Elsevier

Bone

Volume 36, Issue 3, March 2005, Pages 387-398
Bone

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study

https://doi.org/10.1016/j.bone.2004.11.012Get rights and content

Abstract

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50–80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of ‘all falls’ and falls not causing fracture (‘fracture-free’) during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (θ) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF.

In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, ≥1 h/day walking/cycling, and number of ‘all falls’ during follow-up (all P < 0.074). ‘Fracture-free’ falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (θ = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (θ = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates.

In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (θ = 0.081, P = 0.096).

We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Introduction

Aside from major trauma, the occurrence of many limb fractures in those over age 50 is explained by a fall. Those with low bone mineral density (BMD) are at increased risk of fracture as a result of a fall. As argued frequently elsewhere, anticipated risk factors for limb fractures would thus include those associated with both falling and low bone density, including some such as frailty that might be common to both.

In some prospective studies, a decreased bone density has been shown to be an important predictor of future limb fractures. In the Study of Osteoporotic Fractures (SOF), women in the lowest quintile of distal radius BMD had four times the risk of distal forearm fracture and 7.5 times the risk of proximal humerus fracture when compared to those in the highest quintile [1]. In the Dubbo study, there was a 50% increased risk of forearm and wrist fracture per standard deviation reduction in femoral neck BMD, which was observed in both genders [2]. Some retrospective data suggest that low BMD may be of less importance in predicting susceptibility in those aged over 65 [3], while other data support its utility [4]. The data are not entirely consistent with regard to lifestyle risk factors [2], [5], [6], [7], with roles of varying importance for physical inactivity, smoking, body mass, and comorbidity. Some studies have demonstrated a decreased risk of lower limb fracture among the physically active [8], [9], while other studies have shown that the most active persons are at greater risk of an upper limb fracture [1], [10]. Although there is evidence that BMD is important in determining limb fractures, little is known about its relative importance if adjusted for fall risk and other risk factors, especially with data from diverse populations where large variations in BMD and fall risk are to be expected.

We have recently completed a multicenter multinational prospective study of fractures and falls, the European Prospective Osteoporosis Study (EPOS), in which nonspine fractures were identified prospectively over a mean of 3 years and spine fractures over a mean of 3.8 years. In recent papers, we have presented the descriptive epidemiology of the nonspine fractures [11], an analysis of the contribution of center-specific fall rates to the risk of limb fractures [12], and an evaluation of the contribution of lifestyle, gynecological, and fracture history to the risk of distal forearm fracture [13]. In the present paper, we have taken advantage of the fact that 20 of the 31 participating centers in the EPOS limb fracture study obtained measurements of hip and/or spine BMD. We have analyzed the independent contributions of bone density, falls, and other risk factors for limb fractures with a view to defining their importance for predicting upper and lower limb fractures in European women and men in the 6th to 8th decades of age. We also aimed to describe the relative contributions of center-specific BMD vs. center-specific fall rates in explaining variation in fracture rates between centers after adjusting for the risk factors measured at the individual level.

Section snippets

Subjects

The subjects included in the analysis were participants in the European Prospective Osteoporosis Study (EPOS), which was a follow-up study on subjects initially recruited to the European Vertebral Osteoporosis Study (EVOS). Detailed methods of the two studies have been reported elsewhere [11], [14], [15]. In brief, stratified sampling was used to recruit men and women aged 50 years and over from population registers in 36 European centers. The aim was to recruit equal numbers of men and women

Subjects characteristics

In the 20 centers that contributed data to this analysis, 2451 men, mean age 63.7 (SD = 8.0) years, and 2919 women, mean age 62.8 (SD = 7.7) years, were followed for a median of 3.0 years (range = 0.5–5.4 years), for a total of 16,654 person years (pyrs) of follow-up. Owing to resource constraints, not all centers recruited their target numbers of subjects. Table 1 shows summary statistics for other subject characteristics studied. Bone mineral density was measured at the hip in 2565 (88%)

Discussion

Bone mineral density has been shown to be a predictor of fracture in a number of single center studies. The paper presents data from a multicenter multinational prospective study. In this paper, we present the results of modeling limb fracture risk as a function of BMD after adjusting for the other significant risk factors for fracture described by Silman [13] or Roy et al. [12]. The main result is that bone mineral density appeared to be less important in explaining variations in incidence of

Acknowledgments

The study was financially supported by a European Union Concerted Action Grant under Biomed-1 (BMH1CT920182) and also EU grants C1PDCT925102, ERBC1PDCT 930105 and 940229 and QLK6-CT-2002-00491. The central coordination was also supported by the UK Arthritis Research Campaign, the Medical Research Council (G9321536), and the European Foundation for Osteoporosis and Bone Disease. The EU's PECO program linked to BIOMED 1 funded in part the participation of the Budapest, Warsaw, Prague, Piestany,

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