Letter to the Editor 819
Authors
K. Hind, B. Jones, R. F. G. J. King
Affiliation
Carnegie Research Institute, Leeds Metropolitan University, Headingley Campus, Leeds, UK
received 07.03.2014 accepted 13.03.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1372585 Published online: April 10, 2014 Horm Metab Res 2014; 46: 819–820 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence Dr. K. Hind Carnegie Research Institute Fairfax Hall Leeds Metropolitan University Headingley Campus Leeds LS6 3QS UK Tel.: + 44/113/812 000 Fax: + 44/113/812 000 [email protected]
Dear Editors, We write to you with regards to the recently published original manuscript, “Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?” [1]. The authors, Hew-Butler, Stuempfle, and Hoffman have presented an interesting hypothesis which contradicts current thinking on explanations for low bone density frequently observed in competitive endurance athletes. At present, the current theory for bone loss in endurance athletes is based on an uncoupling of bone turnover due to an energy deficit, whereby there is a reduction in collagen synthesis which coincides with reductions in circulating oestradiol, triiodothyronine (T3), and insulin-like growth factor (IGF) 1 [2, 3]. Energy conservation is thought to be the primary reason for hypo-oestrogenism and reduced bone density in athletes who are either intentionally or unintentionally energy deficient, and there is strong evidence to support this. This evidence has accumulated over the last 3 decades, from the initial observations of low bone density in amenorrheic female runners, to observations also in male endurance runners [4, 5]. The research progressed to uncover associations of low body weight, body fat, high volume training, energy deficient diets, with low bone density, and to well-controlled studies where energy deficit has been experimentally induced and a reduction in bone formation markers reported [2, 3]. In contrast to the above, Hew-Butler et al. [1] propose that bone loss in endurance athletes may arise from the dissolution of bone mineral during periods of sodium loss, whereby sodium is extracted from bone to restore equilibrium in plasma sodium levels. The authors state, “Over time, we speculate that a decrease in bone sodium stores (cumulative sweat sodium losses) may potentially manifest as decreased lumbar spine bone mineral density as a transient homeostatic response to protect [Na + ] p levels during
chronic training and competition [1–5]” [1]. Their hypothesis is based upon observations of acute changes in dual energy X-ray absorptiometry (DXA) – measured bone mineral content (BMC), in a group of 6 ultra endurance athletes participating in a 161 km mountain footrace, which correlated with changes in plasma sodium pre and post race. DXA is not a tool that is used for the assessment of changes in bone over a short time period, given that common thought is that at least one bone modelling cycle is required to enable a detectable change in bone mass in response to a given stimuli [6]. One normal bone remodelling cycle takes approximately 3–4 months. Machine precision error should also be considered more fully. The reported %CV in this study was based on just one subject, whereas, a df 30 is recommended. Determining true BMC change in this study is unfortunately not possible, and is particularly problematic at the spine due to interference from the rib cage and sternum (when derived from a total body scan). We also note discrepancies in loss/gain between skeletal sites, for example, gains in BMC at the left and right rib. This may reflect difficulties with reproducibility of regional measurements from a total body scan. Therefore, the proposal that DXA may be used for the assessment of acute bone mineral change is at present difficult to ascertain. To evaluate fully bone as an acute buffer of plasma sodium, assessment of both calcium and sodium gains of both losses from within BMC would be needed. In addition, changes in body mass and sodium loss in sweat would be essential to delineate the concurrent relationship between gains in sodium from exogenous sources (for example fluid and dietary intake), plasma sodium concentration, and putative bone sodium turnover during exhaustive exercise. We recommend that future research is directed by a precise measurement of fluid and sodium balance, and utilises bone biochemistry as a
Hind K et al. Re: Bone … Horm Metab Res 2014; 46: 819–820
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?
