Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.

Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION: This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS: Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (ß-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS: Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS: Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower ß C-terminal cross-linked telopeptide (ß-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and ß-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and ß-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

International consensus on periprosthetic joint infection.

The purpose of this manuscript is to document results and complications of use of a regenerative dermal matrix skin substitute for coverage of extremity wounds. A retrospective review at 3 institutions identified 28 patients and 34 wounds who had undergone use of this material (Integra). Complications included failure in two patients (4 wounds). However, overall "take" of the regenerative matrix was 86.1%. In most cases, a split thickness skin graft was applied on average at 25 days following the initial procedure. Failures were associated with infection and irradiation of the surgical field. In this series, use of the dermal regenerative matrix was associated with a high rate of success for wound coverage, obviating the need for flap coverage or prolonged dressing changes in most cases. Further series are likely to refine the known indications and contraindications to use of this method.

Do patients with osteoporosis have an increased prevalence of periodontal disease? A cross-sectional study.

UNLABELLED: The study examined if women with osteoporosis were at increased risk of periodontal disease. Three hundred eighty females aged 45-65 years with recent dual-energy X-ray absorptiometry (DXA) scans of the spine and proximal femur agreed to a dental examination. No association was established between the presence of severe periodontal disease and osteoporosis. INTRODUCTION: The purpose of this study is to determine whether patients with osteoporosis have an increased severity and extent of periodontal disease, taking full account of confounding factors. METHODS: Volunteer dentate women (45-65 years), who had undergone recent DXA of the femur and lumbar spine, received a clinical examination of their periodontal tissues by a single trained operator who was blind to the subject's osteoporosis status. Clinical examinations were performed within 6 months of the DXA. Basic Periodontal Examination score, gingival bleeding score, periodontal pocket depth, recession and calculus were the periodontal outcome measures. Potential confounding factors were recorded. Logistic regression was performed for the dichotomous outcome measure of severe periodontal disease (present or absent) with osteoporotic status, adjusting for confounding factors. RESULTS: There were 380 dentate participants for whom DXA data were available. Of these, 98 had osteoporosis. When compared with osteoporotic subjects, those with normal bone mineral density were significantly younger (p = 0.01), had a higher body mass index (p = 0.03) and had more teeth (p = 0.01). The prevalence of severe periodontal disease in the sample was 39 %. The unadjusted odds ratio for the association between osteoporosis and severe periodontal disease was 1.21 (0.76 to 1.93). The adjusted odds ratio analysis including other covariates (age, smoking, hormone replacement therapy, alcohol) was 0.99 (0.61 to 1.61). CONCLUSION: No association was established between the presence of severe periodontal disease and osteoporosis.

Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men.

UNLABELLED: The aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMD(a)) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMD(a) and were more likely to have osteoporosis compared with men without sarcopenia. INTRODUCTION: In men, the relationship between reduced muscle mass (sarcopenia) and BMD(a) is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men. METHODS: Men aged 40-79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD(a) were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m(2) plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD(a) and logistic regression to determine the association between sarcopenia and osteoporosis. RESULTS: Six hundred seventy-nine men with a mean age of 59.6 (SD = 10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD(a). Men with RASM at <7.26 kg/m² had significantly lower BMD(a) compared with those with RASM at ≥7.26 kg/m(2). In a multivariable model, aLM was most consistently associated with BMD(a). Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio = 3.0; 95 % CI = 1.6-5.8). CONCLUSIONS: Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.

Semi-automatic determination of detailed vertebral shape from lumbar radiographs using active appearance models.

SUMMARY: The vertebral endplates in lumbar radiographs were located by a semi-automatic annotation method using statistical shape models. INTRODUCTION: Vertebral fractures are common osteoporotic fractures, but current quantitative detection methods (morphometry) lack specificity. We have previously developed more specific quantitative classifiers of vertebral fracture using shape and appearance models. This method has only been applied to DXA vertebral fracture assessment (VFA) images and not to spinal radiographs. The classifiers require a detailed annotation of the outline of the vertebral endplate, so we investigated the application of similar semi-automated annotation methods to lumbar radiographs as the initial step in the generalisation of the statistical classifiers used in VFA images. METHODS: The vertebral body outlines in a training set of 670 lumbar radiographs were manually annotated by expert radiologists. This training set was used to build statistical models of vertebral shape and appearance using triplets of vertebrae. In order to segment vertebrae, the models were refitted using a sequence of active appearance models of vertebral triplets, using a miss-40-out train/test cross-validation experiment. The accuracy was evaluated against the manual annotation and analysed by fracture grade. RESULTS: Good accuracy was obtained for normal vertebrae (0.82 mm) and fracture grades 1 and 2 (1.19 mm), but the localisation accuracy deteriorated for grade 3 fractures to 2.12 mm. CONCLUSION: Vertebral body shape annotation can be substantially automated on lumbar radiographs. However, an occasional manual correction may be required, typically with either severe fractures, or when there is a high degree of projectional tilting or scoliosis. The located detailed shapes may enable the development of more powerful quantitative classifiers of osteoporotic vertebral fracture.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis.

