Peripheral quantitative computed tomography measures are associated with adult fracture risk: The Hertfordshire Cohort Study

doi:10.1016/j.bone.2014.03.040

Bone

Volume 64, July 2014, Pages 13-17

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Highlights

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Peripheral quantitative computed tomography measures different aspects of bone to DXA techniques and can separate cortical and trabecular compartments.
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In this prospective cohort study, cortical area and thickness of the radius and tibia predicted fracture in elderly women.
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When bone density was adjusted for, however, this relationship was attenuated.

Abstract

Peripheral quantitative computed tomography (pQCT) captures novel aspects of bone geometry that may contribute to fracture risk and offers the ability to measure both volumetric bone mineral density (vBMD) and a separation of trabecular and cortical compartments of bone, but longitudinal data relating measures obtained from this technique to incident fractures are lacking. Here we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from pQCT and DXA in 182 men and 202 women aged 60–75 years at baseline with incident fractures over 6 years later. Among women, radial cortical thickness (HR 1.72, 95% CI 1.16, 2.54, p = 0.007) and cortical area (HR 1.91, 95% CI 1.27, 2.85, p = 0.002) at the 66% slice were both associated with incident fractures; these results remained significant after adjustment for confounders (age, BMI, social class, cigarette smoking and alcohol consumption, physical activity, dietary calcium, HRT and years since menopause). Further adjustment for aBMD made a little difference to the results. At the tibia, cortical area (HR 1.58, 95% CI 1.10, 2.28, p = 0.01), thickness (HR 1.49, 95% CI 1.08, 2.07, p = 0.02) and density (HR 1.64, 95% CI 1.18, 2.26, p = 0.003) at the 38% site were all associated with incident fractures with the cortical area and density relationships remaining robust to adjustment for the confounders listed above. Further adjustment for aBMD at this site did lead to attenuation of relationships. Among men, tibial stress–strain index (SSI) was predictive of incident fractures (HR 2.30, 95% CI 1.28, 4.13, p = 0.005). Adjustment for confounding variables and aBMD did not render this association non-significant. In conclusion, we have demonstrated relationships between measures of bone size, density and strength obtained by pQCT and incident fracture. These relationships were attenuated but in some cases remained significant after adjustment for BMD measures obtained by DXA, suggesting that some additional information may be conferred by this assessment.

Introduction

In recent years, new techniques to assess bone strength have been developed, but longitudinal data relating measures obtained from these techniques to incident fractures are lacking [1]. One such technique is peripheral quantitative computed tomography (pQCT) [2]. This technique was introduced some years ago as a method for assessing volumetric bone mineral density (vBMD). This technique confers little risk to the individual because exposure to radiation occurs only at a localised, peripheral site and captures aspects of bone geometry that may contribute to fracture risk such as apparent trabecular bone structure. It also offers the ability to measure volumetric bone mineral density (vBMD) and can estimate trabecular and cortical compartments of bone. This is of particular interest as it has been suggested that alterations of cortical and trabecular structure are differentially associated with fragility fractures in postmenopausal women [3]. Case control studies using QCT techniques have highlighted differences in bone architecture and vBMD between individuals with or without fractures [4], [5], [6], [7] but while results from pQCT of the forearm using single slice acquisition protocols have been shown to differentiate between cases and controls in studies of hip fractures in post-menopausal women, results are mixed with some reporting and some failing to report differences [8], [9], [10], [11], [12], [13]. Furthermore, only one study has reported relationships between pQCT measures and fracture risk in men [14].

Further information about any clinical utility of this technology would therefore be helpful. Here we present results from the Hertfordshire Cohort Study (HCS), where we studied associations between measures obtained at multiple slices of the radius and tibia from pQCT, with incident fracture. Participants in the HCS were all born in Hertfordshire between 1931 and 1939, and at the time of the baseline visit for this study (in 2005–2006), were of mean age 69 years.

Section snippets

Materials and methods

In the late 1990s, 1579 men and 1413 women aged 60–75 years were recruited to a study, which was designed to examine the relationship between growth in infancy and the subsequent risk of adult disease, including osteoporosis (the Hertfordshire Cohort Study). The selection procedure for these individuals was as follows: in brief, with the help of the National Health Service Central Registry at Southport and Hertfordshire Family Health Service Association, we traced men and women who were born

Statistical methods

Normality of variables was assessed by comparing histograms of the data with normal probability curves and by inspecting QQ plots and variables transformed as required. Standard deviation (SD) scores were calculated by subtracting the mean of a pQCT measure from each individual value and dividing by the standard deviation. Negative SD scores were derived by multiplying the SD score by − 1. Cox's proportional hazard models were used to assess the associations between each pQCT measure and

Results

The characteristics of the study population at baseline are displayed in Table 1. The flow of participants through the study is illustrated in Fig. 1. The mean age at follow-up was 75.5 (SD 2.5) years in men and 75.8 (SD 2.6) years in women.

