S. A. Steel

A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations

The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients’ bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90%xa0sensitivity and 90%xa0specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55–70xa0years who met the normal referral criteria for a BMD examination. For each device, at least 70xa0women with osteoporosis at the hip or spine and 70xa0women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers’ reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GExa0Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55–70xa0years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40%xa0of women to have an axial DXA examination.

The technical and logistical feasibility of population densitometry using DXA and directed HRT intervention: A 2-year prospective study

The concept of the primary prevention of disease by screening-directed intervention is as attractive in principle as it is difficult in practice. In order for any screening programme to be acceptable, many criteria need to be satisfied [1], and these broadly reduce to three: there shall be a suitable disease, there shall be a valid test, and there shall be an acceptable intervention. If an inquiry as to the availability of any one of these three central requirements produces a negative response, then any screening exercise must be seriously flawed. Osteoporosis is a prevalent disease in western European and North American populations and is associated with significant morbidity, particularly among postmenopausal women. It is characterized by low bone mass, microarchitectural derangement of bone tissue and a consequent increase in bone fragility and risk of fracture [2]. Quantitatively, the World Health Organization (WHO) has defined osteoporosis as being present when a site-specific bone mineral density (BMD) is shown to be more than 2.5 standard deviations (SD) below the mean of the young adult population [2]. In the United Kingdom the burden of the disease is substantial, with an estimated 60000 fractures of femoral neck in England per year, together with 50 000 distal forearm fractures and 40000 vertebral fractures which come to clinical attention [3]. The implication for National Health Service expenditure is also substantial, with an estimated £742m being utilized to deal with the acute care and aftercare of osteoporosis-related fractures. In the United States, Cummings et al. [4] have estimated that white women have a 15% lifetime risk of hip fracture and of Colles fracture, while in Europe Jensen et al. [5] showed a 21% prevalence of vertebral fracture among 70-year-old Danish women. The trend in fracture incidence is also disquieting. Epidemiologi-

The effect of prior bisphosphonate therapy on the subsequent BMD and bone turnover response to strontium ranelate

Strontium ranelate is an effective treatment for osteoporosis in treatment‐naive women. In the United Kingdom, bisphosphonates are often used first line. Prior bisphosphonate use may blunt the bone mineral density (BMD) response to strontium ranelate by reducing strontium uptake into the bone. Sixty bisphosphonate‐naive women and 60 women discontinuing bisphosphonates were recruited. All women commenced strontium ranelate and calcium/vitamin D. BMD and bone turnover markers were recorded for 12 months. After 12 months, the bisphosphonate‐naive groups BMD increased by 5.6% (pu2009<u2009.001) at the spine, 3.4% (pu2009<u2009.001) at the total hip, and 4.0% (pu2009<u2009.001) at the heel. By comparison, the prior bisphosphonate group had a 2.1% (pu2009=u2009.002) increase at the spine but no change at the hip or heel. At all time points, BMD was significantly greater in the bisphosphonate‐naive group. In the prior bisphosphonate group, there was no significant change in BMD during the first 6 months at the spine, but between months 6 and 12 there was a parallel gain in BMD (0.027 versus 0.020u2009g/cm2, pu2009=u2009.40). The baseline difference in bone markers was no longer significant by 3 months for bone‐specific alkaline phosphatase (BSAP) and 6 months for procollagen type 1 amino‐terminal propeptide (P1NP) and carboxy‐terminal cross‐linking telopeptide of type I collagen (CTX). More women in the prior bisphosphonate group suffered a vertebral fracture (2 versus 8 women, pu2009=u2009.047). After bisphosphonates, bone turnover remains suppressed for up to 6 months, with blunting of the BMD response to strontium ranelate during this time. After 6 months, BMD increases in the spine but not at the hip or heel.

Routine versus targeted vertebral fracture assessment for the detection of vertebral fractures

