An emerging pattern of subtrochanteric stress fractures: A long-term complication of alendronate therapy?

doi:10.1016/j.injury.2007.08.036

Injury

Volume 39, Issue 2, February 2008, Pages 224-231

https://doi.org/10.1016/j.injury.2007.08.036 Get rights and content

Summary

Background

Subtrochanteric insufficiency fractures in post-menopausal patients have not been commonly reported in the literature. A recent increase in the incidence of such fractures occurring in patients while on alendronate therapy led us to conduct a retrospective review of these patients in our institution.

Methods

Seventeen patients, with a mean age of 66 years, sustained low energy subtrochanteric fractures within a 20-month period. These patients were incidentally found to be on alendronate therapy for an average of 4.8 years. Clinical data and history were reviewed and roentgenograms were evaluated by a single investigator. All additional imaging and bone mineral density measurements available were analysed.

Results

A characteristic fracture configuration suggestive of an insufficiency stress fracture was identified on plain radiographs. This consisted of (a) cortical thickening in the lateral side of the subtrochanteric region, (b) a transverse fracture, and (c) a medial cortical spike. In addition, 9 (53%) patients had bilateral findings of stress reactions or fractures, and 13 (76%) had symptoms of prodromal pain.

Conclusions

These insufficiency fractures could possibly have developed from the over suppression of bone turnover from prolonged alendronate therapy, in keeping with recently published evidence. This study further highlights the need for heightened awareness of alendronate's potential adverse effects.

Introduction

Subtrochanteric stress fractures are not widely described in the current literature. In the younger age group, fatigue stress fractures in this region are known to occur in runners and athletes.4, 9 Subtrochanteric insufficiency fractures in the older osteoporotic age group have not been commonly reported, and only isolated cases have been mentioned in relation to patients with hypophosphatemic osteomalacia,⁶ pcynodysostosis,¹⁴ or in whom fluoride therapy has been prescribed.¹⁶

We have noticed a recent increase in incidence of these fractures occurring in older patients in our institution who have been receiving alendronate, a potent inhibitor of bone resorption. Most of these fractures resulted from low energy trauma, and some were preceded by prodromal pain in the affected limb.

A retrospective review of these patients was undertaken to determine if a causal relationship with alendronate usage could be established, and to further define this pattern of fractures. We observed a peculiar but consistent fracture configuration that suggested an insufficiency fracture. Moreover, a number of patients had radiological evidence of stress reactions either before the fracture occurred or on the contralateral femur. These findings were all the more unusual given that they were on anti-resorptive therapy for osteoporosis.

Section snippets

Materials and methods

We retrospectively reviewed all patients admitted to our institution from 1 May 2005 to 31 January 2007 with a low energy subtrochanteric femur fracture whilst on alendronate therapy. Subtrochanteric fracture was defined as a fracture within the region of the femur 5 cm distal to the lesser trochanter. Exclusion criteria included patients with high energy trauma, pathological fractures secondary to underlying malignancies, and subtrochanteric extensions from intertrochanteric fractures. Ethical

Results

Seventeen patients were identified in our study group and their details are tabulated in Table 1. All fractures were sustained in low energy circumstances, commonly a fall after tripping, although seven patients (patients 2, 4, 5, 9, 10, 15 and 17) experienced acute pain before the onset of a fall, for example whilst getting up from a chair. All patients were female of Chinese ethnicity, with an age range of 53–82 years (mean age of 66 years).

All patients were receiving alendronate treatment

Discussion

Alendronate is a potent inhibitor of osteoclast-mediated bone resorption and is widely used as first-line therapy for the prevention of osteoporotic fractures. It acts by suppressing osteoclastic activity and inducing apoptosis of the osteoclasts.

Alendronate has been shown to significantly increase bone density of the spine and hip,² as well as reduce the incidence of osteoporotic fractures by up to 50%. When discontinued after 5 years, the physiological effect on bone resorption remains for 5

Conclusion

Recent concerns on the long-term safety of bisphosphonates and the appropriate duration of therapy have been raised in editorials by Ott.12, 13 This series is currently the largest collection of fractures attributed to alendronate therapy and offers further evidence that long-term alendronate may have potential harmful effects. This paper adds clinical significance to Odvina et al's findings, and further defines the clinical picture and radiological findings of such fractures.

Whilst our study

Conflict of interest statement

No financial or material support has been received or will be received from any commercial party related directly or indirectly to the research and the work. All authors have no potential conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of this manuscript.

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^*: The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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An emerging pattern of subtrochanteric stress fractures: A long-term complication of alendronate therapy?*

Summary

Background

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Conclusion

Conflict of interest statement

Lancet

Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis

N Engl J Med

Effects of continuing of stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial

JAMA

Subtrochanteric stress fractures in runners

Am J Sports Med

Effects of differences in mineralization on the mechanical properties of bone

Phil Trans R Soc Lond Biol Sci

Hip pain in a case of hypophosphatemic osteomalacia

Am J Orthop

CT and MR imaging findings in athletes with early tibial stress injuries: comparison with bone scintigraphy findings and emphasis on cortical abnormalities

Radiology

Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution

J Bone Joint Surg Br