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Context: Low bone mass is a characteristic feature of the adult GH deficiency (GHD) syndrome, but recent dual-energy x-ray absorptiometry (DXA) studies in patients with GH-receptor and GHRH-receptor gene mutations suggest that the situation is more complex. Objective: The objective was to define bone areal and volumetric densities and morphometry in hypopituitary adults. Design: The study was a cross-sectional case-controlled study performed between 1999 and 2001. Setting: The study was undertaken at an endocrine tertiary referral center. Patients: Thirty patients with GHD, 24 with GH insufficiency (GHI) [peak GH, 3–7 μg/liter (9–21 mU/liter)], and 30 age- and sex-matched controls were included for study. Main Outcome Measures: DXA and peripheral quantitative computed tomography (pQCT) derived bone density and morphometry were measured. Results: No densitometric or morphometric abnormalities were detected in GHD patients who acquired their deficiency during adult life. GHD adults of childhood-onset (CO-GHD) showed decreased bone mineral density at the lumbar spine and hip on DXA. pQCT of the radius showed that CO-GHD patients have normal trabecular bone mineral density and only a 2% decrease in cortical density. Radial bone area was reduced 14.5%, cortical thickness 20%, and cortical cross-sectional area 23%, culminating in a reduction in cortical bone of 25%. The “apparent” low DXA bone density in CO-GHD adults therefore relates primarily to reduced cortical thickness and smaller bone area. DXA and pQCT data derived from adults with GHI revealed no evidence of densitometric or morphometric abnormalities. Conclusions: 1) Adult-onset GHD patients have normal bone density and size. 2) CO-GHD adults have marginally reduced cortical density but significantly reduced cortical bone as a result of reduced cortical thickness and bone size. 3) GHI has no measurable impact on the skeleton.

Reduced bone mineral density in adults treated with high-dose corticosteroids for childhood nephrotic syndrome. Background. Children with minimal change nephrotic syn- drome (MCNS) receive repeated courses of high dose oral pred- nisolone. No previous study has investigated the impact of this on final bone mineral density (BMD). Young adults previously reported in a large follow-up study of children with MCNS were invited to participate in a cross-sectional study. Areal BMD (aBMD) of the spine (L1-4), left femoral neck, and total left hip was measured using dual x-ray absorptiometry (DXA), and volumetric BMD (vBMD) of the distal radius was measured by pQCT. BMD results were compared with reference data pro- vided by the manufacturers of the densitometers. Methods. Thirty-four (24 male) of the original cohort of 62 participated in the study. The mean (SD) final height Z score of the cohort was -0.45 (0.92) (P = 0.007) and mean BMI Z score 1.62 (1.53) (P < 0.0001). Results. There was a highly significant reduction in distal ra- dial trabecular vBMD; the mean Z score was -0.95 (0.99) and T score -1.04 (1.01) (both P < 0.0001); however, there was no reduction in distal radial total vBMD, the mean Z score being 0.00 (0.95) and T score −0.08 (0.99), (P = 0.99 and 0.66, respec- tively). The aBMD of the lumbar spine and femoral neck also showed a reduction in T scores (−0.45 (1.27), P = 0.045 and −0.49 (0.86), P = 0.002, respectively), but not Z scores (−0.37 (1.28) and −0.15 (0.87), respectively, both P = NS). Total hip aBMD was not different from the control population. Conclusion. Adult survivors of childhood MCNS have a sig- nificant reduction in forearm trabecular vBMD, placing them at increased fracture risk at this site. Minimal change nephrotic syndrome (MCNS) is the most common glomerular disease of childhood, with an incidence of 2 to 7 per 100,000 child population. The dis- ease presents with heavy selective proteinuria of acute Ke yw ords: childhood minimal change nephrotic syndrome, corticos- teroids, bone mineral density, trabecular bone density, fracture risk.

Objectives: To determine the association between individual radiographic features of lumbar disc degeneration and bone mineral density (BMD) at the spine and hip. Methods: Subjects were recruited from a population register for a screening survey of vertebral osteoporosis. BMD was assessed at the spine and hip using dual energy x ray absorptiometry. Lateral spinal radiographs were evaluated for features of lumbar disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes, end plate sclerosis, and disc space narrowing. Linear regression was used to determine the association between each of these features and BMD at the spine and hip, with adjustments for age, body mass index, and levels of physical activity. Analyses were done separately in men and women. Results: 250 women and 256 men (mean age around 65 years) were studied. At the lumbar spine, after age adjustment there was an increase in BMD with increasing grade for all radiographic features of disc degeneration in both men and women. At the femoral neck, after age adjustment there was an increase in BMD with increasing osteophyte and end plate sclerosis grade though not disc space narrowing. Adjusting for body mass index and physical activity did not influence the strength of the associations. Conclusions: Radiographic features of lumbar disc degeneration are associated with an increase in BMD at the spine. Osteophytes and end plate sclerosis, but not disc space narrowing, are associated with an increase in BMD at the hip.

At birth the fetus will contain 30 g of calcium; during the third trimester the calcium accrual can be up to 340 mg/day. Therefore extremely high demands for calcium provision are placed upon the mother. This review aims to describe the adaptive mechanisms of the female skeleton to pregnancy and lactation which ensure optimal fetal skeletal mineralization without compromise to maternal bone strength. Descriptions of changes in bone status during pregnancy and lactation have been published. One of the only studies to measure pre-conception to post-weaning shows complete recovery of maternal spinal bone mineral density (BMD) and near recovery at the hip. Most studies describe trabecular bone loss but there is evidence for endosteal resorption of the metacarpals. In a retrospective study of former teenage mothers those who breastfed had similar hip BMD to nulliparous age-matched women; those who did not breastfeed had lower hip BMD. Maternal response to low calcium intake differs from that of normal calcium intake. Pregnancy and lactation do not have an overall negative effect upon the maternal skeleton. Retrospective evidence suggests no harmful effect of teenage pregnancy if the teenager breastfed but this requires further investigation. The effects of other situations for example low vitamin D status or low calcium intake require further research to inform future clinical practice. (authors)

The shape and appearance of vertebrae on lateral dual x-ray absorptiometry (DXA) scans were statistically modelled. The spine was modelled by a sequence of overlapping triplets of vertebrae, using Active Appearance Models (AAMs). To automate vertebral morphometry, the sequence of trained models was matched to previously unseen scans. The dataset includes a significant number of pathologies. A new dynamic ordering algorithm was assessed for the model fitting sequence, using the best quality of fit achieved by multiple sub-model candidates. The accuracy of the search was improved by dynamically imposing the best quality candidate first. The results confirm the feasibility of substantially automating vertebral morphometry measurements even with fractures or noisy images.

