HONOLULU, Hawaii—A previously unknown class of giant, multinucleate, malformed, and apparently dysfunctional osteoclasts was observed in bone biopsies from alendronate-(ALN) (Fosamax®, Merck & Co, Inc) treated patients by two research groups at the American Society for Bone and Mineral Research 2007 meeting. The ungainly, detached, oddly constructed cells seem to be dysfunctional in terms of bone resorption but also appear able to signal osteoblasts to produce bone in response to treatment with teriparatide (TPTD) (Forteo® , Eli Lilly and Co).1,2 The risks associated with the giant osteoclasts appear to be mainly those of misdiagnosis, but they might also provide a benefit if (as researchers suspect) they actually increase the efficacy of TPTD in patients with previous ALN exposure.

"Although these abnormal cells may well be dysfunctional and of no direct danger to the patient, awareness of the condition is crucial because giant osteoclasts could lead to a mistaken diagnosis of Paget's disease or hyperparathyroidism."—David W. Dempster, MD.
"Although these abnormal cells may well be dysfunctional and of no direct danger to the patient, awareness of the condition is crucial because giant osteoclasts could lead to a mistaken diagnosis of Paget's disease or hyperparathyroidism," warned Robert S. Weinstein, MD, and colleagues with the center for osteoporosis at Central Arkansas Veterans Healthcare System, in Little Rock.1

Dr. Weinstein's group and a second group led by David W. Dempster, PhD,2 of the regional bone center at Helen Hayes Hospital, in West Haverstraw, New York, both describe the novel osteoclasts as
 

  • unusually large—twice the size of normal osteoclasts
  • multinucleate (15-30 nuclei vs 3-8 in normal osteoclasts)
  • partially detached from bone
  • not associated with lacunae or associated only with shallow lacunae
  • separated from cancellous bone by a layer of mononuclear cells
  • lacking or having only distorted ruffled borders
  • showing various markers of apoptosis
  • oddly resistant to phagocytosis
Furthermore, Dr. Dempster found that the numbers of these huge osteoclasts actually increased after ALN-treated patients switched to TPTD.
 
"We hypothesize that, by 7.5 months, TPTD enhances osteoclast recruitment, but the resorptive capacity of these osteoclasts is inhibited by ALN. Osteoclast nuclear number and size increase as a compensatory response to inhibition of activity. While resorptive function is inhibited, signalling to osteoblasts remains intact, as bone formation is markedly increased by TPTD in ALN-treated subjects," Dr. Dempster said.

References

1. Weinstein RS, Chambers TM, Hogan EA, et al. Giant osteoclast formation after long-term oral aminobisphosphonate therapy for postmenopausal osteoporosis. Presented at: ASBMR 29th Annual Meeting; September 17, 2007; Honolulu, HI. Abstract 1058.

2. Dempster DW, Zhou H, Nieves JW, et al. Unusual osteoclast morphology in teriparatide-treated patients who have been pretreated with alendronate. Presented at: ASBMR 29th Annual Meeting; September 17, 2007; Honolulu, HI. Abstract 1096.