Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies.

PURPOSE: TSH-receptor (TSHR) antibodies (Ab) can be measured with binding or bio-assays. Sensitivity and specificity of five binding and two bio-assays were compared. METHODS: TSHR-blocking (TBAb) and TSHR-stimulating (TSAb) Ab were measured with reporter bio-assays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bTSH alone. TSAb was reported as percentage of specimen-to-reference ratio (SRR%). TSHR-binding inhibitory immunoglobulins (TBII) were measured with Kronus, Dynex, Kryptor, Cobas, and Immulite. RESULTS: Sixty patients with Graves' disease (GD), 20 with Hashimoto's thyroiditis (HT), and 20 healthy controls (C) were included. C tested negative in all assays (specificity 100 %) while all 60 hyperthyroid GD patients tested positive in the TSAb bio-assay (sensitivity 100 %). Among these 60 GD patients, 20 had low TSAb positivity (SRR% 140-279), but were TBII positive in only 20 (100 %), 7 (35 %), 9 (45 %), 11 (55 %), and 18 (90 %) using the Kronus, Dynex, Kryptor, Cobas, and Immulite, respectively. In 20 moderate TSAb-positive (SRR% 280-420) patients, TBII tested positive in 20 (100 %), 14 (70 %), 13 (65 %), 16 (80 %), and 19 (95 %), respectively. The high (SRR% > 420) TSAb-positive patients were all TBII positive. All 20 hypothyroid HT patients tested TBAb positive (sensitivity 100 %) in the bio-assay while they tested TBII positive in 20 (100 %), 18 (90 %), 20, 20, and 18, respectively. Results obtained with two luminometers correlated for TSAb positive (r = 0.99, p < 0.001), TBAb positive (r = 0.88, p < 0.001), and C (r = 0.86, p < 0.001). None of the binding assays differentiated between TSAb and TBAb. CONCLUSIONS: Sensitivity is highly variable between binding and bio-assays for TSHR-Abs.

Comparison of dual-energy X-ray absorptiometry with six quantitative ultrasonometry devices in women with hip fractures.

OBJECTIVES: Dual-energy X-ray absorptiometry (DXA) is the gold standard for assessment of bone mineral density, an important risk factor for osteoporotic fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able to predict fractures; however, only limited data in women with hip fractures are available. METHODS: We examined 91 postmenopausal women who had sustained an osteoporosis-related hip fracture within the past 7 days using DXA and six different QUS devices and compared them with 91 healthy age-matched controls. RESULTS: Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were lower in women with hip fractures compared to matched controls: - 2.38 vs. - 1.64 (p < 0.001), - 2.36 vs. - 1.44 (p < 0.001) and - 2.05 vs. - 1.50 (p = 0.41), respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS devices were also lower in patients with hip fractures compared to matched controls: - 3.20 vs. - 2.36 (p < 0.001), - 2.196 vs. - 1.761 (p = 0.005), - 2.631 vs. - 1.849 (p < 0.001), - 3.707 vs. - 3.030 (p = 0.032), respectively. However, the T-scores of the DBM and QUS-2 did not differ between the two groups: - 4.543 vs. - 4.324 (p = 0.352) and - 1.7 vs. - 2.0 (p = 0.465), respectively. Compared to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were significantly lower (p ≤ 0.05). CONCLUSIONS: Compared to DXA, the Achilles, Sahara and InSight QUS devices showed similar hip fracture discrimination while the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to identify a clinically meaningful risk factor in women at high risk of hip fracture.

Improved adherence with PTH(1-84) in an extension trial for 24 months results in enhanced BMD gains in the treatment of postmenopausal women with osteoporosis.