Mineralization of bone matrix depends on adequate supplies of not only vitamin D but also calcium and phosphorus and the presence of alkaline phosphatase and a normal pH. If there is deficiency of these substances for any reason or if there is severe acidosis, then mineralization of bone will be defective. This results in rickets in childhood and osteomalacia in adults. Radiographically, rickets is evident by bone deformity caused by softening and metaphyseal abnormalities where endochondral ossification is defective. The pathognomonic feature of osteomalacia is the Looser zone (pseudofracture). Many different diseases that result in rickets and osteomalacia (vitamin D deficiency, calcium deficiency, hypophosphatemia, hypophosphatasia, and acidemia) may have similar radiographic appearances. There may be distinguishing features (e.g., dense bones and extraskeletal ossification in X-linked hypophosphatemia (XLH); subperiosteal bone erosions in hyperparathyroidism secondary to vitamin D deficiency; arterial and soft tissue calcification related to phosphate retention in chronic kidney disease). Radiographs remain the most important imaging technique for the diagnosis of metabolic bone disease. Radionuclide scanning and other techniques (ultrasound, computed tomography, magnetic resonance imaging) have a role in localizing tumors that produce fibroblastic growth factor 23 and induce hypophosphatemic (“oncogenic”) osteomalacia; Ga-68 DOTATOC positron emission tomography/computed tomography is currently the optimum imaging technique for localizing such tumors. In some cases (two tumor sites demonstrated) venous hormone sampling may provide further localizing information. Multidetector computed tomography is well suited to demonstrate the intraspinal ossification, which is a rare, but recognized, complication of the enthesopathy associated with XLH osteomalacia.

Item does not contain fulltext As populations age osteoporosis becomes an increasingly important public health issue. Among osteoporotic fractures vertebral fractures are of particular relevance: they are the most common fractures, frequently are asymptomatic but have an important influence on prognosis and morbidity in the osteoporotic patient. Previous studies have suggested that these fractures are frequently not diagnosed and that radiologists miss a high percentage of osteoporotic, vertebral fractures present on lateral chest radiographs. The aims of this review are (1) to emphasize the important role that radiologists play in the accurate and clear reporting of vertebral fractures, (2) to provide guidance in assessing these fractures in radiographs, MRI and computed tomography imaging of the vertebral spine and (3) to sensitize the radiologist in diagnosing fractures in chest radiographs.

We have studied the differences between the peripheral and axial skeleton of pre-pubertal gymnasts and controls. We hypothesised that compared to controls, gymnasts would have larger and stronger radius and tibia diaphyses with greater bone mineral content and larger cross-sectional muscle area. At the distal metaphyseal sites of the radius and tibia, gymnasts would have greater bone cross-sectional area and total and trabecular volumetric bone mineral density (vBMD). Differences between the lumbar spine, total body and body composition in gymnasts versus controls were also studied. Peripheral quantitative computed tomography (pQCT) was used to measure bone geometry, density and muscle of the peripheral skeleton; dual energy X-ray absorptiometry (DXA) for total body and axial measurements. Eighty-six pre-pubertal children, 44 gymnasts (mean age 9.0 years, range 5.4-11.9 years) and 42 controls (mean age 8.8 years, range 5.6-11.9 years) were studied. Eighty-four children were Caucasian, one child was mixed race, one Chinese. Data were adjusted for age, sex and height. Differences in the effect size between sexes were also tested. At the 50% radius diaphysis gymnasts had larger bones (9.2%, p = 0.0054) with greater cortical area (8.2%, p = 0.022) and stress strain index (surrogate measure of bone strength) than controls (13.6%, p = 0.015). The effect size was different between males and females for cortical thickness (p = 0.03). At the 65% tibia diaphysis, gymnasts had greater cortical area (5.3%, p = 0.057) and thickness (6.2%, p = 0.068) than controls; consequently, bone strength was 5.4% higher (p = 0.14). There were no significant differences in cortical volumetric bone mineral density (vBMD) at the radius or tibia diaphysis between the groups. There was a difference in effect size for tibia muscle cross-sectional area between the sexes (p = 0.035). At the distal radius and tibia total and trabecular vBMD was greater (Total: radius 17%, p < 0.0001, tibia: 5.7%, p = 0.0053; trabecular: radius 21%, p < 0.0001, tibia 4.5%, p = 0.11). Bone size was not different in gymnasts compared to controls Lumbar spine BMC (12.3%, p = 0.0007), areal bone mineral density (aBMD) (9.1%, p = 0.0006) and bone mineral apparent density (BMAD) (7.6%, p = 0.0047) were greater in gymnasts but vertebral size was not significantly different. Likewise, total body BMD (3.5%, p = 0.0057) and BMC (4.78%, p = 0.085) were greater in gymnasts but there were no differences in skeletal size. These data suggest site-specific differences in how the pre-pubertal skeleton develops in response to the repetitive loading it experiences when participating in regular gymnastics. At diaphyseal sites these differences are predominantly in the bone and muscle geometry and not density. Conversely, at trabecular sites, the differences are increased density rather than geometry. In conclusion, the present study has demonstrated skeletal differences between gymnasts and controls. These differences appear to be site and sex specific.

