[Therapy of osteoporosis: bisphosphonates, SERM's, teriparatide and strontium]. / Osteoporosebehandlung: Bisphosphonate, SERM's, Teriparatide und Strontium.

The therapy of osteoporosis is mostly based upon the use of drugs which inhibit bone resorption. Among these, the bisphosphonate family is the best known and mostly used by clinicians. Both second and third generation bisphosphonates, like alendronate and risedronate, are now available as weekly tablets which have facilitated the patient compliance to treatment together with a decreased occurrence of gastrointestinal side effects. These compounds are used efficiently to treat postmenopausal osteoporosis and osteoporosis of men as well. Their use did provide good evidence of increased bone mineral density (BMD) and a reduction in fracture rates. The use of intravenous bisphosphonates such as Zoledronate, Ibandronate and Pamidronate remains in most of the cases limited to special indications such as intolerance to the oral formulations and treatment of patients with bone metastases. The selective estrogen modulators (SERM's) family is limited to a single product on the market as of now, Raloxifene, which does inhibit bone resorption and is well documented by postmenopausal women to increase BMD and reduce vertebral fractures. In addition, a large range of positive nonosseous effects have been documented such as the reduction of the incidence of breast cancer. Other substances do have a strong anabolic effect such as Teriparatide, a recombinant human formulation of PTH 1-34. This compound has demonstrated good efficacy in postmenopausal women, increasing vertebral and hip BMD and reducing the incidence of fractures at both sites. The exact role of Teriparatide in the clinical setting is still open but its overall impact in the therapy of osteoporosis could be major due to its major efficiency over shorter periods of time. Strontium ranelate, a new divalent Strontium salt taken orally, acts both as an anti-catabolic and anabolic agent. The first results provided with strontium ranelate are very promising due to its major effect on the increase in BMD both at the vertebral and hip sites and its ability to reduce the incidence of fractures at both locations. Additional data are awaited to confirm these initial positive results.

Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners.

OBJECTIVE: Marathon runners have an increased risk of developing joint disease. During and after a 42-km run, elevation of multiple cytokines occurs in the blood, reflecting inflammatory processes. We compared this cytokine response with serum levels of cartilage oligomeric matrix protein (COMP) and melanoma inhibitory activity (MIA), two markers for joint metabolism and/or damage. METHODS: Serum from eight endurance-trained runners was collected shortly before the start of a marathon run, after 31 km, 42 km, 2 h after the end, on the first and on the second morning after the run. For comparison, serum was obtained from 35 healthy controls and 80 patients with knee joint injury, rheumatoid arthritis or osteoarthritis. Serum levels of C-reactive protein (CRP), interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble interleukin-6 receptor (sIL-6R, gp80), soluble tumor necrosis factor receptor II (sTNFRII, p75), COMP and MIA were measured by ELISA. RESULTS: Compared with healthy controls, the runner's baseline serum levels of TNF-alpha, sIL-6R, COMP and MIA were significantly increased. COMP and MIA levels, higher than the upper normal limits of 5 microg/ml and 6 ng/ml respectively, were found in seven and five of eight runners. The elevated levels of COMP were similar to those found in joint injury or osteoarthritis, and the elevated levels of MIA were comparable to those reported in rheumatoid arthritis. During the run, the serum levels of IL-1RA, IL-6, TNF-alpha and COMP rose significantly, and gradually returned to baseline within 24 h. Only modest changes of CRP, sIL-6R, sTNFRII and MIA occurred during the run. Late elevations of CRP and MIA were observed after 24 and 48 h. The correlation analysis suggests associations between COMP, sIL-6R, TNF-alpha, IL-1RA on one hand and sTNFRII, and MIA and CRP on the other hand. CONCLUSIONS: Elevated baseline levels of COMP and MIA might reflect increased joint matrix turnover and/or damage due to prior extreme physical training. During the run, COMP was increasing possibly due to the severe physical strain on joint structures, associated with the early inflammation. After the run, MIA and CRP increased within 24 h, suggesting a correlation with later inflammatory processes. Thus, our data suggest that COMP and MIA are markers for distinct aspects of joint metabolism and/or damage in both disease and sport.