Twenty seven women and 13 men reported a fracture occurring during the follow-up period after bone assessment by DXA and pQCT. The distribution of fracture was as follows: upper limb: men: 5, women: 12; clinical vertebral: men: 1, women: 2; hip: men: 0,

Discussion

We have shown that measures of bone density and strength as assessed by pQCT are associated with fracture, particularly among women. We also found that in men and in one instance among women, relationships between pQCT measures and fractures remained after adjustment for aBMD, suggesting that these measures of bone mass and strength may contribute additional information regarding fracture risk. The power calculation performed and described below makes us reluctant to over-interpret the sex

Disclosures

EMD, KAJ, MHE, HD, and AAS have no disclosures to declare. CC has received consulting and lecture fees from AMGEN, GSK, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Medtronic and Roche.

Acknowledgments

The Hertfordshire Cohort Study was supported by the Medical Research Council of Great Britain (U.1475.00.003.00010.02/U147585819) and Arthritis Research UK (19583). We thank all of the men and women who took part in the Hertfordshire Cohort Study; the HCS Research Staff; and Vanessa Cox who managed the data.

EMD and CC made substantial contributions to the conception and design of the study. EMD and CC were involved in data acquisition. EMD drafted the manuscript with input from ME, AAS, and CC.

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The age-related loss of skeletal muscle mass and strength is associated with adverse health outcomes. However, to date, peripheral quantitative computed tomography (pQCT)-derived muscle density has been little studied. We used a well characterised cohort of older adults to identify lifestyle and anthropometric determinants of pQCT-derived muscle density measured 11 years later, and to report relationships between pQCT-derived muscle density with history of falls and prevalent fractures.
A lifestyle questionnaire was administered to 197 men and 178 women, aged 59–70 at baseline. After a median of 11.5 (IQR 10.9, 12.3) years, pQCT (Stratec XCT2000) of the radius and tibia was performed to measure forearm muscle density (FMD) and calf muscle density (CMD). Presence of falls and fractures since the age of 45 were determined through participant recall; vertebral fractures were also ascertained through vertebral fracture assessment using iDXA. Total hip BMD (TH aBMD) was assessed using DXA. Baseline characteristics in relation to muscle density at follow-up were examined using linear regression; associations between muscle density and prior falls and fractures were investigated using logistic regression. All analyses were adjusted for sex and age.
Mean (SD) age at muscle density measurement was 76.3 (2.6) years. Mean (SD) FMD was 79.9 (3.1) and 77.2 (3.2) among males and females, respectively; CMD was 80.7 (2.6) and 78.5 (2.6) among males and females, respectively. Significant sex-differences in muscle density were observed at each site (p < 0.001). Female sex, lower weight, and lower body mass index were associated (p < 0.05) with both lower FMD and CMD. Additional correlates of lower CMD included older age and shorter stature. Lifestyle measures were not associated with muscle density in this cohort. Lower FMD was related to increased risk of previous fracture (odds ratio (95 % CI) per SD lower FMD: 1.42 (1.07, 1.89), p = 0.015) but not after adjustment for TH aBMD (p > 0.08). No significant relationships were seen between muscle density and falls.
Female sex, older age, and lower BMI were associated with subsequent lower muscle density in older community-dwelling adults. Lower FMD was related to increased risk of previous fracture. Changes in muscle density over time might precede adverse outcomes such as falls and fractures and may be a long-term predictor of frailty. It could be also suggested that muscle density could be a more clinically meaningful surrogate of functional decline and disability than muscle size or mass, but more studies are needed to support this notion.
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Bone material strength index (BMSi) is measured in vivo using impact microindentation (IMI). However, the associations between BMSi and other bone measures are not clear. This study investigated whether bone parameters derived by peripheral quantitative computed tomography (pQCT) are associated with BMSi.
Participants were men (n = 373, ages 34-96 yr) from the Geelong Osteoporosis Study. BMSi was measured using an OsteoProbe (Active Life Scientific, USA). Bone measures were obtained at both the radius (n = 348) and tibia (n = 342) using pQCT (XCT 2000 Stratec Medizintechnik, Germany). Images were obtained at 4% and 66% of radial and tibial length. Associations between pQCT parameters and BMSi were tested using Spearman's correlation and multivariable regression used to determine independent associations after adjustment for potential confounders. Models were checked for interaction terms.
Weak associations were observed between total bone density (radius 4%; r = +0.108, p = 0.046, tibia 4%; r = +0.115, p = 0.035), cortical density (tibia 4%; r = +0.123, p = 0.023) and BMSi. The associations were independent of weight, height, and glucocorticoid use (total bone density: radius 4%; β = 0.020, p = 0.006, tibia 4%; β = 0.020, p = 0.027 and cortical density: radius 4%; β = 4.160, p = 0.006, tibia 4%; β = 0.038, p = 0.010). Associations with bone mass were also observed at the 66% radial and tibial site, independent of age, weight, and glucocorticoid use (β = 4.160, p = 0.053, β = 1.458, p = 0.027 respectively). Total area at the 66% tibial site was also associated with BMSi (β = 0.010, p = 0.012), independent of weight and glucocorticoid use. No interaction terms were identified.
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Peripheral quantitative computed tomography (pQCT) can provide information complementary to dual x-ray absorptiometry (DXA), however, there is sparse normative data to enable meaningful clinical interpretation and comparison. This study aimed to develop age-stratified normative data for pQCT-derived bone parameters in Australian men.
Participants were men (n = 508, age 33-96 yr) from the Geelong Osteoporosis Study. Bone parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 438) of tibial length were acquired using pQCT (XCT 2000, Stratec Medizintechnik, Pforzheim, Germany). Best models of age, height and weight for each parameter were developed and where parameters exhibited variation with age, age decade mean (±SD) values were determined. Scatterplots were used to visualise the relationships between each of the parameters and age, height and weight.
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This study presents normative data for pQCT-derived bone parameters and describes age related associations in a number of these variables. Broadly, parameters of bone area were positively associated with age, whereas parameters associated with bone density and structure were negatively associated with age. These data have the potential to be used in clinical settings when assessing age-related decline in bone health.
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The assessment of body composition is an integral part in diagnosing sarcopenia. The purpose of this study was to determine the relationships between peripheral quantitative computed tomography (pQCT)-derived measures of body composition and measures of physical performance in older adults.
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Among the three pQCT parameters, especially muscle density was significantly correlated with all of the three measures of physical performance even after adjusting for sex, age, BMI, vitamin D serum level and the level of physical activity. The same analysis for muscle area achieved significance level only for handgrip strength but not for gait speed nor for chair rise time. Fat area was significantly correlated only with gait speed after adjusting for sex and age. The association of muscle density with physical performance held up in an additional subanalysis stratified by body mass index.
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Furthermore, DXA is not able to assess bone structure and geometry (cortical and trabecular dimensions, thickness and density) and bone strength (e.g. polar stress strain index [SSIp]) [12]. These variables can be measured by peripheral quantitative computed tomography (pQCT), which provides additional information for the assessment of bone structure, geometry and strength; thus giving a better understanding of bone deficits associated with future fracture risk [13,14].2 It is not clear whether differences in bone health between the preterm and control groups vary according to sex.
Most infants born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g birthweight) in the post surfactant era (early 1990s) are now surviving into adulthood. Preterm birth/low birthweight are risk factors for reduced bone growth and mineralisation in infants and children. However, little is known about their bone health around peak bone mass and through adult life.
To compare bone health (bone mineral measures, bone structure and strength) in young adults born EP/ELBW with controls (>2499 g birthweight), and within the EP/ELBW group examine perinatal and later variables associated with long term bone health.
A geographic cohort comprising all 297 survivors born EP/ELBW in 1991–92 in the state of Victoria, Australia, and 260 contemporaneous controls (>2499 g birthweight) were recruited into a longitudinal study from birth. At age 25 years, investigations included dual energy X ray absorptiometry and peripheral quantitative computed tomography to measure bone, muscle and soft tissue variables, and fasting blood samples to measure serum 25 hydroxyvitamin D (25(OH)D) and bone turnover markers (BTM). Linear regression analysis, with models fitted using generalised estimating equations, was used to compare outcomes between groups, adjusting for height and weight.
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Original Full Length ArticlePeripheral quantitative computed tomography measures are associated with adult fracture risk: The Hertfordshire Cohort Study