820 Letter to the Editor
Conflict of Interest
▼
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Hind K et al. Re: Bone … Horm Metab Res 2014; 46: 819–820
References 1 Hew-Butler T, Stuempfle KJ, Hoffman MD. Bone: an acute buffer of plasma sodium during exhaustive exercise? Hormon Metab Res 2013; 45: 697–700 2 Zanker CL, Swaine IL. Responses of bone turnover markers to repeated endurance running in humans under conditions of energy balance or restriction. Eur J App Physiol 2000; 83: 434–440 3 Ihle R, Loucks AB. Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res 2004; 19: 1231–1240 4 Drinkwater BL, Nilson K, Chesnut CH III, Bremner WJ, Shainholtz S, Southworth MB. Bone mineral content of amenorrheic and eumenorrheic runners. New Eng J Med 1984; 311: 277–281 5 Hind K, Truscott JG, Evans JE. Low lumbar spine bone mineral density in both male and female endurance runners. Bone 2006; 39: 880–885 6 Heaney RP. The bone remodelling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1994; 9: 1515–1523 7 Noakes TD, Sharwood K, Speedy D, Hew T, Reid S, Dugas J, Almond C, Wharam P, Weschler L. Three independent biological mechanisms cause exercise-associated hyponatremia: evidence from 2,135 weighed competitive athletic performances. Proc Natl Acad Sci USA 2005; 102: 18550–18555 8 Guillemant J, Accarie C, Peres G, Guillemant S. Acute effects of an oral calcium load on markers of bone metabolism during endurance cycling exercise in male athletes. Calcif Tiss Int 2004; 74: 407–414
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
measurement of dynamic, short term changes in skeletal status. The study by Noakes at al. [7] referenced within the paper, demonstrates the large degree of inter-participant variability of sweat loss and the regulation of plasma sodium, thus this must be quantified in a study of this type. In short term, experimental studies of bone metabolism, endurance cycling induces a short, rapid increase in bone resorption [8]. Indeed, should bone act as a buffer for plasma sodium, it would be expected that the mechanism would be through increased bone resorption. Therefore, the proposed theory of bone as an acute buffer for plasma sodium is certainly plausible, but to prove this is a scientific challenge.
Reply to Letter to the Editor 821
Reply to Letter to the Editor by Hind et al. Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?
Affiliations
received 28.03.2014 accepted 02.04.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1374632 Published online: May 5, 2014 Horm Metab Res 2014; 46: 821–822 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence T. Hew-Butler, DPM, PhD Exercise Science Assistant Professor School of Health Science 3157 HHB Oakland University Rochester MI 48309 USA Tel.: + 1/248/364 8686 Fax: + 1/248/370 4227 [email protected]
T. Hew-Butler1, K. J. Stuempfle2, M. D. Hoffman3 1
Exercise Science, School of Health Science, Oakland University, Rochester, MI, USA Health Sciences Department, Gettysburg College, Gettysburg, PA, USA 3 Department of Physical Medicine and Rehabilitation Northern California VA Medical Center 2
Dear Editors, We appreciate the substantive body of evidencebased research that definitely supports low energy availability as the primary driver of athletic osteopenia, as pointed out by Hind et al. in their letter [1]. However, we wish to emphasize that prolonged endurance exercise represents an accelerated physiological model for which shortrange (nongenomic) regulatory circuits likely become more operative [2–5]. Heightened physiological and mental stress necessitates momentto-moment short-loop homeostatic responses that serve to complement the more classic genomic model of steroid activation, which takes hours to days to fully initiate [2]. As such, the metabolic demands of running a 161 km footrace in less than 30 h are 10-fold higher (13 000– 16 000 kcal/day [6]) than the estimated basal metabolic rate of our 6 race finishers (1 531 kcal/ day, using the Harris-Benedict Equation [7]). Thus, our data do not in any way undermine the classic physiological processes that contribute to low bone mineral density chronically in endurance athletes, but seek to build upon existing data to further determine whether or not: 1) pituitary-bone short-range homeostatic circuits exist and if so, 2) does repetitive stimulation of such short-range circuits have long-term pathological consequences related to low energy and serum mineral availability? Short-range regulatory circuits linking sodium and bone metabolism have been previously demonstrated, but in isolated contexts. For example, the nongenomic effects of aldosterone have been shown to activate the epithelial sodium channel in animal models [8]. Additionally, rapid increases in plasma aldosterone concentrations have been confirmed after only 10 min of high intensity exercise in humans, presumably from a nongenomic source [9]. Arginine vasopressin receptors type 1α (AVPR1α) and type 2 (AVPR2) have also been shown to exist on osteoblasts and osteoclasts,
with short-circuit AVP stimulation favoring overall bone resorption in mouse models [3]. Similarly, exercise-induced nonosmotic plasma AVP concentrations have been verified in humans and could hypothetically translate into acute bone remodeling if exercise duration and elevated plasma AVP levels were sustained [9]. Lastly, the heteroionic exchange of ions within the hydration shell of bone – and across the 80 % of quiescent osteoblasts present in the skeleton – can liberate 50–100 mmol of calcium daily from the skeleton to acutely regulate serum calcium levels without activation of the classic remodeling mechanisms [4]. Thus, the ability of hydroxyapatite crystals to dynamically mirror the composition of the surrounding extracellular fluid has been shown to be physicochemically plausible [4]. Whether or not these short-circuit homeostatic responses could potentially lead to irreversible pathology over time (such as in the osteoporosis case documented in a middle aged male with chronic inappropriate AVP secretion) [10], remains uncertain. Systematic investigations aimed at verifying the existence of short-circuit regulatory loops within the pituitary-bone axis are suggested based on our reported results, using endurance exercise as a model to (possibly) accentuate both sodium and bone metabolism. With regards to the potential precision errors in our dual energy X-ray absorptiometry (DEXA) scan measurements, we recognize that the small sampling sizes (cohort and %CV) represent our greatest limitation towards scientific acceptance of these preliminary findings. Nana et al. [11] recently reported a typical error range of 1–3 % in total bone mineral content (BMC) in a repeated measurement study of 31 subjects undergoing 5 DEXA scans within a 2 day period. This variation was well above our %CV of 0.39, reported in one subject repositioned 6 times. However, we reiterate that the strength of our data lie in the robust linear relationships seen between variables,
Hew-Butler T et al. Reply to Letter … Horm Metab Res 2014; 46: 821–822
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Authors
which were not reflected by absolute changes in mean values. Of additional note, it is not clear whether or not the changes seen in our DEXA scans represent: 1) actual changes in sodium ions within either the hydration shell or crystal surface [4]; 2) sodium-mediated displacement of calcium ions [12]; or 3) exercise-induced alterations in interstitial fluid pressure [13]. Despite these limitations and uncertainties, we feel that our results provide insights into the intersection of sodium balance, bone metabolism, and exercise physiology, particularly with regard to the potential importance of short-range homeostatic circuits. Only additional studies employing larger numbers of subjects and sufficiently sensitive technologies will resolve the issues raised by Hind et al. [1].
