Paget's Disease of Bone: Clinical Diagnosis and Management

Paget’s disease of bone is a chronic skeletal disorder characterised by focal areas of excessive osteoclastic resorption followed by disorganised osteoblastic formation. It predominantly affects individuals over the age of 55 and may present with bone pain, deformity, pathological fractures or secondary osteoarthritis. Biochemical evaluation centres on serum alkaline phosphatase in conjunction with liver function tests, while radionuclide bone scanning combined with targeted radiographs delineates the extent and activity of lesions. Genetic screening for pathogenic variants such as those in SQSTM1 has emerged as a tool for early identification in at-risk populations. Management strategies aim to relieve symptoms, preserve skeletal integrity and prevent complications. Bisphosphonates—particularly a single infusion of zoledronic acid—are the cornerstone of therapy, achieving prolonged suppression of bone turnover and pain relief. Prophylactic treatment in asymptomatic carriers of high-risk genotypes is under investigation as a means to avert irreversible skeletal damage. Surgical intervention, including joint replacement or corrective osteotomy, is reserved for cases with severe deformity, osteoarthritis or fracture non-union. Multidisciplinary care and regular monitoring are essential to address comorbidities such as hearing loss and to detect rare complications like osteosarcoma.

Research from Nature Portfolio

Recent studies have leveraged osteoclast-specific expression quantitative trait locus analyses to connect genome-wide association signals with functional gene regulation in Paget’s disease. Variants at established susceptibility loci were shown to modulate expression of STMP1 and DCSTAMP during osteoclast differentiation, implicating these genes in cell fusion and resorptive overactivity. By bridging genetic risk variants and cellular mechanisms, this work refines our understanding of the initial dysregulation in pagetic bone remodelling and highlights potential targets for molecular intervention.

Paget's Disease of Bone: Clinical Diagnosis and Management publication trend

The graph below shows the total number of articles in paget's disease of bone: clinical diagnosis and management across all publications each year (not limited to Nature Index journals).

Technical terms

Osteoclast: A multinucleated cell responsible for bone resorption.

Osteoblast: A cell that synthesises new bone matrix.

Alkaline phosphatase: A serum enzyme marker of increased bone turnover.

Bisphosphonate: A class of drugs that inhibit osteoclast activity and bone resorption.

Radionuclide bone scan: An imaging technique to detect sites of metabolically active bone disease.

RANKL: A cytokine that promotes osteoclast differentiation and activation.

Sclerostin: A protein produced by osteocytes that inhibits bone formation.

References

1. Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline. Journal of Bone and Mineral Research (2019).
2. Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of bone. Annals of the Rheumatic Diseases (2024).
3. Osteoclast-derived IGF1 induces RANKL production in osteocytes and contributes to Pagetic lesion formation. JCI Insight (2023).
4. Genetic regulatory mechanisms in human osteoclasts suggest a role for the STMP1 and DCSTAMP genes in Paget’s disease of bone. Scientific Reports (2019).