UNLABELLED: Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures. INTRODUCTION: Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach. METHODS: We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions. RESULTS: Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]). CONCLUSIONS: This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

The muscle-bone unit of peripheral and central skeletal sites in children and young adults.

UNLABELLED: Changes and gender differences in the muscle bone unit at different skeletal sites were investigated during pubertal development. Females accrued greater BMC in relation to muscle compared to males; these gender differences were greater after adjustment for height and regional fat mass. PURPOSE: To describe changes and gender differences in the muscle-bone unit at different skeletal sites during pubertal development. METHODS: Four hundred forty-two children aged 5-18 years were studied. Measurements of bone mineral content (BMC), lean mass (LM) and fat mass of the whole body (WB), legs, arms and lumbar spine were obtained from dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography was used to measure BMC of the radius diaphysis and cross-sectional muscle area (CSMA) of the mid-forearm. These measurements were used to describe differences between, and within, genders at each pubertal stage in BMC accrual relative to muscle, both before and after adjustment for height, regional fat and muscle at central and peripheral skeletal sites. RESULTS: In males, there were significant increases in adjusted WB and leg BMC at the end of pubertal development. Unadjusted and adjusted lumbar spine BMC increased at the onset of, and at the end, of puberty. Radius BMC increased at most pubertal stages. In females, there were increases in unadjusted and adjusted whole body BMC at late puberty, in leg BMC at the onset of puberty and at pubertal stage four. Unadjusted arm BMC increased at most pubertal stages; however, after adjustment, an increase occurred at pubertal stage four. Both adjusted and unadjusted lumbar spine BMC increased at pubertal stage four. Unadjusted radius BMC increased at most pubertal stages. Females had greater BMC at all skeletal sites, compared to males, except at the radius, where adjusted BMC was greater in males at pubertal stage four. CONCLUSIONS: Males and females accrue more BMC in relation to lean mass at multiple skeletal sites as puberty proceeds. Females accrue more BMC in relation to lean mass, in comparison to males, at most skeletal sites.

Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men.

SUMMARY: The influence of age and sex steroids on bone density and geometry of the radius was examined in two European Caucasian populations. Age-related change in bone density and geometry was observed. In older men, bioavailable oestradiol may play a role in the maintenance of cortical and trabecular bone mineral density (BMD). INTRODUCTION: To examine the effect of age and sex steroids on bone density and geometry of the radius in two European Caucasian populations. METHODS: European Caucasian men aged 40-79 years were recruited from population registers in two centres: Manchester (UK) and Leuven (Belgium), for participation in the European Male Ageing Study. Total testosterone (T) and oestradiol (E(2)) were measured by mass spectrometry and the free and bioavailable fractions calculated. Peripheral quantitative computed tomography was used to scan the radius at distal (4%) and midshaft (50%) sites. RESULTS: Three hundred thirty-nine men from Manchester and 389 from Leuven, mean ages 60.2 and 60.0 years, respectively, participated. At the 50% radius site, there was a significant decrease with age in cortical BMD, bone mineral content (BMC), cortical thickness, and muscle area, whilst medullary area increased. At the 4% radius site, trabecular and total volumetric BMD declined with age. Increasing bioavailable E(2) (bioE(2)) was associated with increased cortical BMD (50% radius site) and trabecular BMD (4% radius site) in Leuven, but not Manchester, men. This effect was predominantly in those aged 60 years and over. In older Leuven men, bioavailable testosterone (Bio T) was linked with increased cortical BMC, muscle area and SSI (50% radius site) and total area (4% radius site). CONCLUSIONS: There is age-related change in bone density and geometry at the midshaft radius in middle-aged and elderly European men. In older men bioE(2) may maintain cortical and trabecular BMD. BioT may influence bone health through associations with muscle mass and bone area.

