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Papers by David Reid

QJM, 2001

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fr... more The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

International Journal of Obesity, 2003

OBJECTIVE: To investigate whether energy intake or energy expenditure affects 5-7 y weight gain i... more OBJECTIVE: To investigate whether energy intake or energy expenditure affects 5-7 y weight gain in perimenopausal and early postmenopausal women, and whether hormone replacement therapy (HRT) use or dietary calcium (Ca) intake are contributory factors. DESIGN: Longitudinal, observational study of healthy women around the menopause. SUBJECTS: A total of 1064 initially premenopausal women, selected from a random population of 5119 women aged 45-54 y at baseline. In all, 907 women (85.2%) returned 6.370.6 y later for repeat measurements. Of these, 36% were postmenopausal (no HRT) and 45% had taken HRT, and 898 women completed the questionnaires. MEASUREMENTS: Weight, height, estimation of energy intake by food frequency questionnaire and physical activity level (PAL) by questionnaire. RESULTS: Change in PAL influenced weight change explaining 4.4% (P ¼ 0.001) of the variation. Alterations in dietary energy intake also had a small but significant effect (0.6% P ¼ 0.013). Dietary Ca intake had no effect on weight or weight change. CONCLUSION: Mean weight had increased and was influenced more by reduced energy expenditure rather than increased energy intake. HRT and dietary Ca intake did not influence weight gain.

Osteoarthritis and Cartilage, 2010

incidence and severity of the KOA. The study favors the biomechanical theory of axial loading and... more incidence and severity of the KOA. The study favors the biomechanical theory of axial loading and local factors being predominantly responsible for cartilage degeneration and onset of the disease. This study disproves the notion of the possibility that the person who were overweight gained weight after developing osteoarthritis because of their knee pain and sedentary level of activity 354

The British Journal of Radiology, 2002

The purpose of this study was to compare hip bone mineral density (BMD) recorded in seven populat... more The purpose of this study was to compare hip bone mineral density (BMD) recorded in seven population based cohorts in Britain with the third National Health and Nutrition Examination Survey (NHANES III) US population-based reference data, in order to assess geographic variation in the prevalence of osteoporosis. Men and women aged 50-80+ years were randomly recruited from population and health registers. Dual X-ray absorptiometry (DXA) equipment was used to measure BMD at the hip, with the femoral neck and the trochanter regions studied. Prevalences of osteopenia and osteoporosis were estimated in accordance with World Health Organisation diagnostic criteria for women. Young normal data, used to establish cutoff criteria, was from NHANES III. Both male and female British subjects over 50-years-old were found to have significantly higher mean BMD at the femoral neck and trochanter than their US counterparts. Decline in BMD with age in British men appeared slower than in US men. Between British centres there were also statistically significant differences in BMD values in both sexes. British age-adjusted prevalences of osteopenia in women averaged 20% less than those of NHANES III, whereas the prevalence of osteoporosis was substantially lower in British subjects of both sexes (55% in women, 68% in men). Thus, applying the US NHANES III data as the referent, osteoporosis of the proximal femur in Britain appears to be less common than in the US, due primarily to differences in the lower tails of the BMD distributions. Providing that the relationship between fracture rates and BMD is the same in Britain and the US, it would still be appropriate to apply the reference data in fracture risk assessment in the UK.

British Journal of Nutrition, 2014

Dietary modification may affect inflammatory processes and protect against chronic disease. In th... more Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997–2000 (n3237, mean age 54·8 (sd2·2) years). Participants (n2130, mean age 66·0 (sd2·2) years) returned during 2007–11 for follow-up. Diet was assessed by FFQ (n1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past ‘prudent’ dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of...

Osteoarthritis and Cartilage, 2009

lower deep UTE-enhanced T2* values (p=0.05) than those retaining OCT form birefringence. For supe... more lower deep UTE-enhanced T2* values (p=0.05) than those retaining OCT form birefringence. For superficial T2, SA without OCT form birefringence had 25% higher values than those with birefringence (p=0.047). No difference was found between the superficial T2* values of cores with and without OCT form birefringence. However a significant decrease in superficial T2* relaxation time was noted between SA with OCT grades B and C (p=0.014). No difference was found between type-II collagen content and OCT grade or quantitative MRI values. Conclusions: This multimodal study shows correlations between OCT grade, MRI T2, MRI UTE-enhanced T2* and PLM. OCT and PLM signs of matrix degeneration increased with increasing T2 and with decreasing T2*. Although no correlation was found between any of the imaging modalities and type-II collagen content, the correlations with PLM suggest that these emerging imaging technologies are more sensitive to changes in collagen structure than collagen content. As changes to collagen and matrix structure can occur prior to breakdown of the articular surface, these results demonstrate the potential of OCT, T2 and UTE-enhanced T2* to detect cartilage injury and degeneration in clinically normal appearing cartilage. Techniques for clinical detection of cartilage damage prior to gross tissue failure could lead to identification of new treatment windows for chondroprotective and chondrorestorative therapies that can delay or prevent the onset of osteoarthritis.