UNLABELLED: The purpose of this study is to examine the effect of PTH(1-84) treatment over 24 months followed by 12 months discontinuation on BMD, bone turnover markers, fractures and the impact of adherence on efficacy. INTRODUCTION: There is limited information about the effect of PTH(1-84) after 18 months and limited data about the impact of compliance on response to anabolic therapy. METHODS: Seven hundred and eighty-one subjects who received active PTH(1-84) in the Treatment of Osteoporosis with Parathyroid hormone trial for approximately 18 months were entered into a 6-month open-label extension. Thereafter, they were followed for 12 additional months after discontinuation of treatment. Endpoints examined included changes in BMD and biochemical markers. RESULTS: PTH(1-84) treatment over 24 months increased BMD at the lumbar spine by 6.8% above baseline (p<0.05).The total corresponding BMD increases at the hip and femoral neck were 1.1 and 2.2% above baseline. Larger increases in spine BMD were observed in participants with ≥80% adherence to daily injections of PTH(1-84) (8.3% in adherent vs 4.9% in poorly adherent patients). Total hip BMD gains were 1.7% in adherent vs 0.6% in poorly adherent participants. Markers of bone turnover (BSAP and NTx) peaked 6 months after starting PTH(1-84) treatment and declined slowly but remained above baseline at 24 months. After discontinuation of PTH(1-84) treatment (at 24 months), bone turnover markers returned to near baseline levels by 30 months. The adherent group sustained significantly fewer fractures than the poorly adherent group. CONCLUSIONS: PTH(1-84) treatment over 24 months results in continued increases in lumbar spine BMD. Adherence to treatment with PTH(1-84) for up to 24 months is also associated with greater efficacy.

Hypergonadotropic hypogonadism in a patient with inv ins (2;4).

We report on a 30-year-old man with azoospermia, primary hypogonadism and minor dysmorphic features who carried a balanced insertional chromosome translocation inv ins (2p24;4q28.3q31.22)de novo. Molecular cytogenetic analyses of the chromosome breakpoints revealed the localization of the breakpoint in 4q28.3 between BACs RP11-143E9 and RP11-285A15, an interval that harbours the PCDH10 gene. In 4q31.22, a breakpoint-spanning clone (RP11-6L6) was identified which contains the genes LSM6 and SLC10A7. On chromosome 2, BACs RP11-531P14 and RP11-360O18 flank the breakpoint in 2p24, a region void of known genes. In conclusion, the chromosome aberration of this patient suggests a gene locus for primary hypogonadism in 2p24, 4q28.3 or 4q31.2, and three possible candidate genes (LSM6, SLC10A7 and PCDH10) were identified by breakpoint analyses.

Image-guided endonasal transsphenoidal microsurgical treatment of recurrent microadenomas of the pituitary gland.

BACKGROUND: Neuronavigation is a commonly used technology that provides continuous, three-dimensional information for the precise localization of and surgical trajectory to brain lesions. This study was performed to evaluate the role that navigation can play in assisting microsurgical transsphenoidal surgery for precise localization and removal of recurrent pituitary tumours while simultaneously preserving pituitary gland function. METHOD: During a 6-month period -- July 2004 until December 2004 -- 9 patients with recurrent pituitary tumours (5 female and 4-male) were treated with navigation-guided transsphenoidal microsurgical resection. Surgery was performed via a paraseptal or endonasal transsphenoidal approach. The navigation system Vector Vision (Brain Lab, Heimstetten, Germany) allowed precise localization of the tumours (7 hormonal active and 2 inactive microadenomas) in respect to the pituitary gland, the carotid arteries and the cavernous sinus. RESULTS: Postoperative MRI investigations of the 9 patients treated with image-guided transsphenoidal microsurgery, showed total tumour removal in 7 (77 %) patients and subtotal removal in 2 patients (23 %). One patient (11 %) developed a cerebral spinal fluid (CSF) leak and was treated conservatively. One patient (11 %) had preoperative insufficiency of the corticotrope axis which remained unchanged postoperatively. Of the remaining 8 patients who did not have preoperative endocrinological disturbance, only one (12 %) developed postoperative insufficiency of the corticotrope axis. Out of the 7 patients with hormone active tumours, 5 (72 %) patients showed no more postoperative hormonal activity. CONCLUSION: Microneurosurgical transsphenoidal techniques combined with image-guided systems can precisely define the localization and removal of lesions in the sella region with respect to the margins of important anatomical structures in the neighbourhood and the endocrinological functionality of the pituitary gland.