Detection of vertebral fractures in DXA VFA images using statistical models of appearance and a semi-automatic segmentation.

SUMMARY: Morphometric methods of vertebral fracture diagnosis lack specificity. We used detailed shape and image texture model parameters to improve the specificity of quantitative fracture identification. Two radiologists visually classified all vertebrae for system training and evaluation. The vertebral endplates were located by a semi-automatic segmentation method to obtain classifier inputs. INTRODUCTION: Vertebral fractures are common osteoporotic fractures, but current quantitative detection methods (morphometry) lack specificity. We used detailed shape and texture information to develop more specific quantitative classifiers of vertebral fracture to improve the objectivity of vertebral fracture diagnosis. These classifiers require a detailed segmentation of the vertebral endplate, and so we investigated the use of semi-automated segmentation methods as part of the diagnosis. METHODS: The vertebrae in a training set of 360 dual energy X-ray absorptiometry images were manually segmented. The shape and image texture of vertebrae were statistically modelled using Appearance Models. The vertebrae were given a gold standard classification by two radiologists. Linear discriminant classifiers to detect fractures were trained on the vertebral appearance model parameters. Classifier performance was evaluated by cross-validation for manual and semi-automatic segmentations, the latter derived using Active Appearance Models (AAM). Results were compared with a morphometric algorithm using the signs test. RESULTS: With manual segmentation, the false positive rates (FPR) at 95% sensitivity were: 5% (appearance) and 18% (morphometry). With semi-automatic segmentations the sensitivities at 5% FPR were: 88% (appearance) and 79% (morphometry). CONCLUSION: Specificity and sensitivity are improved by using an appearance-based classifier compared to standard height ratio morphometry. An overall sensitivity loss of 7% occurs (at 95% specificity) when using a semi-automatic (AAM) segmentation compared to expert annotation, due to segmentation error. However, the classifier sensitivity is still adequate for a computer-assisted diagnosis system for vertebral fracture, especially if used in a triage approach.

Gonadal sex steroid status and bone health in middle-aged and elderly European men.

SUMMARY: The influence of sex steroids on calcaneal quantitative ultrasound (QUS) parameters was assessed in a population sample of middle-aged and elderly European men. Higher free and total E(2) though not testosterone, were independently associated with higher QUS parameters. INTRODUCTION: The aim of this study was to investigate the association between QUS parameters and sex steroids in middle-aged and elderly European men. METHODS: Three thousand one hundred forty-one men aged between 40 and 79 years were recruited from eight European centres for participation in a study of male ageing: the European Male Ageing Study. Subjects were invited by letter to attend for an interviewer-administered questionnaire, blood sample and QUS of the calcaneus (Hologic-SAHARA). Blood was assessed for sex steroids including oestradiol (E(2)), testosterone (T), free and bio-available E(2) and T and sex hormone binding globulin (SHBG). RESULTS: Serum total T was not associated with any of the QUS parameters. Free T and both free and total E(2) were positively related to all QUS readings, while SHBG concentrations were negatively associated. These relationships were observed in both older and younger (<60 years) men. In a multivariate model, after adjustment for age, centre, height, weight, physical activity levels and smoking, free E(2) and SHBG, though not free T, remained independently associated with the QUS parameters. After further adjustment for IGF-1, however, the association with SHBG became non-significant. CONCLUSION: Higher free and total E(2) are associated with bone health not only among the elderly but also middle-aged European men.

The impact of accurate positioning on measurements made by peripheral QCT in the distal radius.

SUMMARY: Data from pQCT sections at the forearm were examined to assess the impact of positioning on measurements. Two thousand five hundred fifty one scans were analysed. The results showed 25% of scans were not performed in the same anatomical location at follow-up when one section was scanned. These results have implications for accurate follow-up BMD measurements. INTRODUCTION: pQCT of the distal radius is routinely performed using a single section of 2 mm thickness. Accurate positioning is essential to maximise long-term repeatability. We perform two adjacent sections which, permits us to select sections at baseline and follow-up that are in the most similar anatomical site for calculating longitudinal change. This study aimed to assess baseline and follow-up pQCT forearm data to examine variability and determine whether performing two sections, as opposed to one section, improved accuracy when monitoring long-term change in BMD. METHODS: Two adjacent 1.2 mm pQCT radial sections were performed at: baseline n = 2,551 (1,896F:655M) and follow-up n = 335F. RESULTS: Baseline: difference between adjacent 1.2 mm forearm sections: total BMD 19.3 mg/cm(3) (females) and 16.7 mg/cm(3) (males); trabecular BMD 3.1 mg/cm(3) (females) and 2.35 mg/cm(3) (males); CSA 16.2 mm(2) (females) and 17.7 mm(2) (males) (all significant). FOLLOW-UP: percentage of scans at baseline and follow-up performed in the same anatomical location: one section performed-75%, two sections performed-95%. CONCLUSION: When performing a single section at the distal radius it is difficult to perform scans in the same anatomical location at visits. Performing two or more sections can overcome this problem in some individuals and provide more accurate BMD measurements.

