Evaluating the impact of COVID-19 on DXA waiting lists and osteoporosis prescription trends in England 2019-2023.

This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication patterns in England. Results show significant increases in DXA waiting list times and variation in prescription rates. Investment is needed to improve waiting list times. PURPOSE: This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment. METHODS: Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis. RESULTS: In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020. CONCLUSION: COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England.

Assessing bone mineralisation in children with chronic kidney disease: what clinical and research tools are available?

Mineral and bone disorder in chronic kidney disease (CKD-MBD) is a triad of biochemical imbalances of calcium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calcification. Maintaining optimal bone health in children with CKD is important to prevent long-term complications, such as fractures, to optimise growth and possibly also to prevent extra-osseous calcification, especially vascular calcification. In this review, we discuss normal bone mineralisation, the pathophysiology of dysregulated homeostasis leading to mineralisation defects in CKD and its clinical consequences. Bone mineralisation is best assessed on bone histology and histomorphometry, but given the rarity with which this is performed, we present an overview of the tools available to clinicians to assess bone mineral density, including serum biomarkers and imaging such as dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. We discuss key studies that have used these techniques, their advantages and disadvantages in childhood CKD and their relationship to biomarkers and bone histomorphometry. Finally, we present recommendations from relevant guidelines-Kidney Disease Improving Global Outcomes and the International Society of Clinical Densitometry-on the use of imaging, biomarkers and bone biopsy in assessing bone mineral density. Given low-level evidence from most paediatric studies, bone imaging and histology remain largely research tools, and current clinical management is guided by serum calcium, phosphate, PTH, vitamin D and alkaline phosphatase levels only.

No benefit of ultrasound-guided transversus abdominis plane blocks over wound infiltration with local anaesthetic in elective laparoscopic colonic surgery: results of a double-blind randomized controlled trial.

AIM: Advances in laparoscopic techniques combined with enhanced recovery pathways have led to faster recuperation and discharge after colorectal surgery. Peripheral nerve blockade using transversus abdominis plane (TAP) blocks reduce opioid requirements and provide better analgesia for laparoscopic colectomies than do inactive controls. This double-blind randomized study was performed to compare TAP blocks using bupivacaine with standardized wound infiltration with local anaesthetic (LA). METHOD: Seventy-one patients were randomized to receive either TAP block or wound infiltration. The TAP blocks were performed by experienced anaesthetists who used ultrasound guidance to deliver 40 ml of 0.25% bupivacaine post-induction into the transverse abdominis plane. In the control group, 40 ml of 0.25% bupivacaine was injected around the trocar and the extraction site by the surgeon. Both groups received patient-controlled analgesia (PCA) with intravenous morphine. Patients and nursing staff assessed pain scores 6, 12, 24 and 48 h after surgery. The primary outcome was overall morphine use in the first 48 h. RESULTS: Of the 71 patients, 20 underwent a right hemicolectomy and 51 a high anterior resection. The modified intention-to-treat analysis showed no significant differences in overall morphine use [47.3 (36.2-58.5) mg vs 46.7 (36.2-57.3) mg; mean (95% CI), P = 0.8663] in the first 48 h. Pain scores were similar at 6, 12, 24 and 48 h. No differences were found regarding time to mobilization, resumption of diet and length of hospital stay. CONCLUSION: In elective laparoscopic colectomies, standardized wound infiltration with LA has the same analgesic effect as TAP blocks post-induction using bupivacaine at 48 h.

Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures.

UNLABELLED: Several established methods are used to size adjust dual-energy X-ray absorptiometry (DXA) measurements in children. However, there is no consensus as to which method is most diagnostically accurate. All size-adjusted bone mineral density (BMD) values were more diagnostically accurate than non-size-adjusted values. The greatest odds ratio was estimated volumetric BMD for vertebral fracture. INTRODUCTION: The size dependence of areal bone density (BMDa) complicates the use of DXA in children with abnormal stature. Despite several size adjustment techniques being proposed, there is no consensus as to the most appropriate size adjustment technique for estimating fracture risk in children. The aim of this study was to establish whether size adjustment techniques improve the diagnostic ability of DXA in a cohort of children with chronic diseases. METHODS: DXA measurements were performed on 450 children, 181 of whom had sustained at least one low trauma fracture. Lumbar spine (L2-L4) and total body less head (TBLH) Z-scores were calculated using different size adjustment techniques, namely BMDa and volumetric BMD for age (bone mineral apparent density (BMAD)); bone mineral content (BMC) and bone area for height; BMC for bone area; BMC for lean mass (adjusted for height); and BMC for bone and body size. RESULTS: Unadjusted L2-L4 and TBLH BMDa were most sensitive but least specific at distinguishing children with fracture. All size adjustments reduced sensitivity but increased post-test probabilities, from a pre-test probability of 40 % to between 58 and 77 %. The greatest odds ratio for fracture was L2-L4 BMAD for a vertebral fracture and TBLH for lean body mass (LBM) (adjusted for height) for a long bone fracture with diagnostic odds ratios of 9.3 (5.8-14.9) and 6.5 (4.1-10.2), respectively. CONCLUSION: All size adjustment techniques improved the predictive ability of DXA. The most accurate method for assessing vertebral fracture was BMAD for age. The most accurate method for assessing long bone fracture was TBLH for LBM adjusted for height.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).

Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.

Studying bone mineral density in young people: The complexity of choosing a pQCT reference database.

BACKGROUND: Many chronic illnesses affect bone health, and commonly lead to mineralization abnormalities in young people. As cortical and trabecular bone may be differentially affected in certain diseases, an imaging technique that allows for detailed study of the bone structure is required. Peripheral quantitative computed tomography (pQCT) overcomes the limitations of dual energy X-ray absorptiometry (DXA) and is perhaps more widely available for use in research than bone biopsy. However, in contrast to DXA, where there are large reference datasets, this is not the case for pQCT. METHODS: Fifty-five children and young adults aged 7 to 30 years had the non-dominant tibia scanned at the 3% & 4% sites for trabecular bone mineral density and the 38% site for cortical bone mineral density and bone mineral content. Image acquisition and analysis was undertaken according to the protocols of two of the largest reference datasets for tibial pQCT. The Z-scores generated were compared to examine the differences between protocols and the differences from the expected median of zero in a healthy population. RESULTS: The trabecular bone mineral density Z-scores generated by the two protocols were similar. The same was true for cortical mineral content Z-scores at the 38% site. Cortical bone mineral density was significantly different between protocols and likely affected by differences in the ethnicity of our cohort compared to the reference datasets. Only one reference dataset extended from childhood to young adulthood. Only trabecular bone mineral density, periosteal and endosteal circumference Z-scores from one methodology were not significantly biased when tested for deviation of the median from zero. CONCLUSIONS: pQCT is a useful tool for studying trabecular and cortical compartments separately but, there are variations in pQCT scanning protocols, analysis methodology, and a paucity of reference data. Reference datasets may not be generalizable to local study populations, even when analysed using identical analysis protocols.

Impact of UK National Guidelines based on FRAX®--comparison with current clinical practice.

OBJECTIVE: To assess whether clinician-determined treatment intervention thresholds are in line with the assessment of fracture risk provided by FRAX® and treatment recommendations provided by UK guidelines produced by the National Osteoporosis Guidelines Group (NOGG). DESIGN, PATIENTS AND MEASUREMENTS: This was a retrospective cohort analysis of 288 patients consecutively referred for dual-energy X-ray absorptiometry (DXA) scanning from primary care immediately prior to the introduction of the FRAX® algorithm. In addition to DXA assessment, patients completed a clinical risk factor questionnaire which included risk factors used in the FRAX® algorithm. Initial risk assessment and treatment decisions were performed after DXA. FRAX® was used, retrospectively, with femoral neck T-score, to estimate fracture risk which was applied to NOGG to generate guidance on treatment intervention. Clinician- and NOGG-determined outcomes were audited for concordance. RESULTS: There was concordance between clinician and NOGG treatment decisions in 215 (74.6%) subjects. Discordance was observed in 73 (25.3%) subjects. In the discordant group, seven subjects were given lifestyle advice when NOGG recommended treatment, 42 given treatment when NOGG recommended lifestyle advice only, and 24 were referred to a metabolic bone clinic for further evaluation. The reasons for treatment differences in subjects recommended treatment by clinician but not NOGG were largely (90.2%) attributed to the use of lumbar spine bone mineral density (BMD). CONCLUSIONS: There is high concordance between clinician-determined and FRAX®-NOGG intervention. The absence of spine BMD from FRAX® is the primary source of discrepancy. This study provides some assurance of the validity of the treatment thresholds generated from FRAX®-NOGG in 'real-world' usage.

Bone status of adolescent girls in Pune (India) compared to age-matched South Asian and white Caucasian girls in the UK.

