The neural bases of the pseudohomophone effect: Phonological constraints on lexico-semantic access in reading.

We investigated phonological processing in normal readers to answer the question to what extent phonological recoding is active during silent reading and if or how it guides lexico-semantic access. We addressed this issue by looking at pseudohomophone and baseword frequency effects in lexical decisions with event-related functional magnetic resonance imaging (fMRI). The results revealed greater activation in response to pseudohomophones than for well-controlled pseudowords in the left inferior/superior frontal and middle temporal cortex, left insula, and left superior parietal lobule. Furthermore, we observed a baseword frequency effect for pseudohomophones (e.g., FEAL) but not for pseudowords (e.g., FEEP). This baseword frequency effect was qualified by activation differences in bilateral angular and left supramarginal, and bilateral middle temporal gyri for pseudohomophones with low- compared to high-frequency basewords. We propose that lexical decisions to pseudohomophones involves phonology-driven lexico-semantic activation of their basewords and that this is converging neuroimaging evidence for automatically activated phonological representations during silent reading in experienced readers.

[Combination of alendronate plus alfacalcidol in the treatment of osteoporosis. Rationale, preclinical data and clinical evidence]. / Kombinierte Osteoporosetherapie mit Alendronat plus Alfacalcidol. Rationale, präklinische Daten und klinische Evidenz.

BACKGROUND: The therapeutic strategy for the reduction of fracture risk in osteoporosis should not only aim to increase bone strength, but should also improve muscle function and reduce falls without increasing the risk of significant side effects. Since 2008 a combination therapy of the antiresorptive active bisphosphonatealendronate and the pleiotropic active D-hormone-prodrug alfacalcidol is licensed in Germanyfor treatment of postmenopausal osteoporosis (Tevabone). METHODS: In the review the results of numerous preclinical and clinical studies are reported, showing the efficacy of the combination of alendronate plus alfacalcidol. RESULTS: In preclinical trials with ovariectomized rats the combination has shown a significantly better effect on increased bone turnover in comparison with bisphosphonate monotherapy. Presumably the "oversuppression" of bone remodeling and the resulting risk of reduced microfracture healing, which is known to occur after long-term therapy with bisphosphonates, will be reduced by the combination. Clinical studies have shown better efficacy of the combination in the increase of bone density and reduction of fracture rate (vertebral and non-vertebral fractures). Less falls were reported compared to alendronate plus genuine vitamin D. The reduction of increased parathormone levels by the alendronate plus alfacalcidol combination compared to alendronate alone was proven to increase the responder rate of the alendronate therapy. The potential risks of alendronate-induced hypocalcemia as well as alfacalcidol-induced hypercalcemia or hypercalcuria are reduced due to the contrasting mode of action of both compounds. CONCLUSION: Treatment with the alendronate plus alfacalcidol combination meets the demands of an optimized therapy for osteoporosis.With the especially developed, self-explanatory combination package better compliance and less dispensing mistakes can be expected.

Long-term changes in the tibia and radius bone mineral density following spinal cord injury.

DESIGN: A prospective inception cohort study with an observational analytic design in a spinal cord injury (SCI) centre hospital. OBJECTIVE: To assess changes in trabecular and compact bone of the tibia and radius prospectively in subjects with SCI. SUBJECTS: In total, 10 individuals with an acute SCI. METHODS: Trabecular and compact bone density of the tibia and radius by peripheral quantitative computerised tomography. RESULTS: Analysis of the individual gradients of the curve coefficient showed changes in trabecular bone between -0.19 and -2.46 and in cortical bone between +0.07 and -0.93 in the tibia within 34 months after the SCI. Both trabecular and cortical bone showed a group mean loss of 99 mg/cm(3). No changes were observed in the radius. CONCLUSION: There is a major decrease in tibia mineral density over 3 years; however, no change is observed for the radius mineral content. Large interindividual differences existed in the patterns of loss in the tibia bone substance after SCI. These patterns indicate that there is no steady state of bone mineral density following 3 years of spinal cord injury.

