Sex‐specific responses of bone metabolism and renal stone risk during bed rest

Abstract

The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex‐specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head‐down‐tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14–90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content (P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women (P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest.

Effects of microgravity simulation on zebrafish transcriptomes and bone physiology—exposure starting at 5 days post fertilization

“…The clinorotation results are also in line with the well-established bone loss experienced by astronauts in space or bed rest studies, 1,2 and with the space experiments performed on rats 25–28 or mice. 29 Microgravity caused effects ranging from decreased trabecular numbers 27,29 and thickness 27 in tibia to a decreased mineral content and number of osteoblasts.…”

Long-duration bed rest as an analog to microgravity

“…However, it should be noted that osteoblastic activity (57,120,127) is decreased in the iliac crest. The release of calcium from bone is expected to suppress parathyroid hormone (PTH), which in turn is associated with a drop in circulating 1,25-dihydroxyvitamin D. This is indeed what occurs in some but not all bed rest studies (6,59,72,100,102,103,116,118). When present, these hormonal changes are likely to occur in response to bone cellular activity alterations.…”

“…At this stage we need to take great care in the interpretation of these sex-specific differences, because individual variability exceeds the variability between sexes (3, 83). Furthermore, by combining data from five HDT bed rest studies (n ϭ 50 men, 24 women) of 14-90 days, Morgan and coworkers (72) report that as far as aBMD, bone biochemistry, and renal stone risk are concerned, men and women do not have different skeletal responses with bed rest.…”

“…Urinary calcium excretion increases as early as the first day of bed rest, and urinary CTX and NTX excretion significantly increases on the second day of bed rest (6,44). Such increases in urinary calcium along with diminished urine volume (38,58,72) bring concerns about the risk of renal stone formation (47,69,79,122,126). It is not yet clear whether bone resorption activity increases with time of inactivity (72,116) or whether a plateau is reached around the 20th day of bed rest at 50 -150% above pre-bed rest values (48,101).…”

“…Such increases in urinary calcium along with diminished urine volume (38,58,72) bring concerns about the risk of renal stone formation (47,69,79,122,126). It is not yet clear whether bone resorption activity increases with time of inactivity (72,116) or whether a plateau is reached around the 20th day of bed rest at 50 -150% above pre-bed rest values (48,101). Of note, urine phosphorus excretion follows a similar trend as calcium but to a lesser extent (29,127).…”