A meta-analysis of previous fracture and subsequent fracture risk
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.
References (64)
- et al.
Epidemiology and outcomes of osteoporotic fractures
Lancet
(2002) - et al.
Association of prevalent vertebral fractures, bone density and alendronate treatment with incident vertebral fractures: effect of number and spinal location of fractures
Bone
(1999) - et al.
Spatial relationships between prevalent and incident spine fractures
Bone
(1999) - et al.
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture intervention trial research group
Lancet
(1996) - et al.
Ten year risk of osteoporotic fracture and the effect of risk factors on screening strategies
Bone
(2002) Diagnosis of osteoporosis and assessment of fracture risk
Lancet
(2002)- et al.
Fractures and low axial bone density in perimenopausal women
J. Clin. Epidemiol.
(1995) - et al.
Refractures in patients at least forty-five years old. A prospective analysis of twenty-two thousand and sixty patients
J. Bone Joint Surg. Am.
(2002) - et al.
Risk of new vertebral fracture in the year following a fracture
JAMA
(2001) - et al.
Acute and long-term increase in fracture risk after hospitalisation for vertebral fracture
Osteoporosis Int.
(2001)