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R Eastell

Publications and source records attributed to R Eastell.

At least 19 recordsLinked to original sources
PubMed2006

Geographic and other determinants of BMD change in European men and women at the hip and spine. a population-based study from the Network in Europe for Male Osteoporosis (NEMO).

INTRODUCTION: While the determinants of BMD change have been studied in women, there have been few longitudinal studies in men. As part of the Network in Europe for Male Osteoporosis (NEMO) study, data were analysed from 1337 men and 1722 women aged 50-86y (mean=67 years) from 13 centres across Europe to assess determinants of BMD change and between-gender contrasts. METHODS: BMD was measured at the femoral neck, trochanter and/or L2-L4 spine on 2 occasions 0.8-8 years apart (mean=3.5 years) using DXA densitometers manufactured by Hologic (n=6), Lunar (n=5) and Norland (n=2). Each was cross-calibrated using the European Spine Phantom and annual rates of BMD change (g/cm(2)/year) were calculated from the standardised paired BMD values. The EPOS risk factor questionnaire was administered at baseline. RESULTS: In multivariate linear regression models, there were large between centre differences in the mean rates of BMD change in all 3 sites for both genders (P<0.0001) with the standard deviation of the between centre heterogeneity in the adjusted means being 0.005 g/cm(2)/year at the femoral neck. The overall adjusted mean annual rates of BMD change in g/cm(2)/year (95% CI) pooled across centres by random effects meta-analysis in men were: femoral neck -0.005 (-0.009, -0.001); trochanter -0.003 (-0.006, -0.001); and spine 0.000 (-0.004, 0.004). In women the respective estimates were: -0.007 (-0.009, -0.005); -0.004 (-0.006, -0.003); and -0.005 (-0.008, -0.001). The I(2) statistic for heterogeneity was between 81% and 94%, indicating strong evidence of between centre heterogeneity. Higher baseline BMD value was associated with subsequent greater decline in BMD (P<0.001). Preserved BMD was associated with higher baseline body weight in all 3 sites in men (P<0.012) but not in women. Weight gain preserved BMD (P<0.039) in all 3 sites for both genders, except the male spine. Increasing age was associated with faster BMD decline at the trochanter in both genders (P<0.026) and with a slower rate of decline at the female spine (P=0.002). Effects of lifestyle, physical activity, medications, and reproductive factors were not consistent across sites or between genders. CONCLUSION: These results show major geographic variations in rates of BMD change in men and women over 50 years of age across diverse European populations and demonstrate that body weight and weight gain are key determinants of BMD change in men.

Absorptiometry, Photon↗
PubMed2006

Different effects of raloxifene and estrogen on interleukin-1beta and interleukin-1 receptor antagonist production using in vitro and ex vivo studies.

The increase in lumbar spine BMD in response to Raloxifene (RLX), a selective estrogen receptor modulator, is smaller in magnitude compared to the response to treatment with estradiol (E2). The reasons for this observation are unclear. Estrogen has a potent effect on the production of proinflammatory cytokines which support osteoclastogenic and bone resorption. Therefore the different response to RLX may relate, at least in part, to a difference in the ability of RLX to modulate the production of proinflammatory cytokines which are abundant in the red marrow of the vertebrae. The aim of this study was to determine the effect of RLX and E2 both in vitro and ex vivo on the production of the pro-resorptive cytokine interleukin-1beta (IL-1beta) and its antagonist, interleukin-1 receptor antagonist (IL-1ra). We obtained samples of peripheral blood from (a) 10 untreated postmenopausal women with osteopenia (ages 53 to 72 years, mean 61 years), (b) 15 postmenopausal women (ages 52 to 72 years, mean 63 years) at baseline and after 6 months of RLX therapy (60 mg/day) and (c) 10 postmenopausal women (ages 60 to 75 years, mean 64 years) at baseline and 6 months after a single E2 implant (25 mg). Cultures of whole blood from the untreated women were incubated with RLX or 17beta-E2 at 1 pM, 100 pM, 10 nM and 1 microM concentrations. LPS-stimulated whole blood cultures from the raloxifene- and estradiol-treated women were prepared at baseline and at 6 months. IL-1beta and IL-1ra were measured by ELISA in the conditioned media. In vitro there was a significant dose-dependent decrease in IL-1beta and IL-1ra in response to 17beta-E2 (both P<0.0001) which was not apparent in response to RLX (both P>0.05). In ex vivo cultures from women receiving 6 months treatment with E2 implants, there was a significant decrease in IL-1beta (-36+/-8%, P=0.01) but no significant change in IL-1ra (+29+/-20%, P=0.3). There was no significant change in either IL-1beta or IL-1ra after 6 months RLX therapy (+20+/-14% and +12+/-10%, both P>0.05). We conclude that treatment with RLX, unlike estradiol does not modulate the production of the proinflammatory cytokines IL-1beta and IL-1ra using in vitro or ex vivo whole blood culture methods. This may account, at least in part for the reduced efficacy of RLX therapy compared to estrogen which has been observed in vivo on bone mineral density, bone turnover and reduction in fracture risk.

