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.

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.

Menopause, Reproductive Life, Hormone Replacement Therapy, and Bone Phenotype at Age 60-64 Years: A British Birth Cohort.

CONTEXT: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross-sectional, or lacking gold standard bone technologies or information on hormone replacement therapy (HRT) or surgical treatment. OBJECTIVE: The objective of the study was to investigate age at menopause, length of reproductive life, and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size, and strength in women aged 60-64 years. DESIGN: This was a birth cohort study that followed up for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories. SETTING: The study was conducted in England, Scotland, and Wales. PARTICIPANTS: Participants included 848 women with a known type of menopause and bone measures at 60-64 years. MAIN OUTCOME MEASURES: Peripheral quantitative computed tomography measurements of the distal radius total and trabecular vBMD were measured. Diaphyseal radius total and medullary cross-sectional area, cortical vBMD, and polar strength strain index (SSI); dual-energy x-ray absorptiometry measurements of aBMD at the lumbar spine and total hip were also measured. RESULTS: A 10-year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% confidence interval [CI] 1.3%-15.1%, P = .02) greater trabecular vBMD and a 6.0% (95% CI 0.51%-11.5%, P = .03) greater total vBMD; findings were similar for length of reproductive life. A 10-year difference in HRT use was associated with a 6.0% (95% CI 2.6%-9.3%, P < .001) greater polar SSI and a 0.9% (95% CI 0.4%-1.5%, P = .001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for peripheral quantitative computed tomography. CONCLUSIONS: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI and aBMD.

Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development.

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.

Ethnic differences in bone geometry between White, Black and South Asian men in the UK.

Relatively little is known about the bone health of ethnic groups within the UK and data are largely restricted to women. The aim of this study was to investigate ethnic differences in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), bone geometry and strength in UK men. White European, Black Afro-Caribbean and South Asian men aged over 40years were recruited from Greater Manchester, UK. aBMD at the spine, hip, femoral neck and whole body were measured by DXA. Bone geometry, strength and vBMD were measured at the radius and tibia using pQCT at the metaphysis (4%) and diaphysis (50% radius; 38% tibia) sites. Adjustments were made for age, weight and height. Black men had higher aBMD at the whole body, total hip and femoral neck compared to White and South Asian men independent of body size adjustments, with no differences between the latter two groups. White men had longer hip axis lengths than both Black and South Asian men. There were fewer differences in vBMD but White men had significantly lower cortical vBMD at the tibial diaphysis than Black and South Asian men (p<0.001). At the tibia and radius diaphysis, Black men had larger bones with thicker cortices and greater bending strength than the other groups. There were fewer differences between White and South Asian men. At the metaphysis, South Asian men had smaller bones (p=0.02) and lower trabecular vBMD at the tibia (p=0.003). At the diaphysis, after size-correction, South Asian men had similar sized bones but thinner cortices than White men; measures of strength were not broadly reduced in the South Asian men. Combining pQCT and DXA measurements has given insight into differences in bone phenotype in men from different ethnic backgrounds. Understanding such differences is important in understanding the aetiology of male osteoporosis.

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.

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.

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.

Automatic location of vertebrae on DXA images using random forest regression.

We provide a fully automatic method of segmenting vertebrae in DXA images. This is of clinical relevance to the diagnosis of osteoporosis by vertebral fracture, and to grading fractures in clinical trials. In order to locate the vertebrae we train detectors for the upper and lower vertebral endplates. Each detector uses random forest regressor voting applied to Haar-like input features. The regressors are applied at a grid of points across the image, and each tree votes for an endplate centre position. Modes in the smoothed vote image are endplate candidates, some of which are the neighbouring vertebrae of the one sought. The ambiguity is resolved by applying geometric constraints to the connections between vertebrae, although there can be some ambiguity about where the sequence starts (e.g., is the lowest vertebra L4 or L5, fig 2a). The endplate centres are used to initialise a final phase of active appearance model search for a detailed solution. The method is applied to a dataset of 320 DXA images. Accuracy is comparable to manually initialised AAM segmentation in 91% of images, but multiple grade 3 fractures can cause some edge confusion in severely osteoporotic cases.

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.

A randomized, controlled trial of vitamin D supplementation upon musculoskeletal health in postmenarchal females.

