Elsevier

Bone

Volume 55, Issue 2, August 2013, Pages 377-383
Bone

Original Full Length Article
Fracture history of healthy premenopausal women is associated with a reduction of cortical microstructural components at the distal radius,☆☆

https://doi.org/10.1016/j.bone.2013.04.025Get rights and content

Highlights

  • We studied healthy premenopausal women with or without a fracture history.

  • We measured aBMD, microstructure and strength estimates in the radial metaphysis.

  • In the whole group, mean radial metaphysis aBMD T-score did not differ from zero.

  • Mean cortical thickness was reduced by ~ 0.4 T-score in women with a fracture history.

  • Low cortical thickness was associated with an approximative 2.5-fold higher fracture risk.

Abstract

Objectives

The objective of this study is to determine in healthy premenopausal women with a history of fracture which bone structural components of the distal radius are the most closely associated with a risk of fracture.

Methods and participants

The method was as follows: measurement of radial areal bone mineral density (aBMD) by DXA, microstructural components by high-resolution quantitative peripheral computerized tomography (HR-pQCT) and strength variables by micro Finite Element Analysis (μFEA) in 196 healthy premenopausal women aged 45.9 ± 3.7 (± SD) years with (FX, n = 96) and without (NO-FX, n = 100) a history of fracture. We evaluated differences in T-scores between FX and NO-FX and risk of fracture by Odds ratios (OR with 95% confidence intervals, CI) per one SD decrease, using logistic regression analysis after adjustment for age, height, weight, menarcheal age, calcium and protein intakes, and physical activity.

Results

In the whole group the mean radial metaphysis aBMD T-score was not significantly different from zero. In the FX as compared to the NO-FX group, the differences in T-scores were as follows: for radial metaphysis: aBMD, − 0.24 (P = 0.005); for distal radius microstructure components: cortical volumetric BMD, − 0.38 (P = 0.0009); cortical thickness, − 0.37 (P = 0.0001); cross-sectional area (CSA), + 0.24 (P = 0.034); and endosteal perimeter, + 0.28 (P = 0.032); and for strength estimates: stiffness, − 0.15 (P = 0.030); failure load, − 0.14 (P = 0.044); and apparent modulus, − 0.28 (P = 0.006). T-scores of trabecular volumetric BMD and thickness did not significantly differ between the FX and the NO-FX group. Accordingly, the risk of fracture (OR, 95% CI) for 1 SD decrease in radius bone parameters was as follows: radial metaphysis aBMD: 1.70 (1.18–2.44), P = 0.004; cortical volumetric BMD: 1.86 (1.28–2.71), P = 0.001; and cortical thickness: 2.36 (1.53–3.63), P = 0.0001. The corresponding fracture risk for the strength estimates was as follows: stiffness: 1.66 (1.06–2.61), P = 0.028; failure load: 1.59 (1.02–2.47), P = 0.041; and apparent modulus: 1.76 (1.17–2.64), P = 0.006.

Conclusions

In healthy premenopausal women, a history of fracture is associated with reduced T-scores in the distal radius, with the cortical components showing the greatest deficit. A reduction of one SD in cortical thickness is associated with a nearly three-fold increased risk of fracture. This finding strengthens the notion that, in healthy women, a certain degree of bone structural fragility contributes to fractures before the menopause and therefore should be taken into consideration in the individual prevention strategy of postmenopausal osteoporosis.

Introduction

In postmenopausal women, low areal bone mineral density (aBMD) is a significant risk factor for fractures [1], [2], [3], [4]. Likewise, it is established that low trauma fracture occurring after the menopause is a risk for further fragility fractures [5], [6], [7], [8]. There is also evidence that, in women aged 65 years and older, fractures before menopause are independent risk factors for subsequent fractures after menopause [9]. This greater risk of about 30% of fracture after menopause is similar to a maternal history of fracture or a history of two or more falls in the previous year [9]. The relation between fracture before menopause and deficit in bone mineral mass and microstructural alterations has been well documented in women with idiopathic osteoporosis [10], [11], [12]. Besides the pathological condition of premenopausal idiopathic osteoporosis, markedly reduced volumetric (v) BMD, as measured by peripheral quantitative computed tomography (pQCT) at the distal radius, is an important risk factor for low-energy or fragility fractures in premenopausal women [13]. In premenopausal women with fragility fracture, aBMD measured at the spine and proximal femur was markedly lower than that measured in postmenopausal women without a fracture history [13]. However, in healthy women without idiopathic osteoporosis, or substantially reduced vBMD due to secondary osteoporosis [14], whether a fracture history recorded before the menopause would be associated with subtle signs of defective bone integrity remains to be documented.

In the context of parent–offspring investigation we assessed several bone variables in healthy premenopausal women (mean age ~ 46 years). These women were mothers of two cohorts of healthy girls [15], [16] and boys [17], [18] whose bone acquisition characteristics were studied over childhood and adolescence. Among them, about half had a history of fracture. In these healthy premenopausal women, we report which, among bone variables measured at the radial level by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computerized tomography (HR-pQCT) and micro-finite element analysis (μFEA), differ in T-score and are significantly associated with an increased risk of fracture before the menopause.

Section snippets

Participants

Fracture history and bone mineral density, and cortical and trabecular microstructure including porosity as well as bone strength estimates assessed by HR-pQCT and μFEA, respectively, were studied in 196 healthy premenopausal women with a mean age of 45.9 ± 3.7 (mean ± SD) years. All subjects lived within the Geneva area. The persistence of regular menstruation at the time of examination was a prerequisite for inclusion in this study. The Ethics Committee of the University Hospitals of Geneva

Fracture history

One hundred and forty-six fractures were reported by 49% of the 196 premenopausal women (Table 1). More than one fracture (2 to 5) was recorded in 34 of them, accounting for 84 fractures and 58% (84 of 146) of all fractures. Fractures occurred in 60 (62.5%) and 36 (37.5%) women up to and after 20 years of age, respectively. Fractures were localized in forearm/wrist (19.2%), hand/fingers (13%), arm/shoulder (10.3%), lower limb (29.5%) and 28.1% at other sites. Anthropometric, nutritional and

Relation between bone deficit and fracture risk

Our study shows that fractures occurring before the menopause in healthy middle-aged women are associated with alterations in several bone variables measurable at the distal radius. As calculated from the radial metaphysis aBMD, the increased risk of fractures (OR: 1.7, 95% CI 1.18.–2.44) is very close to that obtained in postmenopausal women in the important meta-analysis including eleven separate populations with about 90,000 person years of observation time and over 2000 fractures by Marshall

Conclusions

This study shows that, at the distal radius, a history of fracture in healthy premenopausal women is associated with a significantly lower T-score with a predominant deficit in the cortical components. A reduction of one standard deviation in the distal radius cortical thickness nearly triples the risk of fracture occurring before the menopause. This finding strengthens the notion that in healthy women a subtle degree of bone structural fragility contributes to premenopausal fractures and

Acknowledgments

We thank Giulio Conicella and the team of the Division of Nuclear Medicine for DXA and HR-pQCT measurements; Fanny Merminod, certified dietician, for the assessment of food intakes and her assistance in managing the study; Pierre Casez, MD, for the elaboration of the database; François Herrmann, MD, MPH, for the help with statistical analysis. The Swiss National Science Foundation supported this study (Grant 3247BO-109799).

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    Disclosure information's: Bert van Rietbergen is a consultant for Scanco Medical AG.

    ☆☆

    Funding sources: The Swiss National Science Foundation supported this study (Grant 3247B0-109799).

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