Maintenance of Serum Ionized Calcium During Exercise Attenuates Parathyroid Hormone and Bone Resorption Responses

Abstract

Exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption. We used a novel intravenous iCa clamp technique to determine whether preventing a decline in serum iCa during exercise prevents increases in PTH and carboxy-terminal collagen crosslinks (CTX). Eleven cycling-trained men (aged 18 to 45 years) underwent two identical 60-min cycling bouts with infusion of Ca gluconate or saline. Blood sampling for iCa, total calcium (tCa), PTH, CTX, and procollagen type 1 amino-terminal propeptide (P1NP) occurred before, during, and for 4 hours after exercise; results are presented as unadjusted and adjusted for plasma volume shifts (denoted with subscript ADJ). iCa decreased during exercise with saline infusion (p = 0.01 at 60 min) and this was prevented by Ca infusion (interaction, p < 0.007); there were abrupt decreases in Ca content (iCa and tCa ) in the first 15 min of exercise under both conditions. PTH and CTX were increased at the end of exercise (both p < 0.01) on the saline day, and markedly attenuated (-65% and -71%; both p < 0.001) by Ca. CTX remained elevated for 4 hours after exercise on the saline day (p < 0.001), despite the return of PTH to baseline by 1 hour after exercise. P1NP increased in response to exercise (p < 0.001), with no difference between conditions, but the increase in P1NP was not significant. Results for PTH and CTX were similar to unadjusted results. These findings demonstrate that bone resorption is stimulated early in exercise to defend serum iCa. Vascular Ca content decreased early in exercise, but neither the reason why this occurred, nor the fate of Ca, are known. The results suggest that the exercise-induced increase in PTH had an acute catabolic effect on bone. Future research should determine whether the increase in PTH generates an anabolic response that occurs more than 4 hours after exercise. © 2018 American Society for Bone and Mineral Research.

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

“…Importantly, results from endurance exercise trials, particularly in the elderly, are even less convincing, with some studies showing preservation of bone mass and others showing no effect or even bone loss (Braam et al, 2003; Duckham et al, 2013; Scofield and Hecht, 2012). Consistent with the latter effect, brief bouts of endurance training have been shown to increase bone resorption and stimulate sclerostin, an endogenous inhibitor of bone formation (Baron and Kneissel, 2013; Kohrt et al, 2018; Pickering et al, 2017). Sclerostin is produced almost exclusively by osteocytes, the ‘command and control’ cells of the bone remodeling unit (Bonewald, 2011; van Bezooijen et al, 2004).…”

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

“…In addition to the lack of evidence discussed above, the timing of changes in Ca homeostasis during exercise does not agree with the sweat Ca loss hypothesis. As pointed out by Kohrt et al [278], because the decrease in serum ionized [Ca] occurs early in exercise (first 15 min) it is unlikely that the extent of Ca loss would be large enough to impact Ca homeostasis. Furthermore, while in extreme circumstances excess mineral loss cannot be ruled out as a contributing factor to suboptimal trace mineral status [290], for most athletes the main routes of loss are likely through other avenues such as urine or the gastrointestinal tract [249,291,292].…”

“…Other papers have suggested that sweat or dermal Ca losses in athletes may contribute to reduced bone mineral density through stimulation of parathyroid hormone during training [226,272,273]. However, the balance of the evidence suggests that sweat losses probably contribute minimally to whole-body trace mineral and vitamin deficiencies [134,148,250,253,[274][275][276][277][278][279].…”

“…It is important to note that Ca supplementation (or infusion) can attenuate increases in PTH and activation of bone resorption during exercise [278,287,288]; however, the underlying mechanism is apparently unrelated to replacement of sweat Ca loss. In addition to the lack of evidence discussed above, the timing of changes in Ca homeostasis during exercise does not agree with the sweat Ca loss hypothesis.…”

Irisin Directly Stimulates Osteoclastogenesis and Bone ResorptionIn VitroandIn Vivo

“…While further studies are necessary to fully elucidate the mechanisms of irisin actions on bone, the present work adds to previous studies demonstrating this myokine’s ability to both act directly on bone cells of distinct origin, and to modulate signaling from one cell type to one another. This may have major physiologic relevance since one acute effect of intense physical activity is a decrease in serum calcium, followed by a secondary rise in parathyroid hormone 9 . In the context of our experimental paradigm, it is conceivable that irisin represents another but more acute counter-regulatory hormone that works during the first minutes of exercise to tightly maintain serum calcium levels by its direct actions on osteoclasts and through osteocytic osteolysis.…”