Institutional reviews and innovation in clinical research.
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Academies and Institutes↗
Biomedical subjects
Jonathan Reeve
Publications and source records attributed to Jonathan Reeve.
The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis.
BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures. DESIGN: Prospective multicenter large-scale association study. SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. PARTICIPANTS: 26,242 participants (18,405 women). MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
Adult↗
Infant growth influences proximal femoral geometry in adulthood.
UNLABELLED: The relationship between early growth and adult femoral geometry has not been studied previously. In 333 adults, we were able to show that infant weight predicts femoral width and cross-sectional moment of inertia but not femoral neck length. These results support the hypothesis that growth in early life leads to persisting differences in proximal femoral geometry. INTRODUCTION: Both femoral geometry and bone mass have been shown independently to predict both hip strength and fracture risk. Whereas growth during intrauterine and early postnatal life has been shown to influence adult bone mass, the relationship between growth in early life and adult femoral geometry has not been described previously. MATERIALS AND METHODS: We studied the relationship between growth during early life, adult hip geometry, and proximal femur bone mass in a sample of 333 men and women (60-75 years of age), for whom birth weight and weight at 1 year of age were recorded. Hip geometry was derived using Hip Structure Analysis software from proximal femur DXA scans (Hologic QDR 1000). RESULTS: There were significant (p < 0.002) relationships between weight at age 1 year and measures of femoral width as well as intertrochanteric (IT) cross-sectional moment of inertia (CSMI), but not with femoral neck length. The relationships with measures of femoral width but not CSMI remained after adjusting for adult body weight and were independent of proximal femoral BMC. CONCLUSIONS: These results support the hypothesis that different patterns of growth in utero and during the first year of life lead to persisting differences in proximal femoral geometry, thereby mediating in part the effects of early growth on risk of hip fracture in adulthood.
Aged↗
Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study.
BACKGROUND: Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. METHODS AND FINDINGS: Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups (p < 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), (p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. CONCLUSIONS: Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.
Adult↗
Reduced vitamin D in acute stroke.
BACKGROUND AND PURPOSE: Stroke leads to a reduction in bone mineral density, altered calcium homeostasis, and an increase in hip fractures. Vitamin D deficiency is well documented in long-term stroke survivors and is associated with post-stroke hip fractures. Less is known regarding levels in acute stroke. METHODS: We compared the serum 25-dihydroxyvitamin D levels of 44 patients admitted to an acute stroke unit with first-ever stroke with results obtained by measuring 96 healthy ambulant elderly subjects every 2 months for 1 year. Statistical Z scores of serum vitamin D were then calculated after seasonal adjustment for the month of sampling. RESULTS: The mean Z score of vitamin D in acute stroke was -1.4 SD units (95% CI, -1.7, -1.1), with 77% of patients falling in the insufficient range. CONCLUSIONS: Reduced vitamin D was identified in the majority of patients with acute stroke throughout the year and may have preceded stroke. Vitamin D is a potential risk marker for stroke, and the role of vitamin D repletion in enhancing musculoskeletal health after stroke needs to be explored.
Aged↗
Risedronate therapy for prevention of hip fracture after stroke in elderly women.
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Accidental Falls↗
Parathyroid hormone - a bone anabolic and catabolic agent.
A key factor in the control of bone remodelling is parathyroid hormone (PTH), the principal regulator of calcium homeostasis. Elevated levels of PTH increase bone turnover, leading to either anabolic or catabolic effects on the skeleton depending upon the pattern and duration of elevation. New evidence indicating that downregulation of an osteocyte signal (sclerostin, the SOST gene product) occurs in response to intermittent PTH has rekindled interest in the key role played by osteocytes and bone-lining cells in co-ordinating surface anabolic activity. Microarray analysis has also delineated many genes and pathways regulated by intermittent and continuous PTH in osteoblasts and whole bones.
Animals↗
Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation.
