Elsevier

Bone

Volume 35, Issue 2, August 2004, Pages 375-382
Bone

A meta-analysis of previous fracture and subsequent fracture risk

https://doi.org/10.1016/j.bone.2004.03.024Get rights and content

Abstract

Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15 259 men and 44 902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250 000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted β-coefficients.

A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75–1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age.

We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Introduction

It is well established from many cohort, case-control, and cross-sectional studies that a prior osteoporotic fracture increases the risk of future fractures [1], [2], [3], [4], [5], [6], [7], [8]. A prior forearm fracture is associated with about a twofold increase in the subsequent risk of fracture [9], [10], [11], [12], [13]. More recently, significant increases in risk have been described for prior fractures at other sites characteristic of osteoporosis [6], [7], [14], [15], [16], [17], [18], [19], [20], [21]. The risk of another vertebral fracture is particularly high after a spine fracture [7], [22], [23], [24]. Similar observations are found in the setting of randomized clinical trials. In the placebo arm, the risk of vertebral deformities is approximately fivefold higher in patients with a prior vertebral deformity than in those without [4], [25], [26]. The interrelationships between the site of prior fracture and site of subsequent fracture have been summarized by meta-analysis [27] and a large case-control study, published more recently found broadly similar relationships [8].

Increased fracture risk may be in part due to the fact that patients with fracture have low bone mineral density (BMD). Studies that have adjusted for BMD suggest that the relative risk is only modestly downward adjusted [3], [20], [24], [28], [29], [30], [31].

The consistent association between a prior fracture and subsequent fracture risk has led to the inclusion of prior fracture as a risk factor to be used in assessment guidelines [32], [33], [34], [35]. For example, in Europe, it is recommended that patients be identified on the basis of risk factors for subsequent assessment by BMD [33], [34], [35]. Patients are then considered for intervention on the finding of osteoporosis (i.e., a T score of ≤−2.5 SD). This approach is conservative since it does not recognize the independent contribution of the risk factor from BMD. This has been recognized in some guidelines where the intervention threshold is less conservative in the presence of a risk factor such as a prior fragility fracture [32], [36]. The consideration of several independent risk factors permits the more accurate categorization of risk [37], and attention has focussed recently on the assessment of fracture risk using multiple risk factors, rather than the use of BMD alone, to define intervention thresholds [38], [39]. This demands knowledge of the interrelationships between these risk factors.

The aim of the present study was to quantify the risk associated with a history of prior fracture for future fracture in an international setting and to explore the dependence of this risk with age, sex, and BMD.

Section snippets

Methods

We studied 60 161 men and women of whom 26% had a prior fracture history taken from 11 prospectively studied cohorts. Brief details of the cohorts studied are given below and summarized in Table 1.

Results

Of 60 161 men and women studied, 877 men and 4686 women were identified as having a subsequent fracture of any kind, of which 680 and 2850 were characterized as osteoporotic in men and women, respectively. Two hundred and eleven men and 767 women sustained a hip fracture. The total follow-up was 61 938 person years in men and 192 644 in women. BMD measurements were available in 62% of individuals.

Probability of fracture history rose almost linearly with age (Table 3). The probability of recording

Discussion

The present study confirms that a history of prior fracture is a significant risk factor for future fractures. In addition, the effect is over and above that which can be explained by variations in BMD. The risk of subsequent fractures is not as great as that identified in some studies [8], but as expected, falls within the confidence estimates of most estimates [27]. Discrepancies may be related to the duration of follow-up since the risk of subsequent fracture may not be linear over time [4],

Acknowledgements

We are grateful to the International Society for Clinical Densitometry, the National Osteoporosis Foundation, the International Osteoporosis Foundation, and the European Community (EU FP 3/5). We are also grateful to Lilly, Hologic, GE Lunar, Roche, Pfizer, IGEA, the Alliance for Better Bone Health, Novartis, Wyeth, for their unrestricted support of this work.

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