New England Journal of Medicine, 2010

Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascula... more Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. Methods In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of-2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)-positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. Results Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1000 person-years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1000 person-years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1000 person-years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group. Conclusions In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ERpositive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.

Clinica Chimica Acta, 2002

Background: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increase... more Background: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6-12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were

Bone, 2013

Purpose. There is a continuing need to improve the prediction of hip fractures to identify those ... more Purpose. There is a continuing need to improve the prediction of hip fractures to identify those at highest risk, enabling cost-effective use of preventative therapies. Methods. The aim of this work was to validate an innovative imaging biomarker for hip fracture by modelling the shape and texture of the proximal femur assessed from dual energy X-ray absorptiometry (DXA) scans. Scans used were acquired at baseline from elderly patients participating in a prospective, placebo-controlled fracture prevention study of the bisphosphonate, clodronate. 182 subjects who subsequently suffered a hip fracture were age, weight and height matched with two controls who did not suffer a fracture during a median 4year follow-up period. Logistic regression was used to test if variables were good predictors of fracture and adjust for bone mineral density (BMD). Results. Shape mode 2, reflecting variability in neck-shaft angle, neck width and the size of both trochanters, (0.81 (OR), 0.68-0.97 (CI), 0.024 (P)) and appearance mode 6, recording grey-level contrast, (1.33, 1.11-1.59, 0.002) were significant predictors of hip fracture and remained so after adjustment for BMD (shape mode 2 (0.77, 0.64-0.93, 0.006), appearance mode 6 (1.32, 1.10-1.59, 0.003)). Receiver Operating Curve analysis showed the combination of shape mode 2, appearance mode 6 and BMD was 3% better than any single predictor. Conclusion. Variables derived from shape and appearance models gave a prediction of fracture comparable to BMD and in combination with BMD gave an improvement in the prediction of hip fracture that could predict an additional 2000 hip fracture cases per year in the UK, potentially saving more than £20 million per year and 10,000 cases in the US.

Bone, 2013

The objective of this study was to consider whether trabecular bone score (TBS) improves on areal... more The objective of this study was to consider whether trabecular bone score (TBS) improves on areal bone mineral density (aBMD) measurement alone for the prediction of incident fractures in postmenopausal women. The OPUS study was conducted in ambulatory European women aged above 55years, recruited in 5 centers followed over 6years. For the assessment of the performance of TBS, baseline Hologic scans from 3 centers (Kiel, Paris and Sheffield) were available. Follow-up for incident fractures was available for 1007 women (mean age 65.9±6.9years). We compared the performance of TBS, aBMD, and their combination, by using net reclassification improvement (NRI, primary analysis) and receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under the curves (AUCs) (secondary analyses). 82 (8.1%) subjects with incident clinical osteoporotic fractures, and 46 (4.6%) with incident radiographic vertebral fractures were recorded over 6years. Performance of TBS was significantly better than lumbar spine (LS) aBMD for the prediction of incident clinical osteoporotic fractures (NRI=16.3%, p=0.007). For radiographic vertebral fractures, TBS and LS aBMD had similar predictive power but the combination of TBS and LS aBMD increased the performance over LS aBMD alone (NRI=8.6%, p=0.046) but the prediction is similar to hip and femoral neck aBMD. In non osteoporotic women, TBS predicted incident fragility fractures similarly to LS aBMD. This prospective study shows that in general population, TBS is a useful tool to improve the performance of lumbar spine aBMD for vertebral osteoporotic fractures.

Journal of Clinical Densitometry, 2010

Conclusion: In conclusion, once-yearly i.v. ZOL 5 mg substantially reduces the risk of multiple m... more Conclusion: In conclusion, once-yearly i.v. ZOL 5 mg substantially reduces the risk of multiple morphometric and clinical fractures suggesting that treatment mitigates the worsening fragility accompanying a fragility fracture.