Osteonecrosis diagnosed on MR images of the knee. Relationship to reduced bone mineral density determined by high resolution peripheral quantitative CT.

PURPOSE: To evaluate if osteonecrosis diagnosed on MR images of the knee relates to reduced bone mineral density (BMD) and may be caused by an insufficiency fracture. MATERIAL AND METHODS: Thirty-two consecutive patients (8 men, 24 women; age range 27-82 years, mean 62 years) with MR findings of osteonecrosis of the femoral or tibial condyle were prospectively included. Trabecular and cortical BMD were measured with high resolution peripheral quantitative CT in the non-dominant distal radius and the tibia of the involved extremity. One tibia was not measured due to posttraumatic deformity. RESULTS: The mean trabecular BMD of the radius was 81% of the young-adult average peak BMD (range 19-160%). The mean cortical BMD in the radius was 86% (range 63-108%). The mean trabecular BMD in the tibia was 92% (range 28-160%). The mean cortical BMD in the tibia was 86% (range 49-132%). The values of the trabecular bone of the distal radius (tibia) were normal in 11 (15) patients, osteopenic in 12 (4), and osteoporotic in 9 (12), respectively. The cortical bone values of the distal radius (tibia) were normal in 12 (13) patients, osteopenic in 12 (12), and osteoporotic in 8 (6), respectively. CONCLUSION: Osteoporosis and osteopenia are commonly found in patients with osteonecrosis of the knee as diagnosed on MR images. This indicates that for some patients an insufficiency mechanism may be responsible for the MR findings. However, in the patients with normal bone density other reasons for osteonecrosis may be present.

Comparison of three bone ultrasounds for the discrimination of subjects with and without osteoporotic fractures among 7562 elderly women.

UNLABELLED: Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70-80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS. INTRODUCTION: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening. MATERIAL AND METHODS: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 +/- 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS). RESULTS: Eighty-six women had a history of a traumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200. CONCLUSION: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

Quality controls for two heel bone ultrasounds used in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk Study.

Because of the important morbidity and mortality associated with osteoporosis, it is essential to detect subjects at risk by screening methods, such as bone quantitative ultrasounds (QUSs). Several studies showed that QUS could predict fractures. None, however, compared prospectively different QUS devices, and few data of quality controls (QCs) have been published. The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk is a prospective multicenter study that compared three QUSs for the assessment of hip fracture risk in a population of 7609 women age >/=70 yr. Because the inclusion phase lasted 20 mo, and because 10 centers participated in this study, QC became a major issue. We therefore developed a QC procedure to assess the stability and precision of the devices, and for their cross-calibration. Our study focuses on the two heel QUSs. The water bath system (Achilles+) had a higher precision than the dry system (Sahara). The QC results were highly dependent on temperature. QUS stability was acceptable, but Sahara must be calibrated regularly. A sufficient homogeneity among all the Sahara devices could be demonstrated, whereas significant differences were found among the Achilles+ devices. For speed of sound, 52% of the differences among the Achilles+ was explained by the water s temperature. However, for broadband ultrasound attenuation, a maximal difference of 23% persisted after adjustment for temperature. Because such differences could influence measurements in vivo, it is crucial to develop standardized phantoms to be used in prospective multicenter studies.

Time delay of vagally mediated cardiac baroreflex response varies with autonomic cardiovascular control.