Osteocytes are the most abundant cells in bone and are ideally located to influence bone turnover through their syncytial relationship with surface bone cells. Osteocyte-derived signals have remained largely enigmatic, but it was recently reported that human osteocytes secrete sclerostin, an inhibitor of bone formation. Absent sclerostin protein results in the high bone mass clinical disorder sclerosteosis. Here we report that within adult iliac bone, newly embedded osteocytes were negative for sclerostin staining but became positive at or after primary mineralization. The majority of mature osteocytes in mineralized cortical and cancellous bone was positive for sclerostin with diffuse staining along dendrites in the osteocyte canaliculi. These findings provide for the first time in vivo evidence to support the concept that osteocytes secrete sclerostin after they become embedded in a mineralized matrix to limit further bone formation by osteoblasts. Sclerostin did not appear to influence the formation of osteocytes. We propose that sclerostin production by osteocytes may regulate the linear extent of formation and the induction or maintenance of a lining cell phenotype on bone surfaces. In doing so, sclerostin may act as a key inhibitory signal governing skeletal microarchitecture.
Adaptor Proteins, Signal Transducing↗
Predictive value of BMD for hip and other fractures.
UNLABELLED: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.
Absorptiometry, Photon↗
Osteocytic expression of constitutive NO synthase isoforms in the femoral neck cortex: a case-control study of intracapsular hip fracture.
UNLABELLED: NO is an osteocytic signaling molecule that can inhibit osteoclasts. The NO synthases eNOS and nNOS were expressed by >50% of osteonal osteocytes in controls. Hip fracture cases showed +NOS osteocytes only in deep osteonal bone, and 25-35% reduced expression overall. These data are consistent with increased osteonal vulnerability to deep osteoclastic attack. INTRODUCTION: Osteocytes may regulate the response to mechanical stimuli in bone through the production of local signaling molecules such as NO derived from the NO synthase eNOS. Because NO is inhibitory to osteoclastic resorption, it has been suggested that osteocytes expressing eNOS act as sentinels, confining resorption within single osteons. Recently, nNOS has been shown to be present in osteocytes of adult human bone. MATERIALS AND METHODS: Cross-sections of the femoral neck (eight female cases of intracapsular hip fracture and seven postmortem controls; age, 68-91 years) were analyzed by immunohistochemistry. The percentages of osteocytes expressing each of these two isoforms were calculated, and their distances to the nearest canal surface were measured. RESULTS: The percentage of +nNOS osteocytes was lower in the fracture cases than in the controls (cases: 43.12 +/- 1.49, controls: 56.68 +/- 1.45; p < 0.0001). Compared with nNOS, eNOS expression was further reduced (p = 0.009) in the cases but was not different in the controls (cases: 36.41 +/- 1.53, controls: 56.47 +/- 2.41; p < 0.0001). The minimum distance of +eNOS or +nNOS osteocytes to a canal surface was higher in the cases compared with controls (eNOS: controls; 44.4 +/- 2.2 microm, cases: 61.7 +/- 2.0 microm; p < 0.0001; nNOS: controls: 52.4 +/- 1.7 microm, cases: 60.2 +/- 2.1 microm; p = 0.0039). +eNOS osteocytes were closer to the canal surfaces than +nNOS osteocytes in the controls by 8.00 +/- 4.0 microm (p = 0.0012). CONCLUSION: The proportions of osteocytes expressing nNOS and eNOS were both reduced in the fracture cases, suggesting that the capacity to generate NO might be reduced. Furthermore, the reduction in NOS expression occurs in those osteocytes closest to the canal surface, suggesting that the ability of NO to minimize resorption depth might be impaired. Further studies are needed on the regulation of the expression and activity of these distinct NOS isoforms.
Aged↗
A meta-analysis of milk intake and fracture risk: low utility for case finding.
A low intake of calcium is widely considered to be a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the effect of age, gender and bone mineral density (BMD) on this risk. We studied 39,563 men and women (69% female) from six prospectively studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000 person-years. The effect of calcium intake as judged by the intake of milk on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture. There was no difference in risk ratio between men and women. When both sexes were combined there was a small but non-significant increase in the risk of osteoporotic and of hip fracture. There was also a small increase in the risk of an osteoporotic fracture with age which was significant at the age of 80 years (RR = 1.15; 95% CI = 1.02-1.30) and above. The association was no longer significant after adjustment for BMD. No significant relationship was observed by age for low milk intake and hip fracture risk. We conclude that a self-reported low intake of milk is not associated with any marked increase in fracture risk and that the use of this risk indicator is of little or no value in case-finding strategies.