Osteoporotic vertebral fracture is associated with increased morbidity and mortality. As a powerful predictor of future fracture risk, the identification of vertebral fracture helps target individuals who will benefit from anti-fracture therapy. The identification of vertebral fractures is problematic because (1) "normal" radiological appearances in the spine vary greatly both among and within individuals; (2) "normal" vertebrae may exhibit misleading radiological appearances due to radiographic projection error; and (3) "abnormal" appearances due to non-fracture deformities and normal variants are common, but can be difficult to differentiate from true vertebral fracture. Various methods of vertebral fracture definition have been proposed, but there is no agreed gold standard. Quantitative methods of vertebral fracture definition are objective and reproducible, but the major limitation of these methods is their inability to differentiate between vertebral deformity and vertebral fracture. The qualitative visual approach draws on the expertise of the reader, but it is a subjective method with poor interobserver agreement. Semiquantitative assessment of vertebral fracture is a standardized visual method, which is commonly applied in research studies as a surrogate gold standard. This method is more objective and reproducible than a purely qualitative approach, but can be difficult to apply. The established methods focus primarily on the identification of "reduced" or short vertebral height as an indication of vertebral fracture, but this is also a feature of some non-fracture deformities and normal variants. A modified visual approach known as algorithm-based qualitative assessment of vertebral fracture (ABQ) has recently been introduced, and this focuses on radiological evidence of change at the vertebral endplate as the primary indicator of fracture. Preliminary testing of the ABQ method has produced promising results, but the method requires further evaluation. Vertebral imaging by means of dual energy X-ray absorptiometry (DXA) scanner produces images of near-radiographic quality at a fraction of the radiation dose incurred by conventional radiography. There is growing interest in vertebral fracture assessment using this technique as a means of assessing a patient's fracture risk. Given the increasing availability of new technology and the importance of accurate diagnosis of vertebral fracture, there is an urgent need for better awareness of and training in the definition of vertebral fracture. Methods of vertebral fracture definition should be validated by testing the association with clinical outcomes of vertebral fracture, in particular the prediction of incident fractures.

To characterize the occurrence of radiographic features of lumbar disc degeneration including the presence of osteophytes, endplate sclerosis, and disc space narrowing and to determine their relationship with self-reported back pain.Subjects aged 50 years and over were recruited from a primary care based community health index in Aberdeen, UK. Subjects were invited to complete an interviewer administered questionnaire and to have lateral spinal radiographs performed. The questionnaire included questions concerning the occurrence of back pain, both ever and in the past year. The inter-vertebral disc spaces (L1/2 to L4/5) were evaluated for the presence and severity of anterior osteophytes, endplate sclerosis, and disc space narrowing using a semi-quantitative score (grade 0-3). Logistic regression was used to determine the association between these individual radiographic features of lumbar disc degeneration (using for each feature, the most severely affected vertebra) and back pain, with adjustments made for age and gender.There were 286 men (mean age 65.3 years), and 299 women (mean age 65.2 years) with spinal radiographs. Osteophytes were the most frequent radiographic feature. Osteophytes and endplate sclerosis were more frequent in men than women, but there was no gender difference in the frequency of disc space narrowing. All radiographic features increased in frequency with age; for osteophytes this was true only after excluding mild (grade 1) osteophytes. Compared to those without, those with disc space narrowing were more likely to report back pain both ever, [odds ratio (OR) = 2.1; 95% confidence interval (CI): 1.5 to 3.0] and in the past year (OR = 1.7) with the strength of the association increasing with increasing severity of narrowing. Endplate sclerosis was not linked with back pain although moderate (grade 2) sclerosis was associated with back pain, both ever and in the past year. Compared to those without, or those with mild osteophytes, those with more severe osteophytes (grade1) were more likely to report back pain ever (OR = 1.7; 95% CI: 1.2 to 2.5).These data highlight the frequent occurrence, and the increase in frequency with age, of the individual radiographic features of lumbar disc degeneration in population samples of men and women. Disc space narrowing appeared more strongly associated with back pain than the other radiographic features.

The current biochemical definition of severe GH deficiency (stimulated peak GH < 3 micro g/liter) provides good separation of GH-deficient (GHD) adults from normal subjects, although it may not account for all patients with impaired GH secretion. The vast majority of normal subjects display a peak GH level in excess of 7 micro g/liter in response to the insulin tolerance test. Using a peak GH response of 7 micro g/liter as an arbitrary upper limit, we investigated the effects of partial GH deficiency (GH insufficiency, GHI; peak GH response of 3-7 micro g/liter) on the body composition of hypopituitary adults. GHD adults (n = 30, peak GH < 3 micro g/liter) were of shorter stature than the controls. Body mass index was not significantly increased, but waist/hip ratio (0.885 vs. 0.818, P = 0.001) and skinfold thickness (78.2 vs. 59.6 mm, P = 0.003) were greater than control subjects. Bioimpedance analysis revealed these patients to have reduced lean body mass (LBM) (44.4 vs. 51.2 kg, P = 0.023) and increased fat mass (FM) (25.7 vs. 18.4 kg, P = 0.039). Dual-energy x-ray absorptiometry (DXA) analysis of body composition confirmed reduced LBM (43.6 vs. 50.6 kg, P = 0.010) and increased FM (26.0 vs. 19.2 kg, P = 0.015). The excess FM was observed to be primarily truncal in distribution. Similarly, GHI adults were of shorter stature but with increased waist/hip ratio (0.871 vs. 0.818, P = 0.006) and skinfold thickness (80.8 vs. 59.6 mm, P = 0.003), compared with controls. Bioimpedance analysis revealed a reduction in LBM (44.9 vs. 51.2 kg, P = 0.020). DXA studies confirmed the reduced LBM (45.0 vs. 50.6 kg, P = 0.041) and additionally noted an increase in percent FM (32.9 vs. 27.4%, P = 0.019). All measures of body composition in the GHI patients were intermediate between those of the controls and GHD patients. Serum leptin levels were significantly elevated in both the GHD (41.5 vs. 20.7 ng/ml, P = 0.009) and GHI (36.7 vs. 20.7 ng/ml, P = 0.022) adults, compared with healthy controls. The excess FM observed using DXA in the GHD and GHI adults equated to 6.5 kg (8%) and 3.5 kg (5.5%), respectively, relative to healthy controls. In summary, we have shown that adults with GHI have abnormalities of body composition characteristic of GHD. The degree of abnormality of body composition lies between that of healthy subjects and GHD adults and correlates with the IGF-I level. Any future trials of GH replacement in patients with GHI must await further studies to establish the exact impact of this relative deficiency on the broad spectrum of biological end points influenced by GH status.

