Comparative study of dual energy X‐ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia

Summary. Our aim was to evaluate bone status in boys with haemophilia using dual energy X‐ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty‐six boys with a mean decimal age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK‐L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z‐scores Z‐scores between ?1 and ?2. Only one patient had radial and other two had tibial QUS Z‐scores P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK‐L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL^?1, P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng mL^?1, P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL^?1, P < 0.001) compared with controls. QUS Z‐scores at tibia significantly correlated with HJH Scores (r = ?0.450, P = 0.040), whereas lumbar BMD Z‐scores significantly correlated with body mass index Z‐scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs.     

Performance of calcaneus quantitative ultrasound and dual-energy X-ray absorptiometry in the discrimination of prevalent asymptomatic osteoporotic fractures in postmenopausal women

Due to its low cost, portability, and nonionizing radiation, quantitative ultrasound (QUS) of the heel is an alternative to the measurement with dual X-ray absorptiometry (DXA) in the evaluation of bone status. The objective of the study is to compare in asymptomatic postmenopausal women the ability of QUS and DXA to discriminate between those with and without prevalent vertebral fractures (VFs). The study cohort consists of a population of 295 postmenopausal women aged between 60 and 84 (mean age, weight and BMI of 66.3 years, 72.0 kg and 29.4 kg/m², respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained by two technologists using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. All women had a calcaneous QUS examination. The mean age of the women in our sample was 66.3 (±5.3) years, ranging from 60 to 84 years. Eighty-seven (29.3%) women had VFs Genant grade 2 and 3. Patients with VFs had an age and a number of years of menopause higher to those without VFs, but showed lower height, weight, and BMI. All densitometric and ultrasonometric measurements were significantly reduced in women with VFs. The intercorrelations of BMD at different sites were high, and the correlations of BUA with BMD were lower. BUA correlated weakly with total hip BMD (r = 0.36), lumbar spine BMD (r = 0.32), and much less with femur BMD (r = 0.30); all correlations were significant (P < 0.01). Analysis of the AUC for the ROC curves showed lumbar spine T-score below −2.5 to provide consistently the highest AUC (0.64). Age-adjusted ORs after correction for confounding variables (years of menopause, weight, height, and BMI) for QUS and BMD measurements showed that only lumbar spine T-score below −2.5 could predict significantly the presence of VFs (OR, 1.94; 95%CI, 1.02–3.41). Lumbar spine BMD (and not QUS) was able to discriminate asymptomatic postmenopausal women with prevalent VFs from women without VFs and independently contributed to determining the association with fracture. The combination of QUS and BMD did not improve the diagnostic ability of either individual technique.     

The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial

Background Patients with Turner syndrome (TS) are treated with GH to increase adult height. Although it is well established that GH promotes longitudinal bone growth, the effects of GH treatment on bone density are less clear. Objective To determine how GH treatment affects trabecular bone mineral density (BMD) in girls with TS at prepubertal ages in a prospective multicentre study. Patients and method Twenty‐two patients with TS in the prepubertal period with a mean age of 9·8 ± 2·5 (range 3·6–12·8) years were included in the study. All girls with TS underwent measurement of areal BMD using dual‐energy X‐ray absorptiometry (DXA) to obtain pretreatment anteroposterior (AP) lumbar spine values at L1–L4. Patients received GH (Genotropin) subcutaneously for 1 year at a dose of 0·05 mg/kg/day. Height and weight were measured at 3‐monthly intervals. The AP lumbar spine areal BMD was remeasured using the same technique after 1 year of treatment. Lumbar spine BMD Z‐scores and volumetric BMD (vBMD) Z‐scores were calculated using national standards. Results The height SDS of our cases showed a significant increase with GH therapy. The pretreatment lumbar spine (L1–L4) BMD Z‐score was –1·2 ± 1·2 SD and the vBMD Z‐score was –0·8 ± 1·6 SD. There were no significant changes in these values after 1 year of GH treatment. Prepubertal TS girls more than 11 years of age had lower vBMD Z‐scores (–1·7 ± 1·7 SD) than the girls aged less than 11 (–0·1 ± 1·0 SD) (P < 0·05) at the onset of therapy. No significant changes were observed in these values after 1 year of GH therapy. Conclusions Osteopaenia becomes apparent in prepubertal TS patients as they reach pubertal age. BMD evaluation may be necessary in these prepubertal TS girls at diagnosis. Short‐term GH therapy in these TS patients does not have a significant effect on bone density when measured at a site with a predominance of trabecular bone.     