To examine whether changes in autonomic activity have an effect on the latency of the vagally mediated cardiac baroreflex response in humans, we investigated the effects of neck suction fluctuating sinusoidally at 0.2 Hz on R-R intervals (known to be mediated mainly by vagal activity) in the supine position, during 15 degrees head-down tilt and 60 degrees head-up tilt, and during vagotonic (2 microg/kg) and vagolytic (10 microg/kg) doses of atropine while the subjects breathed at 0.25 Hz. The phase shift between fluctuations in neck chamber pressure and in R-R interval was calculated by complex transfer function analysis and was used as a measure of the time delay between carotid baroreceptor stimulation and cardiac effector response. Cardiac baroreflex responsiveness increased significantly during low-dose atropine and decreased during head-up tilt or 10 microg/kg atropine. With increasing tilt angle, the time delay between cyclic baroreceptor stimulation and oscillations in R-R interval increased from 0.32 +/- 0.27 s (head down), to 0.59 +/- 0.25 s (supine position, P < 0.05 vs. head down), and to 0.86 +/- 0.27 s (head up, P < 0.01 vs. supine). Low-dose atropine had a similar effect to head-down tilt on baroreflex latency, whereas 10 microg/kg atropine increased the time delay markedly to 1.24 +/- 0.30 s. Our results demonstrate that changes in autonomic activity, generated either by gravitational stimulus or by atropine, not only affect baroreflex responsiveness but also have a major influence on the latency of the vagally mediated carotid baroreceptor-heart rate reflex. The prolonged baroreflex latency during decreased parasympathetic function may contribute to an unstable regulation of heart rate in patients with cardiac disease.

Dynamic cardiocirculatory control during propofol anesthesia in mechanically ventilated patients.

UNLABELLED: We evaluated dynamic cardiovascular control by spectral analytical methods in 20 young adults anesthetized with propofol (2.5 mg/kg, followed by continuous infusion of 0.1 mg/kg/min) and in an awake control group during cyclic stimulation of the carotid baroreceptors via sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and at 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity). During anesthesia and mechanical ventilation at 0.25 Hz, major underdampened hemodynamic oscillations occurred at 0.055 +/- 0.012 Hz. The response of RR intervals to baroreceptor stimulation at 0.2 Hz was markedly decreased during anesthesia (median of transfer function magnitude between neck suction and RR intervals 3% of the awake control). Blood pressure response to baroreceptor stimulation at 0.1 Hz was significantly decreased during anesthesia to 26% (systolic blood pressure), and 44% (diastolic blood pressure) of the awake control. There was a significant delay in baroreflex effector responses during anesthesia. Our results demonstrate a markedly depressed vagally mediated heart rate response and an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia in mechanically ventilated patients. The disturbed baroreflex control is accompanied by an irregular dynamic behavior of cardiovascular regulation, indicating a decreased stability of the control system. IMPLICATIONS: An irregular dynamic behavior of the cardiovascular control system, associated with an impaired baroreflex control of heart rate and blood pressure, can be observed during propofol anesthesia in mechanically ventilated subjects.

Cardiocirculatory coupling during sinusoidal baroreceptor stimulation and fixed-frequency breathing.

The question of whether respiratory sinus arrhythmia (RSA) originates mainly from a central coupling between respiration and heart rate, or from baroreflex mechanisms, is a subject of controversy. If there is a major contribution of baroreflexes to RSA, cardiocirculatory coupling during breathing and during cyclic baroreflex stimulation should show similarities. We applied a sinusoidal stimulus to the carotid baroreceptors and generated heart rate fluctuations of the same magnitude as RSA with a frequency similar to, but different from, the breathing frequency (0.2 Hz, compared with 0.25 Hz), and at 0.1 Hz, in 17 supine healthy subjects (age 28-39 years). The data were analysed using discrete Fourier-transform and transfer function analysis. Respiratory fluctuations in systolic blood pressure preceded RSA with a time lag equal to that between baroreceptor stimulation and oscillations in RR interval (0.62+/-0.18 s compared with 0.57+/-0.28 s at 0.2 Hz neck suction). The response of systolic blood pressure to neck suction at 0.2 Hz was 5 times less than the respiratory blood pressure fluctuations. Neck suction at 0.1 Hz largely increased fluctuations in blood pressure and RR interval, whereas the spontaneous phase relationship between blood pressure and RR interval remained unchanged. Our results are not consistent with the hypothesis that the origin of RSA is predominantly a central phenomenon which secondarily generates fluctuations in blood pressure, but suggest that, under the condition of fixed-frequency breathing at 0.25 Hz, baroreflex mechanisms contribute to respiratory fluctuations in RR interval.