The high precision and stable calibration of dual X-ray absorptiometry (DXA) scanners have led to their widespread use in longitudinal studies for research and the follow-up of individual patients who are receiving treatment for osteoporosis. However, difficulties in maintaining the continuity of the bone mineral density (BMD) calibration scale can arise when an old DXA system is replaced by a newer model. We report the results of an in vivo cross-calibration study performed when a GE-Lunar Prodigy fan-beam system replaced a DPX-L pencil-beam scanner. Lumbar spine and hip DXA scans were performed in 133 patients (104 female, 29 male) attending long-term BMD monitoring. On average, lumbar spine BMD measurements on the two systems agreed closely, with Prodigy values 1% lower than those on the DPX-L. However, after allowing for this difference, the root mean square error (RMSE) of 0.037 g/cm2 was larger than in previous cross-calibration studies reported in the literature, and was 3 times the value expected from the precision of the BMD measurements. Mean femoral neck BMD also agreed closely between the two systems, although for Prodigy, the spread of measurements was 10% smaller than that for the DPX-L. For the trochanter and Ward's triangle regions, mean BMD was 4% and 6% lower, respectively, on the Prodigy system, and the results were affected by a similar compression of the range of values. RMSE values were 0.037 g/cm2, 0.044 g/cm2, and 0.044 g/cm2, respectively, for the femoral neck, trochanter, and Ward's triangle sites. When the high value of the RMSE was investigated, it was found that for lumbar spine BMD, patient body weight and the difference between the two systems in the percentage fat reported in the soft tissue reference region explained 40% of the variance. This enabled equations to be developed that significantly improved the agreement between scans performed on the two systems. Smaller improvements were obtained for the femur BMD measurements.

Background: Severely disabled children with cerebral palsy (CP) are prone to low trauma fractures, which are associated with reduced bone mineral density. Aims: To determine whether participation in 50% longer periods of standing (in either upright or semi-prone standing frames) would lead to an increase in the vertebral and proximal tibial volumetric trabecular bone mineral density (vTBMD) of non-ambulant children with CP. Methods: A heterogeneous group of 26 pre-pubertal children with CP (14 boys, 12 girls; age 4.3–10.8 years) participated in this randomised controlled trial. Subjects were matched into pairs using baseline vertebral vTBMD standard deviation scores. Children within the pairs were randomly allocated to either intervention (50% increase in the regular standing duration) or control (no increase in the regular standing duration) groups. Pre- and post-trial vertebral and proximal tibial vTBMD was measured by quantitative computed tomography (QCT). Results: The median standing duration was 80.5% (9.5–102%) and 140.6% (108.7–152.2%) of the baseline standing duration in the control group and intervention group respectively. The mean vertebral vTBMD in the intervention group showed an increase of 8.16 mg/cm3 representing a 6% mean increase in vertebral vTBMD. No change was observed in the mean proximal tibial vTBMD. Conclusion: A longer period of standing in non-ambulant children with CP improves vertebral but not proximal tibial vTBMD. Such an intervention might reduce the risk of vertebral fractures but is unlikely to reduce the risk of lower limb fractures in children with CP.

Poor nutritional status adversely affects long term survival of patients with cystic fibrosis (CF).1 Body composition measured by dual energy x ray absorptiometry (DXA) has been shown to correlate well with other established techniques such as bioelectric impedance analysis and total body potassium estimation.2 This study was designed to compare the whole body and regional bone mineral density of children with CF with that of controls, the results of which have been reported previously.3 Here, we present the results of post hoc comparison of DXA measured whole body lean body …

Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk. Introduction: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself. Methods: We studied 677 women and men with osteoporosis, 28 - 88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score 2.5 and 3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry. Results: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health—including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age—the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI. 0.93, 6.23). Conclusions: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk. J Bone Miner Res 2003;18:1254 -1260

BACKGROUND: No study has compared the bone histopathologic findings in renal transplant patients receiving cyclosporine A (CsA) monotherapy with those in patients receiving a non-CsA regimen. The aim of this study was to compare bone densitometry and histomorphometry findings in patients receiving CsA monotherapy versus those receiving azathioprine + prednisolone dual therapy. METHODS: A bone biopsy and densitometry were performed in 13 patients receiving CsA monotherapy and 12 patients receiving azathioprine + prednisolone, who had been on these regimens since the time of transplantation. Fourteen men and 11 women, age 51+/-12 years, with 140+/-75 months since transplantation, were included. RESULTS: A low bone mineral density (BMD) was observed in patients on both immunosuppressive schemes-most notably at the distal radius and less significantly at the lumbar spine. No significant differences in BMD were observed between immunosuppressive groups. Histopathologic analysis of the group as a whole revealed mixed uremic bone disease in 42%, adynamic bone in 29%, hyperparathyroid disease in 17%, and normal bone in 12%. Patients showed a slight increase in osteoclast number and function, decreased osteoblast number and function, and retardation of dynamic parameters. No differences in histopathologic diagnosis or histomorphometric findings were observed between the immunosuppressive therapy groups. In addition to the immunosuppressive drugs, male gender and old age negatively affected bone mass. CONCLUSIONS: Both prednisolone and CsA were associated with slight osteoclast stimulation and osteoblast suppression and marked retardation of mineral apposition and bone formation rates. Both drugs were also associated with reduced BMD at the axial and appendicular skeleton, even though a nonsignificant trend to a better-preserved lumbar spine BMD was observed in the CsA group.

Due to the introduction of new therapeutic regimen aimed at increasing and maintaining bone mass, bone densitometry in children has gained interest. As in all new fields of medicine we expect the interest in bone densitometry in children to increase in the coming years. Children pose a unique problem for those involved in the field of bone densitometry, because as time progresses the measured subject changes in shape and volume. It is therefore of importance that radiologists and clinicians gain insight in the available techniques. It is also important to keep in mind that all bone densitometry techniques have been exclusively designed, developed and validated for use in an adult population. In this article we give an overview of the available techniques and discuss the specific problems that can be expected when these techniques are used in children. In the discussion section general problems regarding bone densitometry in children are presented.

Statistical models of shape and appearance are powerful tools for interpreting medical and other images. However there can remain problems with under-trained models being too constrained. We have combined a global model with a sequence of partially overlapping sub-models, in a manner that exploits all the statistical information, whilst mitigating the under-training problem. Instead of applying one global model, we use a global model to apply iteratively-updated soft constraints on a sequence of sub-models. These sub-models may also partially overlap, and thus previously fit sub-models can also impose soft constraints on the next iteration. The algorithm has been applied to dual x-ray absorptiometry scans of the spine in order to automate vertebral morphometry measurements, using overlapping triplets of vertebrae as the sub-models, together with a global model of the entire spine. Combining a global model in this way with a sequence of sub-models gives substantially better results than using the former alone.