Aged↗
PubMed2006

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Age Factors↗
PubMed2006

Device-specific thresholds to diagnose osteoporosis at the proximal femur: an approach to interpreting peripheral bone measurements in clinical practice.

INTRODUCTION: A single T score criterion cannot be universally applied to different peripheral bone measurement devices, since measurements in an identical population result in a tenfold difference in the prevalence of osteoporosis. The use of peripheral devices is increasing in clinical practice, despite the difficulties in interpreting results. We propose the use of two thresholds, which have either 95% sensitivity or 95% specificity, to identify (1) individuals who require treatment or (2) individuals who require no treatment, both based on a peripheral measurement alone, or (3) individuals who require additional central densitometry measurements. METHODS: We recruited 500 postmenopausal women, 100 premenopausal women and 279 women with proximal femoral, vertebral, distal forearm or proximal humeral fractures. All subjects underwent dual energy X-ray absorptiometry (DXA) measurements of the lumbar spine, total hip and distal forearm, quantitative computed tomography (QCT) of the distal forearm and quantitative ultrasound (QUS) of the heel (four devices), finger (two devices), radius and metatarsal. We identified the threshold for each device that identified women without osteoporosis with the same sensitivity (upper threshold set at 95%) as total hip DXA and women with osteoporosis with the same specificity (lower threshold set at 95%) as total hip DXA. Individuals between the two thresholds required additional examination by central densitometry. RESULTS: The correlation between devices varied from 0.173 (QUS finger) to 0.686 (DXA forearm) compared with total hip DXA (P<0.0001). The area under the curve (AUC) between devices varied from 0.604 (QUS finger) to 0.896 (DXA forearm) compared with total hip DXA (P<0.0001). In a population-based cohort (prevalence of osteoporosis 9.8%) the threshold approach appropriately identified between 26% (QUS heel) and 68% (DXA forearm) of subjects in whom a treatment decision could be made without additional central DXA with 95% certainty. In a fracture cohort (prevalence of osteoporosis 36%) between 16% (QUS finger) and 37% (QCT forearm) of subjects were appropriately identified. CONCLUSION: The threshold approach to interpreting peripheral bone measurements enables a substantial number of individuals with either normal bone mineral density (BMD) or osteoporosis to be selected and treated appropriately.

Absorptiometry, Photon↗
PubMed2006

Influence of baseline deformity definition on subsequent vertebral fracture risk in postmenopausal women.

INTRODUCTION: Approaches for recognizing vertebral fractures remain controversial. METHODS: An age-stratified population sample of 512 postmenopausal women was followed with serial radiographs for up to 12 years (4455 person-years). RESULTS: 112 women experienced a new vertebral fracture (20% reduction in any vertebral height from baseline) within this study period, for an annual age-adjusted (to US white women > or =50 years of age in 2000) incidence of 23 per 1000. Depending on the morphometric definition used, the prevalence of vertebral deformities at baseline ranged from 3 to 90%. A recent method to standardize vertebral heights produced the best agreement with a qualitative clinical reading of the films [kappa (kappa), 0.53]. Almost all of the different baseline definitions predicted future vertebral fractures, but most of the predictive power was attributable to the severe (e.g., 4 SD) deformities included within more generous (e.g., 3 SD) classifications. Whereas the generous definitions were more sensitive, and the restrictive ones more specific, their overall abilities to predict a new vertebral fracture were roughly comparable as evaluated by the c-index (analogous to the area under an ROC curve). CONCLUSION: This result suggests that the choice of a morphometry definition depends on the particular application and, in particular, on whether it is more important to maximize sensitivity or specificity.

Aged↗
PubMed2006

Relationship between risk factors and QUS in a European Population: The OPUS study.

