Severely Suppressed Bone Turnover: A Potential Complication of Alendronate Therapy

Abstract

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 nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 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 eight patients, and eroded surface was decreased in four. 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, nonspinal fractures. Although coadministration of estrogen or glucocorticoids appears to be a predisposing factor, 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.

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

“…(114,115,122) In only a minority of cases have BTMs been suppressed. (13,109,116) Thus BTMs, at least when measured after atypical femoral fractures have occurred, do not suggest oversuppression of bone turnover in the majority of patients. However, since fractures per se are associated with increased BTMs, measurements obtained after a fracture may reflect fracture healing rather than the rate of bone remodeling throughout the skeleton.…”

“…(107) Relatively few reports included bone turnover markers (BTMs). (13,109,(113)(114)(115)(116)122,123) When measured, however, bone resorption markers are usually within the normal premenopausal range (109,(114)(115)(116)123,124) and occasionally are elevated. (114,115,122) In only a minority of cases have BTMs been suppressed.…”

“…Also, where available, biochemical markers of bone turnover are often not reduced to the same degree as that seen in the biopsy and may be within the normal range. (13,109,(113)(114)(115)(116)122,123) The findings of Somford and colleagues (119) at both the ilium and the fracture site and of Visekruna and colleagues (12) at the ilium suggest an alternate pathogenetic mechanism that involves increased resorption coupled with reduced bone formation. Clearly, more information is needed about bone histopathology at the site of atypical femur fractures (see ''Key Research Questions'' below).…”

The Effect of Antiresorptives on Bone Quality

“…Therefore, it is difficult to understand the relationship between suppression of remodeling during BP treatment and the occurrence of ''atypical'' fractures [54]. Fortunately, they are rare in patients receiving BP therapy, and since they occur rarely in patients not exposed to BPs [9], the etiology may not be associated with antiresorptive therapy.…”

Update in Women’s Health for the General Internist

“…Several case series have reported an increased risk of atypical femoral shaft fractures (fractures of the subtrochanteric or diaphyseal femur) with alendronate. [30][31][32][33][34][35][36][37][38][39][40][41][42] However, it has not previously been possible to estimate population prevalence or identify risk factors.…”