[Osteoporosis in the male]. / Die Osteoporose des Mannes.

BACKGROUND: Osteoporotic fractures occur frequently also in men. Epidemiologic data from Germany indicate that more than 900,000 men are affected by osteoporotic fractures. Diagnosis and therapy of male osteoporosis are hampered by a lack of clinical studies. DIAGNOSIS: Risk factor analysis, conventional spine X-rays, bone densitometry and a limited number of serum and urine analyses contribute to the diagnosis of osteoporosis and the assessment of future fracture risk. Bone densitometry at the femoral neck is superior to measurements at the lumbar spine because of the high prevalence of degenerative changes at the lumbar spine in elderly men. Major risk factors for osteoporosis are hypogonadism, glucocorticoid therapy, hypercalciuria, gastrointestinal disease, and high alcohol consumption. In individual cases, bone histology or additional biochemical studies are needed to establish the cause of osteoporosis. THERAPY: Calcium and vitamin D deficits should be substituted both in prevention and treatment of male osteoporosis. Testosterone replacement therapy is effective in hypogonadism. In primary osteoporosis and in corticosteroid-induced osteoporosis, bisphosphonates (cyclical etidronate, alendronate) and fluorides are therapeutic options. CONCLUSION: Important principles in the care of men with osteoporosis are the transfer of knowledge established for postmenopausal osteoporosis and the rigorous search for secondary osteoporosis aiming at treatment of the underlying cause. Large prospective randomized trials aiming at the reduction of fracture rate in male osteoporosis are missing. They are urgently needed.

Peripheral volumetric bone mineral density in pre- and postmenopausal Chinese women in Hong Kong.

The aim of this cross-sectional study was to use a newly available precise and multislice pQCT (Densiscan 2000) for establishing reference data of volumetric bone mineral density (vBMD) of the distal radius. vBMD of the nondominant wrist was measured in 118 healthy Hong Kong Chinese women aged 41-60. Anthropometric parameters, menstrual status, and handgrip strength were also measured. Results showed that there was a significant age-related decline in trabecular BMD (tBMD), integral BMD (iBMD), and cortical BMD (cBMD), with correlation coefficients ranging from -0.401 to -0.547 (P < 0.001). The annual decline of vBMD was 2.22%, 1.79%, and 0.88% in tBMD, iBMD, and cBMD, respectively. When subjects were divided into premenopausal and postmenopausal groups, we found an age-related decline in tBMD and iBMD, but not in cBMD in both groups. The vBMD values interpreted in mg/cm3 in premenopausal women were 238.4 +/- 57.2 in tBMD, 604.6 +/- 82.9 in iBMD, 1415.5 +/- 129.9 in cBMD, and declined significantly (all P < 0.001) to 193.7 +/-54.7 in tBMD, 500.0 +/- 90.3 in iBMD, and 1306.7 +/- 153.5 in cBMD in the postmenopausal women. On average, 16.7% of the subjects showed their vBMDs to be below-1 SD and only 1.7% of them lower than -2 SD. Linear regression showed that the annual decline of vBMD was faster in postmenopausal women with 2.42% in tBMD, 1.90% in iBMD, and 0.88% in cBMD compared with 1.91% in tBMD, 0.98% in iBMD, and 0.55% in cBMD in the premenopausal women. After adjustment for age, only the iBMD with dominant trabecular elements showed a significantly accelerated decrease after the onset of menopause (P = 0.008). Weak or no association was found among vBMDs with anthropometric parameters, years since menopause, or handgrip strength. In conclusion, we found a significant age-related decline of vBMDs in Hong Kong Chinese women aged 41-60 years, characterized by the early reduction of metabolically active trabecular bone after entering the fourth decade of life, with an accelerated decline after the onset of menopause.

Longitudinal changes in bone in men with spinal cord injury.