CONTEXT: There has been a resurgence of vitamin D deficiency rickets throughout the developed world, with infants and adolescents being primarily affected. Adolescence is a crucial period for muscle and bone mineral accumulation. OBJECTIVE: The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system. DESIGN AND SETTING: We conducted a community-based, double-blind, randomized controlled trial in a secondary school. PARTICIPANTS: Postmenarchal 12- to 14-yr-old females participated in the trial. Ninety-nine were screened, 73 were included in randomized controlled trial, and 69 completed the trial. There were no adverse events. INTERVENTION: Four doses of 150,000 IU vitamin D(2) (ergocalciferol) were given over 1 yr. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and jumping mechanography were used. RESULTS: At follow-up, 25-hydroxyvitamin D [25(OH)D] status was 56.0 ± 8.9 nmol/liter in the intervention group and 15.8 ± 6.6 nmol/liter in controls. There were no effects of supplementation on bone; however, for muscle function, efficiency of movement improved in the vitamin D-treated group. There was an interaction between baseline 25(OH)D concentration and response to vitamin D supplementation for muscle jump velocity. CONCLUSIONS: Despite improvements in 25(OH)D status, treatment with vitamin D(2) was not shown to increase mineral accretion, bone geometry or strength, muscle force, or power. There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations. Lack of effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is required.

Body composition and bone status of children born to mothers with type 1 diabetes mellitus.

BACKGROUND: Altered growth, body composition and abnormalities of skeletal mineralisation have been reported in offspring of mothers with type 1 and type 2 diabetes mellitus. AIMS: The authors hypothesised that children born to mothers with type 1 diabetes mellitus (CDM) would be taller, have higher body mass index (BMI), greater fat mass, thicker diaphyseal bone cortices and reduced trabecular bone mineral density (BMD), as compared to those born to non-diabetic mothers. METHODS: Anthropometric, body composition and bone parameters were assessed using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative CT in 67 white Caucasian CDM (35 boys; age 5-18 years) and in 246 (121 boys) age-matched controls. RESULTS: CDM were taller (p<0.0001), heavier (p<0.0001) and had higher BMI (p=0.02), and had 32% more total body fat mass and 7.5% more total body lean mass than controls. At the total body and lumbar spine (L1-L4) sites, CDM had significantly higher bone area and bone mineral content compared with controls. However, areal BMD at both these sites and lumbar spine bone mineral apparent density were not significantly different in the two groups, indicating that CDM have bigger bones compared with controls but their mineral content per unit area or volume is not substantially different. The distal radial trabecular and total volumetric BMD in CDM was not demonstrably different from controls. At the mid-radius, both periosteal (2.4%; p=0.03) and endosteal circumferences (5.7%; p=0.02) were bigger in CDM compared with controls. CONCLUSION: The authors speculate that the intrauterine diabetic environment is associated with an increase in linear growth, adiposity and larger bone dimensions during childhood and adolescence.

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.

Prediction of osteoporosis with dental radiographs and age.

OBJECTIVES: In this study age and the trabecular pattern present on dental radiographs were used to predict the presence of osteoporosis. The objective was to evaluate the contribution of the trabecular pattern to the prediction. METHODS: In this project, 671 women between 45 and 71 years of age were recruited. Medical history was obtained and dental radiographs were made. Bone mineral density (BMD) was measured at three sites to assess the presence of osteoporosis according to the World Health Organization criteria. The radiographs were subjected to image analysis methods yielding measurements of the trabecular pattern. Thereafter, discriminant analysis was used to predict the presence of osteoporosis by means of the trabecular pattern and age. Sensitivity and specificity of age and the trabecular pattern were compared. Also, it was checked whether the inclusion of the trabecular pattern improved the sensitivity and specificity that were obtained when only age was used as the predictor. RESULTS: The sensitivity and specificity of the trabecular pattern present on dental radiographs were almost equal to those of age. However, combining age with the trabecular pattern increased the sensitivity from 0.71 to 0.75 and the specificity from 0.72 to 0.78; the latter increase was statistically significant. CONCLUSIONS: The trabecular pattern predicts the presence of osteoporosis just as well as age does. When combining the trabecular pattern with age, the sensitivity and specificity increased. Only the latter increase was statistically significant.

Management and outcome of 103 acute fractures of the coronoid process of the ulna.

A series of 103 acute fractures of the coronoid process of the ulna in 101 patients was reviewed to determine their frequency. The Regan-Morrey classification, treatment, associated injuries, course and outcomes were evaluated. Of the 103 fractures, 34 were type IA, 17 type IB, ten type IIA, 19 type IIB, ten type IIIA and 13 type IIIB. A total of 44 type-I fractures (86%) were treated conservatively, while 22 type-II (76%) and all type-III fractures were managed by operation. At follow-up at a mean of 3.4 years (1 to 8.9) the range of movement differed significantly between the types of fracture (p = 0.002). Patients with associated injuries had a lower Mayo elbow performance score (p = 0.03), less extension (p = 0.03), more pain (p = 0.007) and less pronosupination (p = 0.004), than those without associated injuries. The presence of a fracture of the radial head had the greatest effect on outcome. An improvement in outcome relative to that of a previous series was noted, perhaps because of more aggressive management and early mobilisation. While not providing complete information about the true details of a fracture and its nature, the Regan-Morrey classification is useful as a broad index of severity and prognosis.