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This version published online on December 14, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0952
A more recent version of this article appeared on March 1, 2005
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Submitted on May 19, 2004
Accepted on December 1, 2004

SEVERELY SUPPRESSED BONE TURNOVER: A POTENTIAL COMPLICATION OF ALENDRONATE THERAPY

Clarita V. Odvina M.D.*, Joseph E. Zerwekh Ph.D., D. Sudhaker Rao M.B, B.S., Naim Maalouf M.D., Frank A. Gottschalk M.D., and Charles Y.C. Pak M.D.

Clarita V. Odvina Center for Mineral Metabolism and Clinical Research and Division of Orthopedic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8885; and Division of Bone and Mineral Metabolism, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202

* To whom correspondence should be addressed. E-mail: clarita.odvina{at}utsouthwestern.edu.

Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on 9 patients who sustained spontaneous non-spinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months-2 yr during therapy.

Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low normal in 8 patients and eroded surface was decreased in 4. Matrix synthesis was markedly diminished with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces.

Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of non-spinal fractures. Although co-adminstration of estrogen or glucocorticoids appears to be predisposing factors, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.




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