Highlights

Abstract

Introduction

Section snippets

Materials and methods

Statistical methods

Results

Discussion

Disclosures

Acknowledgments

Eur J Radiol

Bone

Bone

Correlation of calcaneal QUS with pQCT measurements at distal tibia and non-weight-bearing distal radius

J Bone Miner Metab

Role of trabecular microarchitecture and its heterogeneity parameters in the mechanical behaviour of ex-vivo lumbar L3 vertebrae

J Bone Miner Res

Classification of women with and without hip fracture based on quantitative computed tomography and finite element analysis

Osteoporos Int

Fractures in healthy females followed from childhood to early adulthood are associated with later menarcheal age and with impaired bone microarchitecture at peak bone mass

J Clin Endocrinol Metab

Osteoporotic fractures in men (MrOS) study group. Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: the osteoporotic fractures in men (MrOS) study

J Bone Miner Res

The discriminative ability of peripheral and axial bone measurements to identify proximal femoral, vertebral, distal forearm and proximal humeral fractures: a case control study

Osteoporos Int

Comparative assessment of bone mineral measurements using dual X-ray absorptiometry and peripheral quantitative computed tomography

Osteoporos Int

Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur

Osteoporos Int

Bone quality parameters of the distal radius as assessed by pQCT in normal and fractured women

Osteoporos Int

Original Full Length Article
Peripheral quantitative computed tomography measures are associated with adult fracture risk: The Hertfordshire Cohort Study