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_ADJ and tCa_ADJ ) 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_ADJ was not significant. Results for PTH_ADJ and CTX_ADJ 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.

Keywords: BIOCHEMICAL MARKERS OF BONE TURNOVER; BONE MODELING AND REMODELING; EXERCISE.

Fig. 1.

Experimental approach. Black arrows indicate blood sampling times for the measurement of serum iCa, PTH, and CTX. Gray arrows indicate urine collection times.

Fig. 2.

Serum ionized (A) and total calcium (C) concentrations before, during, and after 60 min of cycling exercise during conditions of saline (open symbols, dashed lines) and calcium infusion (closed symbols, solid lines). Adjustments for plasma volume shifts (iCa_ADJ, B; tCa_ADJ, D) reflect changes in vascular iCa and tCa content. Exercise and recovery data were analyzed separately. Statistical results for the condition-by-time interaction and main effects of condition and time for the exercise interval: (i) iCa: condition-by-time (p = 0.007), condition (p < 0.001), time (p < 0.001); (ii) iCa_ADJ: condition-by-time (p = 0.020), condition (p = 0.560), time (p = 0.060); (iii) tCa: condition-by-time (p = 0.010), condition (p = 0.001), time (p < 0.001); and (iv) tCa_ADJ: condition-by-time (p = 0.120), condition (p = 0.004), time (p < 0.001). Statistical results for the condition-by-time interaction and main effects of condition and time for the recovery interval: (i) iCa: condition-by-time (p = 0.100), condition (p < 0.001), time (p < 0.001); and (ii) iCa_ADJ: condition-by-time interaction (p = 0.040), condition (p = 0.010), time (p < 0.001). EX = exercise.

Fig. 3.

Serum PTH (A) and CTX (C) concentrations before, during, and after 60 min of cycling exercise during conditions of saline (open symbols, dashed lines) and calcium infusion (closed symbols, solid lines). Adjustments for plasma volume shifts (PTH_ADJ, B; CTX_ADJ, D) reflect changes in vascular PTH and CTX content. Exercise and recovery data were analyzed separately. Statistical results for the condition-by-time interaction and main effects of condition and time for the exercise interval: (i) PTH: condition-by-time (p = 0.130), condition (p = 0.002), time (p < 0.001); (ii) PTH_ADJ: condition-by-time (p = 0.070), condition (p = 0.004), time (p < 0.001); (iii) CTX: condition-by-time (p < 0.001), condition (p = 0.530), time (p < 0.001); and (iv) CTX_ADJ: condition-by-time (p < 0.001), condition (p = 0.480), time (p < 0.001). Statistical results for the condition-by-time interaction and main effects of condition and time for the recovery interval: (i) PTH: condition-by-time (p < 0.001), condition (p = 0.007), time (p < 0.001); (ii) PTH_ADJ: condition-by-time (p = 0.001), condition (p = 0.006), time (p < 0.001); (iii) CTX: condition-by-time (p < 0.001), condition (p = 0.040), time (p < 0.001); and (iv) CTX_ADJ: condition-by-time (p < 0.001), condition (p = 0.030), time (p < 0.001). PTH = parathyroid hormone; CTX = c-telopeptide cross-links of type 1 collagen.

Fig. 4.

Urine Ca excretion during exercise and the first 2 hours and last 2 hours of recovery under conditions of saline (white bars) and calcium infusion (black bars). There was a condition-by-time interaction (p = 0.023) and a main effect of time (p < 0.001). Ca = calcium.