27th February 2025

Paget’s disease of bone and sclerotic bone diseases

Paget’s disease of bone

Paget’s disease of bone is characterised by disordered localised bone remodelling leading to osteosclerotic bone. The aetiology is unclear, though some predisposing genetic factors are known. Pagetic lesions are commonly seen in the skull, spine, pelvis, femurs and tibia, though any area can be affected.

Although most are asymptomatic, some may experience pain at disease foci (often sites of muscle insertion or previous fracture). Secondary osteoarthritis due to disrupted load distribution, hearing loss, bone deformity (e.g. frontal bossing, kyphosis, bowing of the legs), and pathological fractures are all common presentations in symptomatic patients. Rarer presentations include bone overgrowth leading to nerve impingement and increased bone vascularity leading to high-output heart failure. Of note, hearing loss is less commonly sensorineural secondary to CN VIII impingement, but rather, most cases are conductive due to temporal bone osteosclerosis. Osteosarcoma is one complication that should be suspected in any patient reporting an increase in pain or new swelling, though it occurs in fewer than 1% of patients.

As most patients are asymptomatic, diagnosis is most often incidental via an isolated raised ALP or an X-ray or CT requested for another purpose. Such imaging directly visualises pagetic lesions, characterised by a mix of osteosclerosis and radiolucency ± pathological fractures. ALP may be normal if disease is minimal, restricted to a single site, or inactive (particularly post-treatment). In these circumstances, or in concurrent hepatobiliary disease, bone-specific ALP may be useful. As with osteomalacia, bone biopsy is rarely required.

Unless due to a complication of the disease (e.g. osteoarthritis or pathological fracture), pain due to a pagetic lesion, nerve impingement and hearing loss following temporal bone involvement can be treated with limited courses of bisphosphonates. Bisphosphonates may also be used before orthopaedic surgery as lesions are highly vascular and may lead to excessive blood loss. Caution is required, however, as concurrent vitamin D deficiency is common in the elderly (i.e. those susceptible to Paget’s disease), in which case bisphosphonates may result in symptomatic hypocalcaemia. Where bisphosphonates are contraindicated, calcitonin may be considered.

Sclerosing bone dysplasia

Sclerosing bone dysplasia is a term used to refer to a variety of congenital disorders that range in severity from mild to fatal and in age of onset from childhood to late life, depending on the nature of the genetic abnormality. Cranial nerve palsies can occur in many of these conditions as bone overgrowth narrows cranial foramina, which may cause vision and hearing loss.

In osteopetrosis, general loss of osteoclast function results in a diffuse increase in bone mass, as demonstrated by a ‘marble bone’ appearance on X-ray. Poor remodelling in childhood forms of osteopetrosis result in bone marrow failure due to narrowed marrow cavity. If completed in early life, bone marrow transplantation can provide a cure as osteoclast progenitors are replaced.

Other sclerosing bone dysplasias may affect different parts of the skeleton in unequal ways. These include melorheostosis, which usually affects one limb only, and pyknodysostosis, a lysosomal storage disease affecting osteoclasts, which presents with blue sclera, rhizomelic dwarfism, and osteosclerosis.

Other causes of osteosclerosis

Sclerotic metastases may arise from a number of primaries, particularly of the prostate and breast. Myeloma, too, has an uncommon osteosclerosing subtype affecting bones in a focal or diffuse manner, while osteosclerosis in myelofibrosis, where present, sees changes restricted to medullary cavities. Though predominantly associated with diffuse osteopenia, cases of osteosclerosis in hyperparathyroid patients have been recorded. Sickle cell crises affecting bone also result in osteosclerosis. Hepatitis C-associated osteosclerosis has been reported in patients with prior infection, severe diffuse bone pain and high levels of ALP. Where exposure via poisoned water wells or industrial sources is a possibility, fluorosis should be considered in patients with soft tissue calcification, osteosclerosis and skeletal abnormalities, such as ankylosis, kyphosis and osteosclerosis.

References

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