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Giant osteoclasts after long-term bisphosphonate therapy: diagnostic challenges

Nature Reviews Rheumatology volume 5, pages 341–346 (2009)Cite this article

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.

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Figure 1: A photomicrograph of giant, detached, hypernucleated osteoclasts after long-term oral aminobisphosphonate therapy.
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.
Figure 3: A photomicrograph of secondary hyperparathyroidism resulting from renal insufficiency with a deep resorption cavity containing multinucleated osteoclasts.
Figure 4: Multinucleated giant cells in a giant cell tumor of bone.
Figure 5: A focus of multinucleated giant cells in fibrous dysplasia.

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Acknowledgements

The authors thank Dr. Antoine Makdissi and Dr. Vitaly Kantorovich for their careful reading of the manuscript. This work was supported by a VA Merit Review Grant from the Office of Research and Development, Department of Veterans Affairs and the National Institutes of Health (PO1-AG13918) and Tobacco Settlement Funds provided by the University of Arkansas for Medical Sciences, College of Medicine. Désirée Lie, University of California, Orange, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. Division of Endocrinology and Metabolism, Department of Internal Medicine and the Central Arkansas Veterans Healthcare System, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Nidhi Jain & Robert S. Weinstein

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  1. Nidhi Jain
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Correspondence to Robert S. Weinstein.

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Jain, N., Weinstein, R. Giant osteoclasts after long-term bisphosphonate therapy: diagnostic challenges. Nat Rev Rheumatol 5, 341–346 (2009). https://doi.org/10.1038/nrrheum.2009.87

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