UNLABELLED: Underprivileged adolescent girls in Pune, India, were shorter and lighter, and had reduced lean body mass (LBM) compared with relatively 'well off' age-matched South Asian and white Caucasian girls in the UK. Pune girls had low bone mass for projected bone area (BA) in comparison to their UK counterparts, but they had the appropriate amount of bone mineral content (BMC) for their LBM. PURPOSE: To determine whether adolescent girls from a low socioeconomic group in Pune, India, who had low dietary calcium intake (449 mg/day; range 356-538 mg/day) and hypovitaminosis D (median serum 25-hydroxyvitamin D 23.4 nmol/l; range 13.5-31.9 nmol/l), would have lower lumbar spine (LS) bone mineral apparent density (BMAD), and total body (TB) BMC adjusted for LBM. METHODS: Dual energy X-ray absorptiometry was used to measure TB and LS BMC, BA and TB LBM in 50 postmenarcheal girls in Pune. These variables were compared with data from 34 South Asian and 82 white Caucasian age-matched girls in the UK. RESULTS: Pune girls were shorter and lighter, and had less LBM for height, compared to both UK groups, and they had later age of menarche than UK Asians. BA-adjusted TB BMC and LS BMAD were lower in Pune girls (mean+/-SE 1,778+/-17 g; 0.332+/-0.005 g/cm(3)), compared to the UK South Asians (mean+/-SE 1,864+/-18 g; 0.355+/-0.006 g/cm(3)) and UK white Caucasians (mean+/-SE 1,864+/-13 g; 0.345+/-0.004 g/cm(3)). In contrast both LS and TB BMC adjusted for TB LBM were not significantly different between the groups. CONCLUSION: Pune girls had low bone mass for projected BA relative to UK South Asian and white Caucasian girls, but had the appropriate amount of BMC for their LBM.

Assessment of procedural skills in anaesthesia.

A key aspect of the practice of anaesthesia is the ability to perform practical procedures efficiently and safely. Decreased working hours during training, an increasing focus on patient safety, and greater accountability have resulted in a paradigm shift in medical education. The resulting international trend towards competency-based training demands robust methods of evaluation of all domains of learning. The assessment of procedural skills in anaesthesia is poor compared with other domains of learning and has fallen behind surgical fields. Logbooks and procedure lists are best suited to providing information regarding likely opportunities within training programmes. Retrospective global scoring and direct observation without specific criteria are unreliable. The current best evidence for a gold standard for assessment of procedural skills in anaesthesia consists of a combination of previously validated checklists and global rating scales, used prospectively by a trained observer, for a procedure performed in an actual patient. Future research should include core assessment parameters to ensure methodological rigor and facilitate robust comparisons with other studies: (i) reliability, (ii) validity, (iii) feasibility, (iv) cost-effectiveness, and (v) comprehensiveness with varying levels of difficulty. Simulation may become a key part of the future of formative and summative skills assessment in anaesthesia; however, research is required to develop and test simulators that are realistic enough to be suitable for use in high-stakes evaluation.

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.

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

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

Body fat estimation using bioelectrical impedance.

BACKGROUND/AIMS: Although childhood obesity is a major problem, routine assessment methods do not reflect fat mass. Body mass index, which is most commonly used, gives an indication of weight for height and not a degree of adiposity. METHODS: Bioelectrical impedance and dual-energy X-ray absorptiometry (DEXA) were used in a group of obese children to assess body fat. RESULTS: Comparison between DEXA and commercial bioelectrical impedance scales in 46 children showed a highly significant correlation (R = 0.944, p < 0.001) in fat mass. Fat mass measured using bioelectrical impedance was 2.4 kg lower compared to measurement using DEXA. CONCLUSION: These bioelectrical scales may prove useful in the management of childhood obesity as they are able to provide important clinical information regarding fat mass and adiposity.

Vertebral fractures assessment in children: Evaluation of DXA imaging versus conventional spine radiography.