Clinical Drug Investigation, 2006

acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers o... more acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. Methods: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score ≤-2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70mg weekly (Fosamax ®) and placebo identical to risedronic acid weekly or active risedronic acid 35mg weekly (Actonel ®) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phospha-12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. Conclusions: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Osteoporosis International, 2011

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone miner... more This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤3 months) subpopulations] were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤74 years (P<0.05) in the treatment and 65-74 years (P=0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05),

Our previous studies have demonstrated the inadequate nutritional status of Vietnamese female mar... more Our previous studies have demonstrated the inadequate nutritional status of Vietnamese female marriage immigrants in Korea. Major possible reasons include food insecurity due to economic problems as well as a lack of adjustment to unfamiliar Korean foods and limited access to Vietnamese foods; however, no study has investigated food insecurity among such intermarried couples. This study was performed to investigate the prevalence of food insecurity in Korean-husband-Vietnamese-wife couples and to determine whether they exhibit an intrahousehold discrepancy regarding food insecurity. A cross-sectional analysis of the Cohort of Intermarried Women in Korea study was performed with 84 intermarried couples. Among the 84 Vietnamese immigrants, 48.8% and 41.7% had food insecurity due to economic problems and a lack of foods appealing to their appetite, respectively. There was a marked discrepancy in reporting food insecurity between Vietnamese wives (22.6-38.1%) and their Korean husbands (6.0-15.5%). Vietnamese wives were five and two times more food-insecure due to economic problems and no foods appealing to their appetite, respectively, than their Korean spouses. A follow-up study is needed to investigate the causes of this discrepancy and ways of reducing food insecurity among female marriage immigrants living in low-income, rural communities.

This paper compares dual-energy X-ray absorptiometry (DXA) of the spine and hip and broadband ult... more This paper compares dual-energy X-ray absorptiometry (DXA) of the spine and hip and broadband ultrasound attenuation (BUA) of the os calcis in 1000 perimenopausal women aged between 45 and 49 years who attended a randomized Osteoporosis Screening Programme. Significant correlations were found between all DXA results and BUA, with the trochanter giving the best numerical correlation with BUA (r = 0.354, p &lt; 0.0001). BUA was not successful in predicting women with low DXA measurements, with only 44.0% of the women whose spinal DXA falls within the lowest quartile being in the lowest quartile of BUA. Although BUA is a poor predictor of spinal and hip bone mineral density it may provide additional structural information important in fracture prediction.

Calcified Tissue International

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral nec... more There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS-FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS-FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in ...

Menopause International, 2009

The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tra... more The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tragic result of the 2002 WHI study. Although their hostility to estrogen therapy antedated these studies, the flawed data is now used as justification for the denial of estrogens for treatment of low bone density and various types of hormone responsive depression in women. Estrogens

The shape of the proximal femur has been demonstrated to be important in the occurrence of fractu... more The shape of the proximal femur has been demonstrated to be important in the occurrence of fractures of the femoral neck. Unfortunately, multiple geometric measurements frequently used to describe this shape are highly correlated. A new method, active shape modeling (ASM) has been developed to quantify the morphology of the femur. This describes the shape in terms of orthogonal modes of variation that, consequently, are all independent. To test this method, digitized standard pelvic radiographs were obtained from 26 women who had suffered a hip fracture and compared with images from 24 age-matched controls with no fracture. All subjects also had their bone mineral density (BMD) measured at five sites using dual-energy X-ray absorptiometry. An ASM was developed and principal components analysis used to identify the modes which best described the shape. Discriminant analysis was used to determine which variable, or combination of variables, was best able to discriminate between the groups. ASM alone correctly identified 74% of the individuals and placed them in the appropriate group. Only one of the BMD values (Ward&#39;s triangle) achieved a higher value (82%). A combination of Ward&#39;s triangle BMD and ASM improved the accuracy to 90%. Geometric variables used in this study were weaker, correctly classifying less than 60% of the study group. Logistic regression showed that after adjustment for age, body mass index, and BMD, the ASM data was still independently associated with hip fracture (odds ratio (OR)=1.83, 95% confidence interval 1.08 to 3.11). The odds ratio was calculated relative to a 10% increase in the probability of belonging to the fracture group. Though these initial results were obtained from a limited data set, this study shows that ASM may be a powerful method to help identify individuals at risk of a hip fracture in the future.