Discrepancy in bone mineral densities at different skeletal sites in hip osteoarthritis patients

Abstract

Objective. Increased femoral neck bone mineral density (BMD) in a hip with osteoarthritis (OA) has been previously reported, however, it is possible that increased BMD at sites other than the hip joint is influenced by the disease process of OA. Therefore, we measured BMD at locations different from the hip joint and determined whether higher BMD was also observed at these different skeletal sites in hip OA patients.

Methods. We measured BMD in 68 women (average age 61.0 years) scheduled to undergo total hip arthroplasty for end-stage OA and 100 healthy women (average age 60.9 years) as age-matched controls. BMD at the lumbar spine, radius, and calcaneus was measured by dual-energy X-ray absorptiometry (DXA). Moreover, we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index of the calcaneus by quantitative ultrasonography (QUS).

Results. BMD obtained by DXA at the lumbar spine and radius was significantly higher in hip OA patients than in controls. However, at the calcaneus, no significant differences were observed between the groups in BMD obtained by DXA. SOS, BUA, and stiffness index obtained by QUS were significantly lower in the OA group than in controls.

Conclusion. Higher BMDs of the spine and radius suggest that the incidence of osteoporosis is inversely associated with the incidence of OA. However, it remains unclear whether lack of difference in BMD and lower SOS, BUA, and stiffness index of the calcaneus in the OA group was secondary to the effect walking disturbance resulting from hip pain. Our data suggest that hip OA patients have higher BMD than healthy women, and that inactivity or immobilization caused by hip OA may reduce BMD in the lower limb.     

Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients

To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis.We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1–L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined.In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was –1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was –2.35, the sensitivity was 37.2% and the specificity was 100%.Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is –1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤–2.35, it can be diagnosed as osteoporosis.     

Bone mineral density in young males with ankylosing spondylitis

Objective: To assess bone mineral density (BMD) abnormalities in young Indian males with ankylosing spondylitis (AS) and factors influencing this. Methods: Eighty AS male subjects were compared with 160 age/sex matched controls for BMD of lumbar spine and proximal femur. AS subjects were evaluated and followed up every 3 months for disease activity. BMD was estimated at spine and proximal femur using the dual‐energy X‐ray absorptiometry (DXA) technique. Results: All subjects were males with mean age of 32.9 ± 8.3 years and mean duration of disease was 8.1 ± 5.8 years. AS subjects had significantly lower BMD at the spine and femur as compared with controls (both P < 0.001). Using WHO standards, osteoporosis (OP) in spine and femur neck was seen in 28.75% (controls: 1.84%, P < 0.001) and 11.54% (controls: 1.23%, P < 0.001), respectively. No statistically significant difference in prevalence of OP was seen with disease duration, C‐reactive protein levels and disease activity indices (all P > 0.05). Syndesmophytes were seen in 22.5% (n = 18) of AS subjects. There was no significant difference between BMD values at spine in AS subjects with or without syndesmophytes (0.91 + 0.16 g/cm²vs. 0.90 + 0.14 g/cm², P = 0.79). Conclusion: OP is a significant complication in AS even in young males with early disease, and more prevalent in the spine compared to femur. In our study, BMD was not influenced by disease activity indices, inflammatory markers or total disease duration. Spinal BMD is the most sensitive site for defining OP in AS.     