Background. Bone loss is an important problem in renal transplantation recipients. The role of sex hormones in this setting has not been previously addressed. The objective was to investigate whether sex hormone status is associated with bone mass loss in renal transplant recipients. Methods. Thirty patients (16 men and 14 women, of which eight were post-menopausal) were studied by bone densitometry and bone biopsy. In women, serum oestradiol levels and menopausal status were determined; in men, serum testosterone levels were assessed. Results. Mean age was 48 ± 11 years. Time on dialysis was 13 ± 17 months, and time since transplantation was 125 ± 67 months. Thirteen patients were on cyclosporine A (CsA) monotherapy, 12 on azathioprine plus prednisolone (PRED) dual therapy, and five on CsA, azathioprine and PRED triple therapy. In men, serum testosterone levels were 19.7 ± 6.8 nmol/l (mean ± SD). In pre-menopausal women, oestradiol serum levels were 209(128-289) pmol/l (median (percentiles 25-75%)), and in post-menopausal women 93(54-299) pmol/l (non-significant). Univariate analysis in women demonstrated that serum oestradiol levels were positively correlated with Z scores of osteoblast surface (r = 0.70, P = 0.005), osteoid surface (r = 0.75, P = 0.002) and trabecular wall thickness (r = 0.68, P = 0.008). In men, a weak correlation was seen between serum testosterone levels and the cumulative dose of PRED (r = -0.52, P = 0.06). In the multivariate analysis, two models of multiple regression were employed (one for women and one for men), considering the densitometric and histomorphometric variables (Z scores) as dependent variables. Serum testosterone in men did not predict any of the densitometric nor histomorphometric variables analysed, while serum oestradiol in women was an independent predictor for the osteoblast surface (r = 0.81, P = 0.003), osteoid surface (r = 0.82, P = 0.009) and trabecular wall thickness (r = 0.54, P= 0.05). Conclusions. In female renal transplant recipients, serum oestradiol levels independently predict the bone status, while in men, factors other than testosterone seem to influence bone loss. Our results give rise to the hypothesis that sex hormone replacement therapy may play a role in prevention and or treatment of the bone loss in women following renal transplantation.

BACKGROUND Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. The aim of this study was to assess the effect of intravenous pamidronate on BMD in these subjects. METHODS Patients were invited to participate if they had a BMD Z score of –2 or less in the lumbar spine, proximal femur, or distal forearm. Patients were randomised to receive either 30 mg intravenous pamidronate every 3 months + 1 g calcium daily (pamidronate group) or 1 g calcium daily (control group). All pancreatic insufficient patients were prescribed oral vitamin D supplements. RESULTS After 6 months of treatment the pamidronate group (n=13) showed a significant increase in absolute BMD compared with the control group (n=15) in the lumbar spine (mean difference 5.8% (CI 2.7% to 8.9%)) and total hip (mean difference 3.0% (CI 0.3% to 5.6%)). However, the pamidronate group showed a reduction in BMD compared with the control group in the distal forearm (mean difference –1.7% (CI –3.7% to 0.3%)). The use of pamidronate was associated with a high incidence of bone pain in non-corticosteroid treated individuals. CONCLUSION Intravenous pamidronate increases axial BMD in adults with cystic fibrosis, but the high incidence of bone pain associated with this treatment might limit its use.

When the World Health Organization (WHO) guidelines for the definition of osteoporosis in postmenopausal women were identified similar proposals were not developed for men as there was insufficient evidence about the relationship between bone density and fracture in men. We have therefore examined the relationship between bone density and vertebral fracture in men and women attending for assessment of possible osteoporosis. Two hundred and sixty-four women (age 64 [SD 10] years) and 37 men (age 55 [10] years) were studied. Bone density was measured in the lumbar spine and femoral neck by dual-energy X-ray absorptiometry and expressed both as bone mineral density (BMD; g/cm2) and as T-scores. In both sexes there was a sigmoid relationship between the cumulative frequency of vertebral fracture and bone density at both sites. There was a linear relationship between the log odds of fracture and bone mass for both sexes and both sites (r= 0.97–0.99; p

To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n = 14) or treatment group (n = 16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 microg/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, -0.8 +/- 0.8 versus -0.6 +/- 0.9; treatment, -1.0 +/- 1.0 versus -1.0 +/- 1.1). However, a significant increase (P < 0.05) was found at the lumbar spine in both groups (control, 0.1 +/- 1.6 versus 0.4 +/- 1.6; treatment, -0.1 +/- 1.5 versus 0.3 +/- 1.5) and only in the treatment group at the femoral neck (control, -0.9 +/- 1.0 versus -0.8 +/- 1.0; treatment, -0.5 +/- 0.9 versus -0.3 +/- 1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (-2.2 +/- 6.1 versus -3.4 +/- 3.9), osteoid surface (-2.3 +/- 3.5 versus -3.1 +/- 3.9), and osteoclast surface (0.2 +/- 5.0 versus -1.3 +/- 3.3). Consequently, there was a significant reduction (P < 0.05) in mineralizing surface (-9.8 +/- 11.0 versus -15.8 +/- 12.3) and appositional rate (-5.8 +/- 2.7 versus -7.6 +/- 2.2). In the treatment group, a significant reduction (P < 0.05) in osteoclast surface was observed at the end of the study (3.9 +/- 6.8 versus -1.2 +/- 4.1), and although a trend to reduce osteoblast surface (-2.5 +/- 2.6 versus -3.2 +/- 5.7) and osteoid surface (-2.1 +/- 2.5 versus -3.2 +/- 2.8) was also found, patients maintained approximately the same level of wall thickness (-5.2 +/- 5.3 versus -5.3 +/- 3.3) and bone volume (-2.7 +/- 1.8 versus -2.5 +/- 1.7). However, there was no improvement in mineralizing surface (-4.2 +/- 2.9 versus -10.4 +/- 3.6) or appositional rate (-5.8 +/- 3.1 versus -8.1 +/- 2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.