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.

Retroperitoneal abscess and bacteremia due to Mycoplasma hominis in a polytraumatized man.

We report a case of a retroperitoneal abscess due to Mycoplasma hominis in a young polytraumatized man who developed septicemia under treatment with rifampin and flucloxacillin. M. hominis was recovered from blood cultures as well as from the abscess near the left iliac spine. After 10 days of therapy with clindamycin the patient improved, and intraoperatively taken swabs were culture negative but still positive by PCR.

Metabolic effects of a protein-supplemented carbohydrate drink in marathon runners.

A field study was performed to investigate the acute influence of a milk protein hydrolysate supplemented drink (CHO+PRO) on metabolism during and after a marathon run compared to the same drink without protein (CHO). Carbohydrate metabolites and hormones were not influenced by CHO+PRO. Levels of plasma free fatty acids were significantly lower and levels of urea and most amino acids were significantly higher with CHO+PRO. Sweat urea and ammonia nitrogen excretion during the run as well as urinary 3-methylhistidine excretion during the entire exercise day was similar in both treatments. Urinary total nitrogen was significantly increased and urinary pH decreased with CHO+PRO. It was concluded that the supplemented protein was absorbed and probably at least partially oxidized during the run and that no obvious negative metabolic effects occurred. CHO+PRO did not acutely affect myofibrillar protein breakdown as assessed by the 3-methylhistidine method; however, total body protein breakdown was not measured.

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.

Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run.

BACKGROUND: Athletes consume arginine and/or aspartate as potential nutritional ergogenics. Their metabolic effects are controversial and there is some evidence that ingestion of large doses of single amino acids can adversely affect the nitrogen balance or induce an amino acid imbalance. Nevertheless, the general metabolic influence of an arginine aspartate supplementation during a prolonged exercise bout has not yet been investigated. AIM OF THE STUDY: The aim of this study was, therefore, to investigate the general metabolic impact of a chronic supplementation with arginine aspartate in endurance-trained athletes at rest and during a marathon run. METHODS: Fourteen endurance-trained runners participated in this field study which was carried out according to a double-blind crossover design. 15 g of arginine aspartate or a carbohydrate-based placebo were supplemented daily for 14 days before a marathon run. Blood samples for analysis of metabolites and hormones were collected shortly before the run, after 31 km, at the end of the run, and after a recovery period of two hours. Additionally, the respiratory exchange ratio was determined during the run. RESULTS: The plasma level of carbohydrate (glucose, lactate, pyruvate) and fat metabolites (fatty acids, glycerol, beta-hydroxybutyrate), cortisol, insulin, ammonia, lactate dehydrogenase, and creatine kinase as well as the respiratory exchange ratio were unaffected by the supplementation. In contrast, the plasma level of somatotropic hormone, glucagon, urea, and arginine were significantly increased, and the level of most of the remaining plasma amino acids as well as their sum was significantly reduced. CONCLUSIONS: There was no obvious metabolic benefit derived from the chronic supplementation with arginine aspartate. And since furthermore the consequences of a reduction of the total plasma amino acid level are not known, the practice of using single amino acid supplements as potential ergogenics should be critically reevaluated.

Exercise-induced sweat nitrogen excretion: evaluation of a regional collection method using gauze pads.