Quantitative ultrasound of the proximal phalanges and dual-energy X-ray absorptiometry in Crohn's disease patients with osteopenia

Background: Osteopenia and osteoporosis are frequent complications in Crohn's disease, and these features are associated with an increased risk of vertebral and appendicular fractures. Bone mineral density (BMD) measurements are widely accepted to assess the fracture risk in postmenopausal osteoporosis. In recent years, quantitative ultrasound (QUS) has become attractive for the diagnosis of osteopenia as a nonionizing method. The aim of the present study was to investigate QUS and BMD measurements in osteopenic patients with Crohn's disease. Methods: BMD of the lumbar spine and femoral neck and QUS of proximal phalanges II-V (DBM Sonic 1200; IGEA) were performed prospectively in 171 patients with Crohn's disease. The amplitude-dependent sound-of-speed (AD-SoS) and the ultrasound bone profile score (UBPS) were calculated using the WinSonic PRO 1.1 software program. X-ray examination of the spine was performed in 131 patients. Vertebral deformity was morphometrically defined according to the published methods of McCloskey and Eastell. Results: BMD of the lumbar spine and femoral neck correlated significantly (r = 0.62), but no correlation between BMD and QUS could be demonstrated. Vertebral deformities (VD) were detected in 28/131 (21.4%) patients. Two patients had a history of femoral fracture (FF). Lumbar BMD was lower in patients with either VD or FF than in those patients with no preexisting fractures (T-score: −2.46 vs −2.04; P = 0.0233). QUS parameters correlated negatively to patients' age but could not be used to discriminate between patients with and without VD/FF. Conclusions: Osteoporosis-related fractures are associated with a low lumbar bone density in Crohn's disease patients. QUS of the proximal phalanges cannot detect manifest osteoporosis in Crohn's disease patients and is therefore not valuable as a screening tool for these patients. Received: January 10, 2002 / Accepted: August 30, 2002 Acknowledgments. Morphometry of vertebral radiographs was supported by the Osteoporosis Study Group of the Clinic for Radiology and Nuclear Medicine, Klinikum Benjamin Franklin, Berlin, Germany. Reprint requests to: C. von Tirpitz     

Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency

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.     

Assessment of bone involvement in patients with multiple myeloma using bone densitometry

Abstract: To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L₁–L₄) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21–79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score –0.46±0.23, p=0.05) and lumbar spine BMD (Z-score –0.56±0.23, p=0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score –1.34±0.22, p<0.001), as had non-fractured vertebrae in the same individuals (Z-score –1.42±0.25, p<0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r –0.37, p=0.03) and stronger with the incidence of vertebral fractures (r –0.64, p<0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.     

Differences between measurements of bone mineral densities by quantitative ultrasound and dual-energy X-ray absorptiometry in type 2 diabetic postmenopausal women

CONTEXT: Quantitative ultrasound (QUS) may be more helpful than dual-energy X-ray absorptiometry (DXA) in detecting bone deficits in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: The objective of the study was to compare differences in bone mass measurement by DXA and QUS in T2DM and nondiabetic postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: This clinical investigation was a cross-sectional study in 76 patients with T2DM and 86 nondiabetic postmenopausal women. MAIN OUTCOME MEASURES: The primary outcomes were speed of sound (SOS) at the radius, phalanx, and tibia measured by QUS and bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) measured by DXA. RESULTS: BMDs in T2DM patients were higher (LS, 1.06 +/- 0.12 vs. 0.90 +/- 0.23 g/cm(2); FN, 0.80 +/- 0.13 vs. 0.74 +/- 0.12 g/cm(2); TH, 0.87 +/- 0.14 vs. 0.80 +/- 0.13 g/cm(2), respectively, P < 0.001), whereas SOSs were lower than those in nondiabetics (radius, 4044 +/- 178 vs. 4129 +/- 182 m/sec; phalanx, 3902 +/- 207 vs. 3999 +/- 214 m/sec, respectively, P < 0.001). The positive relationships between SOS and BMD (r = 0.26-0.75, P < 0.05) in nondiabetics were not observed in women with T2DM. T2DM impacted negatively on SOSs (radius, beta= -0.223, P <0.01; phalanx, beta= -0.219, P <0.01) but positively on BMDs (LS, beta = 0.314, P < 0.001; FN, beta = 0.173, P < 0.05; TH, beta = 0.203, P <0.01). CONCLUSIONS: Differences in bone mass as measured by DXA and QUS in postmenopausal T2DM and nondiabetic women do not change in parallel. QUS can provide useful information in the skeletal assessment of patients with T2DM.     

Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages

OBJECTIVES We wished to appraise the effectiveness of hormone replacement therapy (HRT) in early (<67 years) and late (>67 years) post-menopausal women referred to a metabolic outpatient clinic for assessment of their bone status. Because older women often experience side-effects with conventional HRT, a low dose preparation (Estraderm 25) was also compared with conventional HRT (Estraderm 50). DESIGN AND SETTING Since all patients were symptomatic, the investigation was open and not placebo controlled. Patients were offered HRT and told about the two dosages. If they wished to use HRT, allocation of dosage was made randomly unless there were reasons to use a specific dose. PATIENTS One hundred and ninety-six women were studied over 1 or 2 years with 80 reaching 3 years of treatment. Patients were divided into those under 67 years and those over 67 years at the start of treatment. Each group was further divided into those taking Estraderm 25 and those taking Estraderm 50 with norethisterone if appropriate. MEASUREMENTS Bone mineral density (BMD) was measured (DXA, Hologic) at the lumbar spine and femoral neck at 0 year (196 patients), at 1 year (169 patients), at 2 years (139 patients) and at 3 years (80 patients). Patients losing bone were expressed as those whose 3 year BMD was lower than initial or as those whose BMD at 3 years had fallen by more than twice the coefficient of variation for that site (non-responders). RESULTS In lumbar spine, BMD increased maximally in the first year in all groups and the gain was maintained after 3 years. The change was similar whether patients were divided by age or dosage. For those on Estraderm 25, mean change after 3 years was 8.1 ± 6.8% and on Estraderm 50, 9.0 ± 8.3% (combined 8.7 ± 7.8%). Only 3.9% of patients were non-responders at the lumbar spine after 3 years. At femoral neck, changes were significant at 3 years only in the Estraderm 25 >67 years and Estraderm 50 <67 years groups and averaged 2.3 ± 5.4% for all patients. At the femoral neck, 10.4% of patients were non-responders after 3 years. Percentage change of BMD over 3 years at lumbar spine correlated with that at the femoral neck (r = 0.56). Percentage change of BMD at lumbar spine over 3 years correlated with menopausal age (r = 0.295). No relation was found between dosage of Estraderm/kg body weight and response of BMD at either site. CONCLUSIONS Transdermal oestrogen is effective at preventing bone loss in the spine at all post-menopausal ages and is capable of doing this in low dosage. Prevention of bone loss at the femoral neck is less certain and the average change in BMD over 3 years was significantly lower (P < 0.001) than in the lumbar spine. Use of Estraderm 50 is not associated with a greater response of bone mass and there was no evidence of an increasing BMD response as oestradiol dosage/kg body weight increased.     

Associations with subregional BMD-measurements in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P < 0.01) lower BMD values in the carpus (0.405 ± 0.004 g/cm²), metacarpal joint II (0.318 ± 0.036 g/cm²) and metacarpal joint III (0.326 ± 0.022 g/cm²) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P < 0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P < 0.001) with pyridinolines (r = 0.378), desoxypyridinolines (r = 0.183), forearm (r = −10, P < 0.05), MCP II (r = −0.190, P < 0.001), MCP III (r = 0.204, P < 0.001) and carpus (r = 0.191, P < 0.001).     

Measurement of hand bone mineral density in early rheumatoid arthritis using dual energy X‐ray absorptiometry

Aims: The earliest radiological change in rheumatoid arthritis (RA) is periarticular osteopenia, which occurs prior to the appearance of erosions and clinically apparent deformities. The aim of the study was to measure periarticular bone mineral density (BMD) in the hands of patients with early RA, using dual energy X‐ray absorptiomentry (DEXA) and to correlate this with markers of disease activity and radiological progression. Methods: The study population (n = 50) of patients with RA of < 3 years duration underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine and clinical assessment at baseline, 6 and 12 months. Hand radiographs were performed at baseline and 12 months. Thirty age‐ and sex‐matched controls also underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine. Results: Hand BMD correlated strongly with sex, height, weight and lumbar and femoral neck BMD in both RA subjects and controls. Baseline hand BMD in RA subjects correlated with baseline serum C‐reactive protein (r = ?0.36, P = 0.01) and 12‐month radiographic score (r = 0.36, P = 0.02). There were small non‐significant decreases in hand, femoral neck and lumbar spine BMD over the 12‐month period. Conclusion: Hand BMD measurement using DEXA is a reproducible, well‐tolerated procedure that warrants further investigation as a component of routine assessment in early RA.     