References 1 Hind K, Jones B, King RF. Re: Bone: an acute buffer of plasma sodium during exhaustive exercise? Horm Metab Res 2014; Apr 10 [Epub ahead of print] 2 Losel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 2003; 4: 46–56 3 Tamma R, Sun L, Cuscito C, Lu P, Corcelli M, Li J, Colaianni G, Moonga SS, Di Benedetto A, Grano M, Colucci S, Yuen T, New MI, Zallone A, Zaidi M. Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia. Proc Natl Acad Sci USA 2013; 110: 18644–18649 4 Green J. The physicochemical structure of bone: cellular and noncellular elements. Miner Electrolyte Metab 1994; 20: 7–15
Hew-Butler T et al. Reply to Letter … Horm Metab Res 2014; 46: 821–822
5 Guillemant J, Accarie C, Peres G, Guillemant S. Acute effects of an oral calcium load on markers of bone metabolism during endurance cycling exercise in male athletes. Calcif Tissue Int 2004; 74: 407–414 6 Stuempfle KJ, Hoffman MD, Weschler LB, Rogers IR, Hew-Butler T. Race Diet of Finishers and Non-Finishers in a 100 Mile (161 km) Mountain Footrace. J Am Coll Nutr 2011; 30: 529–535 7 Hew-Butler T, Stuempfle KJ, Hoffman MD. Bone: an acute buffer of plasma sodium during exhaustive exercise? Horm Metab Res 2013; 45: 697–700 8 Boldyreff B, Wehling M. Non-genomic actions of aldosterone: mechanisms and consequences in kidney cells. Nephrol Dial Transplant 2003; 18: 1693–1695 9 Hew-Butler T, Noakes T, Soldin S, Verbalis J. Acute changes in endocrine and fluid balance markers during high intensity, steady-state and prolonged endurance running: unexpected increases in oxytocin and brain natriuretic peptide during exercise. Eur J Endocrinol 2008; 159: 729–737 10 Sejling AS, Pedersen-Bjergaard U, Eiken P. Syndrome of inappropriate ADH secretion and severe osteoporosis. J Clin Endocrinol Metab 2012; 97: 4306–4310 11 Nana A, Slater GJ, Hopkins WG, Burke LM. Effects of daily activities on dual-energy X-ray absorptiometry measurements of body composition in active people. Med Sci Sports Exerc 2012; 44: 180–189 12 Wigertz K, Palacios C, Jackman LA, Martin BR, McCabe LD, McCabe GP, Peacock M, Pratt JH, Weaver CM. Racial differences in calcium retention in response to dietary salt in adolescent girls. Am J Clin Nutr 2005; 81: 845–850 13 Turner CH. Site-specific skeletal effects of exercise: importance of interstitial fluid pressure. Bone 1999; 24: 161–162
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
822 Reply to Letter to the Editor
Copyright of Hormone & Metabolic Research is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Authors
K. Hind, B. Jones, R. F. G. J. King
Affiliation
Carnegie Research Institute, Leeds Metropolitan University, Headingley Campus, Leeds, UK
received 07.03.2014 accepted 13.03.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1372585 Published online: April 10, 2014 Horm Metab Res 2014; 46: 819–820 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence Dr. K. Hind Carnegie Research Institute Fairfax Hall Leeds Metropolitan University Headingley Campus Leeds LS6 3QS UK Tel.: + 44/113/812 000 Fax: + 44/113/812 000 [email protected]
Dear Editors, We write to you with regards to the recently published original manuscript, “Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?” [1]. The authors, Hew-Butler, Stuempfle, and Hoffman have presented an interesting hypothesis which contradicts current thinking on explanations for low bone density frequently observed in competitive endurance athletes. At present, the current theory for bone loss in endurance athletes is based on an uncoupling of bone turnover due to an energy deficit, whereby there is a reduction in collagen synthesis which coincides with reductions in circulating oestradiol, triiodothyronine (T3), and insulin-like growth factor (IGF) 1 [2, 3]. Energy conservation is thought to be the primary reason for hypo-oestrogenism and reduced bone density in athletes who are either intentionally or unintentionally energy deficient, and there is strong evidence to support this. This evidence has accumulated over the last 3 decades, from the initial observations of low bone density in amenorrheic female runners, to observations also in male endurance runners [4, 5]. The research progressed to uncover associations of low body weight, body fat, high volume training, energy deficient diets, with low bone density, and to well-controlled studies where energy deficit has been experimentally induced and a reduction in bone formation markers reported [2, 3]. In contrast to the above, Hew-Butler et al. [1] propose that bone loss in endurance athletes may arise from the dissolution of bone mineral during periods of sodium loss, whereby sodium is extracted from bone to restore equilibrium in plasma sodium levels. The authors state, “Over time, we speculate that a decrease in bone sodium stores (cumulative sweat sodium losses) may potentially manifest as decreased lumbar spine bone mineral density as a transient homeostatic response to protect [Na + ] p levels during