Usefulness of quantitative ultrasound in evaluating structural and mechanical properties of bone: comparison of ultrasound, dual-energy X-ray absorptiometry, micro-computed tomography, and mechanical testing of human phalanges in vitro.

INTRODUCTION: Ultrasound studies evaluating bone tissue generally concentrate on two parameters--velocity and attenuation. This study aimed to determine whether ultrasound signal analysis techniques could provide additional information on the structural and mechanical characteristics of bone. MATERIALS AND METHODS: In vitro measurements were made on 26 left index fingers from human cadavers. Ultrasound measurements at the distal metaphysis and epiphysis; dual-energy X-ray absorptiometry of the whole phalanx; micro-computed tomography at the distal quarter of the phalanx (that is, the distal epiphysis and metaphysis), and mechanical three-point bending tests were performed. Univariate and multivariate linear regression techniques were used to analyze the results. RESULTS: The ultrasound parameters, speed of sound and ultrasound peak amplitude correlated significantly with the three micro-computed tomography measures used to describe the characteristics of mineralized material (r=0.69-0.79, p<0.05). Low frequency ultrasound correlated significantly with micro-computed tomography parameters describing inter-trabecular or marrow spaces (r=0.68-0.78, p<0.05). Comparison of ultrasound parameters with geometric characteristics showed that while speed of sound and ultrasound peak amplitude were related to the cortical area, moment of inertia, and mechanical load (r=0.57-0.83, p< 0.05), the amplitude of the fastest part of the ultrasound signal and full width at 80% maximum of the low frequency peak were related to the relative area of the medullary canal (r=0.40-0.43, p<0.05). DISCUSSION: Quantitative ultrasound may provide information on structural, material and mechanical characteristics of bone to the same extent and even better than DXA Bone Mineral Density. These results have been obtained by a complete and exhaustive use of QUS technology in situ but under clinical conditions. The ultrasound parameters, correctly used and combined, seem to be effective tools for investigating bone tissue.

Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma.

BACKGROUND AND PURPOSE: In clinically non-functional pituitary macroadenomas, prospective follow-up magnetic resonance imaging (MRI) was conducted after transsphenoidal surgery both to study the changes of the sellar contents at the post-operative site over time and to assess the amount of residual adenoma tissue. METHODS: A total of 50 patients with clinically non-functional pituitary macroadenomas were treated by transsphenoidal tumour resection and were examined by MRI before and directly after surgery (early MR) and 3 months (intermediate MR) and 1 year after surgery (late MR). Changes in the sellar contents over time and the degree of tumour excision were studied on T1-weighted enhanced and unenhanced scans. All patients underwent complete neuro-ophthalmological and endocrinological assessments before and 3 months after surgery. For the interpretation of the post-operative images the results of the endocrinological examinations after surgery were also taken into account. RESULTS: The maximum size of tumour extension on coronal T1-weighted images ranged from 1.2 cm to 5.0 cm (mean 2.3 cm). Despite tumour resection, early post-operative images still showed a persistent mass in the sella in 83% that was usually caused by post-operative haemorrhage, fluid collection and implanted fat material. However, rapid improvement in visual symptoms was noted in 89%. Changes in the sellar region at the early post-operative site markedly hindered the interpretation of MR images for detecting residual tumour tissue, which was suspected in half of the patients (1 intrasellar, 13 suprasellar, and 11 parasellar). Regression of the post-operative mass in the sella was present 3 months after surgery, resulting in a 50% change in the volume of the coronal sellar extension, which also improved the reliability in interpreting the post-operative MR images. On the intermediate MR images residual tumour tissue was detected in 30% of the patients (4 intrasellar, 2 suprasellar and 9 parasellar). Because the suprasellar mass descended over time, an increasing rate of tumour remnant within the sella was seen 3 months following surgery. Before surgery the pituitary gland was visible superiorly or posterosuperiorly to the macroadenomas in 35 patients. However, at the early post-operative site the remaining gland was only visible in 12 patients. Under the condition that endocrinological function tests confirmed adequate hormonal function, the remaining gland was detectable by MRI in 36 patients 3 months after surgery. CONCLUSION: Delayed regression of the sellar contents after transsphenoidal surgery of pituitary macroadenomas was demonstrated by this prospective MR study. Owing to the changes at the post-operative site, it was difficult to interpret early post-operative images and detect residual adenoma tissue. With respect to the delayed regression of the sellar contents, the interpretation of post-operative images for detection of residual adenoma was improved 3 months after surgery. At this time, residual adenoma tissue was found in 30% of clinically non-functional macroadenomas, mostly at the parasellar and, after descent from the suprasellar space, at the intrasellar site.