SummaryFracture risk is underestimated in women with unknown vertebral fractures. Using VFA, we compared two screening methods: targeted (6,388 women) and routine (2,176 women). Routine screening detected fractures in 20%. Targeted screening only required 5% attending for DXA to undergo VFA but only detected 9.6% of women with fractures.IntroductionBMD alone underestimates fracture risk in women with unknown vertebral fractures. We report the results of routine vertebral fracture assessment (VFA) screening and compare with targeted screening.MethodOur centre initially targeted VFA at women with reasons to suspect a vertebral fracture. Later we changed to routine VFA screening for all women over 65. We retrospectively compare each screening method’s ability to detect vertebral fractures.ResultsSix thousand three hundred and eighty-eight women over 65 underwent DXA during the period of targeted VFA and 2,176 during routine VFA. Routine VFA detected 420 (20.0%) women with fracture. Most vertebral fractures (56.2%) occurred in women with osteopenia. Routine VFA would be expected to alter the management of 1 in 6 osteopenic women. Targeted VFA was performed in 332 (5.2%) women detecting 122 (1.9%) women with fractures. It was estimated that targeted VFA only detected 9.6% of women with a vertebral fracture. Targeted VFA failed to detect fractures in 18.1% of the population attending for DXA and in 29% of those with osteoporosis.ConclusionRoutine VFA detects vertebral fractures in 20% of women over 65. Targeted VFA greatly reduces the number of VFAs performed but only detects a minority of the women with vertebral fractures.

The effect of prior bisphosphonate therapy on the subsequent therapeutic effects of strontium ranelate over 2 years

SummaryMany osteoporotic women prescribed strontium ranelate have previously received bisphosphonates. Prior bisphosphonate use blunted the spinal bone mineral density (BMD) response for 6xa0months. Hip BMD was blunted to a degree for 2xa0years, although there was an overall increase in hip BMD in contrast to the heel where BMD did not increase.IntroductionMany osteoporotic women commenced on strontium ranelate have already received treatment with bisphosphonates. This study investigates whether prior bisphosphonate use impairs the subsequent therapeutic response to strontium ranelate.MethodsWomen were recruited who were either bisphosphonate naïve or currently receiving a bisphosphonate. All women received strontium ranelate and were followed up for 2xa0years.ResultsOne hundred and twenty women were recruited. After 2xa0years, the bisphosphonate-naïve group had significant BMD increases of 8.9%, 6.0% and 6.4% at the spine, hip and heel, respectively. In the prior bisphosphonate group, BMD increased significantly at the spine (4.0%) and hip (2.5%) but not at the heel. At all time points at all sites, the BMD increase was greater in the bisphosphonate-naïve group. BMD at the spine did not increase during the first 6xa0months in the prior bisphosphonate group but then increased in parallel with the bisphosphonate-naïve group. In contrast, the difference between the two groups in hip BMD continued to increase throughout the 2xa0years. P1NP was suppressed in the prior bisphosphonate group for the first 6xa0months.ConclusionsAfter bisphosphonate exposure, the BMD response to strontium ranelate is blunted for only 6xa0months at the spine. At the hip, a degree of blunting was observed over 2xa0years, although there was an overall increase in hip BMD in contrast to the heel where no increase in BMD was observed.

Which Women Should Be Selected for Vertebral Fracture Assessment? Comparing Different Methods of Targeting VFA

Vertebral fracture assessment (VFA) is a potential screening tool for vertebral fractures, but it is uncertain how to optimize the selection of women for VFA. We investigate the use of a probability score (VFscore) to select women for VFA screening and compare this to other means of targeting VFA. We identified 1,572 treatment-naive women over age 65 who had undergone routine VFA screening. Risk factors for fracture on VFA were identified using multivariate logistic regression, and a VFscore was created. Different thresholds of VFscore were examined and compared to using BMD as a means of targeting screening. After multivariate logistic regression, the risk factors significantly associated with the presence of a fracture on VFA were age, femoral neck BMD, prior clinical fracture, and height loss/kyphosis. The VFscore derived from these factors had a 65.5% sensitivity and a 65.5% specificity for determining vertebral fracture status. For equal resource requirements, the VFscore identified more women with fracture than using BMD category to target VFA. Compared to routinely screening all women, VFscore enabled a 30% reduction in the number of women undergoing VFA while still identifying >90% of women with a vertebral fracture. Overall, a large proportion of the population is required to undergo VFA in order to ensure that the majority of women with a vertebral fracture are selected for screening. The VFscore increased the efficiency of VFA screening to a modest degree compared to screening routinely or according to BMD category.

Image resolution of the Lunar Expert-XL.