chronic training and competition [1–5]” [1]. Their hypothesis is based upon observations of acute changes in dual energy X-ray absorptiometry (DXA) – measured bone mineral content (BMC), in a group of 6 ultra endurance athletes participating in a 161 km mountain footrace, which correlated with changes in plasma sodium pre and post race. DXA is not a tool that is used for the assessment of changes in bone over a short time period, given that common thought is that at least one bone modelling cycle is required to enable a detectable change in bone mass in response to a given stimuli [6]. One normal bone remodelling cycle takes approximately 3–4 months. Machine precision error should also be considered more fully. The reported %CV in this study was based on just one subject, whereas, a df 30 is recommended. Determining true BMC change in this study is unfortunately not possible, and is particularly problematic at the spine due to interference from the rib cage and sternum (when derived from a total body scan). We also note discrepancies in loss/gain between skeletal sites, for example, gains in BMC at the left and right rib. This may reflect difficulties with reproducibility of regional measurements from a total body scan. Therefore, the proposal that DXA may be used for the assessment of acute bone mineral change is at present difficult to ascertain. To evaluate fully bone as an acute buffer of plasma sodium, assessment of both calcium and sodium gains of both losses from within BMC would be needed. In addition, changes in body mass and sodium loss in sweat would be essential to delineate the concurrent relationship between gains in sodium from exogenous sources (for example fluid and dietary intake), plasma sodium concentration, and putative bone sodium turnover during exhaustive exercise. We recommend that future research is directed by a precise measurement of fluid and sodium balance, and utilises bone biochemistry as a
Hind K et al. Re: Bone … Horm Metab Res 2014; 46: 819–820
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?
820 Letter to the Editor
Conflict of Interest
▼
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Hind K et al. Re: Bone … Horm Metab Res 2014; 46: 819–820
References 1 Hew-Butler T, Stuempfle KJ, Hoffman MD. Bone: an acute buffer of plasma sodium during exhaustive exercise? Hormon Metab Res 2013; 45: 697–700 2 Zanker CL, Swaine IL. Responses of bone turnover markers to repeated endurance running in humans under conditions of energy balance or restriction. Eur J App Physiol 2000; 83: 434–440 3 Ihle R, Loucks AB. Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res 2004; 19: 1231–1240 4 Drinkwater BL, Nilson K, Chesnut CH III, Bremner WJ, Shainholtz S, Southworth MB. Bone mineral content of amenorrheic and eumenorrheic runners. New Eng J Med 1984; 311: 277–281 5 Hind K, Truscott JG, Evans JE. Low lumbar spine bone mineral density in both male and female endurance runners. Bone 2006; 39: 880–885 6 Heaney RP. The bone remodelling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1994; 9: 1515–1523 7 Noakes TD, Sharwood K, Speedy D, Hew T, Reid S, Dugas J, Almond C, Wharam P, Weschler L. Three independent biological mechanisms cause exercise-associated hyponatremia: evidence from 2,135 weighed competitive athletic performances. Proc Natl Acad Sci USA 2005; 102: 18550–18555 8 Guillemant J, Accarie C, Peres G, Guillemant S. Acute effects of an oral calcium load on markers of bone metabolism during endurance cycling exercise in male athletes. Calcif Tiss Int 2004; 74: 407–414
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
measurement of dynamic, short term changes in skeletal status. The study by Noakes at al. [7] referenced within the paper, demonstrates the large degree of inter-participant variability of sweat loss and the regulation of plasma sodium, thus this must be quantified in a study of this type. In short term, experimental studies of bone metabolism, endurance cycling induces a short, rapid increase in bone resorption [8]. Indeed, should bone act as a buffer for plasma sodium, it would be expected that the mechanism would be through increased bone resorption. Therefore, the proposed theory of bone as an acute buffer for plasma sodium is certainly plausible, but to prove this is a scientific challenge.
