Risedronate use to attenuate bone loss following sleeve gastrectomy: Results from a pilot randomized controlled trial.

The purpose of this study was to explore the efficacy of 150 mg once monthly oral risedronate use in the prevention of sleeve gastrectomy (SG) associated bone loss. Twenty-four SG patients (56 ± 7 years, 83% female, 21% black) were randomized to risedronate or placebo for 6 months, with an optional 12-month assessment. Outcome measures included 6 (n = 21) and 12 (n = 14) month change in dual energy x-ray absorptiometry-acquired regional areal bone mineral density (aBMD). Six-month treatment effect estimates [mean (95% CI)] revealed significant between group aBMD differences at the femoral neck [risedronate: +0.013 g/cm2 (-0.021, 0.046) vs. placebo: -0.041 g/cm2 (-0.067, -0.015)] and lumbar spine [risedronate: +0.028 g/cm2 (-0.006, 0.063) vs. placebo: -0.029 g/cm2 (-0.054, -0.004)]; both p ≤ 0.02. When followed postoperatively to 12 months, differential aBMD treatment effects were observed at the total hip [risedronate: -0.035 g/cm2 (-0.061, -0.009) vs. placebo: -0.072 g/cm2 (-0.091, -0.052)] and lumbar spine [risedronate: +0.012 g/cm2 (-0.038, 0.063) vs. placebo: -0.052 g/cm2 (-0.087, -0.017)]; both p < 0.05. Preliminary treatment effect estimates signal 6 months of risedronate use may be efficacious in reducing aBMD loss at the axial skeleton post-SG, with benefit largely maintained throughout the 1-year postoperative period. Confirmatory data from an adequately powered trial are needed.

Maintaining serum ionized calcium during brisk walking attenuates the increase in bone resorption in older adults.

BACKGROUND: Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption, reflected by serum carboxy-terminal collagen crosslinks (CTX). We developed a calcium clamp to prevent the decrease in iCa during exercise, which attenuated increases in PTH and CTX during vigorous cycling in young men. The goal was to determine whether this occurs in older adults during brisk walking. METHODS: Twelve older adults (6 men, 6 women) performed two identical 60-min treadmill walking bouts with Ca gluconate or half-normal saline infusion. Blood sampling for iCa, total calcium (tCa), phosphate (P), PTH, and CTX, occurred before, during, and for 4 h after exercise. RESULTS: iCa decreased during exercise with the saline infusion (p = 0.04) and this provoked increases in PTH and CTX (both p < 0.01). The Ca clamp prevented the decrease in serum iCa during exercise and attenuated the PTH and CTX responses. CONCLUSIONS: Preventing the exercise-induced decrease in iCa markedly attenuated the increases in PTH and CTX. The cause of the decrease in iCa during exercise remains unclear, but the increases in PTH and CTX are likely counter-regulatory responses to defend serum iCa. This contention is supported by previous observations that the disruption of Ca homeostasis during exercise occurs regardless of training status. It will be important to establish whether this acute catabolic effect of exercise diminishes the potential chronic anabolic effects of exercise on bone.

Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) taken before exercise have been shown to impair bone formation. NSAIDs also suppress inflammatory cytokines, such as interleukin-6 (IL-6), that can have pro-resorptive effects. It is unclear how taking NSAIDs timed around exercise influences inflammatory and bone biomarkers following an acute exercise bout in older adults. PURPOSE: To determine if timing of ibuprofen use relative to a single exercise bout has acute effects on serum IL-6, bone-specific alkaline phosphatase (BAP, marker of bone formation), and c-telopeptide of type I collagen (CTX, marker of bone resorption). METHODS: As part of a 36-week exercise intervention, participants aged 60 to 75 years were randomized to 3 groups: placebo before and after exercise (PP), ibuprofen before and placebo after exercise (IP), or placebo before and ibuprofen after exercise (PI). Acute responses were studied in a subset of participants (12 PP, 17 IP, 13 PI). Blood was sampled before and immediately, 30 min, and 60 min after exercise for IL-6, BAP, and CTX. RESULTS: The exercise-induced increase in IL-6 was blunted in response to IP when compared to PI 60-min after exercise (p < 0.001). There were no significant differences in the change in BAP or CTX between groups at any time points CONCLUSION: Ibuprofen taken before exercise dampened the inflammatory response to exercise but had no effects on bone biomarkers in older adults. It may be necessary to monitor changes for a longer time interval after an acute exercise bout to determine whether bone turnover is altered by ibuprofen or other NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00462722; Posted 04/19/2007.

Bone Biomarker Response to Walking under Different Thermal Conditions in Older Adults.

Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-terminal telopeptide of type I collagen (CTX), which may be due to Ca loss in sweat. PURPOSE: This study aimed to determine whether exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared with a cool environment in older adults. METHODS: Twelve women and men 61-78 yr old performed two identical 60-min treadmill bouts at ~75% of maximal heart rate under warm and cool conditions. Serum iCa, PTH, and CTX were measured every 15 min starting 15 min before and continuing for 60 min after exercise. Sweat Ca loss was estimated from sweat volume and sweat Ca concentration. RESULTS: Sweat volume was low and variable; there were no differences in sweat volume or Ca concentration between conditions. iCa decreased after 15 min of exercise, and the change was similar in both conditions. Increases in PTH (warm: 16.4, 95% confidence interval [CI] = 6.2, 26.5 pg·mL; cool: 17.3, 95% CI = 8.1, 26.4 pg·mL) and CTX (warm: 0.08, 95% CI = 0.05, 0.11 ng·mL; cool: 0.08, 95% CI = 0.01, 0.16 ng·mL) from before to immediately after exercise were statistically significant and similar between conditions. Adjusting for plasma volume shifts did not change the results. CONCLUSION: The increases in PTH and CTX, despite the low sweat volume, suggest that dermal Ca loss is not a major factor in the decrease in iCa and increases in PTH and CTX observed during exercise in older adults.

Dermal Calcium Loss Is Not the Primary Determinant of Parathyroid Hormone Secretion during Exercise.

INTRODUCTION: Exercise can cause a decrease in serum ionized calcium (iCa) concentration, which stimulates parathyroid hormone (PTH) secretion and activates bone resorption. We postulated that dermal Ca loss during cycling exercise is the major determinant of the serum iCa, PTH, and bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) responses. METHODS: To investigate this, women (n = 13) and men (n = 12) age 18 to 45 yr performed the same exercise bout under cool (18°C) and warm (26°C) conditions. Exercise was 60 min of cycling at ~75% of peak aerobic power. Sweat samples were obtained during exercise using a skin patch method, and blood samples were obtained before and during exercise and during 60 min of recovery. RESULTS: Sweat volume and estimated sweat Ca loss were 50% higher for the warm condition than the cool condition. Despite this, there were no differences between thermal conditions in the changes (mean, 95% confidence interval [95% CI]) in iCa (cool, -0.07 mg·dL; 95% CI, -0.16 to 0.03); warm, -0.07 mg·dL; 95% CI, -0.20 to 0.05), PTH (cool, 34.4 pg·mL; 95% CI, 23.6-45.2; warm: 35.8 pg·mL; 95% CI, 22.4-49.1), or CTX (cool, 0.11 ng·mL; 95% CI, 0.08-0.13; warm, 0.15 ng·mL; 95% CI, 0.11-0.18). Adjusting for exercise-related shifts in plasma volume revealed a marked decline in vascular iCa content in the first 15 min of exercise (cool, -0.85 mg·dL; 95% CI, -1.01 to -0.68; warm, -0.85 mg·dL; 95% CI, -1.05 to -0.66), before substantial sweat Ca loss had occurred. CONCLUSIONS: This indicates that dermal Ca loss was not the primary trigger for the increases in PTH and CTX during exercise. Further research is necessary to understand the causes and consequences of the disruption in Ca homeostasis during exercise and specifically the extravascular shift in iCa.

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

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 (iCaADJ and tCaADJ ) 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 P1NPADJ was not significant. Results for PTHADJ and CTXADJ 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.

Calcium Supplementation Attenuates Disruptions in Calcium Homeostasis during Exercise.

An exercise-induced decrease in serum ionized calcium (iCa) is thought to trigger an increase in parathyroid hormone (PTH), which can stimulate bone resorption. PURPOSE: The purpose of this study was to determine whether taking a chewable calcium (Ca) supplement 30 min before exercise mitigates disruptions in Ca homeostasis and bone resorption in competitive male cyclists. METHODS: Fifty-one men (18 to 45 yr old) were randomized to take either 1000 mg Ca (CA) or placebo (PL) 30 min before a simulated 35-km cycling time trial. Serum iCa and PTH were measured before and immediately after exercise and a marker of bone resorption (C-terminal telopeptide of type I collagen) was measured before and 30 min after exercise. RESULTS: Serum iCa decreased in both groups from before to after exercise (mean ± SD, CA = 4.89 ± 0.16 to 4.76 ± 0.11 mg·dL, PL = 4.92 ± 0.15 to 4.66 ± 0.22 mg·dL, both P ≤ 0.01); the decrease was greater (P = 0.03) in the PL group. There was a nonsignificant (P = 0.07) attenuation of the increase in PTH by Ca supplementation (CA = 30.9 ± 13.0 to 79.7 ± 42.6 pg·mL, PL = 37.1 ± 14.8 to 111.5 ± 49.4 pg·mL, both P ≤ 0.01), but no effect of Ca on the change in C-terminal telopeptide of type I collagen, which increased in both groups (CA = 0.35 ± 0.17 to 0.50 ± 0.21 ng·mL, PL = 0.36 ± 0.13 to 0.54 ± 0.22 ng·mL, both P ≤ 0.01). CONCLUSION: It is possible that ingesting Ca only 30 min before exercise was not a sufficient time interval to optimize gut Ca availability during exercise. Further studies will be needed to determine whether adequate Ca supplementation before and/or during exercise can fully mitigate the exercise-induced decrease in serum iCa and increases in PTH and bone resorption.