The negative effect of unloading exceeds the bone-sparing effect of alkaline supplementation: a bed rest study.

Potassium bicarbonate was administrated to an already alkaline diet in seven male subjects during a 21-day bed rest study and was able to decrease bed rest induced increased calcium excretion but failed to prevent bed rest-induced bone resorption. INTRODUCTION: Supplementation with alkali salts appears to positively influence calcium and bone metabolism and, thus, could be a countermeasure for population groups with an increased risk for bone loss. However, the extent to which alkalization counteracts acid-induced bone resorption or whether it merely has a calcium and bone maintenance effect is still not completely understood. In the present study, we hypothesized that additional alkalization to an already alkaline diet can further counteract bed rest-induced bone loss. METHODS: Seven healthy male subjects completed two parts of a crossover designed 21-day bed rest study: bed rest only (control) and bed rest supplemented with 90 mmol potassium bicarbonate (KHCO3) daily. RESULTS: KHCO3supplementation during bed rest resulted in a more alkaline status compared to the control intervention, demonstrated by the increase in pH and buffer capacity level (pH p = 0.023, HCO3p = 0.02, ABE p = 0.03). Urinary calcium excretion was decreased during KHCO3 supplementation (control 6.05 ± 2.74 mmol/24 h; KHCO3 4.87 ± 2.21 mmol/24 h, p = 0.03); whereas, bone formation was not affected by additional alkalization (bAP p = 0.58; PINP p = 0.60). Bone resorption marker UCTX tended to be lower during alkaline supplementation (UCTX p = 0.16). CONCLUSIONS: The more alkaline acid-base status, achieved by KHCO3 supplementation, reduced renal calcium excretion during bed rest, but was not able to prevent immobilization-induced bone resorption. However, advantages of alkaline salts on bone metabolism may occur under acidic metabolic conditions or with respect to the positive effect of reduced calcium excretion within a longer time frame. TRIAL REGISTRATION: Trial number: NCT01509456.

Whey protein plus bicarbonate supplement has little effects on structural atrophy and proteolysis marker immunopatterns in skeletal muscle disuse during 21 days of bed rest.

OBJECTIVES: To investigate the effect of whey protein plus potassium bicarbonate supplement on disused skeletal muscle structure and proteolysis after bed rest (BR). METHODS: Soleus (SOL) and vastus lateralis (VL) biopsies were sampled from ten (n=10) healthy male subjects (aged 31±6 years) who did BR once with and once without protein supplement as a dietary countermeasure (cross-over study design). The structural changes (myofibre size and type distribution) were analysed by histological sections, and muscle protein breakdown indirectly via the proteolysis markers, calpain 1 and 3, calpastatin, MuRF1 and 2, both in muscle homogenates and by immunohistochemistry. RESULTS: BR caused size-changes in myofiber cross-sectional area (FCSA, SOL, p=0,004; VL, p=0.03), and myofiber slow-to-fast type transition with increased hybrids (SOL, p=0.043; VL, p=0.037) however with campaign differences in SOL (p<0.033). No significant effect of BR and supplement was found by any of the key proteolysis markers. CONCLUSIONS: Campaign differences in structural muscle adaptation may be an issue in cross-over design BR studies. The whey protein plus potassium bicarbonate supplement did not attenuate atrophy and fibre type transition during medium term bed rest. Alkaline whey protein supplements may however be beneficial as adjuncts to exercise countermeasures in disuse.

Whole-body vibration can reduce calciuria induced by high protein intakes and may counteract bone resorption: A preliminary study.

Excess protein intake can adversely affect the bone via an increase in calcium excretion, while suitable mechanical loading promotes osteogenesis. We therefore investigated whether vibration exposure could alleviate the bone mineral losses associated with a metabolic acidosis. Ten healthy individuals aged 22 - 29 years (median = 25) underwent three 5-day study periods while monitoring their dietary intake. The study consisted of recording the participants' usual dietary intake for 5 consecutive days. Participants were then randomly divided into two groups, one of which received a protein supplement (2 g x kg(-1) body mass x day(-1); n = 5) and the other whole-body low-magnitude (3.5 g), low-frequency (30 Hz) mechanical vibration (WBV) delivered through a specially designed vibrating plate for 10 min each day (n = 5). Finally, for the third treatment period, all participants consumed the protein supplement added to their normal diet and were exposed to WBV exercise for 10 min per day. Daily urine samples were collected throughout the experimental periods to determine the excretion of calcium, phosphate, titratable acid, urea, and C-telopeptide. As expected, when the participants underwent the high protein intake, there was an increase in urinary excretion rates of calcium (P < 0.001), phosphate (P < 0.003), urea (P < 0.001), titratable acid (P < 0.001), and C-telopeptide (P < 0.05) compared with baseline values. However, high protein intake coupled with vibration stimulation resulted in a significant reduction in urinary calcium (P = 0.006), phosphate excretion (P = 0.021), and C-telopeptide (P < 0.05) compared with protein intake alone, but did not affect titratable acid and urea output. The participants showed no effect of WBV exercise alone on urinary excretion of calcium, phosphate, urea, titratable acid, or C-telopeptide. The results indicate that vibration stimulation can moderate the increase in bone resorption and reduction in bone formation caused by a metabolic acidosis.

Dietary treatment enhances bone formation in malnourished patients.

Patients with anorexia nervosa often suffer from osteopenia or osteoporosis. We therefore examined if a dietary treatment including an individually determined high caloric intake, Calcium and Vitamin D supplementation would improve bone metabolism in these patients. We studied 19 female patients aged 14.1 years, BMI 14.2 kg/m 2 and a healthy control group aged 15.1 years, BMI 20.8 kg/m 2 . The subjects were studied at baseline and at several fixed points of time during one year of treatment for bone formation and resorption markers. During the treatment there were no changes in the resorption marker CTX. After 15 weeks we found a significant increase of the bone formation marker PICP. Thus dietary treatment seems to be a promising tool to counteract bone loss in these patients.

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.

Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts.

BACKGROUND: Microgravity induces bone loss by mechanism(s) that remain largely unknown. METHODS: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. RESULTS: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. CONCLUSION: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

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.

Biological dosimetry to determine the UV radiation climate inside the MIR station and its role in vitamin D biosynthesis.

The vitamin D synthesis in the human skin, is absolutely dependent on UVB radiation. Natural UVB from sunlight is normally absent in the closed environment of a space station like MIR. Therefore it was necessary to investigate the UV radiation climate inside the station resulting from different lamps as well as from occasional solar irradiation behind a UV-transparent quartz window. Biofilms, biologically weighting and integrating UV dosimeters successfully applied on Earth (e.g. in Antarctica) and in space (D-2, Biopan I) were used to determine the biological effectiveness of the UV radiation climate at different locations in the space station. Biofilms were also used to determine the personal UV dose of an individual cosmonaut. These UV data were correlated with the concentration of vitamin D in the cosmonaut's blood and the dietary vitamin D intake. The results showed that the UV radiation climate inside the Mir station is not sufficient for an adequate supply of vitamin D, which should therefore be secured either by vitamin D supplemental and/or by the regular exposure to special UV lamps like those in sun-beds. The use of natural solar UV radiation through the quartz window for 'sunbathing' is dangerous and should be avoided even for short exposure periods.