Adult↗
Calcaneum broadband ultrasound attenuation relates to vegetarian and omnivorous diets differently in men and women: an observation from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study.
Vegetarian diets have been suggested to be beneficial for bone health due to increased consumption of plant foods, including soya, or reduced consumption of meat. However, meat may also be beneficial for bone health. The evidence relating diet to bone health is based largely on studies of women, often in those at high risk of osteoporosis. Few studies have investigated dietary inter-relationships in men as well as women from general populations. We examined broadband ultrasound attenuation (BUA) of the calcaneum, using a CUBA clinical instrument, in 6,369 men and 5,379 postmenopausal women. The population was divided into four groups according to vegetarian status and frequency of soya consumption, which was defined by response to a food frequency questionnaire that estimates frequency of consumption of food types over the year prior to completion. Regular soya consumers were defined as those who ate soya products with a frequency of between once a day and once a week. Calcaneum BUA in vegetarian men was significantly lower than omnivores by approximately 6% (5 dB/MHz) and was 15% (13.6 dB/MHz) lower in those who were also regular soya consumers. This difference remained after adjustment for age, height, weight, smoking habit, physical activity, selected foods and nutrients and exclusion of those with a prior history of osteoporosis, fractures or cancer. Calcaneum BUA in omnivorous men with regular soya consumption was not lower than the remaining population. In women, there were no significant differences by usual dietary pattern. This surprising finding indicates that regular soya intake is not associated with better bone indices in vegetarian men. The difference in BUA was not explained by the known common covariates; however, it is possible that other aspects of lifestyle associated with these eating behaviors might explain this observation. Plausible mechanisms exist for our findings; soya contains phytoestrogens, likened to naturally occurring estrogens, and meat has been shown to influence levels of IGF-1 and sex hormone binding globulin, which may be related to bone health. Our findings emphasize the need for further research and investigation into dietary inter-relationships and bone health and the effects of vegetarian status, including consumption of soya-based foods, in men as well as women.
Adult↗
When should the doctor order a spine X-ray? Identifying vertebral fractures for osteoporosis care: results from the European Prospective Osteoporosis Study (EPOS).
UNLABELLED: Vertebral fractures are common but usually remain unrecognized in primary care. Data from 2908 women and 2653 men in the EPOS study were used to derive algorithms to indicate the need for a spine X-ray to identify a fracture using easily elicited determinants. At a sensitivity of 50% for identifying cases, the specificity was increased from 50% to 78% in women and from 50% to 72% in men compared with a random allocation of X-rays. Use of X-rays can be optimized by selecting patients at high risk using a short screening procedure. INTRODUCTION: Previous osteoporotic fracture is an independent risk factor for further fractures and an indication for treatment. Vertebral fractures are the most common osteoporotic fractures before age 75, accounting for 48% of all fractures in men and 39% in women over 50. They usually remain unrecognized, so many patients requiring treatment are denied it, doubling their risk of a further fracture. Our objective was to develop an efficient algorithm indicating the need for an X-ray. MATERIALS AND METHODS: Data from 2908 women and 2653 men >or=50 years of age in the European Prospective Osteoporosis Study (EPOS) were analyzed. Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. Prevalent fractures were qualitatively diagnosed by an experienced radiologist. Fracture risk was modeled as a function of age, statural height loss since age 25, gender, and fracture history including limb fractures in the last 3 years using negative binomial regression. Receiver operating characteristic (ROC) curves were used to summarize a model's predictive ability, and a prediction algorithm was devised to identify those most likely to have a fracture. RESULTS: In a multivariate model for women, the risk of prevalent vertebral fracture significantly increased with age (RR, 1.67 [95% CI, 1.46, 1.93] per decade), statural height loss (1.06, [1.03, 1.10] per centimeter decrease), self-reported history of spine fracture (7.52 [5.52, 10.23]), and history of other major fracture (1.83 [1.46, 2.28]). Higher body weight reduced risk (0.86 [0.79, 0.95] per 10-kg increase). In men, the respective RR estimates were as follows: age (1.32 [1.18, 1.49]); height loss (1.06 [1.04, 1.09]); self-reported spine fracture (5.05 [3.69, 6.90]); other major fracture (1.42 [1.12, 1.81]); and weight (0.86 [0.79, 0.94]). Using algorithms based on these easily elicited determinants, specificity was increased from 50% to 78% in women and from 50% to 72% in men at a sensitivity of 50% compared with a random allocation of X-rays. At a sensitivity of 75%, the specificity was 50% in women and 40% in men. Inclusion of hip BMD (femoral neck or trochanter), measured in 1360 women and 1046 men, significantly improved the area under the ROC curves by 4% in women (p < 0.002) but not in men (p > 0.350). Spine BMD, measured in 982 women and 847 men, produced a significant 5% AUC improvement in women (p = 0.007) but not in men (p = 0.554). CONCLUSION: A woman 65 years of age with one vertebral fracture has a one in four chance of another fracture over 5 years, which can be reduced to one in eight by treatment. Positive treatment decisions are often contingent on identifying a vertebral fracture. Selective use of lateral vertebral X-rays can be optimized using a 2-minute screening procedure administered by a nurse.