PLoS Genetics, 2011

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral den... more Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age-and gender-adjusted BMD zscores of +1.5 to +4.0, n = 1055, or 24.0 to 21.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

QJM, 2001

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fr... more The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

International Journal of Obesity, 2003

OBJECTIVE: To investigate whether energy intake or energy expenditure affects 5-7 y weight gain i... more OBJECTIVE: To investigate whether energy intake or energy expenditure affects 5-7 y weight gain in perimenopausal and early postmenopausal women, and whether hormone replacement therapy (HRT) use or dietary calcium (Ca) intake are contributory factors. DESIGN: Longitudinal, observational study of healthy women around the menopause. SUBJECTS: A total of 1064 initially premenopausal women, selected from a random population of 5119 women aged 45-54 y at baseline. In all, 907 women (85.2%) returned 6.370.6 y later for repeat measurements. Of these, 36% were postmenopausal (no HRT) and 45% had taken HRT, and 898 women completed the questionnaires. MEASUREMENTS: Weight, height, estimation of energy intake by food frequency questionnaire and physical activity level (PAL) by questionnaire. RESULTS: Change in PAL influenced weight change explaining 4.4% (P ¼ 0.001) of the variation. Alterations in dietary energy intake also had a small but significant effect (0.6% P ¼ 0.013). Dietary Ca intake had no effect on weight or weight change. CONCLUSION: Mean weight had increased and was influenced more by reduced energy expenditure rather than increased energy intake. HRT and dietary Ca intake did not influence weight gain.

Osteoarthritis and Cartilage, 2010

incidence and severity of the KOA. The study favors the biomechanical theory of axial loading and... more incidence and severity of the KOA. The study favors the biomechanical theory of axial loading and local factors being predominantly responsible for cartilage degeneration and onset of the disease. This study disproves the notion of the possibility that the person who were overweight gained weight after developing osteoarthritis because of their knee pain and sedentary level of activity 354

The British Journal of Radiology, 2002

The purpose of this study was to compare hip bone mineral density (BMD) recorded in seven populat... more The purpose of this study was to compare hip bone mineral density (BMD) recorded in seven population based cohorts in Britain with the third National Health and Nutrition Examination Survey (NHANES III) US population-based reference data, in order to assess geographic variation in the prevalence of osteoporosis. Men and women aged 50-80+ years were randomly recruited from population and health registers. Dual X-ray absorptiometry (DXA) equipment was used to measure BMD at the hip, with the femoral neck and the trochanter regions studied. Prevalences of osteopenia and osteoporosis were estimated in accordance with World Health Organisation diagnostic criteria for women. Young normal data, used to establish cutoff criteria, was from NHANES III. Both male and female British subjects over 50-years-old were found to have significantly higher mean BMD at the femoral neck and trochanter than their US counterparts. Decline in BMD with age in British men appeared slower than in US men. Between British centres there were also statistically significant differences in BMD values in both sexes. British age-adjusted prevalences of osteopenia in women averaged 20% less than those of NHANES III, whereas the prevalence of osteoporosis was substantially lower in British subjects of both sexes (55% in women, 68% in men). Thus, applying the US NHANES III data as the referent, osteoporosis of the proximal femur in Britain appears to be less common than in the US, due primarily to differences in the lower tails of the BMD distributions. Providing that the relationship between fracture rates and BMD is the same in Britain and the US, it would still be appropriate to apply the reference data in fracture risk assessment in the UK.

British Journal of Nutrition, 2014

Dietary modification may affect inflammatory processes and protect against chronic disease. In th... more Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997–2000 (n3237, mean age 54·8 (sd2·2) years). Participants (n2130, mean age 66·0 (sd2·2) years) returned during 2007–11 for follow-up. Diet was assessed by FFQ (n1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past ‘prudent’ dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of...

Osteoarthritis and Cartilage, 2009

lower deep UTE-enhanced T2* values (p=0.05) than those retaining OCT form birefringence. For supe... more lower deep UTE-enhanced T2* values (p=0.05) than those retaining OCT form birefringence. For superficial T2, SA without OCT form birefringence had 25% higher values than those with birefringence (p=0.047). No difference was found between the superficial T2* values of cores with and without OCT form birefringence. However a significant decrease in superficial T2* relaxation time was noted between SA with OCT grades B and C (p=0.014). No difference was found between type-II collagen content and OCT grade or quantitative MRI values. Conclusions: This multimodal study shows correlations between OCT grade, MRI T2, MRI UTE-enhanced T2* and PLM. OCT and PLM signs of matrix degeneration increased with increasing T2 and with decreasing T2*. Although no correlation was found between any of the imaging modalities and type-II collagen content, the correlations with PLM suggest that these emerging imaging technologies are more sensitive to changes in collagen structure than collagen content. As changes to collagen and matrix structure can occur prior to breakdown of the articular surface, these results demonstrate the potential of OCT, T2 and UTE-enhanced T2* to detect cartilage injury and degeneration in clinically normal appearing cartilage. Techniques for clinical detection of cartilage damage prior to gross tissue failure could lead to identification of new treatment windows for chondroprotective and chondrorestorative therapies that can delay or prevent the onset of osteoarthritis.