Renal bone disease: Radiological investigation. The bone disease associated with chronic renal impairment is complex and multifactorial, and has changed over past decades. Whereas originally features of vitamin D deficiency (rickets/osteomalacia) and secondary hyperparathroidism (erosions, osteosclerosis, brown cysts) predominated, improvement in management and therapy have resulted in such readiographic features being present in a minority of patients. Metastatic calcification and "adynamic" bone develop as a complication of disease (phosphate retention) and treatment (phosphate binders). New complications (amyloid deposition, noninfective spondyloarthropathy, osteonecrosis) are now seen complicating long-term hemodialysis and/or renal transplantation. Radiographs remain the most important imaging technique, but occasionally other imaging and quantitative techniques (CT, MRI, bone densitometry) are relevant to diagnosis and management.

Patients with cystic fibrosis have several risk factors for the development of low bone mineral density (BMD). To identify the prevalence and clinical correlates of low BMD in adult patients with cystic fibrosis, densitometry was performed in 151 patients (83 men) aged 15-52 years.BMD was measured in the lumbar spine (L1-4) using dual energy x ray absorptiometry (DXA) and quantitative computed tomography (QCT). It was also measured in the proximal femur (total hip and femoral neck) using DXA, and in the distal and ultra distal forearm using single energy x ray absorptiometry (SXA). Biochemical markers of bone turnover, vitamin D levels, parathyroid hormone levels, and a variety of anthropometric variables were also assessed.The mean (SD) BMD Z score was -0.73 (0.85) in the distal forearm, -0.31 (0.92) in the ultra distal forearm, -1.21 (1. 18) in the lumbar spine using DXA, -0.56 (1.36) in the lumbar spine using QCT, -1.25 (1.30) in the femoral neck, and -1.01 (1.14) in the total hip. 34% of patients had a BMD Z score of -2 or less at one or more skeletal sites. Body mass index (0.527, p = 0.01), percentage predicted forced expiratory volume in one second (0.388, p = 0.01), and physical activity (0.249, p = 0.05) were positively related to the mean BMD Z score. Levels of C reactive protein (-0.328, p = 0. 01), parathyroid hormone (-0.311, p = 0.01) and biochemical markers of bone turnover (osteocalcin -0.261 and bone specific alkaline phosphatase -0.249, p = 0.05) were negatively related to the mean BMD Z score. Vitamin D insufficiency (25-hydroxyvitamin D15 ng/ml) was prevalent (53/139 patients, 38%) despite supplementation with 900 IU vitamin D per day.Low bone density is prevalent in adult patients with cystic fibrosis. Current levels of vitamin D supplementation appear to be inadequate.

Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.

Osteoporosis is prevalent in adults with CF Longitudinal data have not been collected and so the natural history is unknown. The aetiology is not known. There are no published randomized controlled trials evaluating treatments for osteoporosis in CF patients.

The Singh Index, which describes trabecular patterns in the proximal femur, has been used as a predictor for hip fractures and as an indicator of osteopenia. Evidence suggests that its contribution to the assessment of hip fracture risk is in its description of the structural properties of the femur. However, subjectivity in its determination may limit its practical value. In this study, we have used computer texture analysis to characterize the textural changes in trabecular bone which occur in osteoporosis. Texture analysis of the proximal femur was used to rank radiographs of 25 cadaver femora by Singh grading. These rankings were compared with those performed by two experienced radiologists. The computer method performed better than the least consistent individual radiologist, but not as well as the two radiologists in combination. The method required no radiologist's time after the system had been 'trained' from a set of example radiographs. The method has potential for use in large studies in which speed and consistency of measurement are important.

The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50–80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20–100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between-centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2–4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthro-pometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.

The authors describe how active shape models (ASMs) have been used to accurately and robustly locate vertebrae in lateral dual energy X-ray absorptiometry (DXA) images of the spine. DXA images are of low spatial resolution, and contain significant random and structural noise, providing a difficult challenge for object location methods. All vertebrae in the image were searched for simultaneously, improving robustness in location of individual vertebrae by making use of constraints on shape provided by the position of other vertebrae. They show that the use of ASMs with minimal user interaction allows accuracy to be obtained which is as good as that achievable by human operators using a standard manual method.

The spinal bone mineral density (SBMD) and calcaneal broadband ultrasound attenuation (BUA) was measured in 27 children with cerebral palsy. They were categorised into four mobility groups: mobile with an abnormal gait, mobile with assistance, non-mobile but weight bearing, non-mobile or weight bearing. Mean SD scores for BUA and SBMD differed among mobility groups (analysis of variance, p < 0.001 and p = 0.078, respectively).

Bone density measurements by dual X-ray absorptiometry (DXA) of the spine can now be made precisely, but there is no uniformity in reporting results and in presenting reference data. A European Union Concerted Action therefore devised a uniform procedure for cross-calibrating and standardizing instruments, using the European spine phantom (ESP) prototype. This phantom differs in a number of respects from the final version of the ESP. Eighteen centers in nine countries obtained 1619 records (1035 women) from Caucasian subjects, aged 20–80 years, drawn from normal populations. The DXA machines used were made by the Hologic, Lunar, and Norland companies. Highly statistically significant differences were evident between populations, both in apparent rates of bone loss with age and in the spread of values about the age-adjusted means. There were small residual differences in the results obtained with the three machine brands which could have been due to the relatively large between-center population differences we observed. The alternative or additional explanation that they were attributable, in part, to the design differences between the ESP prototype and the definitive ESP, which became available after this study was completed, was shown to be a valid possibility. Results from postmenopausal women reported in relation to the years that have elapsed since menopause showed reduced population variance when compared with conventional reporting in relation to age. After cross-calibration, the center with the highest age-adjusted normal density value averaged 23% more than the center with the lowest. It is therefore crucially important to select appropriate reference data in clinical and epidemiological studies. These results provide a basis for designing protocols for multicenter studies using currently installed densitometers. ( Bone 17:247–254; 1995 )

Summary OBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS Twenty-two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency. MEASUREMENTS Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD. RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change −0.009g/cm2, P=0.01), forearm Integral BMD (SPA: median change −0.016g/cm2, P=0.03), lumbar spine BMD (DXA: median change −0.022g/cm2; P=0.003) and femoral neck BMD (DXA: median change −0.029g/cm2, P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change −0.035 g/cm2, P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass.