A reference database for the Stratec XCT-2000 peripheral quantitative computed tomography (pQCT) scanner in healthy children and young adults aged 6-19 years.

SUMMARY: We have produced paediatric reference data for forearm sites using the Stratec XCT-2000 peripheral quantitative computed tomography scanner. These data are intended for clinical and research use and will assist in the interpretation of bone mineral density and bone geometric parameters at the distal and mid-shaft radius in children and young adults aged between 6-19 years. INTRODUCTION: Peripheral quantitative computed tomography (pQCT) provides measurements of bone mineral content (BMC), density (BMD) and bone geometry. There is a lack of reference data available for the interpretation of pQCT measurements in children and young adults. The aim of this study was to provide reference data at the distal and mid-shaft radius. METHODS: pQCT was used to measure the 4% and 50% sites of the non-dominant radius in a cohort of healthy white Caucasian children and young adults aged between 5 and 25 years. The lambda, mu, sigma (LMS) technique was used to produce gender-specific reference centile curves and LMS tables for calculating individual standard deviations scores. RESULTS: The study population consisted of 629 participants (380 males). Reference centile curves were produced; total and trabecular BMD for age (distal radius) and for age and height, bone area (distal and mid-shaft radius), cortical area, cortical thickness, BMC, axial moment of inertia, stress-strain index and muscle area (mid-shaft radius). CONCLUSIONS: We present gender-specific databases for the assessment of the distal and mid-shaft radius by pQCT. These data can be used as control data for research studies and allow the clinical interpretation of pQCT measurements in children and young adults by age and height.

Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone.

Relief of intractable pain was produced in six human patients by stimulation of electrodes permanently implanted in the periventricular and periaqueductal gray matter. The level of stimulation sufficient to induce pain relief seems not to alter the acute pain threshold. Indiscriminate repetitive stimulation produced tolerance to both stimulation-produced pain relief and the analgesic action of narcotic medication; this process could be reversed by abstinence from stimulation. Stimulation-produced relief of pain was reversed by naloxone in five out of six patients. These results suggest that satisfactory alleviation of persistent pain in humans may be obtained by electronic stimulation.

Expression and characterization of recombinant interferon gamma (IFN-gamma) from the nine-banded armadillo (Dasypus novemcinctus) and its effect on Mycobacterium leprae-infected macrophages.

Armadillos (Dasypus novemcinctus) manifest the full histopathological spectrum of leprosy, and are hosts of choice for in vivo propagation of Mycobacterium leprae. Though potentially useful as a model of leprosy pathogenesis, few armadillo-specific reagents exist. We have identified a region of high homology to the interferon gamma (IFN-gamma) of other mammals within the recently published armadillo whole genomic sequence. cDNA was made from ConA-stimulated armadillo peripheral blood mononuclear cells (PBMC), amplified, and cloned into a pET expression vector for transformation and over-expression in Escherichia coli. The recombinant protein (rDnIFN-gamma) was characterized by western blot and its biological function confirmed with bioassays including intracellular killing of Toxoplasma gondii and induction of indoleamine 2, 3-dioxygenase activity. In using rIFN-gamma to activate macrophages from mice, humans or armadillos, similar to humans, rIFN-gamma-activated armadillo MPhi did not produce nitrite and or inhibit the viability of M. leprae in vitro. Conversely, murine rIFN-gamma-activated mouse MPhi produced high levels of nitrite and killed intracellular M. leprae in vitro. These data indicate that the response of armadillo MPhi to rDnIFN-gamma is similar to that which occurs in humans, and demonstrates a potentially important value of the armadillo as a model in leprosy research.

Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen.