Endosteal bone storage in young adults born small for gestational age - a study using peripheral quantitative computed tomography

Objective Poor growth early in life is associated with numerous adverse conditions including decreased bone mass. The aim is to investigate bone and body composition in young adults born small for gestational age (SGA). Design Observational study. Participants A total of 76 young adults born SGA (34f) at a mean age of 19·68 ± 0·5 years were enrolled. Method Bone mineral density (BMD), bone geometry and body composition were analysed using peripheral quantitative computed tomography. Results Adults born SGA had significantly lower z‐score for height (?0.86 ± 0·87), weight (?0·61 ± 0·78) and BMI (?0·38 ± 1·04) as well as fat cross‐sectional area (CSA) (?0·62 ± 0·80) compared with a healthy reference population (P < 0·05). Z‐scores for trabecular and cortical BMD were normal. After correction for reduced height, z‐scores for total CSA (?0·14 ± 1·11) and muscle CSA (?0·21 ± 0·99) were normal and medullary cavity (?0·71 ± 0·80) was reduced. Those with a birthweight of ≤1500 g had even lower height‐corrected z‐scores for medullary cavity (?1·12 ± 0·69) and total bone CSA (?0·58 ± 0·93) (P < 0·05). After adjustment for sex and weight, significant partial correlations were detectable between BMI at the age of 48 months and height‐corrected z‐scores for medullary cavity (r = 0·33, P = 0·020) and total CSA (r = 0·29, P = 0·04). Conclusion Environmental factors early in life seem to influence bone geometry in adulthood. Young adults born SGA have normal total bone CSA but smaller medullary cavity. Those with very low birthweight, however, show compromised bone size development that may alter bone stability later in life.     

Bone density and health‐related quality of life in adult patients with severe haemophilia

Summary. Severe haemophilia and reduced bone density can negatively influence perception of patient’s health‐related quality of life (HRQoL), especially considering future aspects, the risk of losing independence or pain suffering. The aim of this study was to assess levels of HRQoL in severe haemophilia patients and to compare HRQoL to those of the general population as well as to determine whether reduced bone density is correlated to the perceived HRQoL. Patients were divided into two groups based on timing of being treated with prophylaxis: Group A (started prophylaxis at age of ≤3 years; n = 22); Group B (at age of >3 years; n = 15). The bone mineral density (BMD g cm^?2) of different measured sites was measured by dual energy X‐ray absorptiometry (DXA). HRQoL was assessed using SF‐36 questionnaire. Group A have mean BMD T‐score >?1.0 (i.e. normal score) at all measured sites, and have almost similar scores in the SF‐36 domains compared with the reference population. Group B have mean BMD T‐score ?1.0 at lumbar spine and total body, and their scores in the SF‐36 domains were lower compared with the reference population. Moreover, significant correlations were found between BMD at femoral neck and total body with physical domains. With adequate long‐term prophylaxis since early childhood, adult patients with haemophilia report a comparable BMD and HRQoL to the Swedish reference population. Reduced BMD in group B correlated with impaired physical health, which underscores the importance of early onset of adequate prophylactic treatment.     

Comparison of quantitative ultrasound parameters with dual energy X-ray absorptiometry in pre- and postmenopausal women