New England Journal of Medicine, 2010

Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascula... more Background The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. Methods In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of-2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)-positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. Results Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1000 person-years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1000 person-years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1000 person-years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group. Conclusions In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ERpositive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.

Clinica Chimica Acta, 2002

Background: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increase... more Background: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6-12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were

Bone, 2013

Purpose. There is a continuing need to improve the prediction of hip fractures to identify those ... more Purpose. There is a continuing need to improve the prediction of hip fractures to identify those at highest risk, enabling cost-effective use of preventative therapies. Methods. The aim of this work was to validate an innovative imaging biomarker for hip fracture by modelling the shape and texture of the proximal femur assessed from dual energy X-ray absorptiometry (DXA) scans. Scans used were acquired at baseline from elderly patients participating in a prospective, placebo-controlled fracture prevention study of the bisphosphonate, clodronate. 182 subjects who subsequently suffered a hip fracture were age, weight and height matched with two controls who did not suffer a fracture during a median 4year follow-up period. Logistic regression was used to test if variables were good predictors of fracture and adjust for bone mineral density (BMD). Results. Shape mode 2, reflecting variability in neck-shaft angle, neck width and the size of both trochanters, (0.81 (OR), 0.68-0.97 (CI), 0.024 (P)) and appearance mode 6, recording grey-level contrast, (1.33, 1.11-1.59, 0.002) were significant predictors of hip fracture and remained so after adjustment for BMD (shape mode 2 (0.77, 0.64-0.93, 0.006), appearance mode 6 (1.32, 1.10-1.59, 0.003)). Receiver Operating Curve analysis showed the combination of shape mode 2, appearance mode 6 and BMD was 3% better than any single predictor. Conclusion. Variables derived from shape and appearance models gave a prediction of fracture comparable to BMD and in combination with BMD gave an improvement in the prediction of hip fracture that could predict an additional 2000 hip fracture cases per year in the UK, potentially saving more than £20 million per year and 10,000 cases in the US.

Bone, 2013

The objective of this study was to consider whether trabecular bone score (TBS) improves on areal... more The objective of this study was to consider whether trabecular bone score (TBS) improves on areal bone mineral density (aBMD) measurement alone for the prediction of incident fractures in postmenopausal women. The OPUS study was conducted in ambulatory European women aged above 55years, recruited in 5 centers followed over 6years. For the assessment of the performance of TBS, baseline Hologic scans from 3 centers (Kiel, Paris and Sheffield) were available. Follow-up for incident fractures was available for 1007 women (mean age 65.9±6.9years). We compared the performance of TBS, aBMD, and their combination, by using net reclassification improvement (NRI, primary analysis) and receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under the curves (AUCs) (secondary analyses). 82 (8.1%) subjects with incident clinical osteoporotic fractures, and 46 (4.6%) with incident radiographic vertebral fractures were recorded over 6years. Performance of TBS was significantly better than lumbar spine (LS) aBMD for the prediction of incident clinical osteoporotic fractures (NRI=16.3%, p=0.007). For radiographic vertebral fractures, TBS and LS aBMD had similar predictive power but the combination of TBS and LS aBMD increased the performance over LS aBMD alone (NRI=8.6%, p=0.046) but the prediction is similar to hip and femoral neck aBMD. In non osteoporotic women, TBS predicted incident fragility fractures similarly to LS aBMD. This prospective study shows that in general population, TBS is a useful tool to improve the performance of lumbar spine aBMD for vertebral osteoporotic fractures.

Journal of Clinical Densitometry, 2010

Conclusion: In conclusion, once-yearly i.v. ZOL 5 mg substantially reduces the risk of multiple m... more Conclusion: In conclusion, once-yearly i.v. ZOL 5 mg substantially reduces the risk of multiple morphometric and clinical fractures suggesting that treatment mitigates the worsening fragility accompanying a fragility fracture.