Reply to Letter to the Editor 821
Reply to Letter to the Editor by Hind et al. Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?
Affiliations
received 28.03.2014 accepted 02.04.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1374632 Published online: May 5, 2014 Horm Metab Res 2014; 46: 821–822 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence T. Hew-Butler, DPM, PhD Exercise Science Assistant Professor School of Health Science 3157 HHB Oakland University Rochester MI 48309 USA Tel.: + 1/248/364 8686 Fax: + 1/248/370 4227 [email protected]
T. Hew-Butler1, K. J. Stuempfle2, M. D. Hoffman3 1
Exercise Science, School of Health Science, Oakland University, Rochester, MI, USA Health Sciences Department, Gettysburg College, Gettysburg, PA, USA 3 Department of Physical Medicine and Rehabilitation Northern California VA Medical Center 2
Dear Editors, We appreciate the substantive body of evidencebased research that definitely supports low energy availability as the primary driver of athletic osteopenia, as pointed out by Hind et al. in their letter [1]. However, we wish to emphasize that prolonged endurance exercise represents an accelerated physiological model for which shortrange (nongenomic) regulatory circuits likely become more operative [2–5]. Heightened physiological and mental stress necessitates momentto-moment short-loop homeostatic responses that serve to complement the more classic genomic model of steroid activation, which takes hours to days to fully initiate [2]. As such, the metabolic demands of running a 161 km footrace in less than 30 h are 10-fold higher (13 000– 16 000 kcal/day [6]) than the estimated basal metabolic rate of our 6 race finishers (1 531 kcal/ day, using the Harris-Benedict Equation [7]). Thus, our data do not in any way undermine the classic physiological processes that contribute to low bone mineral density chronically in endurance athletes, but seek to build upon existing data to further determine whether or not: 1) pituitary-bone short-range homeostatic circuits exist and if so, 2) does repetitive stimulation of such short-range circuits have long-term pathological consequences related to low energy and serum mineral availability? Short-range regulatory circuits linking sodium and bone metabolism have been previously demonstrated, but in isolated contexts. For example, the nongenomic effects of aldosterone have been shown to activate the epithelial sodium channel in animal models [8]. Additionally, rapid increases in plasma aldosterone concentrations have been confirmed after only 10 min of high intensity exercise in humans, presumably from a nongenomic source [9]. Arginine vasopressin receptors type 1α (AVPR1α) and type 2 (AVPR2) have also been shown to exist on osteoblasts and osteoclasts,
with short-circuit AVP stimulation favoring overall bone resorption in mouse models [3]. Similarly, exercise-induced nonosmotic plasma AVP concentrations have been verified in humans and could hypothetically translate into acute bone remodeling if exercise duration and elevated plasma AVP levels were sustained [9]. Lastly, the heteroionic exchange of ions within the hydration shell of bone – and across the 80 % of quiescent osteoblasts present in the skeleton – can liberate 50–100 mmol of calcium daily from the skeleton to acutely regulate serum calcium levels without activation of the classic remodeling mechanisms [4]. Thus, the ability of hydroxyapatite crystals to dynamically mirror the composition of the surrounding extracellular fluid has been shown to be physicochemically plausible [4]. Whether or not these short-circuit homeostatic responses could potentially lead to irreversible pathology over time (such as in the osteoporosis case documented in a middle aged male with chronic inappropriate AVP secretion) [10], remains uncertain. Systematic investigations aimed at verifying the existence of short-circuit regulatory loops within the pituitary-bone axis are suggested based on our reported results, using endurance exercise as a model to (possibly) accentuate both sodium and bone metabolism. With regards to the potential precision errors in our dual energy X-ray absorptiometry (DEXA) scan measurements, we recognize that the small sampling sizes (cohort and %CV) represent our greatest limitation towards scientific acceptance of these preliminary findings. Nana et al. [11] recently reported a typical error range of 1–3 % in total bone mineral content (BMC) in a repeated measurement study of 31 subjects undergoing 5 DEXA scans within a 2 day period. This variation was well above our %CV of 0.39, reported in one subject repositioned 6 times. However, we reiterate that the strength of our data lie in the robust linear relationships seen between variables,
Hew-Butler T et al. Reply to Letter … Horm Metab Res 2014; 46: 821–822
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Authors
which were not reflected by absolute changes in mean values. Of additional note, it is not clear whether or not the changes seen in our DEXA scans represent: 1) actual changes in sodium ions within either the hydration shell or crystal surface [4]; 2) sodium-mediated displacement of calcium ions [12]; or 3) exercise-induced alterations in interstitial fluid pressure [13]. Despite these limitations and uncertainties, we feel that our results provide insights into the intersection of sodium balance, bone metabolism, and exercise physiology, particularly with regard to the potential importance of short-range homeostatic circuits. Only additional studies employing larger numbers of subjects and sufficiently sensitive technologies will resolve the issues raised by Hind et al. [1].
