Why do older women with diabetes have an increased fracture risk?

By definition, osteoporosis is characterized by low bone mass, architectural deterioration, increased fragility, and an increased fracture risk (1). A multitude of studies has demonstrated the relationship between low bone mass and increased fracture risk, mainly in white populations. Conversely, populations with high bone mass generally have a lower fracture risk. However, an apparent paradox emerges from the study by Schwartz et al. (2), in this issue of the journal. They report that a population with relatively high bone mass—people with type 2 diabetes—have an increased fracture risk compared with people without diabetes (2). This is perhaps more surprising because of the association between type 2 diabetes and obesity, and the presumed protective effect of obesity against osteoporosis and fractures. So why do these older women with diabetes have more fractures? Can these fractures be attributed to osteoporosis? Although type 1 diabetes seems to be associated with a low bone mass, most studies have indicated a relatively normal bone mass in type 2 diabetes. However, the importance of bone quality and the likelihood of injury (e.g. from falls) in determining fracture risk (3) should not be underestimated. The consensus definition of osteoporosis given above differs from earlier concepts in that it includes the deterioration of bone architecture, and bone fragility, in addition to low bone mass. When assessing whether a fracture in a person with normal bone density is osteoporotic, one must consider these other elements of the disease. In diabetes, there are many factors that could predispose patients to injury sufficient to cause bone fractures. These include altered proprioception, balance, and gait due to neuropathy and visual impairment from diabetic retinopathy and cataracts. If these do increase the frequency of falls (and there is some evidence that people with diabetes have frequent falls; Ref. 4), then fractures at certain skeletal sites are predictable. Little is known about bone quality in people with diabetes, although abnormal vascular function could theoretically have an adverse effect on bone remodeling and, therefore, on bone quality. The combination of poor bone quality and frequent, injurious falls would be expected to increase fracture risk independently of bone mass. Schwartz et al. (2) were able to take into account more than two dozen covariates that might be relevant to the analysis of fracture risk in their cohort, who were participating in the Study of Osteoporotic Fractures (SOF). This is a large cohort of 9654 white women over the age of 65, followed for an average of 9.4 yr. The main outcome variables in SOF are osteoporosis and fractures, although the study is so large and comprehensive that many other diseases and variables can be meaningfully assessed. For example, SOF has data on covariates that are relevant to the diabetes study, such as factors that could be indicators of diabetic retinopathy and neuropathy. These include vibratory perception, pressure sensitivity, grip strength, hip extensor strength, static balance, and gait speed for diabetic neuropathy; and corrected visual acuity, depth perception, and contrast sensitivity (2). As one might expect, the women with diabetes had poorer scores on measures of balance and gait, peripheral neuropathy, and vision compared with the nondiabetic subjects. Despite this wealth of information, because SOF was not designed to study diabetes, there are several potentially relevant variables that are not available in the database. For example, while data are available on lower extremity vibratory perception and pressure sensitivity of the great toe, the authors acknowledge that they do not have data on more sensitive measures of peripheral neuropathy such as nerve conduction velocity. There are only a few other studies of bone mass and fractures in diabetic subjects that approach the magnitude of SOF. The Rotterdam Study, with 3450 elderly women, of whom 335 had type 2 diabetes, found a higher bone mass among the women with diabetes compared with those without (5). In contrast with the SOF study, the women with diabetes in the Rotterdam Study reported fewer nonvertebral fractures, but this was for the 5 yr preceding their baseline visit (odds ratio, 0.63; 95% confidence interval, 0.44–0.90) (6). The Nord-Trondelag Health Survey of 35,444 people 50 yr and older determined hip fracture incidence over 9 yr of follow-up (7). They found that among women ages 50–74 with type 2 diabetes of long duration, the relative risk of hip fracture was 1.8 (95% confidence interval, 1.1–2.9), a rate that is similar to that reported for SOF. Schwartz et al. (2) also reported that the duration of diabetes was associated with a higher risk of hip fracture and that there was a tendency for any fracture risk to be higher among insulin-treated diabetics, who may have more severe disease. It is instructive to consider what types of fractures are associated with diabetes in the SOF study, and whether these are typical of osteoporosis. After adjusting for age, body mass index, and bone density, Schwartz et al. (2) found that the risk of hip and proximal humerus fractures were increased in noninsulin users, whereas there was an increased risk of foot fractures in insulin users. Certainly, hip fractures, and probably humerus fractures, are characteristic of osteoporosis, but would foot fractures fall into this category? An earlier paper from the SOF group identified which fractures were associated with low bone mass in their study: the hip, humerus, and foot were all included in the list, whereas fractures of the ankle, elbow, finger, and face were not (8). In Received November 16, 2000. Accepted November 16, 2000. Address correspondence and requests for reprints to: Dorothy A. Nelson, Ph.D., Department of Internal Medicine, Wayne State University, Hutzel Hospital, 1 Lobby Center, 4707 St. Antoine, Detroit, Michigan 48201. E-mail: dnelson@intmed.wayne. edu. 0021-972X/01/$03.00/0 Vol. 86, No. 1 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society