Nitrogen Metabolism and Bone Metabolism Markers in Healthy Adults during 16 Weeks of Bed Rest

Abstract

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.

Bone resorption is induced on the second day of bed rest: results of a controlled crossover trial

“…Enhanced osteoclast activity is seen in astronauts or people in bed rest (3,4,17,19). In the ambulatory control phase, the volunteers showed a daily calcium excretion of 206 mg. During bed rest, calcium excretion rose significantly to 240 mg/day while their diet was unchanged.…”

“…Several studies (7,18) have provided evidence for a close correlation between bone mass and muscle mass. Recent human studies (2,17) have also demonstrated that body nitrogen and muscle mass rapidly decrease with bed rest. Scheld et al (17) have even shown that there is a rapid loss of body nitrogen during the first 2 wk of bed rest.…”

“…Recent human studies (2,17) have also demonstrated that body nitrogen and muscle mass rapidly decrease with bed rest. Scheld et al (17) have even shown that there is a rapid loss of body nitrogen during the first 2 wk of bed rest. However, the kinetics of changes in nitrogen metabolism compared with bone turnover during short-term bed rest are, to the best of our knowledge, not yet known.…”

Using biochemical markers of bone turnover in clinical practice

“…Studies of normal volunteers placed on bed rest indicate that urinary CTx and NTx excretion increase significantly after 24 hours, no Early changes in formation markers predict later changes in density 49 In a 16-week study of bed rest in volunteers, markers of bone formation were reduced and markers of bone resorption increased, demonstrating the mechanisms for the profound and rapid loss of bone in immobilized patients. 50 In a long-term cross-sectional study of paraplegic men with spinal cord injuries, bone turnover patterns changed over time. 51 During the first year after injury, urinary deoxypyridinoline excretion was markedly elevated, whereas blood total alkaline phosphatase and osteocalcin levels were normal to slightly elevated.…”

Effects of 60‐day head‐down bed rest on osteocalcin, glycolipid metabolism and their association with or without resistance training

“…Scheld reported that serum osteocalcin was already reduced and renal calcium and phosphorus excretions were increased at the second week during bed rest. 22 Kim et al showed that levels of osteocalcin declined with an absolute increase in bone resorption and reduced bone formation after simulated microgravity for 14 days. 23 During 90-day bed rest, osteocalcin and bone resorption markers such as serum RANKL, OPG did not show consistent change at all time points.…”