STRESS FRACTURES AND MATERIAL FATIGUE Stress fracture syndrome manifests as bone tenderness and an increase in radioactively labeled technetium uptake seen in bone scans with or without positive findings on X-ray films and arises from repetitive stresses, none of which is individually capable of producing fracture (1). Stress fractures are a primary medical concern confronting the army during recruit-training, causing roughly 5% of trainees to seek medical care, and are a problem for non-military athletes as well (1–6). Despite the drastic physical, economic, and morale burden caused by this condition, the pathophysiology of the lesion is poorly understood. Stress fractures are widely thought to arise from fatigue damage, wherein the repetitive activity inherent in physical training generates small microfractures in loca- tions of maximum cyclic strain, and this microdamage accumulates until the material fails (7–9). The fatigue microdamage hypothesis is not consistent with the typical stress fractures generated in young, healthy adults subjected to even the most rigorous of training regimens. First, the number of cycles required to cause true fatigue fractures in bone, in vitro, are enormous in comparison to the numbers of cycles associated with early signs of stress fracture symptoms in military recruits (10–12). Second, the stress fracture syndrome does not occur at sites in the bone where the strain magnitudes are greatest, but often where they are least (in two animal models, at least) (12–14). Finally, focal intracortical osteopenia precedes any evidence of micro-cracks, even in humans, suggesting the lesion is a tissue reaction to altered loading, not a material failure caused by fatigue (12). It has been estimated that at peak physiological strain levels (4000–5000 με) (8,13), it would take on the order of 10 6 cycles or more to produce fatigue fractures (10,11). If an army recruit were able to load each leg once a second at maximal force, for 12 hours a day (not a trivial exercise regimen), it would still require loading for one month to achieve 10 6 load reversals. Furthermore, at the more moderate strains (500–1000 με) which have been Medical Hypotheses (1999) 53(5), 363–368 © 1999 Harcourt Publishers Ltd Article No. mehy.1998.0782 Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome? M. W. Otter, Y. X. Qin, C. T. Rubin, K. J. McLeod Biomedical Engineering Program, Department of Orthopedics, State University of New York, Stony Brook, NY, USA Summary Stress fractures have been proposed to arise from repetitive activity of training inducing an accumulation of microfractures in locations of peak strain. However, stress fractures most often occur long before accumulation of material damage could occur; they occur in cortical locations of low, not high, strain; and intracortical osteopenia precedes any evidence of micro-cracks. We propose that this lesion arises from a focal remodeling response to site- specific changes in bone perfusion during redundant axial loading of appendicular bones. Intramedullary pressures significantly exceeding peak arterial pressure are generated by strenuous exercise and, if the exercise is maintained, the bone tissue can suffer from ischemia caused by reduced blood flow into the medullary canal and hence to the inner two-thirds of the cortex. Site specificity is caused by the lack, in certain regions of the cortex, of compensating matrix-consolidation-driven fluid flow which brings nutrients from the periosteal surface to portions of the cortex. Upon cessation of the exercise, re-flow of fresh blood into the vasculature leads to reperfusion injury, causing an extended no-flow or reduced flow to that portion of the bone most strongly denied perfusion during the exercise. This leads to a cell-stress-initiated remodeling which ultimately weakens the bone, predisposing it to fracture. © 1999 Harcourt Publishers Ltd Received 10 February 1998 Accepted 25 August 1998 Correspondence to: Mark W. Otter PhD, Biomedical Engineering Program, Department of Orthopedics, State University of New York, Stony Brook, NY 11794-8181, USA 363