There are many risk factors associated with low bone mineral density. Quantitative ultrasound (QUS) is a generally accepted method for measurement of bone and has been shown to be strongly associated with future fracture risk. The Osteoporosis and Ultrasound Study (OPUS) is a multi-centre European wide study examining 5 different QUS scanners (4 calcaneal, 1 finger device). The aim of this paper was to examine the relationship between risk factors (as assessed by questionnaire) and QUS measurements. 449 younger women (aged 20 to 39 years) and 2283 older women (aged 55 to 79 years) were included in this analysis. As expected, those with a self-reported previous fracture had lower QUS measurements than those without (P < 0.001). However, no significant difference was seen between those reporting a maternal hip fracture and those who did not report such an event. Differences were found for smokers vs. non-smokers for SOS but not for BUA measurements. Weight was positively correlated with all BUA variables but only with some SOS variables. We determined which risk factors were most strongly associated with QUS measurements by using step-wise multiple regression. Models for each QUS measurement were calculated, and the R2 values ranged from 0.18 to 0.28 for SOS, 0.27 to 0.32 for BUA and 0.31 to 0.42 for the finger QUS device. The most common risk factors across all models were age, use of hormone replacement therapy, self-reported previous fracture, self-reported diagnosis of osteoporosis, current weight, pulse rate and self-reported estimated height at age 20 years. We analysed relationships across the 5 centres and detected some geographical differences in the prevalence of the risk factors. In conclusion, similar relationships are seen with QUS measurements as are found for bone mineral density. However, the strength of the association is dependent on the type of QUS device and variable measured.

Adult↗
PubMed2006

Clinical and radiological outcome of total hip replacement five years after pamidronate therapy. A trial extension.

Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known. The aims of this randomised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients (56 hips) over a five-year period, following total hip replacement. At five years, 37 patients (42 hips) returned for assessment. The Harris hip scores were similar in the pamidronate and placebo groups throughout the study. Also at five years, four patients, two from each group had osteolytic lesions on plain radiography. These were located around the acetabular component in three patients and in the femoral calcar in one. The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years. Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement.

Absorptiometry, Photon↗
PubMed2006

Bone remodelling around a cemented polyethylene cup. A longitudinal densitometry study.

The aims of this study were to examine the repeatability of measurements of bone mineral density (BMD) around a cemented polyethylene Charnley acetabular component using dual-energy x-ray absorptiometry and to determine the longitudinal pattern of change in BMD during the first 24 months after surgery. The precision of measurements of BMD in 19 subjects ranged from 7.7% to 10.8% between regions, using a four-region-of-interest model. A longitudinal study of 27 patients demonstrated a transient decrease in net pelvic BMD during the first 12 months, which recovered to baseline at 24 months. The BMD in the region medial to the dome of the component reduced by between 7% and 10% during the first three months, but recovered to approximately baseline values by two years. Changes in BMD in the pelvis around cemented acetabular components may be measured using dual-energy x-ray absorptiometry. Bone loss after insertion of a cemented Charnley acetabular component is small, transient and occurs mainly at the medial wall of the acetabulum. After two years, bone mass returns to baseline values, with a pattern suggesting a uniform transmission of load to the acetabulum.

Absorptiometry, Photon↗
PubMed2005

Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism.

Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit. We evaluated the response to testosterone in men with borderline hypogonadism. A randomized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level (total testosterone <10 nmol/L or free androgen index <30%). Patients were randomized to Testoderm TTS body patch (5 mg/day, n = 20) or a placebo patch (n = 19) for 6 months, followed by open-label testosterone replacement for a further 6 months in all patients. During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment (p = 0.004); this was associated with a decrease in total body fat mass (p = 0.019) and increase in haemoglobin level (p = 0.036). There were no significant changes in lean body mass, markers of bone turnover, and measures of bone mineral density (BMD). There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life questionnaire (MEDQoL score, p = 0.017), mainly accounted for by deterioration in the placebo arm. When the active treatment period was combined for placebo and testosterone groups, the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption (uNTX/Cr, p = 0.007; iFDPD/Cr, p = 0.0006) and to increase lean body mass (p = 0.001). There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction. However, there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD.

Adipose Tissue↗
PubMed2005

Identification of vertebral fractures: an update.

