To the Editor: Our experience has been very similar to thatdescribed by Lenart et al. (March 20 issue)1 in their reporton atypical fractures of the femoral diaphysis. These fractureshave a distinctive pattern and most likely represent completionof a stress fracture (Figure 1). In our series,2 64.3% of thepatients had involvement of the contralateral femur. In addition,76% of the patients had documented prodromal symptoms of thighpain, vague discomfort, or subjective weakness; these symptomswere often dismissed or treated as symptoms of spinal stenosis."Giving way" of the involved limb immediately preceded the fallin 23.1% of the patients.3 We suggest that any patient receivingbisphosphonates who has thigh pain should undergo radiographicexamination of the femur, and patients with a documented fractureshould undergo radiographic examination of the contralateralfemur. Prefracture diagnosis is challenging, as is definingthe need for prophylactic fixation of a lateral cortical stressreaction that has been characterized by means of computed tomographicand magnetic resonance imaging (MRI) studies as a callus formingover an incomplete stress fracture.
Figure 1. Radiograph Showing a Subtrochanteric Stress Fracture Associated with a Typical Cortical Stress Reaction.
Ernest B.K. Kwek, M.B., B.S. Joyce S.B. Koh, M.B., B.S. Tet Sen Howe, M.B., B.S. Singapore General Hospital Singapore S169608, Singapore kwekasc{at}pacific.net.sg
References
Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008;358:1304-1306. [Free Full Text]
Kwek EBK, Goh SK, Koh JS, Png MA, Howe TS. An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury 2008;39:224-231. [CrossRef][Web of Science][Medline]
Goh SK, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br 2007;89:349-353. [CrossRef][Medline]
To the Editor: We previously reported a case similar to thosereported by Lenart et al. Our patient, a 73-year-old woman,sustained multiple atraumatic femoral insufficiency fractureswhile receiving alendronate therapy.1 The bone-specific alkalinephosphatase level was 7.9 µg per liter (range, 3.8 to22.6), and the ratio of urinary deoxypyridinoline to creatininewas suppressed, at a value of less than 3 nmol per millimole.Although suppressed bone turnover theoretically raises the possibilityof bisphosphonate-related "frozen bone," as previously reported,2histomorphometrically proven suppression of bone formation wasincompatible with the demonstration of normal bone-turnovermarkers in the series reported by Odvina et al.
Femoral insufficiency fractures are associated with increasedmortality, and they are probably markers of ill health withmultifactorial causes.1 These fractures are not limited to patientswho are receiving bisphosphonates. Nonadherence to prescribedbisphosphonates is associated with a 15 to 20% increase in ratesof subsequent fractures. We agree that clinicians should becautious about the hazards of long-term administration of bisphosphonates.However, until further studies can provide definitive evidenceof bisphosphonate-associated fractures, it is premature to attributeatypical fractures to oversuppression of bone turnover alone,while disregarding secondary and patient-related factors. Thefractures in our patient healed while alendronate therapy wascontinued.
Paul Lee, M.B., B.S. Markus J. Seibel, M.D., Ph.D. Concord Repatriation General Hospital Sydney, NSW 2139, Australia p.lee{at}garvan.org.au
References
Lee P, van der Wall H, Seibel MJ. Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. J Endocrinol Invest 2007;30:590-597. [Web of Science][Medline]
Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:1294-1301. [Free Full Text]
The authors reply: We agree with Kwek et al. and with Lee andSeibel that stress fractures of the femoral diaphyses commonlyoccur in association with prolonged bisphosphonate use. We alsoagree with Kwek et al. that careful scrutiny of the contralateralfemur is important, but radiography may not be adequate. A painfullimb may require additional imaging. MRI and bone scanning havegreater sensitivity than radiography for an incipient stressfracture.
In response to Lee and Seibel: low bone turnover may not bethe only cause of stress fractures associated with prolongedbisphosphonate use. In our series, markers of bone turnoverwere not directly measured, since diagnosis-related groups didnot cover a workup for metabolic bone disease, including markersof bone turnover, for the care of patients with fractures. Microfractures,inadequate mineralization, and outdated collagen are severalcandidate causes. Although the fractures reported by Lee etal. healed with continued bisphosphonate treatment, an anabolicagent such as parathyroid hormone (1-34) may be preferable.Parathyroid hormone not only has activated bone-formation markersin trials in humans but has also enhanced the healing of fracturesin studies in animals.1,2
Brett A. Lenart, M.D. Dean G. Lorich, M.D. Joseph M. Lane,M.D. Weill Medical College of Cornell University New York, NY 10021 lanej{at}hss.edu
References
Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003;349:1207-1215. [Free Full Text]
Alkhiary YM, Gerstenfeld LC, Krall E, et al. Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am 2005;87:731-741. [Free Full Text]
Kennel, K. A., Drake, M. T.
(2009). Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management. Mayo Clin Proc.
84: 632-638
[Abstract][Full Text]
Leung, F., Lau, T.-W., To, M., Luk, K. D.-K., Kung, A. W. C.
(2009). Atypical femoral diaphyseal and subtrochanteric fractures and their association with bisphosphonates. BMJ Case Reports
2009: bcr1020081073-bcr1020081073
[Abstract][Full Text]
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