Oral glucocorticoids (GC) preserve muscle strength and prolong walking in boys with Duchenne muscular dystrophy (DMD). Although vertebral fractures have been reported in boys taking GC, fracture rates for different GC regimes have not been investigated. The aim of this pragmatic longitudinal study was to compare growth, body mass, bone mineral density (BMD), vertebral fractures (VF) and ambulatory status in boys with DMD on daily (DAILY) or intermittent (INTERMITTENT), oral GC regimens. A convenience sample of 50 DMD boys from two centres was included in the study; 25 boys each were on the DAILY or INTERMITTENT regimen. Size adjusted lumbar spine BMD (LS BMAD), total body less head BMD (TBLH), by DXA and distal forearm bone densities by pQCT, GC exposure, VF assessment and ambulatory status were analysed at three time points; baseline, 1 and 2 years. At baseline, there were no differences in age, GC duration or any bone parameters. However, DAILY boys were shorter (height SDS DAILY = -1.4(0.9); INTERMITTENT = -0.8(1.0), p = 0.04) with higher BMI (BMI SDS DAILY = 1.5(0.9); INTERMITTENT = 0.8(1.0), p = 0.01). Over 2 years, DAILY boys got progressively shorter (delta height SDS DAILY = -0.9(1.1); INTERMITTENT = +0.1(0.6), p < 0.001). At their 2 year assessment, 5 DAILY and 10 INTERMITTENT boys were non-ambulant. DAILY boys had more VFs than INTERMITTENT boys (10 versus 2; χ2 p = 0.008). BMAD SDS remained unchanged between groups. TBLH and radius BMD declined significantly but the rate of loss was not different. In conclusion, there was a trend for more boys on daily GCs to remain ambulant but at the cost of more VFs, greater adiposity and markedly diminished growth. In contrast, boys on intermittent GCs had fewer vertebral fractures but there was a trend for more boys to loose independent ambulation.

Calcium supplementation and weight bearing physical activity--do they have a combined effect on the bone density of pre-pubertal children?

The adaptation of bone to exercise has been shown to be modified by dietary calcium intake. The aim of this randomised controlled trial was to investigate whether there was a differential response to calcium supplementation in elite gymnasts and school children controls. The primary hypothesis was that gymnasts who took calcium supplements would have greater increases in cortical and trabecular volumetric bone mineral density (vBMD) at the radius and tibia. Secondary outcomes studied were changes in bone geometry at the radius and tibia and lumbar spine and whole body measurements. Children were randomised to 12 months daily supplementation of 500 mg elemental calcium (1250 mg (in the form of calcium carbonate salt)) or placebo. Outcome measures were assessed using peripheral quantitative computed tomography (pQCT) (distal and diaphyseal radius and tibia) and dual energy X-ray absorptiometry (DXA) (lumbar spine and whole body). Eighty-six subjects participated in the trial (44 gymnasts, 42 controls) and 75 subjects completed the trial (39 gymnasts, 36 controls). Data were analysed by analysis of covariance adjusting for baseline value of bone parameters, age, height, gender and puberty, and delay between baseline measurement and start of intervention. The primary analysis was for a calcium-exercise interaction; a pooled calcium effect with no interaction was also tested. Results are presented as ratios (95% confidence intervals). At the distal tibia, trabecular vBMD showed a significant interaction (p=0.04), with controls (1.00: 0.99, 1.09) responding more than gymnasts (0.98: 0.94, 1.02) to supplementation. At the distal radius, change in trabecular vBMD was not significant (p=0.05). There were no differences in change in cortical vBMD at either site between the gymnasts and controls (tibia: p=0.82, radius: p=0.88). For all other secondary outcomes at radius, tibia, spine and whole body no significant interactions were found. In conclusion, there was no beneficial effect of additional calcium in gymnasts who already consume their recommended nutrient intake (888 mg/day; United Kingdom reference nutrient intake for 8- to 11-year-olds is 555-800 mg/day) for calcium. We speculate that gymnasts have already adapted their bones (geometry and vBMD) to the demands imposed upon them by the loading they are subjected to during gymnastics and do not benefit from additional calcium supplementation.

Forearm bone geometry and mineral content in UK women of European and South-Asian origin.

