Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest.

BACKGROUND: The associations between nitrogen metabolism and bone turnover during bed rest are still not completely understood. METHODS: We measured nitrogen balance (nitrogen intake minus urinary nitrogen excretion) and biochemical metabolic markers of calcium and bone turnover in six males before head-down tilt bed rest (baseline), during 2, 10, and 14 weeks of immobilization, and after reambulation. RESULTS: The changes in nitrogen balance were highest between baseline and week 2 (net change, -5.05 +/- 1.30 g/day; 3.6 +/- 0.6 g/day at baseline vs -1.45 +/- 1.3 g/day at week 2; P<0.05). In parallel, serum intact osteocalcin (a marker of bone formation) was already reduced and renal calcium and phosphorus excretions were increased at week 2 (P <0.05). Fasting serum calcium and phosphorus values and renal excretion of N-telopeptide (a bone resorption marker) were enhanced at weeks 10 and 14 (P <0.05-0.001), whereas serum concentrations of parathyroid hormone, calcitriol, and type I collagen propeptide (a marker of bone collagen formation) were decreased at week 14 (P <0.05-0.01). Significant associations were present between changes of serum intact osteocalcin and 24-h calcium excretion (P <0.001), nitrogen balance and 24-h phosphorus excretion (P <0.001), nitrogen balance and renal N-telopeptide excretion (P <0.05), and between serum osteocalcin and nitrogen balance (P <0.025). CONCLUSIONS: Bone formation decreases rapidly during immobilization in parallel with a higher renal excretion of intestinally absorbed calcium. These changes appear in association with the onset of a negative nitrogen balance, but decreased bone collagen synthesis and enhanced collagen breakdown occur after a time lag of several weeks.

Microgravity inhibits intestinal calcium absorption as shown by a stable strontium test.

BACKGROUND: Little is known about the onset and degree of biochemical and functional alterations in calcium metabolism during microgravity. OBJECTIVE: To evaluate the effect of microgravity on intestinal calcium absorption and calcium-regulating hormones under metabolic ward conditions. MATERIALS AND METHODS: Fractional calcium absorption (Fc240 in percentage of dose administered) was determined pre-flight, in-flight and post-flight, by use of a stable strontium test in one cosmonaut who spent 20 days in space. Moreover, a sequence of blood samples was collected for the determination of serum parathyroid hormone (PTH), 25-hydroxyvitamin D, calcitriol and serum C-telopeptide (CTx, biomarker of bone resorption) levels. During all periods of data collection, calcium intake was held constant at a minimum level of 1.000 mg day(-1) and a daily supplement of 16.6 microg vitamin D2 was given. Personal ultraviolet (UV) light exposure was measured during the whole mission using a biologically weighting UV dosimeter. RESULTS: Fc240 was markedly reduced on flight day 19 (4.4%) as compared to pre-flight and post-flight data (13.4% and 17.2%, respectively). Serum calcitriol levels fell from 40.6 pg mL(-1) (mean pre-flight level) to 1.3 pg mL(-1) on flight day 18 and returned into the normal range after recovery. Serum CTx increased during the flight, while serum PTH and 25-hydroxyvitamin D levels did not change significantly. CONCLUSIONS: Intestinal calcium absorption can be diminished after only three weeks of microgravity. Changes are associated with a severe suppression of circulating calcitriol levels, but are independent of exogenous vitamin D supply and serum PTH levels.

Calcium metabolism in microgravity.

Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission where we investigated the effects of high calcium intake (>1000 mg/d) and vitamin D supplementation (650 IU/d) on the calcium and bone metabolism during 21 days in microgravity. In the MIR 97 mission high calcium intake and vitamin D supplementation led to high ionized calcium levels and a marked decrease in calcitriol levels together with decreased bone formation and increased bone resorption markers. Our conclusion from the MIR 97 mission is that an adequate calcium intake and vitamin D supplementation during space missions is mandatory but, in contrast to terrestrial conditions, does not efficiently counteract the development of space osteoporosis.

Effects of elevated carbon dioxide environment on calcium metabolism in humans.