INTRODUCTION: Quantitative bone assessment today is primarily based on the analysis of bone mineral density (BMD). The geometric and structural properties of bone, which are important parameters for skeletal strength, are generally not considered in the routine clinical assessment of spinal cord injury-related osteopenia. OBJECTIVE: To study changes in structural and geometric properties of tibia bone longitudinally by means of peripheral quantitative computerized tomography and a biomechanical test method (bone stiffness measurement device Swing) in 12 subjects with spinal cord injury. DESIGN: Measurements were conducted in the 5th week and around the 104th week after the spinal cord injury in a university hospital. RESULTS: Paired Student's t-tests showed a significant decrease in trabecular (p < 0.05) and cortical bone (p < 0.05), as well as a significant decrease in geometric properties of tibia bone (p < 0.05) within two years after the spinal cord injury. Phase velocity propagation changed in three subjects within two years following the spinal cord injury. CONCLUSIONS: This study indicates that beside changes in tissue composition, changes in bone geometric indices and in structural properties occur in the lower extremity after a spinal cord injury. In the tibia, consideration of geometric and biomechanical parameters of bone combined with bone mineral density measurements could result in an improved screening for spinal cord injury-related osteopenia and the prediction of fracture risk in spinal cord injury.

Bone mineral density in upper and lower extremities during 12 months after spinal cord injury measured by peripheral quantitative computed tomography.

OBJECTIVE: To evaluate the loss of trabecular and cortical bone mineral density in radius, ulna and tibia of spinal cord injured persons with different levels of neurologic lesion after 6, 12 and 24 months of spinal cord injury (SCI). DESIGN: Prospective study in a Paraplegic Centre of the University Hospital Balgrist, Zurich. SUBJECTS AND METHODS: Twenty-nine patients (27 males, two females) were examined by the highly precise peripheral quantitative computed tomography (pQCT) soon after injury and subsequently at 6, 12 and in some cases 24 months after SCI. Using analysis of the bone mineral density (BMD), various degrees of trabecular and cortical bone loss were recognised. A rehabilitation program was started as soon as possible (1-4 weeks) after SCI. The influence of the level of neurological lesion was determined by analysis of variance (ANOVA). Spasticity was assessed by the Ashworth Scale. RESULTS: The trabecular bone mineral density of radius and ulna was significantly reduced in subjects with tetraplegia 6 months (radius 19% less, P<0.01; ulna 6% less, P>0.05) and 12 months after SCI (radius 28% less, P<0.01; ulna 15% less, P<0.05). The cortical bone density was significantly reduced 12 months after SCI (radius 3% less, P<0.05; ulna 4% less, P<0.05). No changes in BMD of trabecular or cortical bone of radius and ulna were detected in subjects with paraplegia. The trabecular BMD of tibia was significantly reduced 6 months (5% less, P<0.05) and 12 months after SCI (15% less, P<0.05) in all subjects with SCI. The cortical bone density of the tibia only was decreased after a year following SCI (7% less, P<0.05). No significant difference between both groups, subjects with paraplegia and subjects with tetraplegia was found for tibia cortical or trabecular BMD. There was no significant influence for the physical activity level or the degree of spasticity on bone mineral density in all subjects with SCI. CONCLUSIONS: Twelve months after SCI a significant decrease of BMD was found in trabecular bone in radius and in tibia of subjects with tetraplegia. In subjects paraplegia, a decrease only in tibia BMD occurred. Intensity of physical activity did not significantly influence the loss of BMD in all subjects with para- and tetraplegia. However, in some subjects regular intensive loading exercise activity in early rehabilitation (tilt table, standing) can possibly attenuate the decrease of BMD of tibia. No influence was found for the degree of spasticity on the bone loss in all subjects with SCI.

Is the amount of trabecular bone-loss dependent on bone mineral Density? A study performed by three centres of osteoporosis using high resolution peripheral quantitative computed tomography.