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic "vertebrae" of different densities made of stimulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is ns yet no agreement on normal ranges and how to cross-calibrate between different machines. In tits Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bins due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm 2 ) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean walues at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout

Summary OBJECTIVE Growth hormone replacement of adults with childhood onset GH deficiency results In an Increase In bone mineral density (BMD) after 6-12 months of OH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to Investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn. DESIGN BMD was measured 13 ± 1 (mean ± SE, range 11-16) months after discontinuation of OH replacement. PATIENTS Ten adults, age 23·;2 ±1·;4 (range 18·8-32·4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of OH replacement on BMD. MEASUREMENTS Forearm cortical bone mineral content (BMC) was measured using single-photon absorptlometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal rites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography. RESULTS Forearm cortical BMC was significantly greater than that measured at the time of discontinuation of OH (1·48 ±0·04 vs 1·44 ± 0·05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of OH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH. CONCLUSION After discontinuation of OH replacement the further increase In forearm cortical bone mineral content without a significant Increase In forearm bone width suggests that the Increase In cortical bone mineral content Is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass lo reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to Increase bone turnover has been withdrawn.

Morphological granulometry has been shown to be effective in a range of texture analysis applications. We describe an extension to the standard approach which allows truly local properties of the texture to be measured at each pixel. The result is a set of texture features which are analogous to those which could be measured for individual texture primitives, if they could be isolated. We demonstrate the ability of the method to estimate the known properties of the primitives in synthetic texture images and show that reasonably accurate results can be obtained over a range of practically useful conditions. We describe the application of the method to a difficult texture analysis problem - grading the degree of osteoporosis in radiographs of the femoral neck - and show that better results can be obtained than with either Laws' texture features or conventional granulometry.

Discussion: This study showed that there is a relatively constant rate of decrease in BMD along the radius, from the 1/3rd to about the 10% locations. Prior studies have generally reported BMD at either the 1/3rd or the ultra-distal (UD) sites. It would be interesting to examine whether the axial profile of BMD at the radius might be relevant in terms of estimating the risk of radius fracture, as compared with using the 1/3rd or UD sites alone. This study also shows that ultrasound is an excellent proxy for BMD, with a correlation coefficient of r5 0.9. The data also indicates that ultrasonic assessment of BMD at the radius is very robust with respect to variations in geometry (radial width in the 16 forearms was observed to increase almost 30% from the 1/3rd to the 10% locations) as well as to changes in percentages of trabecular bone content (trabecular bone increases from 1% to 20% from the 1/3rd to the 10% locations).

Background Fat and lean mass have important implications for health and physical functioning. Studies have reported associations between low socioeconomic position (SEP) and high body mass index (BMI) in adulthood, but few have examined associations with fat and lean mass which BMI does not completely distinguish. We examined the associations between multiple indicators of SEP across life and objective measures of fat and lean mass in later adulthood. Methods Data were from 1350 men and women in England, Scotland and Wales participating in the MRC National Survey of Health and Development who underwent dual-energy X-ray absorptiometry scans at age 60–64 years and had valid data for all indicators of SEP were included in analyses. Whole body fat and appendicular lean mass were ascertained and, to account for differences in height across SEP groups, height-adjusted indices were created. Associations of prospectively ascertained childhood SEP (paternal occupational class at 4 years), educational attainment (at 26 years) and adult SEP (household income at 60–64 years) with these outcomes were examined using the slope index of inequality (SII). Since high fat mass may increase muscle loading and lead to higher lean mass, associations with lean mass were adjusted for fat mass. Results Low SEP was consistently associated with high fat mass index: childhood SEP (mean difference in fat mass index comparing the lowest with the highest SEP (SII) in males: 0.92kg/m 1.2 , 95% CI –0.04 to 1.89; females: 2.49, 1.17 to 3.82), education (males: 1.61, 0.69 to 2.53; females: 2.20, 0.88 to 3.53), and adult SEP (males: 1.42, 0.47 to 2.38; females: 2.20, 0.88 to 3.53). In males, after adjustment for fat mass childhood SEP (0.16kg/m 2 , –0.07 to 0.38) and education (0.09, –0.13 to 0.30) were not associated with lean mass index, however, low adult SEP was associated with low lean mass index (–0.21, –0.44 to 0.01). Low SEP was consistently associated with low lean mass index in females after adjustment for fat mass: childhood SEP (–0.24, –0.42 to –0.07), education (–0.36, –0.55 to –0.17) and adult SEP (–0.20, –0.38, –0.03). Conclusion Low SEP across life was associated with high fat mass in early old age. In contrast, low SEP in adulthood in males and across life in females was associated with low lean mass (after adjustment for fat mass). Although further research is required to better understand the pathways underlying these associations, the socioeconomic patterning of these measures is likely to have important public health implications.

OBJECTIVE To investigate the prevalence of radiographie bone and joint abnormalities in the feet of diabetic patients. RESEARCH DESIGN AND METHODS In a blinded randomized study, 94 diabetic patients with peripheral neuropathy (54 with a history of foot ulcers) and 43 non-neuropathic patients were drawn at random from the data base of a large university diabetes clinic in the United Kingdom. Fifty nondiabetic age-matched control subjects also were studied. Lateral and dorsi-plantar weight-bearing plain radiographs of the foot and ankle were taken by a single radiographer. Abnormalities in the bones and joints were determined according to a structured reading of the radiographs by a single radiologist. RESULTS Diabetes per se resulted in no excess of bony abnormality. Diabetic patients with neuropathy had significantly more radiographic abnormalities of the bones and joints than non-neuropathic and age-matched nondiabetic control subjects. However, except for periosteal reaction, this was predominantly caused by an excess of abnormalities in diabetic patients with a history of foot ulceration. Traumatic fractures (most previously unrecognized) were found in 12 (22%) of the 54 neuropathic patients with previous foot ulceration, and 9 (16%) patients who had experienced foot ulcers exhibited characteristic Charcot changes. CONCLUSIONS These results suggest that bony abnormalities, particularly Charcot changes and traumatic fractures, are more frequent than previously recognized in neuropathic diabetic patients, especially in those with a history of foot ulceration. Early recognition of bony abnormality and appropriate treatment may prevent progression of foot deformity and thereby reduce the morbidity caused by ulceration or reulceration.