BACKGROUND: Chronic respiratory acidosis induced by an elevated carbon dioxide (CO2) environment should provoke hypercalciuria with related total body and subsequent bone calcium losses. We examined this hypothesis in four healthy male volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment within a deep diving isolation chamber. Three months later the same subjects were reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere. METHODS: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium intake minus urinary and fecal calcium output) was evaluated. Serum calcium concentrations and biomarkers of bone metabolism were measured, in order to evaluate bone turnover. Additionally, the response to an acute oral calcium load was examined as a sensitive measure of changes in calcium metabolism. RESULTS: Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/- SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to 996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2 atmosphere. Although more calcium was retained in the body during the 1.2% than during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone formation were significantly lower in the higher CO2 campaign. Furthermore, bone resorption was slightly increased in the 1.2% experiment. CONCLUSION: Elevated CO2 atmosphere may dose-dependently preserve body calcium without a parallel improvement of bone substance.

Plasmatic factors of haemostasis remain essentially unchanged except for PAI activity during n-3 fatty acid intake in type I diabetes mellitus.

Diabetic patients are prone to develop vascular complications. Increased procoagulatory factors and a reduced fibrinolytic potential are considered as thrombogenic risk factors, although controversy remains. In epidemiological and dietary intervention studies fish or fish oil, rich in the two n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have demonstrated a potential to reduce cardiovascular disease. We compared the plasmatic coagulatory and fibrinolytic profile of 13 near normoglycaemic type I diabetics almost free of cardiovascular disease with healthy volunteers, matched for age and sex. Except for fibrinogen levels and tPA activity being elevated and soluble fibrin and fibrinopeptide A being reduced, no differences could be discerned between type I diabetics and controls in all investigated plasmatic parameters. In a dietary intervention study we investigated the effects of 5.4 g EPA and 2.7 g DHA per day during and after a 4-week dietary supplementation in the diabetic patients. The factors, inhibitors and activation products of coagulation and fibrinolysis measured were at best transiently affected by the diet. Only plasminogen activator inhibitory activity in plasma significantly increased during the dietary supplementation and returned to prediet values after cessation of n-3 fatty acids. Changes in PAI activity were negatively correlated to changes in serum triglycerides. We conclude that well adjusted type I diabetics show an almost unchanged haemostatic profile compared to matched healthy controls. A dietary intervention with n-3 fatty acids in these patients does not affect the plasmatic haemostatic pattern except for an increase in PAI activity.

Pilot study on omega-3 fatty acids in type I diabetes mellitus.

Patients with diabetes mellitus are prone to develop vascular complications. Because omega-3 polyunsaturated fatty acid (omega 3FA) intake has a potential protective effect on cardiovascular disease, we studied the influence of omega 3FA supplementation (5.4 g eicosapentaenoic acid and 2.3 g docosahexaenoic acid daily) for 4 wk in 13 well-controlled type I (insulin-dependent) diabetic subjects on a vascular risk profile. Each subject served as his/her own control in a pre- and post-omega 3FA-intake phase. In plasma and platelets, phospholipids eicosapentaenoic acid and docosahexaenoic acid increased at the expense of arachidonic acid and linoleic acid. There was no significant change in blood pressure and glycosylated proteins. Only small changes were noted in blood glucose levels and insulin dose. Side effects were not noted. Triglycerides decreased significantly in the first 14 days, and total cholesterol increased slightly, probably because of an elevation of high-density lipoprotein cholesterol, although low-density lipoprotein cholesterol remained unchanged. Platelet aggregation induced by low doses of ADP and collagen, which was higher in diabetic than nondiabetic subjects, decreased during omega 3FA intake to levels of healthy control subjects. Thromboxane production after ADP- and collagen-induced platelet aggregation decreased significantly. Thromboxane liberation during clotting of whole blood and urinary excretion of thromboxane were markedly lowered during omega 3FA supplementation. The results show that even short-term intake of omega 3FAs leads to beneficial changes of vascular risk factors without significant changes in glucose homeostasis.