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The aim of this study is to determine the incidence and to quantify the risk factors for developing long-term regional osteopenia/osteoporosis (RO) following tibial fractures. We studied 42 adult subjects (8 females and 34 males) who had sustained a tibial fracture 16 yr prior to the study. Mechanism and type of injury, method of treatment, length of immobilization, weight-bearing status, and healing time were determined from the patient records. A questionnaire covering known causes of generalized osteoporosis (GO), including history of smoking, alcohol consumption, medications, other fractures, thyroid/parathyroid disorders, epilepsy, and renal disorders, was answered by all the subjects. Bone mineral density (BMD) of lumbar vertebrae 1–4 and both proximal femurs was assessed using dual-energy X-ray absorptiometry (DXA) scanning. T- and Z-scores were generated. Assessment of risk factors was done by calculating the odds ratio (OR) and 95% confidence interval (CI). The incidence of significant loss of BMD as defined by the World Health Organization (T-score <−1) of the ipsilateral neck of femur and/or lumbar spine was found to be 40%. None of our subjects had any known cause for GO. The following risk factors were found to be statistically significant in unadjusted models: smoking (OR 22, 95% CI = 4 − >40), alcohol >20 units/wk (OR 11, 95% CI 2 = 2–54), open fracture (OR 17, 95% CI = 2.9 − >40), nonweight bearing >4 wk (OR 15, 95% CI 2.9− >40), and delayed union defined as healing time more than 6 mo (OR 15, 95% CI 1.54 − >40). Permanent regional loss of BMD occurs in a significant proportion of tibial shaft fracture patients. Modern fracture management should include identifying “at-risk” patients and appropriate preventive measures to prevent fragility fractures.