Osteoporotic vertebral fracture is associated with increased morbidity and mortality. As a powerful predictor of future fracture risk, the identification of vertebral fracture helps target individuals who will benefit from anti-fracture therapy. The identification of vertebral fractures is problematic because (1) "normal" radiological appearances in the spine vary greatly both among and within individuals; (2) "normal" vertebrae may exhibit misleading radiological appearances due to radiographic projection error; and (3) "abnormal" appearances due to non-fracture deformities and normal variants are common, but can be difficult to differentiate from true vertebral fracture. Various methods of vertebral fracture definition have been proposed, but there is no agreed gold standard. Quantitative methods of vertebral fracture definition are objective and reproducible, but the major limitation of these methods is their inability to differentiate between vertebral deformity and vertebral fracture. The qualitative visual approach draws on the expertise of the reader, but it is a subjective method with poor interobserver agreement. Semiquantitative assessment of vertebral fracture is a standardized visual method, which is commonly applied in research studies as a surrogate gold standard. This method is more objective and reproducible than a purely qualitative approach, but can be difficult to apply. The established methods focus primarily on the identification of "reduced" or short vertebral height as an indication of vertebral fracture, but this is also a feature of some non-fracture deformities and normal variants. A modified visual approach known as algorithm-based qualitative assessment of vertebral fracture (ABQ) has recently been introduced, and this focuses on radiological evidence of change at the vertebral endplate as the primary indicator of fracture. Preliminary testing of the ABQ method has produced promising results, but the method requires further evaluation. Vertebral imaging by means of dual energy X-ray absorptiometry (DXA) scanner produces images of near-radiographic quality at a fraction of the radiation dose incurred by conventional radiography. There is growing interest in vertebral fracture assessment using this technique as a means of assessing a patient's fracture risk. Given the increasing availability of new technology and the importance of accurate diagnosis of vertebral fracture, there is an urgent need for better awareness of and training in the definition of vertebral fracture. Methods of vertebral fracture definition should be validated by testing the association with clinical outcomes of vertebral fracture, in particular the prediction of incident fractures.

Absorptiometry, Photon↗
PubMed2004

Accuracy of height loss during prospective monitoring for detection of incident vertebral fractures.

Vertebral fractures are the most common type of osteoporotic fracture, but more than two-thirds remain undetected. We have examined the relationship between height loss and the development of new vertebral fractures to determine whether there is a height loss threshold that has useful clinical accuracy to detect new fractures. We studied 985 postmenopausal women with osteoporosis in the placebo arms of the Vertebral Efficacy with Risedronate Therapy studies. Height was measured annually for 3 years using a wall-mounted stadiometer. New fractures were determined using quantitative and semi-quantitative radiographic morphometry. The relationship between height loss over three years and the number of new vertebral fractures was: height loss (cm) = 0.95 x number of new vertebral fractures-0.4 cm (r = 0.33). The odds ratio for the development of a new fracture increased up to 20.6 (95% confidence interval, 9.3, 45.8) when height loss was greater than 4.0 cm. At a threshold of > 2.0 cm height loss over 3 years, sensitivity was 35.5% for detecting new vertebral fractures and specificity was 93.6%. These findings show that there is a strong relationship between the amount of height loss and the risk of a new vertebral fracture. While there is no cut-off that can reliably rule in a new fracture, height loss of < or = 2.0 cm over 1-3 years has acceptable accuracy for ruling out an incident fracture.

Aged↗
PubMed2004

Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis.

The identification of vertebral fracture in osteoporosis is based mainly on the identification of abnormal variation in vertebral shape, but this can be misleading in the presence of a non-fracture deformity or normal variant of vertebral shape. Qualitative identification of vertebral fracture (Qual) is influenced by the subjectivity of the approach, and although more objective, the semiquantitative method (SQ) can be difficult to apply. In addition, there has been little independent evaluation of SQ in relation to other approaches. We aimed to evaluate a new algorithm-based approach for the qualitative identification of vertebral fracture (ABQ) and to compare it with SQ and Qual. Two radiologists reported spinal radiographs for 372 postmenopausal women using Qual (reader 1), and SQ and ABQ (reader 2). Non-fracture deformities and normal variants were also reported using Qual and ABQ. The prevalence of vertebral fracture by subjects was higher for SQ (24%) than for Qual (11%) and ABQ (7%). Agreement was poor between SQ and the other methods, and moderate between Qual and ABQ. Twenty-two women with vertebral fracture were agreed by all three methods, similar to the total identified by ABQ (25 women). Seventeen women diagnosed with fracture by Qual, had non-fracture deformity or normal variant (but no fracture) according to ABQ. Of the women with SQ fractures, 53% and 70% were identified negative for fracture but positive for non-fracture deformity or normal variant by ABQ and Qual. The main sources of discrepancy between SQ and the other methods were Scheuermann's disease, normal variation, and degenerative change accompanied by short anterior vertebral height. For all methods, bone mineral density (BMD) and BMD Z-scores were lower in women with vertebral fractures than in those with no fractures. Bone mineral density and BMD Z-scores were also lower at the lumbar spine and total body in women with vertebral fractures according to Qual and ABQ than they were for SQ, and were lower in women with SQ fractures agreed by Qual and ABQ, compared with those diagnosed negative for fracture by Qual and ABQ (p<0.01). We conclude that poor agreement between methods arises mainly from difficulties in differentiating true fracture from non-fracture deformity. Our new approach attempts to address this problem but requires further testing in a larger study population.