Use of quantitative ultrasound densitometry (QUS) in male osteoporosis.

Bone densitometry is a key factor in the early diagnosis of osteoporotic bone disorders. Cut-off values for WHO classification for male osteoporosis and all densitometry techniques such as dual x-ray absorptiometry (DXA), quantitative ultrasound (QUS), and quantitative computed tomography (QCT) need to be developed. Hereby, QCT, DXA, and QUS are equivalent methods in the prospective assessment of fracture risk. Where men and women have similar BMD values, they also have similar fracture probability. QUS has several advantages compared to the radiological devices. The QUS systems, which are commercially available at present, are non-invasive methods, which are safe, simple, free of radiation, portable, and relatively inexpensive. QUS can be measured at the calcaneus and phalanges or with multi-site systems. Phalangeal ultrasound is especially useful as being easily accessible.

Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH-deficient adults.

OBJECTIVE: Adults with growth hormone (GH) deficiency are often osteopenic. Short-term GH replacement therapy has been shown to improve bone mineral density (BMD). However, whether the increases in BMD are progressive with time is still unclear. We therefore examined long-term changes in BMD with GH treatment in GH-deficient adults over a period of 6 years. DESIGN: Open prospective GH therapeutic study. PATIENTS: Twelve GH-deficient patients (four women, eight men) with a mean age of 42.5 years (range 24-61 years) at the beginning of GH replacement. Eleven patients suffered in addition from LH/FSH insufficiency, eight from TSH insufficiency and eight from ACTH insufficiency. Before the start of GH substitution, the insufficient anterior pituitary axes were fully substituted for an average of 9.8 years (range 2-22 years). Average daily GH dose was 2.4 IU (SD 0.86). MEASUREMENTS: BMD and bone area were measured at annual intervals at the lumbar spine and at the proximal femur using dual-X-ray absorptiometry. RESULTS: Under GH substitution, serum insulin-like growth factor I concentrations increased by 140 microg/l compared to pretherapeutic values (P = 0.0003). BMD at the lumbar spine increased by 0.16 g/cm2 (P = 0.0005), corresponding to a mean increase of 15.9% or an increase of the BMD Z-score by 1.53 SD. Increases in BMD were independently observed from years 3 to 6 by a mean of 5.8% (P = 0.0087). This increase was paralleled by an increase in the area of the lumbar vertebrae. Bone area also increased at selected sites of the proximal femur, but there was no consistent increase in BMD at the proximal femur. CONCLUSION: GH therapy in GH-deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years. However, our study has several limitations, making it necessary to confirm these findings in further long-term studies.

The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. .

To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large-scale pharmacoepidemiological survey (the Pharmacia & Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non-GH-deficient EVOS population. Adult-onset hypopituitarism with GHD was associated with a higher fracture risk than childhood-onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L-thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large-scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy.

Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS Study Group and the KIMS International Board. Pharmacia and Upjohn International Metabolic Database.

OBJECTIVE: Although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of growth hormone (GH) responsiveness on dynamic testing, there are few data available on response to GH replacement. The objective of this study was to compare the baseline characteristics and longitudinal response to GH replacement in patients aged > 65 years with that observed in younger patients enrolled in KIMS (Pharmacia and Upjohn International Metabolic Database). KIMS is a physician-managed, open, long-term surveillance study of adult GH-deficient patients receiving GH replacement. Patients were entered and data provided by interested physicians. PATIENTS: Baseline characteristics were studied in 109 patients (66 males) aged > 65 years commencing GH replacement at time of entry into KIMS and the effects of GH replacement on blood pressure, lipids and quality of life in 64 patients who had completed at least 6 months of GH replacement. Data were compared with baseline data on 863 patients aged < 65 years with adult onset GH deficiency, who had not received GH for at least 6 months prior to entry into KIMS, 220 of whom went on to complete > 6 months GH therapy in KIMS. RESULTS: Blood pressure, cholesterol and LDL cholesterol were positively correlated with age, particularly in females, and older patients had a predictably higher prevalence of diabetes mellitus and history of hypertension. The frequency of previous fractures was increased in females but not in males aged > 65 years. Body mass index, waist/hip ratio and quality of life (AGHDA score) was similar in both groups prior to commencement of GH therapy. GH replacement doses were similar in younger and older patients and the percentage of patients with serum IGF-I of > 2SD above the age-related normal mean was not significantly different between the groups (< 65 years, 20%; > 65 years, 11%). After 6 months of GH replacement significant improvements were evident in waist circumference, waist/hip ratio, diastolic blood pressure, total and LDL cholesterol and AGHDA score in patients aged < 65 years. Similar significant reductions in total and LDL cholesterol were evident in patients > 65 years. In addition, male patients aged > 65 years demonstrated significant reductions in diastolic blood pressure and AGHDA score but no change in waist circumference whereas females aged > 65 years demonstrated a trend to reduction in waist circumference and AGHDA score. CONCLUSIONS: These data, derived from the largest series of GH-treated hypopituitary patients published to date, confirm similar baseline characteristics and positive benefit from GH replacement in older compared with younger hypopituitary patients particularly in relation to quality of life.

Phalangeal osteosonogrammetry study: age-related changes, diagnostic sensitivity, and discrimination power. The Phalangeal Osteosonogrammetry Study Group.

Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude-dependent speed of sound [AD-SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD-SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X-ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD-SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD-SOS was odds ratio (OR) 1.71 (CI, 1.58-1.84). The AD-SoS in fractured subjects was significantly lower than in a group of age-matched nonfractured subjects (p < 0.0001). In a small cohort of hip-fractured patients UBPI proved to be lower than in a control age-matched group (p < 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD-SoS we found a T score of -3.2 and for UBPI we found a T score of -3.14. Sixty-six percent of vertebral fractures were below the AD-SoS -3.2 T score and 62% were below UBPI -3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD-SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.

Experience with deflazacort in children and adolescents after renal transplantation.

Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1-9 years after TX in 20 patients aged 5-20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4 +/- 2.4 mg DFZ/m2 per day. The drug was continued for a mean of 3.7 (1.2-5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from -2.64 to -1.96 after 4 years, P = 0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P = 0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L2-4) increased after 1 year on DFZ (P = 0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty.

Sex difference in the validity of vertebral deformities as an index of prevalent vertebral osteoporotic fractures: a population survey of older men and women.

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n = 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62-86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31-68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score < -2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9-85.0% in women and 20.8-50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07-2.70) and (3.69; 1.33-10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30-10.24) and (15.40; 4.65-51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p < 0.01) and lumbar spine (p < 0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis.

