Weight change was an influencing factor of osteoporosis and fracture in a controversial way. Based on a nationally representative data, we found that weight change from obesity in midlife to non-obesity in late adulthood was associated with a reduction in the risk of osteoporosis and wrist fracture in male, but not in female.Obesity is usually recognized as a protective factor to osteoporosis and osteoporotic fracture. However, it is still unclear whether historical weight status was associated with the risk of osteoporosis and fracture. The aim of this study was to investigate the relationship between weight change patterns across adulthood and the prevalence of osteoporosis and fracture.Data from the National Health and Nutrition Examination Survey (NHANES) with 8725 US adults aged ≥ 40 years were analyzed in this study. Weight change patterns were categorized as "stable non-obese," "obese with earlier weight gain," "obese with recent weight gain," and "revert to non-obese" based on the body mass index (BMI) at 25 years old, 10 years prior to baseline and at baseline. Body mineral density (BMD) was measured using dual x-ray absorptiometry (DXA), and osteoporosis was diagnosed based on the World Health Organization criteria. Self-reported occurrence of osteoporotic fractures were determined by questionnaires.Compared with subjects in "stable non-obese" group, obese with earlier weight gain were positively related to the increase of BMD in both genders, while elevated BMD was only observed in female of "obese with recent weight gain" group and in male of "revert to non-obese" group after multiple adjustment. Moreover, changing from the obesity to non-obesity in the 10 years period before baseline was associated with a 81.6% lower risk of osteoporosis (odds ratio (OR) 0.184, 95% confidence interval (CI) 0.037-0.914 (P = 0.039)) and a 69.8% lower risk of wrist fracture (OR 0.302, 95%CI 0.120-0.757 (P = 0.012)) in male, but not in female.Weight change from obesity in midlife to non-obesity in late adulthood was associated with a reduction in the risk of osteoporosis and wrist fracture in male. Our findings support the importance of investigating the mechanism of weight change in different life period.© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.