BACKGROUND: Quantitative ultrasound (QUS) has been claimed as an alternative technique for risk assessment of hip fractures associated with osteoporosis. However, reports concerning modest correlations between QUS parameters and dual energy X-ray absorptiometry (DXA) in women raise questions about the reliability of QUS technology to predict bone mineral density (BMD). Partially, the lack of stronger correlations may be due to heterogeneity in bone architecture deterioration which may be more pronounced in older than in younger women. Therefore, it was thought important to study QUS/DXA interrelationships in subgroups of pre- and postmenopausal women. METHODS: We studied 217 pre- and postmenopausal women between the ages of 25 and 75 years, who were referred for a BMD measurement because of osteoporosis in at least one family member either in the first or in the second degree. All women had a calcaneal QUS and a DXA measurement at the lumbar spine, total hip and femoral neck. RESULTS: The linear regression coefficients between the QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) and DXA at the various sites in the group as a whole were 0.53 to 0.54 (P<0.0001). Significantly lower regression coefficients between BUA and DXA at the total hip and the femoral neck were found in premenopausal women (r=0.31 and 0.38, P<0.0001) compared to postmenopausal women (r=0.56 and 0.53, P<0.0001). For SOS there was no significant difference between the regression coefficients in the pre- and postmenopausal group. The overall prevalence of osteoporosis as assessed by DXA in the total group was 25% (6% in the pre- and 36% in the postmenopausal group). BUA failed to detect osteoporosis in all five premenopausal women but also in 20 out of 50 postmenopausal women with osteoporosis according to DXA measurements. SOS measurements were even worse in this respect. CONCLUSIONS: Linear regression coefficients between calcaneal QUS parameters and DXA are only modest considering a group of 25--75-year-old Dutch women. In the subgroup of premenopausal women correlations between BUA and BMD at the hip and femoral neck are worse compared to those in postmenopausal women. The predictive value of QUS parameters for BMD is limited, therefore it is not appropriate to use QUS as a surrogate for DXA.     

Insulin sensitivity assessment with euglycemic insulin clamp in adult beta-thalassaemia major patients

Objective: To assess insulin sensitivity in young adult normoglycemic β‐thalassaemia major patients. Methods: We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 ± 2.45 yrs) normoglycemic β‐thalassaemia major patients and 10 sex‐ & age‐ matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI). Results: Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 ± 63.5 mg/m²·min vs. 355.6 ± 35.3 mg/m²·min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/I_s‐s) and glucose metabolic clearance rate (M/G_s‐s). There was significant negative correlation between ferritin levels and glucose infusion rate (r = ?0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with β‐thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI‐derived liver iron content (r = ?0.733, P = 0.03). Conclusions: Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with β‐thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.     

Normal DXA bone mineral density but frail cortical bone in Turner's syndrome

CONTEXT: Patients with Turner's syndrome have normal bone mineral density by dual energy X-ray absorptiometry (DXA), but a predisposition for fractures. Quantitative ultrasonography (QUS) measures cortical bone strength. OBJECTIVE: To compare QUS with DXA in patients with Turner's syndrome. PATIENTS AND METHODS: Twenty-seven Turner's syndrome patients, aged 21.1 +/- 6.3 years (mean +/- SD), were evaluated by DXA, measuring two-dimensional bone mineral density (BMD), and QUS, measuring speed of sound (SOS) of the radius and tibia. The results were compared to sex- and age-matched (Ctr A, n = 53) and height-matched (Ctr B, n = 34) control groups. RESULTS: Fracture incidence per 1000 women years was 4.76 in Ctr A, 5 in Ctr B and 7.69 in Turner's patients. In Turner's syndrome patients, QUS results were significantly lower than in controls, whereas DXA Z-scores were not different from reference values. Correlation between tibia and radius SOS and height and age in controls (P < 0.0001) was not evident in Turner's syndrome. Oestrogen or growth hormone therapy had no effect on either QUS or DXA parameters. CONCLUSIONS: Bone fragility in Turner's syndrome is reflected by low SOS but not by DXA BMD. Low QUS, which assesses the cortical bone only, supports a defect in cortical bone in Turner's syndrome. Lack of SOS correlation with age, height and hormonal therapy in Turner's syndrome suggests a primary bone defect, rather than enhanced resorption of endocrine origin.     

Inverse relationship between circulating levels of leptin and bone mineral density in chronic liver disease

Background and Aim: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease. Methods: Fifty‐eight patients, 39 females and 19 males, and age‐ and gender‐matched controls were included. Bone mineral density was measured by using dual energy X‐ray absorptiometry. Serum leptin was measured by using a radioimmunoassay. Results: The mean serum leptin concentration was 10.4 ± 11.3 and 15.2 ± 17.9 ng/mL; P = 0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r = 0.40; P = 0.003) and in controls (r = 0.55; P < 0.0001). In patients classified as Child–Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r = –0.78; P = 0.04 and r = –0.86; P = 0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r = –0.99; P = 0.002 and r = –0.86; P = 0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls. Conclusion: An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.