Aged↗
PubMed2003

Health-related quality of life and radiographic vertebral fracture.

BACKGROUND: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). METHODS: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. RESULTS: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. CONCLUSIONS: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.

Aged↗
PubMed2003

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Age Distribution↗
PubMed2003

Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

Adult↗
PubMed2003

The renal clearance of free and peptide-bound deoxypyridinoline: response to pamidronate treatment of Paget's disease.

Bisphosphonate treatment of Paget's disease results in a large decrease in urinary peptide-bound pyridinolines but a smaller decrease in urinary free pyridinolines. This discrepancy could be explained by changes in renal handling of pyridinoline forms. We studied eight patients with Paget's disease treated with pamidronate. We collected blood and urine at baseline and at 3 and 14 days after treatment. We measured free and total deoxypyridinoline (DPD) in serum (S) and urine (U) by high-performance liquid chromatography (HPLC). The ratio of free to total DPD at baseline was (mean +/- SE) 13 +/- 1% in serum and 37 +/- 3% in urine; at 3 days, this had increased to 25 +/- 3% in serum and 62 +/- 7% in urine. Peptide-bound (pb) DPD decreased significantly 3 days after treatment: UpbDPD -63 +/- 11%, p < 0.001; SpbDPD -51 +/- 8%, p < 0.01. Free DPD decreased in the urine after 14 days: UfDPD -48 +/- 5%, p < 0.01; there was no significant change in SfDPD. The fractional excretion of pbDPD relative to creatinine was less than one at all time-points; however, the fractional excretion of fDPD was significantly greater than one throughout the study. As a consequence, the proportion of free DPD in the urine increased as bone turnover decreased. This resulted in a smaller decrease in urine free compared with peptide-bound DPD in response to bisphosphonate therapy. Thus, the conversion of peptide-bound to free DPD in the kidney may become more efficient as bone turnover decreases as a consequence of pamidronate treatment.

Aged↗
PubMed2003

Visual identification of vertebral fractures in osteoporosis using morphometric X-ray absorptiometry.

Visual identification of vertebral fractures from spinal radiographs (visual XR) makes use of the reader's expertise in ruling out non-fracture deformities or normal variants. Scan images of the spine acquired by DXA may be analyzed quantitatively (morphometric X-ray absorptiometry [quantitative MXA]) or visually (visual MXA). The aims of this study were to compare visual and quantitative MXA with visual XR for the identification of vertebral fractures. Spinal radiographs and MXA scans were acquired at baseline and 1 year in 70 women referred with osteoporosis. These were assessed visually by two expert readers (observer A, a radiologist; observer B, a physician with expertise in osteoporosis) for evidence of prevalent and incident vertebral fractures. Observer C (a radiographer with expertise in vertebral morphometry) performed visual and quantitative assessments of the MXA scans. Visual assessment of spinal radiographs by observer A was used as the gold standard for comparison of methods. Sensitivity for the identification of prevalent fractures by MXA was best for visual MXA by observer A (92%), whereas quantitative MXA had the lowest sensitivity (82%). Specificity was >90% for both visual and quantitative MXA. Kappa scores for agreement for identification of prevalent fractures between visual XR (observer A) and visual MXA (all three observers), and between visual XR and visual MXA performed by reader B were similar (kappa = 0.85-0.87). Agreement with visual XR performed by observer A was slightly lower for quantitative MXA (kappa = 0.77). Interobserver agreement between the two expert readers (observers A and B) was the same for both visual XR and visual MXA (kappa = 0.86). Seven incident vertebral fractures were identified in four patients at follow-up. All four patients were identified by visual MXA, and three patients were identified by quantitative MXA. Observers A and B identified all seven incident fractures by visual MXA, and observer C missed one fracture that was also missed by quantitative MXA. An incident fracture of vertebra T6 was excluded from analysis by quantitative MXA because of poor image quality. We conclude that visual identification of vertebral fractures from MXA scans is superior to quantitative assessment. Used as a screening tool for conventional radiography, this approach could help reduce the radiation dose to the patient in the diagnosis and monitoring of osteoporosis.

Absorptiometry, Photon↗