Age Factors↗
Rapid long-term bone loss following stroke in a man with osteoporosis and atherosclerosis.
Bone loss in humans has been reported where there is reduced mechanical loading such as in space flight, spinal cord injury, and stroke. Whether osteoporotic patients are susceptible to further bone loss in states of underloading such as hemiparesis is unknown. Here we report the case of a 64-year-old man with established idiopathic osteoporosis and atherosclerosis who presented with a right middle cerebral artery territory stroke. Annual bone mineral density measurements were made at the left hip and spine before and after left hemiparesis. The left total hip T-score was -3.2 before the stroke. Following stroke, there was rapid and sustained bone loss with a reduction in bone mineral density (BMD) of 21.6% over 3 years despite oral bisphosphonate therapy. There was also an unexpected decline in vertebral BMD after the stroke. This is the first report of the accelerated effect of hemiplegia on bone loss in an already osteoporotic skeleton.
Absorptiometry, Photon↗
Nutritional and exercise-related determinants of bone density in elite female runners.
Although the female athletic triad is widely recognized clinically, there have been few studies quantitating the effect of disordered eating on bone mineral density. The purpose of this study was to explore the mechanisms through which disordered eating might influence the skeleton in nationally or internationally competitive runners. Fifty British national or higher standard middle and long-distance female runners aged under 36 years were recruited; 24 had amenorrhea (AM), nine had oligomenorrhea (OL) and the others were eumenorrheic (EU). Bone mineral density (BMD g.cm(-2)) of the proximal femur (femoral neck and trochanter) and lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry (DXA) and compared with population-based European reference data. Dietary eating patterns were assessed with the Eating Attitudes Test (EAT26) and Bulimia Investigatory Test Edinburgh (BITE) questionnaires. High eating disorder scores were common; the EAT26 score predicted menstrual disorders (P=0.014) and correlated with body mass index (BMI). BMD was generally low in the AM group, but was raised in the proximal femur in the EU group. In the AM group, younger age at start of training was associated with higher trochanteric BMD. In addition, years of eumenorrhea were positively associated with spine BMD. Although a high EAT26 score was associated with lower BMD in the proximal femur, this could be explained by the intermediary effect of menstrual disorders. Osteocalcin, a marker of bone formation, was reduced in the AM group and was also reduced by high VO2max and high BITE score, consistent with a central (hypothalamic) pathway for suppressing osteoblastic bone formation. Eumenorrheic runners had increased femoral BMD compared with European controls, consistent with a positive effect of increased mechanical loading. The effect of disordered eating to reduce BMD could be explained by its association with menstrual dysfunction. Lumbar spine BMD was reduced most in those athletes who menstruated for the shortest time in adolescence.
Adult↗
Broadband ultrasound attenuation (BUA) of the heel bone and its correlates in men and women in the EPIC-Norfolk cohort: a cross-sectional population-based study.
