity of the lower leg, developing without trauma and associated with pain, local swelling, curvature and later hardening. Czerny reviewed earlier reports by Scoutetten, Solly, Mosetig and Weinlechner and concluded that existing terms such as osteohalisteresis or local malacia captured only part of the disease process.

1876 – Paget first presented the condition to the Royal Medico-Chirurgical Society on November 14, 1876 (published in 1877) as On a Form of Chronic Inflammation of Bones (Osteitis Deformans). His first patient was a previously healthy man who developed progressive skeletal deformity from the age of forty-six.

At forty-six, from no assigned cause, unless it were that he lived in a rather cold and damp place in the North of England, he began to be subject to aching pains in his thighs and legs. They were felt chiefly after active exercise, but were never severe; yet the limbs became less agile or, as he called them, “less serviceable,” and after about a year he noticed that his left shin was misshapen.

Paget provided the classic description of progressive bone enlargement and deformity:

The left femur and tibia became larger, heavier, and somewhat more curved. Very slowly those of the right limb followed the same course…

The skull became gradually larger, so that nearly every year, for many years, his hat, and the helmet that he wore as a member of a Yeomanry Corps needed to be enlarged.

The spine very slowly became curved and almost rigid. The whole of the cervical vertebrae and the upper dorsal formed a strong posterior, not angular, curve; and an anterior curve, of similar shape, was formed by the lower dorsal and lumbar vertebrae. The length of the spine thus seemed lessened, and from a height of six feet one inch he sank to about five feet nine inches.

Paget’s post-mortem description linked the clinical enlargement to skeletal pathology. The microscopic examination, performed by Henry Trentham Butlin, provided Paget a pathological basis for separating the disorder from rickets, osteomalacia, syphilitic osteitis and other hyperostoses.

The whole microscopical architecture of the bone has been altered; the structure appears to have been, almost entirely removed and laid down afresh on a different plan and in a larger mould.

Paget interpreted the process as chronic inflammation and proposed the name

Holding, then, the disease to be an inflammation of bones, I would suggest that, for brief reference, and for the present, it may be called, after its most striking character, Osteitis deformans. A better name may be given when more is known of it.

1882 – Paget returned to the subject with seven additional cases and to define the disease more clearly. In a footnote, Paget acknowledged Czerny’s earlier use of the term ostitis deformans, but distinguished Czerny’s local disease of the lower leg from his own chronic skeletal disorder:

After the publication of the paper I found that the name ostitis deformans had been given by Prof. Czerny, of Freiburg, to a disease described by him in the ‘Wiener medizinische Wochenschrift,’ September 27th, 1873. It Is mainly, as he says, “Eine locale Malacie des Unterschenkels,” a rather acute inflammation of the lower part of the tibia and fibula, inducing softening and angular bending, and then followed by hardening.

Paget 1882

Paget’s disease summary:

The seven cases now related seem sufficient when added to the five recorded in the 60th volume, to justify the giving of a distinctive name and a definite general description of the disease observed in them. It usually affects many bones, most frequently the long bones of the lower extremities, the clavicles, and the vault of the skull. The affected bones become enlarged and heavy, but with such weakening of their structure that those which have to carry weight or to bear much muscular traction become unnaturally curved and misshapen.

---

Associated Persons

• James Paget (1814–1899)
• Vincenz Czerny (1842-1916)

---

References

Historical references

• Czerny V. Eine locale Malacie des Unterschenkels. Wiener medizinische Wochenschrift 1873; 23(39): 895-899
• Paget J. On a Form of Chronic Inflammation of Bones (Osteitis Deformans). Medico-Chirurgical Transactions 1877;60:37-64
• Paget J. Additional cases of osteitis deformans, notes on seven cases. Medico-Chirurgical Transactions 1882; 65: 225-36

Review articles

• Colman E. Sir James Paget: the man and the eponym. Calcif Tissue Int. 2002 May;70(5):430-1
• Menéndez-Bueyes LR, Soler Fernández MD. Paget’s Disease of Bone: Approach to Its Historical Origins. Reumatol Clin. 2017 Mar-Apr;13(2):66-72.
• Kravets I. Paget’s Disease of Bone: Diagnosis and Treatment. Am J Med. 2018 Nov;131(11):1298-1303.
• Anastasopoulou C, Mikes BA. Paget Bone Disease. 2023 Nov 12. In: StatPearls [Internet]
• Rendina D et al. Diagnosis and treatment of Paget’s disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS). J Endocrinol Invest. 2024 Jun;47(6):1335-1360.
• Ralston SH. Latest developments in Paget’s disease of bone. Eur J Endocrinol. 2025 Sep 30;193(4):R43-R49.