Original articleSeverity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial
Introduction
Patients with osteoporosis are susceptible to fractures due to multifactorial changes in bone quality and/or quantity, which together contribute to bone strength [1]. Additional risk factors for osteoporotic fractures include age, previous osteoporotic fractures, genetic predisposition, and falls [2]. Acceleration of bone turnover with aging leads to bone loss, which is manifest as decreased bone mineral density (BMD) [3] and disruption of trabecular architecture [4], which in turn results in impaired bone strength and increased fracture risk [5].
Baseline BMD and prevalent radiographic vertebral fractures are independent predictors of subsequent vertebral and nonvertebral fractures [6], [7], [8]. Observational case-control studies have found that patients with existing vertebral fractures have an increased risk of new vertebral and nonvertebral fractures [9], [10], [11], [12]. In randomized prospective clinical trials, women with radiographic vertebral fractures at baseline have a higher incidence of new vertebral fractures at endpoint, compared to women without baseline vertebral fractures, irrespective of therapeutic intervention [13], [14], [15]. The number of prevalent radiographic vertebral fractures also predicts the risk of subsequent vertebral and nonvertebral fractures [16], [11], [10], [17]. Furthermore, the occurrence of a new vertebral fracture increases the risk of subsequent vertebral fractures within the following year, and this increased risk is exacerbated by the number of prevalent vertebral fractures [17]. Patients with more severe degrees of vertebral deformities, measured as a relative decrease in vertebral height, have an increased risk of subsequent vertebral and nonvertebral fractures [11].
Although several lines of evidence indicate that baseline BMD, the presence and number of vertebral fractures at baseline, and the severity of prevalent vertebral fractures all contribute to decreased bone strength and increased fracture risk, no study to date has directly compared each of these contributing factors on their ability to predict subsequent fracture risk. All of these factors were assessed in the 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) clinical trial in which vertebral fracture severity was determined by semiquantitative (SQ) assessment. The analysis of fracture incidence in the placebo group of MORE provided the opportunity to determine the relationships between each of these contributing osteoporosis risk factors and subsequent fracture risk.
The present analyses examined the relationship between the severity of baseline vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures and compared the prediction of new fracture risk by baseline vertebral fracture severity to other baseline osteoporosis risk factors in the placebo group of the MORE trial. Because women with severe baseline vertebral fractures were found to have the greatest risk of subsequent fracture, further analyses examined the efficacy of raloxifene in reducing the risk of new fractures in this subgroup.
Section snippets
Subjects and treatment
The Multiple Outcomes of Raloxifene Evaluation (MORE) trial enrolled 7705 women with osteoporosis, as defined by low bone mineral density (femoral neck or lumbar spine BMD T-score ≤−2.5) and/or radiographically apparent vertebral fractures, who were at least 2 years postmenopausal. Complete inclusion and exclusion criteria, and procedures for subject recruitment and follow-up, were previously described [13]. The institutional review board at each study center approved the study protocol, and
Results
There were no statistically significant differences in any of the baseline characteristics between the placebo and raloxifene treatment groups in the overall MORE study population [13], [28]. The women in the placebo group of MORE who took at least one dose of study medication were 66.6 ± 7.1 years of age (mean ± standard deviation) and 18.9 ± 8.5 years postmenopausal, with a body mass index of 25.2 ± 4.0 kg/m2. The baseline BMD in the placebo group was 0.81 ± 0.14 g/cm2 in the lumbar spine (t
Discussion
Women in the placebo group of the MORE study with severe (SQ3) vertebral fractures at baseline had the greatest risk of subsequent vertebral and nonvertebral fractures, compared to women without or with less severe prevalent fractures. The relationship between baseline fracture severity and subsequent fracture risk remained significant even after controlling for differences in baseline characteristics between women with more severe prevalent vertebral fractures and those with less severe
Acknowledgements
Eli Lilly and Company provided funding for the Multiple Outcomes of Raloxifene Evaluation (MORE) Trial. The authors thank the following individuals for reviewing the scientific content of this article: Willard H. Dere, M.D.; Adolfo Diez-Perez, M.D., Ph.D.; Erik F. Eriksen, M.D.; Kristine D. Harper, M.D.; and Fernando Marin, M.D., Ph.D.; and Daniel Thiebaud, M.D., and Derek Elmerick, M.S., for validation of statistical results.
These data were presented in part at the International Osteoporosis
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