The exercise-induced sweat nitrogen excretion was investigated during a 45-minute run at moderate intensity on a treadmill. Sweat was collected with a regional collection technique using gauze pads and compared with the whole-body wash-down (WBW) method. In the regional collection, sweat was sampled from the upper back (UB), lower back (LB), abdomen (AB), and thigh (TH). Additionally, the relation of sweat urea, ammonia, and amino acids was investigated with the regional collection method during a second 45-minute run. Independent of the sweat collection method, a significant and positive correlation was found between sweat rate and the excretion rate of the largest nitrogen fraction urea, suggesting that the sweating response to exercise might be one of the most important factors determining absolute sweat nitrogen losses. The urea nitrogen excretion was nearly 140 mg.h-1 in the second run, representing the largest nitrogen fraction. Ammonia nitrogen and amino acid-derived nitrogen rate were approximately 30 mg.h-1 and 10 mg.h-1, respectively. The comparison of the sampling methods during the first run revealed that the urea nitrogen rate was significantly higher, but the ammonia nitrogen rate significantly lower in the WBW. After summing urea and ammonia nitrogen, no significant difference between the methods was observed anymore, except for UB. It is concluded that the regional collection method using gauze pads is a valuable approach to measure exercise-induced sweat nitrogen losses during moderate running exercise.

Breakfasts with different fiber and macronutrient contents do not differentially affect timing, size or microstructure of the subsequent lunch.

The effects of four equienergetic breakfasts with varying fiber and macronutrient contents on hunger and satiety ratings, on subsequent lunch intake, and on postprandial carbohydrate and fat metabolism were investigated in normal weight male subjects in two experiments, in which lunch was offered at a predetermined time (Experiment 1) or in which the subjects were free to choose when to eat lunch (Experiment 2). Consumption of either a commercially available high fiber cereal (HFC, 10% fiber), a medium fiber cereal (MFC, 7% fiber), a low fiber cereal (LFC, 3% fiber), or a standard continental breakfast (0% fiber) on nonconsecutive days did not differentially affect hunger and satiety ratings, the size or microstructure of the subsequent lunch, and the breakfast to lunch intermeal interval (in Experiment 2). Plasma concentrations of glucose, lactate, and insulin increased more after the LFC breakfast than after the other breakfast varieties. A reactive postprandial hypoglycaemia occurred after the LFC breakfast, shortly before lunch. The plasma concentrations of fat metabolites (triglycerides, free fatty acids, beta-hydroxybutyrate) and of glucagon were not differentially affected by the breakfast varieties. The results are consistent with the assumption that energy content of a meal is the major determinant of subsequent energy intake in man and the fiber content and macronutrient composition have only a modulating effect.

Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study.

A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, beta-hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.

[Muscle aches and biochemical changes following a ultra-marathon in the cold--modification by diclofenac]. / Muskelschmerzen und biochemische Veränderungen nach einem Ultramarathon in der Kälte--Beeinflussung durch Diclofenac.

After the Swiss Alpine Marathon in Davos (67 km, altitude difference of 2300 m) the majority of the athletes are suffering from muscle soreness. The goal of the study was therefore to investigate muscle damage, inflammatory reactions and soreness perception during and after this ultramarathon. 27 athletes took part in the study. Creatine-kinase (CK) and C-reactive protein (CRP) were measured 24 hours before the race, immediately before and after the race as well as 2 hours, 24 hours and 48 hours, after the race respectively. Muscle soreness of the lower extremities before and during stretching were assessed at the same time points using a visual analog scale from 1 to 10 (VAS). Significant CK elevations were found in all runners ranging from 600 to 28,000 U/l. Compared to the values before and 48 hours after the start all athletes showed 24 hours after the start significantly elevated CRP values, indicating a pronounced systemic inflammatory reaction. Immediately after the race all runners reported a significantly elevated muscle soreness with maximal pain in the posterior muscles of the lower leg. In order to assess the influence of a nonsteroidal antiinflammatory agent on muscle damage, muscle soreness and inflammatory reactions 16 of the 27 runners received *Diclofenac SR. We were unable to find a difference in the mean plasma CK and CRP activity after the race between both groups, but there was a highly significant, till now to our knowledge never described correlation between the degree of muscle damage and systemic inflammatory reaction (r = 0.75, p < 0.02) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)