References 1 Hind K, Jones B, King RF. Re: Bone: an acute buffer of plasma sodium during exhaustive exercise? Horm Metab Res 2014; Apr 10 [Epub ahead of print] 2 Losel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 2003; 4: 46–56 3 Tamma R, Sun L, Cuscito C, Lu P, Corcelli M, Li J, Colaianni G, Moonga SS, Di Benedetto A, Grano M, Colucci S, Yuen T, New MI, Zallone A, Zaidi M. Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia. Proc Natl Acad Sci USA 2013; 110: 18644–18649 4 Green J. The physicochemical structure of bone: cellular and noncellular elements. Miner Electrolyte Metab 1994; 20: 7–15
Hew-Butler T et al. Reply to Letter … Horm Metab Res 2014; 46: 821–822
5 Guillemant J, Accarie C, Peres G, Guillemant S. Acute effects of an oral calcium load on markers of bone metabolism during endurance cycling exercise in male athletes. Calcif Tissue Int 2004; 74: 407–414 6 Stuempfle KJ, Hoffman MD, Weschler LB, Rogers IR, Hew-Butler T. Race Diet of Finishers and Non-Finishers in a 100 Mile (161 km) Mountain Footrace. J Am Coll Nutr 2011; 30: 529–535 7 Hew-Butler T, Stuempfle KJ, Hoffman MD. Bone: an acute buffer of plasma sodium during exhaustive exercise? Horm Metab Res 2013; 45: 697–700 8 Boldyreff B, Wehling M. Non-genomic actions of aldosterone: mechanisms and consequences in kidney cells. Nephrol Dial Transplant 2003; 18: 1693–1695 9 Hew-Butler T, Noakes T, Soldin S, Verbalis J. Acute changes in endocrine and fluid balance markers during high intensity, steady-state and prolonged endurance running: unexpected increases in oxytocin and brain natriuretic peptide during exercise. Eur J Endocrinol 2008; 159: 729–737 10 Sejling AS, Pedersen-Bjergaard U, Eiken P. Syndrome of inappropriate ADH secretion and severe osteoporosis. J Clin Endocrinol Metab 2012; 97: 4306–4310 11 Nana A, Slater GJ, Hopkins WG, Burke LM. Effects of daily activities on dual-energy X-ray absorptiometry measurements of body composition in active people. Med Sci Sports Exerc 2012; 44: 180–189 12 Wigertz K, Palacios C, Jackman LA, Martin BR, McCabe LD, McCabe GP, Peacock M, Pratt JH, Weaver CM. Racial differences in calcium retention in response to dietary salt in adolescent girls. Am J Clin Nutr 2005; 81: 845–850 13 Turner CH. Site-specific skeletal effects of exercise: importance of interstitial fluid pressure. Bone 1999; 24: 161–162
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
822 Reply to Letter to the Editor
Copyright of Hormone & Metabolic Research is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