Vertebral fracture assessment (VFA) by DXA is an accepted tool in adults. However, its use in children has not been assessed. The aim of this study was to evaluate DXA VFA and morphometric analysis (MXA) using a GE Lunar iDXA bone densitometer against spinal radiographic assessment (RA) for the identification of vertebral fractures in children. Spine RA and VFA (T3-L5) were acquired on the same day in 80 children. Forty children considered high risk for fracture by their metabolic bone specialist were referred for spinal RA. Another 40 children were recruited as part of a prospective fracture study and were considered low risk for vertebral fracture. Agreement between RA and VFA was assessed by an expert paediatric radiologist and two paediatricians with expertise in bone pathology. Agreement between RA and MXA was assessed by an expert paediatric radiologist, two clinical scientists and an experienced paediatric radiographer. Vertebrae were ranked as normal, mild, moderate or severe if they had <10%, 11-25%, 26-50% and >50% deformity, respectively. Levels of agreement were calculated using the Cohen kappa score. Evaluating the data from all readable vertebrae, 121 mild, 44 moderate and 16 severe vertebral fractures were identified; with 26, 8, and 5 subjects having at least one mild, moderate or severe fracture, respectively. Depending on rater, 92.8-94.8% of the vertebrae were evaluable by RA. In contrast, 98.4% were evaluable by VFA and only 83.6% were evaluable by MXA. Moderate agreement was found between raters for RA [kappa 0.526-0.592], and VFA [kappa 0.601-0.658] and between RA and VFA [kappa 0.630-0.687]. In contrast, only slight agreement was noted between raters for MXA [kappa 0.361-0.406] and between VFA and MXA [kappa 0.137-0.325]. Agreement substantially improved if the deformities were dichotomised as normal or mild versus moderate or severe [kappa 0.826-0.834]. For the detection of moderate and/or severe fractures the sensitivities & specificities were 81.3% & 99.3%, and 62.5% & 99.2% for VFA and MXA, respectively. This study demonstrates that VFA is as good as RA for detecting moderate and severe vertebral fractures. Given the significant radiation dose saving of VFA compared with RA, VFA is recommended as a diagnostic tool for the assessment of moderate or severe vertebral fracture in children.

Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome.

CONTEXT: Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how ALMS1 mutations relate to the characteristic phenotype. OBJECTIVES: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists. DESIGN AND PATIENTS: We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of ALMS1 were directly sequenced. SETTING: The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic. RESULTS: AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = -0.37, P = 0.2; r = -0.84, P = 0.002; and r = -0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = -0.64, P = 0.02). ALMS1 mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed. CONCLUSIONS: We identified mutations in ALMS1 in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.

Intracapsular hip fracture and the region-specific loss of cortical bone: analysis by peripheral quantitative computed tomography.

Generalized bone loss within the femoral neck accounts for only 15% of the increase in intracapsular hip fracture risk between the ages of 60 and 80 years. Conventional histology has shown that there is no difference in cancellous bone area between cases of intracapsular fracture and age and sex-matched controls. Rather, a loss of cortical bone thickness and increased porosity is the key feature with the greatest change occurring in those regions maximally loaded during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now reexamined this finding using peripheral quantitative computed tomography (pQCT) to analyze cortical and cancellous bone areas, density, and mass in a different set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female, n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95 years; male, n = 11, aged 56-86 years). Within-neck location was standardized by using locations at which the ratio of maximum to minimum external diameters was 1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial profiles from the center of area of each of the gray level images using a full-width/half-maximum algorithm. In both male and female controls, cancellous bone mass increased toward the femoral head and the rate of change was gender independent. Cancellous bone mass was similar in cases and controls at all locations. Overall, cortical bone mass was significantly lower in the fracture cases (by 25%; p < 0.001) because of significant reductions in both estimated cortical area and density. These differences persisted at locations that are more proximal. The mean cortical width in the cases was significantly lower in the IA (22.2%;p = 0.002) and inferior regions (19%;p < 0.001). The SP region was the thinnest in both cases and controls. These data confirm that a key feature in the etiology of intracapsular hip fracture is the site-specific loss of cortical bone, which is concentrated in those regions maximally loaded during a fall on the greater trochanter. An important implication of this work is that the pathogenesis of bone loss leading to hip fracture must be by a mechanism that varies in its effect according to location within the femoral neck Key candidate mechanisms would include those involving locally reduced mechanical loading. This study also suggests that the development of noninvasive methodologies for analyzing the thickness and estimated densities of critical cortical regions of the femoral neck could improve detection of those at risk of hip fracture.

Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading.

The aim of this 1-year prospective study of acute stroke patients was to determine the effects of walking and asymmetrical weight bearing on the loss of bone mineral in the upper and lower femoral neck. Forty patients were followed. Eight remained unable to walk, whereas 32 relearned to walk independently within 7 months (12 shortly after the stroke, 15 by 2 months, 5 by 7 months). Bone mineral density (BMD) was measured in the proximal femur within the first week after stroke and 1 year later; regional BMD changes were computed for the lower and upper femoral neck. The lower part of the femoral neck is mainly influenced by compressive stresses of the hip, the upper part by tensile stresses during walking. When comparing mean BMD loss in groups of patients according to when they relearned to walk, a statistically significant trend in BMD loss was found in the lower femoral neck on both the paretic and nonparetic sides (p < 0.01 and p = 0.01, respectively), whereas, for the upper femoral neck, no significant trend was seen (p >/= 0.1). In addition, the body weight distribution during standing was assessed by use of a force-plate in 38 patients who could stand independently at the 7 month evaluation. The only significant correlation between changes in BMD and asymmetrical weight bearing was found in the lower femoral neck on the paretic side (r = 0.6, p < 0.001). In conclusion, this study shows that the reduction in BMD in the femoral neck occurs mainly in the lower part of the neck and on the paretic side. The BMD loss depended on when or if the patients relearned to walk, but also on the amount of body weight born on the paretic leg. Thus, measuring the lower part of the femoral neck gives a better estimate of the impact of gait and weight bearing than measuring the total femoral neck.