Clinical Drug Investigation, 2006

acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers o... more acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. Methods: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score ≤-2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70mg weekly (Fosamax ®) and placebo identical to risedronic acid weekly or active risedronic acid 35mg weekly (Actonel ®) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phospha-12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. Conclusions: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Osteoporosis International, 2011

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone miner... more This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤3 months) subpopulations] were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤74 years (P<0.05) in the treatment and 65-74 years (P=0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05),

Our previous studies have demonstrated the inadequate nutritional status of Vietnamese female mar... more Our previous studies have demonstrated the inadequate nutritional status of Vietnamese female marriage immigrants in Korea. Major possible reasons include food insecurity due to economic problems as well as a lack of adjustment to unfamiliar Korean foods and limited access to Vietnamese foods; however, no study has investigated food insecurity among such intermarried couples. This study was performed to investigate the prevalence of food insecurity in Korean-husband-Vietnamese-wife couples and to determine whether they exhibit an intrahousehold discrepancy regarding food insecurity. A cross-sectional analysis of the Cohort of Intermarried Women in Korea study was performed with 84 intermarried couples. Among the 84 Vietnamese immigrants, 48.8% and 41.7% had food insecurity due to economic problems and a lack of foods appealing to their appetite, respectively. There was a marked discrepancy in reporting food insecurity between Vietnamese wives (22.6-38.1%) and their Korean husbands (6.0-15.5%). Vietnamese wives were five and two times more food-insecure due to economic problems and no foods appealing to their appetite, respectively, than their Korean spouses. A follow-up study is needed to investigate the causes of this discrepancy and ways of reducing food insecurity among female marriage immigrants living in low-income, rural communities.

This paper compares dual-energy X-ray absorptiometry (DXA) of the spine and hip and broadband ult... more This paper compares dual-energy X-ray absorptiometry (DXA) of the spine and hip and broadband ultrasound attenuation (BUA) of the os calcis in 1000 perimenopausal women aged between 45 and 49 years who attended a randomized Osteoporosis Screening Programme. Significant correlations were found between all DXA results and BUA, with the trochanter giving the best numerical correlation with BUA (r = 0.354, p &lt; 0.0001). BUA was not successful in predicting women with low DXA measurements, with only 44.0% of the women whose spinal DXA falls within the lowest quartile being in the lowest quartile of BUA. Although BUA is a poor predictor of spinal and hip bone mineral density it may provide additional structural information important in fracture prediction.

Calcified Tissue International

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral nec... more There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. We studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS-FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculated using FN BMD. To examine the effect of an adjustment for ΔLS-FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in ...

Menopause International, 2009

The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tra... more The reluctance of physicians to use estrogens in women with hormone responsive disorders is a tragic result of the 2002 WHI study. Although their hostility to estrogen therapy antedated these studies, the flawed data is now used as justification for the denial of estrogens for treatment of low bone density and various types of hormone responsive depression in women. Estrogens

The shape of the proximal femur has been demonstrated to be important in the occurrence of fractu... more The shape of the proximal femur has been demonstrated to be important in the occurrence of fractures of the femoral neck. Unfortunately, multiple geometric measurements frequently used to describe this shape are highly correlated. A new method, active shape modeling (ASM) has been developed to quantify the morphology of the femur. This describes the shape in terms of orthogonal modes of variation that, consequently, are all independent. To test this method, digitized standard pelvic radiographs were obtained from 26 women who had suffered a hip fracture and compared with images from 24 age-matched controls with no fracture. All subjects also had their bone mineral density (BMD) measured at five sites using dual-energy X-ray absorptiometry. An ASM was developed and principal components analysis used to identify the modes which best described the shape. Discriminant analysis was used to determine which variable, or combination of variables, was best able to discriminate between the groups. ASM alone correctly identified 74% of the individuals and placed them in the appropriate group. Only one of the BMD values (Ward&#39;s triangle) achieved a higher value (82%). A combination of Ward&#39;s triangle BMD and ASM improved the accuracy to 90%. Geometric variables used in this study were weaker, correctly classifying less than 60% of the study group. Logistic regression showed that after adjustment for age, body mass index, and BMD, the ASM data was still independently associated with hip fracture (odds ratio (OR)=1.83, 95% confidence interval 1.08 to 3.11). The odds ratio was calculated relative to a 10% increase in the probability of belonging to the fracture group. Though these initial results were obtained from a limited data set, this study shows that ASM may be a powerful method to help identify individuals at risk of a hip fracture in the future.

PLoS Genetics, 2011

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral den... more Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age-and gender-adjusted BMD zscores of +1.5 to +4.0, n = 1055, or 24.0 to 21.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.