We have demonstrated previously that adults with isolated GH deficiency of childhood onset have a reduced bone mineral density (BMD) of vertebral trabecular bone [quantitative computed tomography (QCT): median Z score -1.3, P < 0.01, n = 12] and of cortical bone in the forearm [single photon absorptiometry (SPA): median Z score -2.9, P = 0.001, n = 7]. We have now examined BMD in 26 patients (13 men, 13 women), aged between 23.6 and 59.5 (mean 42.4) yr, with adult onset GH deficiency, defined as a GH response of less than 5 micrograms/L to provocative testing, of at least two years duration. BMD was measured using QCT for vertebral trabecular bone, dual energy x-ray absorptiometry (DXA) in the lumbar spine and femoral neck, and SPA in the forearm. There was a highly significant reduction in QCT (median Z score -1.07, P < 0.00005), in DXA of the lumbar spine (median Z score -0.76, P = 0.0001) and in SPA of the forearm (median Z score -0.86, P = 0.0001) but not in DXA of the femoral neck (median Z score -0.38, P = 0.35). There were no significant differences in Z scores between those patients with isolated GH deficiency and those with GH and gonadotrophin deficiency. There was a significant positive correlation between age at which BMD was measured and Z score (the older the patient, the higher the Z score) for QCT (r = 0.38, P < 0.05) and SPA (r = 0.48, P < 0.01) with a trend to a positive correlation for DXA of the lumbar spine and femoral neck. Patients were grouped according to estimated duration of GH deficiency (less than 5 yr, n = 7; 5-10 yr, n = 10; greater than 10 yr, n = 9). These groups did not show a significant difference in BMD at any site. We conclude that patients with adult onset GH deficiency (isolated or in conjunction with other pituitary hormone deficiencies) have a reduced BMD. Age at development of GH deficiency may be more important than duration of GH deficiency in determining the degree of reduction in bone mass. The impact of GH treatment on BMD in adults with adult onset GH deficiency requires investigation.

Background The composition of the body (amount of fat and lean mass) has important implications for health and physical functioning and may be influenced by factors in early life. Studies have reported positive associations between birth weight, an indicator of prenatal growth, and lean mass in adolescence and adulthood. However, inconsistent findings have been reported between birth weight and fat mass, and few studies have been conducted in later adulthood. Objectives To examine the associations of birth weight with fat and lean mass measured in later adulthood (60–64 years); to examine whether any associations found are independent of potential confounders/mediators (childhood socioeconomic circumstances, indicated by father9s occupational class at age 4, and adult height). Design Birth cohort study. Setting England, Scotland and Wales. Participants A subsample of 531 men and women from the Medical Research Council (MRC) National Survey of Health and Development, followed up since birth in March 1946 who attended two regional clinics (from a total of 6) where data collection was completed between 2008 and 2011. Main outcome measures Whole body fat and lean mass (excluding the head), measured using dual energy X-ray absorptiometry at 60–64 years. Results Birth weight was positively associated with lean mass in both sexes, with a modest increase in lean mass per 1 kg increase in birth weight of 1.71 kg in men (95% CI: 0.24 to 3.17) and 2.42 kg in women (95% CI: 1.07 to 3.76). These associations remained after adjustment for childhood socioeconomic circumstances in both sexes, but were largely attenuated after adjustment for adult height in men (β per kg increase in birth weight: 0.35 kg; 95% CI: −0.98 to 1.68), but not women (β: 1.29 kg; 95% CI: 0.12 to 2.45). Birth weight was not associated with fat mass in either sex, before or after adjustments. Conclusions These findings suggest that prenatal growth affects lean mass, but not fat mass, in later adulthood. A high birth weight may reflect a greater number of muscle fibres attained at birth, which then track into adulthood. Attenuation of effect after adjustment for height suggests that this association is largely driven by increased body size in men, and additional factors in women. Optimal growth before birth may protect against the detrimental impacts of low muscle mass in later life.

Introduction The health of the post war ‘baby boomers’ will dominate the health and social care systems for decades to come. We know little about the prevalence of clinical problems in these postwar birth cohorts. Objectives To describe the prevalence of significant clinical problems at 60–64 years in the Medical Research Council (MRC) National Survey of Heath and Development; to examine whether these problems cluster in the same individuals and the extent of undiagnosed disease. Design setting and participants Between 60–64 years, participants in a national British birth cohort study completed postal questionnaires (2467/2866) and, by March 2011, 2243/2767 had either visited one of six UK clinical research facilities (n=1700) or had been visited by the research nurse at home (n=543). Participants underwent a physical examination and fasting blood and urine samples were collected. Self reported problems were compared with clinical problems revealed by blood and urine tests, electrocardiogram (ECG) results, Bone Density Scan ( DXA ), and General Practitioner (GP) and hospital records. Outcome measures The proportion with cardiovascular diseases (CVD eg, hypertension, myocardial infarction, stroke, arrhythmia), endocrine diseases (diabetes, thyroid disease), kidney disease, impaired liver function, and reduced bone mineral density (BMD; osteoporosis and osteopenia as defined by the World Health Organisation). Results Preliminary results based on about 60% of the sample show a high prevalence of CVD risk (46% hypertension, 36% raised cholesterol) and although only 2% had arrhythmia and 2% had already had a myocardial infarct, 14% had been in hospital for CVD investigative tests in the last 10 years. In endocrine disease, 9% have diabetes, 15% impaired fasting glucose, 2% have overt thyroid dysfunction and 9% any thyroid dysfunction. Around 4% have estimated glomerular filtration rate 2 and 28% impaired liver function (γ-glutamyl transferase (GGT)≥51IU/l (men) and ≥33IU/l (women). In regards to bone health, 13% have osteoporosis (T score ≤ −2.5) and 59% osteopenia (T score≤ −1.0. With data on the full sample (June 2011), we will assess how nationally representative this sample remains, define the level of undiagnosed disease, and identify individuals who have several of these clinical problems and those who have none, and relate these to lifetime risk factor burden. Conclusion This cohort of the first of the UK baby boomers, studied just at statutory retirement age, has many medical problems, which will pose a considerable load on health and social services in the coming years, particularly in this time of economic restraint.