Osteoporotic fractures have substantial clinical and public health impact. Bone quality is an important determinant of fracture risk. Quantitative ultrasound (QUS) of bone measured as broadband ultrasound attenuation (BUA) has been shown to predict fracture risk. However, there have been very few large population studies, particularly in men. We investigated the correlates of calcaneal BUA using a CUBA clinical machine in 15,668 middle and older aged men and women (42-82 years) from the UK, EPIC-Norfolk cohort. At all ages mean BUA was significantly greater in men than women (men, 90.1+/-17.6; women 72.1+/-16.5). The age-related decline in BUA was five times greater in women than men (-0.77 vs. -0.15 dB/MHz per year). Pre- and post-menopausal bone loss was 0.39 and 0.85 dB/MHz per year, respectively. In univariate regression BUA increased with weight and height by 0.45 dB/MHz per kg and 0.68 per cm in women and 0.24 dB/MHz per kg and 0.33 per cm in men. BUA increased with body mass index (BMI) by 0.84 dB/MHz per kg/m2 in women and 0.55 in men. However, weight was twice as influential as height in men and seven times as great in women. Age, weight and height explained 27% of the variance of BUA in women, but only 3% in men. Adjusted BUA was significantly lower in men and women with an existing history of any hip, wrist or spinal fracture both overall and when analysed for specific site. Figures were: all fractures 66.8 vs. 72.5 dB/MHz ( P<0.001), women; 84.1 vs. 90.5 ( P<0.001), men; hip fractures 61.9 vs. 72.2 dB/MHz ( P<0.001), women; 81.5 vs. 90.2 ( P<0.001), men; wrist fractures 66.6 vs. 72.5 dB/MHz ( P<0.001), women; 81.5 vs. 90.2 ( P<0.001), men; spinal fractures 68.1 vs. 72.1 dB/MHz ( P<0.01), women; 85.1 vs. 90.2 ( P<0.01), men. These differences equate to reductions of 14, 9 and 6% and 10, 7 and 6% for fractures of the hip, wrist and spine in the BUA of women and men, respectively. Thus, despite the overall gender difference in BUA the relative magnitude of a previous history of fracture was equally important in both men and women. Adjusted BUA was also lower in those with previous history of osteoporosis. In women currently taking hormone replacement therapy (HRT) the adjusted BUA was 5 dB/MHz or one-third of an SD greater than in those who did not. The BUA of those with a current smoking habit was 1.7% lower in women and 3.2% lower in men. Overall, there are substantial sex differences in the relationship of the physical and osteoporotic risk factors associated with BUA. A better understanding of these determinants of heel ultrasound may provide insights into how some of the sex differences in bone health can be explained and bone loss in later life minimised.
Adult↗
A meta-analysis of prior corticosteroid use and fracture risk.
UNLABELLED: The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
Adrenal Cortex Hormones↗
Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study.
BACKGROUND: A quarter of fractures needing admission happen in men, but few data are available that show the value of bone measures for prediction of fracture risk in men. We aimed to assess quantitative ultrasound of the calcaneum and fracture incidence in a prospective observational population study. METHODS: Calcaneum broadband ultrasound attenuation (BUA) was measured in men and women in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) between 1997 and 2000. Incident fractures were ascertained by hospital record linkage. FINDINGS: In 14824 men and women aged 42-82 years, during mean follow-up of 1.9 years (SD 0.7), there were 121 incident fractures that needed admission, including 31 hip fractures. Men and women in the lowest 10% of the calcaneum BUA distribution had a relative risk of fracture of 4.44 (95% CI 2.24-8.89, p<0.0001) compared with those in the upper 30% of the distribution. A fall of about 1 SD in BUA (20 db/MHz) was associated with a relative risk of fracture of 1.95 (95% CI 1.50-2.52, p<0.0001), independent of age, sex, weight, height, cigarette smoking habit, and past history of fracture. BUA predicted fractures with consistent magnitude in subgroups stratified by sex, age 65 years or older and younger than 65 years, smoking habit, past history of fracture, and hip and non-hip fractures separately. The sex difference in fracture risk was largely accounted for by differences in BUA. INTERPRETATION: Quantitative calcaneum ultrasound predicts total and hip fracture risk in men and women in a continuous relation. The challenge now is to identify interventions to improve bone health in the whole population.
Adult↗