The relationship between lean body mass and bone mineral content in paediatric health and disease.

INTRODUCTION: The correct interpretation of DXA data is critical to the diagnosis and management of children with suspected bone disease. This study examines the various influences on bone mineral content (BMC), as measured by dual-energy X-ray absorptiometry (DXA). MATERIALS AND METHODS: Six hundred and forty-six healthy school children and forty-three children with chronic diseases, aged 5-18 years, had their lumbar spine and whole body measured using a Lunar DPX-L DXA scanner. RESULTS: Stepwise linear regression identified lean body mass (LBM) as the strongest single predictor of BMC in the lumbar spine and the total body. A significant gender difference was observed in the relationship between BMC and LBM with girls having significantly more bone per unit LBM from 9 years of age in the spine and 13 years of age in the total body. To investigate the relationship between LBM and BMC in children with chronic disease, a two-stage algorithm based upon calculation of Z scores from the normative data was applied. Stage 1 assessed LBM for height and stage 2 assessed BMC for LBM. Ten children with spinal muscular atrophy had a mean LBM for height Z score of -1.8(1.4) but a mean BMC for LBM Z score of 1.2(1.3) indicating their primary abnormality was reduced muscle mass (sarcopenia) with no evidence of osteopenia. In contrast, 21 children with osteogenesis imperfecta had a mean LBM for height Z score of 0.4(1.7) but a mean BMC for LBM Z score of -2.5(1.8) indicating normal LBM for size but significantly reduced BMC for LBM (i.e. osteopenia) confirming a primary bone abnormality. A third group consisting of 12 children with low trauma fractures demonstrated little evidence of sarcopenia [mean LBM for height Z score -1.1(2.1)] but significant osteopenia [mean BMC for LBM Z score -1.9(1.5)]. CONCLUSION: The results from this study demonstrate how the relationship between height and lean body mass, and lean body mass and bone mineral content can be a useful method of diagnosing osteoporosis in children and how the relationships can be used to identify if the primary abnormality is in muscle or bone.

Does hip strength analysis explain the lower incidence of hip fracture in the People's Republic of China?

To explore whether there are ethnic differences in calculated hip strength that might explain the low incidence of hip fracture in China, we used Lunar DPX 'beta' version of hip strength analysis (HAS) and hip axis length (HAL) programs to compare hip geometry, calculated strength and densitometric values from Chinese subjects in Shenyang to those of Caucasian subjects in Oslo and Leuven participating in the European Prospective Osteoporosis Study (EPOS). Subjects were 210 Chinese and 403 Caucasian men and women aged 53-77 years. Parameters investigated included bone mineral density (BMD), bone mineral content (BMC), bone area (BA), cross-sectional moment of inertia (CSMI) and section modulus (both indicating strength and rigidity of the femoral neck), HAL, neck length (NL), neck diameter, tensile stress (Tstress) and compressive stress (Cstress) (indicating the stress in the femoral neck at its weakest cross section arising from walking or a standard fall, respectively), safety factor (SF, indicating the resistance to fracture for forces generated during walking) and fall index (FI, indicating the resistance to fracture from force generated during a fall in the greater trochanter). The Chinese men and women were significantly shorter and lighter than their Caucasian counterparts (P<0.01) and had significantly lower BMD, BMC and BA of the femoral neck (P<0.01). After adjusting for BA, weight and height, there was no significant ethnic difference in either gender in BMC. CSMI and section modulus were significantly lower, and HAL, NL and neck diameter were significantly shorter in the Chinese men and women (P<0.01). These differences all remained after adjusting for weight and height. There were no significant differences in Tstress, Cstress, SF and FI between ethnic groups in either gender. Most of the parameters of calculated hip strength in the Chinese subjects were similar to or poorer than those in the Caucasian subjects. There was no evidence to indicate that Shenyang Chinese have superior BMD or BMC or better calculated hip strength. The short HAL and NL of the population, however, could be an independent factor contributing to the low incidence of hip fracture.