Ethnic variation in areal bone mineral density (BMD) has been well documented. Such variation may, however, reflects differences in bone geometry rather than volumetric BMD (vBMD). The aim of the study was to compare bone geometry, mineral content (BMC) and vBMD in two ethnic groups, and study the influence of body size, physical activity, reproductive variables, 25 hydroxy-vitamin D (25(OH)D) and parathormone (PTH) status on any observed differences. The data were from a population-based, cross-sectional survey of peak bone mass in South Asian and European women, the population consisted 230 pre-menopausal South Asian (n=118, mean age 28.6+/-4.6 years) and European (n=112, mean age 30+/-4.3 years) women of UK origin. Women who participated completed an interviewer assisted questionnaire, had blood taken for assessment of 25(OH)D and PTH and had measurements of their distal (4%) and diaphyseal (50%) radius geometry, BMC and vBMD using peripheral quantitative computed tomography. At the 50% radius, South Asians had lower vBMD (p<0.001), BMC (p<0.001), cortical area (p<0.001), cortical thickness (p<0.001), cross-sectional area (p=0.04) and increased medullary area (p<0.04). Cross-sectional muscle area and stress strain index, however, were not different. Adjustment for age, height and weight attenuated, the difference in cross-section area but did not account for any of the other observed differences. Further adjustment for reproductive variables a physical activity index, 25(OH)D and PTH, attenuated ethnic differences in cortical BMC, area and thickness which became non-significant; however, ethnic differences in cortical vBMD and medullary area persisted. At the 4% site, after adjusting for age, height and weight, there was no difference in total area, total or trabecular vBMD between ethnic groups. After further adjustment for physical activity, reproductive variables, 25(OH)D and PTH, trabecular vBMD was higher in the South Asians. In conclusion, there are differences in bone geometry, BMC and vBMD at the radial diaphysis between UK South Asians and Europeans which are not explained by differences in body size. Polar stress-strain index was similar, however, suggesting no important differences in bone strength.

Automated osteoporosis risk assessment by dentists: a new pathway to diagnosis.

General dental practitioners use a vast amount of panoramic radiography in their routine clinical work, but valuable information about patients' osteoporotic status is not collected. There are many reasons for this, but one of the prime reasons must be the disruption involved in clinical routine with lengthy manual radiographic assessment. We have developed computer software, based on active shape modeling that will automatically detect the mandibular cortex on panoramic radiographs, and then measure its width. Automatic or semi-automatic measurement of the cortical width will indicate the osteoporotic risk of the patient. The aim of our work was to assess the computer search technique's ability to measure the mandibular cortical width and to assess its potential for detection of osteoporosis of the hip, spine and femoral neck. Mandibular cortical width was measured using the manually initialized (semi-automatic) method and, when assessed for diagnosing osteoporosis at one of the three measurement sites, gave an area under the ROC curve (A(z))=0.816 (95% CI=0.784 to 0.845) and for the automatically initialized searches, A(z)=0.759 (95% CI=0.724 to 0.791). The difference between areas=0.057 (95% Confidence interval=0.025 to 0.089), p<0.0001. For diagnosing osteoporosis at the femoral neck, mandibular cortical width derived from the manually initialized fit gave an area under the ROC curve (A(z))=0.835 (95% CI=0.805 to 0.863) and for the automatically initialized searches A(z)=0.805 (95% CI=0.773 to 0.835). The difference in A(z) values between active shape modeling search methods=0.030 (95% CI=-0.010 to 0.070), and this was not significant, p=0.138. We concluded that measurement of mandibular cortical width using active shape modeling is capable of diagnosing skeletal osteoporosis with good diagnostic ability and repeatability.

Accuracy in osteoporosis diagnosis of a combination of mandibular cortical width measurement on dental panoramic radiographs and a clinical risk index (OSIRIS): the OSTEODENT project.

Clinical questionnaires and dental radiographic findings have both been suggested as methods of identifying women at risk of having osteoporosis and who might benefit from bone densitometry. The aim of this study was to measure the diagnostic accuracy of a combination of mandibular cortical width (MCW) measured from dental panoramic radiographs (DPRs) and the osteoporosis index of risk (OSIRIS) in the diagnosis of osteoporosis. 653 women (age range 45-70 years, mean age 54.95 years) in four European centres underwent standardised dual X-ray energy absorptiometry (DXA) to provide reference data on osteoporosis status. Each subject was interviewed to derive OSIRIS scores and underwent DPR examination. MCW was measured directly by five observers. Receiver Operating Characteristic (ROC) curve analysis was used to calculate sensitivities and specificities of the clinical and radiographic tests for the diagnosis of osteoporosis. 512 (78.4%) of the study population were classified as having normal BMD and 141 (21.6%) as having osteoporosis. Using ROC analysis, OSIRIS gave a ROC curve area (A(z)) of 0.838, with a sensitivity of 70.9% and a specificity of 79.5% at a diagnostic threshold of