Abstract: The Lunar Expert-XL is an example of the latest generation of fan beam densitometers, with the X-ray source and detector array mounted on a C-arm to enable supine lateral imaging. Image resolution for anteroposterior (AP) spine, femur, hand, forearm and lateral morphometry on the Expert-XL were assessed in vitro with the 07-541 Nuclear Associates line pair test pattern. Each scan type was investigated at all available tube currents and scan speeds, and at the maximum, minimum and default bed heights. The effect of soft tissue thickness on resolution was investigated by using varying amounts of Perspex attenuator. The in vitro median lateral (x-axis) resolutions at the default bed height for the default scan types were 0.9 line pairs (lps)/mm for the 5 mA fast AP spine and femur scans, and l.0 lps/mm for 1 mA fast hand, forearm and 5 mA fast morphometry scans. This equates to a resolution of about 1 mm. The best resolution achieved was 1.2 lps/mm (0.83 mm), obtainable on all scan modes with the bed at maximum elevation, but only consistently with the forearm mode. Lower tube current did not affect resolution but did change the range of soft tissue thickness over which an image could be resolved. Turbo scan modes greatly reduced longitudinal (y-axis) resolution but had little effect on lateral resolution. This study demonstrates the importance of including an assessment of resolution when validating new equipment, especially if morphometric investigations are to be conducted.

Development and Evaluation of a Phantom for Morphometric X-ray Absorptiometry

Abstract: Morphometric X-ray absorptiometry (MXA) provides the potential to assess vertebral deformity using a technique with much lower radiation dose to the patient than standard radiographic procedures. MXA overcomes many other limitations such as cone beam distortion observed in conventional plane radiographs. A phantom has been designed to assess the accuracy of the MXA technique, to monitor long-term precision and to assess inter- and intra-operator variability. The phantom consists of two columns of 12 cylinders representing the vertebral bodies, one of regular components and one representing vertebral deformities. Each column may be inserted, as required, into a Perspex torso-mimicking block. Initial assessment on the Lunar Expert-XL demonstrates that the phantom provides image parameters reflecting those found clinically. Measurement of vertebral height was found to be consistently underestimated by 4.9%. Operator precision ranged from 0.6% for posterior height measurement to 1.0% for middle height measurement of the regular component column. The corresponding precision range for the column representing vertebral deformation was 0.6% (posterior) and 1.1% (middle). Analysis of 10 scans of each column by two independent operators demonstrated a few significant differences in height assessment confined to the ‘thoracic’ region of the regular column. However, inter-operator variability was found to increase with increasing complexity of vertebral shape producing several differences, particularly in posterior height assessment of the deformed column.

Premature Greying of the Hair Is Not Associated with Low Bone Mineral Density

Abstract: In two recent case–control studies premature greying of the hair was associated with a lowering of bone mineral density (BMD) and osteopenia, suggesting that this might be a clinically useful risk marker for osteoporosis. We report a further re-examination of this proposal in 52 prematurely grey-haired women from East Yorkshire who responded to an advertisement inviting them for bone densitometry. Thirty-five had no clinical or drug history that could influence bone density. All were Caucasian with a mean age of 52.8 years. In the group as a whole the mean BMD values at the lumbar spine and femoral neck were no different from those of a young adult, but there was a trend toward a greater than average BMD than that of the local age-matched population (p= 0.097 and 0.218, respectively). Twenty women were premenopausal, with an average age of 45.3 years. Mean BMD values at the lumbar spine and femoral neck in this group were no different from those of young adults. There was, however, a trend toward a BMD greater than that of the local age-matched population at the femoral neck (p= 0.117). Fifteen women were postmenopausal with an average age of 62.9 years and an average age at menopause of 51.1 years. Mean BMD values at both the lumbar spine and femoral neck in this group were lower than those of young adults, but no different from those of the local age-matched population. In conclusion, our group of prematurely grey-haired women had average BMD for their age, and we are therefore unable to support the proposed clinical usefulness of premature greying as a risk marker for osteoporosis.

Hyperparthyroidism in elderly osteopenic women

Raised levels of parathyroid hormones (PTH) predispose to osteoporotic fracture particularly in the elderly. The true prevalence of primary or secondary hyperparathyroidism is unknown, as PTH evaluation is not performed as a screening test in the elderly. We report raised PTH levels in 27 of 190 (14.2%) community living fully mobile postmenopausal women with densitometrically established osteopenia, consuming an average of 645 (+/-191) mg of calcium per day. Twenty-five of the 27 women with raised PTH were normocalcaemic, hypercalcaemia been found only in two. Serum 25 hydroxy vitamin D levels were all within the normal range (above 22 nmol/l). Women with a raised PTH were significantly older and their serum 25 hydroxy vitamin D levels were significantly lower than those women with normal PTH values. These data suggest that in community leaving healthy postmenopausal women, normocalcaemic hyperparathyroidism, in the presence of what are still considered normal vitamin D levels, may be common. This may suggests that widespread supplementation with calcium and vitamin D may be required in postmenopausal women for PTH suppression and preservation of bone mass.