Giant osteoclasts after long-term bisphosphonate therapy: diagnostic challenges

Abstract

Background: A 55-year-old woman with a 5-year history of osteoporosis treated for 4 years with an oral aminobisphosphonate presented with a recent vertebral fracture. A bone biopsy specimen revealed giant osteoclasts with more than 40 nuclear profiles.

Investigations: Bone mineral density determinations, measurement of serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium, inorganic phosphorus, alkaline phosphatase and creatinine levels, urinary excretion levels of the N-telopeptide of type 1 collagen, and bone biopsy. Examination of the patient and review of the bone specimen.

Diagnosis: Giant osteoclasts after long-term bisphosphonate use, without evidence of malignancy.

Management: Interpretation of the bone biopsy specimen listed several bone disorders. The bone specimen was reviewed and the histological differential diagnosis was carefully considered. The giant osteoclasts were detached from bone and frequently apoptotic in a normal marrow stroma, with low-to-normal amounts of osteoid and osteoblasts. These features are typical of giant osteoclast formation after long-term aminobisphosphonate therapy. the patient was reassured that the bone findings were unlikely to be detrimental. Aminobisphosphonate treatment was reinstituted, and 1 year later the patient was asymptomatic.

Figure 1

A photomicrograph of giant, detached, hypernucleated osteoclasts after long-term oral aminobisphosphonate therapy. Modified Masson stain, original magnification × 400.

Figure 2

A photomicrograph showing more than 40 nuclear profiles in a giant detached osteoclast, a finding that was previously considered virtually pathognomonic of Paget disease of bone. Only when combined with the excess osteoid (stained red) and abundant osteoblasts (arrow), however, do the findings suggest Paget disease. Modified Masson stain, original magnification × 400.

Figure 3

A photomicrograph of secondary hyperparathyroidism resulting from renal insufficiency with a deep resorption cavity containing multinucleated osteoclasts. The osteoclasts are firmly attached to the bone and usually contain no more than 9–20 nuclear profiles. The bone marrow shows peritrabecular fibrous tissue. Modified Masson stain, original magnification × 400.

Figure 4

Multinucleated giant cells in a giant cell tumor of bone. The giant cells are in close contact with fibroblastic stromal cells, but are often detached from bone. Hematoxylin and eosin stain, original magnification × 400.

Figure 5

A focus of multinucleated giant cells in fibrous dysplasia. These cells are often detached from bone and located amidst a stroma that contains spindle-shaped fibroblasts and a loose pattern of reticulin fibers. Hematoxylin and eosin stain, original magnification × 400.