For the risk getting osteoporosis as well as for diagnosis of osteoporosis 3 facts are highly important: bone-mass, the amount of bone-loss and bone-structures (microarchitecture of bone). All three parameters can be validated today with high precision but the amount of bone-loss seems to be the most important one, even for the decision of either antiresorptive or bone-stimulating therapy. But to calculate the amount of bone-loss until now at least two measurements of bone mineral density (BMD) are necessary which have to be performed within a certain period of time, depending on the reproducibility of the method to be used. If on the other hand the amount of bone-loss would be dependent on actual base-line bone-mass the right therapy could be started already after only one measurement of BMD. The aim of this study was therefore to investigate if there is any relation between the amount of bone-loss and base-line volumetric BMD. For this we separately measured trabecular and cortical bone densities of 135 women in three independent centres of osteoporosis in Zurich and Munich using the method of high resolution quantitative computed tomography - pQCT - with the Densiscan 1000, Scanco Medical, Zurich. We did this at least twice and then compared absolute volumetric BMD in the first step before we calculated trabecular and cortical bone loss per year for each woman. We could not only confirm again that bone loss in trabecular bone was significantly higher than in cortical bone and that the non-weight-bearing trabecular bone as could be found in the distal radius seems to be the skeletal site of maximum bone-loss, but moreover - and this is the more important finding - we could show that the amount of relative bone-loss was the higher the lower trabecular base-line volumetric BMD was. According to this the rate of fast-loser (more than 3.5% per year) increased the lower trabecular base-line volumetric BMD was. These results may lead to a new screening-test for the assessment of the individual risk of osteoporosis and for the individual risk of fast bone-loss which now can be evaluated with only one single measurement of BMD, to treat the so classified patients not only earlier but even more rational, dependent if either antiresorptive therapy or stimulation of bone-formation seems to be more important.

Changes of tibia bone properties after spinal cord injury: effects of early intervention.

OBJECTIVE: To evaluate the effectiveness of an early intervention program for attenuating bone mineral density loss after acute spinal cord injury (SCI) and to estimate the usefulness of a multimodality approach in diagnosing osteoporosis in SCI. DESIGN: A single-case, experimental, multiple-baseline design. SETTING: An SCI center in a university hospital. METHODS: Early loading intervention with weight-bearing by standing and treadmill walking. PATIENTS: Nineteen patients with acute SCI. OUTCOME MEASURES: (1) Bone density by peripheral computed tomography and (2) flexural wave propagation velocity with a biomechanical testing method. RESULTS: Analysis of the bone density data revealed a marked decrease of trabecular bone in the nonintervention subjects, whereas early mobilized subjects showed no or insignificant loss of trabecular bone. A significant change was observed in 3 of 10 subjects for maximal and minimal area moment of inertia. Measurements in 19 subjects 5 weeks postinjury revealed a significant correlation between the calculated bending stiffness of the tibia and the maximal and minimal area moment of inertia, respectively. CONCLUSION: A controlled, single-case, experimental design can contribute to an efficient tracing of the natural history of bone mineral density and can provide relevant information concerning the efficacy of early loading intervention in SCI. The combination of bone density and structural analysis could, in the long term, provide improved fracture risk prediction in patients with SCI and a refined understanding of the bone remodeling processes during initial immobilization after injury.

[Prevention of osteoporosis]. / Prävention der Osteoporose.

The European Parliament presented June 10th in Brussels the 'Osteoporosis Report in EU--Means for Prevention'. It was emphasized that in the EU more than 3500 million Ecu have to be spent for hospitalization and that more than 500,000 hospitals beds are being used by osteoporotic patients. According to some calculations this number will double within the next 50 years. The EU has set up eight steps to be considered, e.g. have densitometric measurements available for persons with high risk and have these measurement paid by the insurances to further finance and support research for the very important areas of prevention and treatment. One distinguishes between primary, secondary and tertiary prevention of osteoporosis. Primary prevention aims at reaching at adolescent age a peak bone mass as high as possible. Secondary prevention aims at reducing bone loss peri- and postmenopausal. The tertiary prevention with manifest osteoporosis aims at preventing fractures. Emphasis of the primary prevention is, besides a sufficient calcium intake, to omit risk factors; with secondary prevention the use of medical treatments such as estrogens/gestagens, bisphosphonates, and recently also SERMs is applied. The tertiary prevention tries mostly to reduce the femur fractures. In addition to drugs such as vitamin D/calcium, vitamin D metabolites and bisphosphonates it is very important to create 'a fall-proof home'. Also very useful are hip protectors.

Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures. Consequences for prophylaxis and treatment.

The importance of serial examinations over time with peripheral quantitative computed tomography (pQCT) is that they enable the detection of patients at high risk of osteoporosis, and the individualisation of prophylaxis and treatment. We have shown that postmenopausal patients with high bone turnover evaluated by biochemical markers are identical to fast bone losers as determined by pQCT. As a consequence, we use agents that inhibit bone resorption in patients who are fast bone losers and agents that stimulate bone formation in patients who are slow bone losers. To visualise bone microarchitecture, and to evaluate bone density and the rate of bone loss, we used a highly sensitive pQCT system (DENSISCAN 1000, reproducibility of 0.3% in a mixed population of normal individuals and patients with osteopenia or osteoporosis). This system enabled us to separately assess trabecular and cortical bone density in the radius and tibia, and to differentiate between fast and slow bone losers within a few months (threshold: 3% loss of trabecular bone density in the radius per year). We have shown that the lower the trabecular bone density in the distal radius, the higher the relative bone loss. To classify patients as slow and fast losers in the future, we may need only one measurement. With this highly precise measurement method, we have shown that calcitonin and etidronate are more effective in fast than in slow bone losers, and that vitamin D metabolites (calcitriol or 1 alpha-calcidol) and estrogens can halt fast bone loss. In conclusion, highly sensitive pQCT enables us to adapt the treatment to different forms of osteoporosis and bone turnover, resulting in an increase in the number of patients successfully treated and also in patient compliance. Because our treatment is based on precise, objective measurements, treatment modifications--especially in those who change from a slow to a fast bone-loser state--can be easily justified.

[Epidemiology of osteoporosis]. / Epidemiologie der Osteoporose.

Osteoporosis is a systemic disease of the skeleton characterized by decreased bone mass and a disturbed microarchitecture of the bone. Its consequences is an increase in fracture risk. In women, the risk of experiencing an osteoporotic fracture once in life is twice as high (30-40%) as in men. In a model using population-based data, it is estimated that 54% of 50-year-old women present an osteoporotic fracture once in their remaining life. Typical osteoporotic fractures involve vertebral bodies, the proximal femur and the forearm. The number of fractures caused by osteoporosis is steadily increasing, due to greater life expectancy in particular. In addition, there is a secular increase in the incidence of fractures. In Switzerland, the number of fractures of the hip per year increased from 5,500 in 1980 to 9,800 in 1990 (VESKA data). The consequences of these fractures for the patients and their life quality and the direct and indirect effects on society are generally underestimated. Mortality and morbidity are both increased in comparison with unfractured persons of the same age. One of the most serious consequences of hip fractures is the loss of functional independence in the elderly; 10% of patients lose their functional independence after such fractures, and about 10% need to be placed in homes. Fractures of the waist lead to hospitalization in about 70% of patients aged over 85, and in many patients with forearm fractures algodystrophy occurs. Hip fractures are responsible for about 175,000 days in hospital per year for all Switzerland. Applied to all fractures caused by osteoporosis, this number may be much higher. Lack of epidemiological data, insufficient methods of investigation and the symptomless and silent development of osteoporosis in its beginnings have in many respects led to severe underestimation of this disease in the past. The extension of this growing worldwide health problem has only recently become apparent in Switzerland, essentially because of increasing life expectancy. The frequency of hip fractures is well documented in Switzerland and comparable with that in the US. It justifies in itself the development of a strategy for prevention and treatment. But because osteoporosis is a systemic disease of the skeleton, additional Swiss data on fractures other than that of the hip, such as vertebral and forearm fractures, would be of great interest, especially in the sector of ambulatory medicine.