Assessment by quantitative ultrasonometry of the effects of hormone replacement therapy on bone mass.

OBJECTIVE: This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel. STUDY DESIGN: A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped <6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index. RESULTS: Women who were using hormone replacement therapy had significantly higher values (P <.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for >3 years had significantly higher values (P <.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use. CONCLUSION: Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management.

No advantage of the new combined octreotide-GHRH test over established GH-stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults.

OBJECTIVE: To evaluate the sensitivity and specificity of a combined octreotide (SMS)-GHRH test we compared it with established GH stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults. DESIGN: Because there is no universally agreed gold standard for the diagnosis of GHD in adults it is difficult to define the relative merits of different tests in patients with structural pituitary disease. We have addressed this by grouping patients according to the degree of concordance between three established tests (insulin (IHT), arginine (ARG) and GHRH stimulation test (GHRH)) and serum IGF-I levels and have subsequently analysed the frequency destribution of test results across defined groups: group 1, with complete GHD in all tests, group 2, with differences between tests with regard to the diagnosis of GHD and group 3, with normal GH response in all tests. The patients also underwent a new combined SMS-GHRH test, the results of which were compared with IHT, ARG and GHRH. MEASUREMENTS: Five hours after an octreotide injection GHRH was given intravenously and GH measured. RESULTS: ARG had the highest sensitivity (Se = 100%) and specificity (Sp = 100%) of the tests used. The IHT also diagnosed GHD with precision but showed false positive as well as false negative results (Se = 90%, Sp = 100%). Se and Sp of GHRH were lower than those of IHT and ARG (Se = 100%, Sp = 89%). The SMS-GHRH worked well and was superior to GHRH but had less precision than IHT and ARG (Se = 88%, Sp = 100%). CONCLUSION: We conclude that there is discordance between the three established tests and that the octreotide-GHRH test does not have any advantages for diagnosing GHD in adults. IGF-I levels can be used as a screening test only. The arginine test was the best conventional test in our study.

Assessment of bone architecture with ultrasonometry: experimental and clinical experience.

Over the last decade, ultrasound technology has been introduced as a method of analysing bone tissue in clinical practice, and several studies have compared various ultrasound devices with dual-energy X-ray absorptiometry (DXA). Unlike DXA, the ultrasound technique is not limited to the measurement of bone density - it also has the potential to provide information on the mechanical and architectural characteristics of bone. The first generation of ultrasound devices used the speed of sound and attenuation of the ultrasound signal to obtain information on bone mineral content. Second generation ultrasound devices, which analyse the ultrasound signal received, permit the study of bone structure and elasticity, in addition to its mineral content, in both experimental studies and clinical practice. This is accomplished by signal processing analysis, the study of backscattering and the application of Biot's theory. This approach to the study of bone tissue represents the future for the development of ultrasound technology for use in clinical practice.

Fracture rates in patients with growth hormone deficiency.

There is some evidence that bone mass is reduced in the majority of adult patients with growth hormone deficiency (GHD), suggesting that such patients have an increased risk of fractures and clinically significant osteoporosis. To date, there have been only two reports of fracture rates in patients with hypopituitarism. Both these retrospective studies show an increased fracture prevalence in this patient group compared with the general population, but patient numbers were low for assessing fracture rates. However, an analysis of data from a large-scale pharmacoepidemiological survey of adults with GHD, KIMS (Pharmacia International Metabolic Database), confirms the findings of these earlier studies. The prevalence of all fractures among patients in KIMS was 2.7 times that in the control population, and the risk of fracture was independent of whether patients had isolated GHD or multiple pituitary hormone deficiencies. The results suggest that GHD is a risk factor for fractures, if a direct endocrine cause is assumed. Notably, there are some data on subgroup analyses from KIMS suggesting that growth hormone replacement therapy may help to reduce fracture risk, although further evidence is needed to confirm this effect.