Calcif Tissue Int (2009) 85:277–286
DOI 10.1007/s00223-009-9277-z
REVIEW
Effect of Physical Activity on Calcium Homeostasis
and Calciotropic Hormones: A Review
Laurent Maı̈moun Æ Charles Sultan
Received: 7 May 2009 / Accepted: 12 July 2009 / Published online: 16 September 2009
Ó Springer Science+Business Media, LLC 2009
Abstract Physical exercise has frequently been shown to
improve bone mass, especially at load-bearing bone sites. It
is widely acknowledged that the anabolic effects of exer-
cise on bone tissue are related to the application of
mechanical constraints, but part of the osteogenic response
may be due to other factors. In particular, various hormonal
parameters that are modified by training, such as insulin-
like growth factor-1 and sexual hormones, may modulate
the bone response. In contrast, little is known about the
involvement of calciotropic hormones in the adaptation
mechanism of bone tissue. These hormones, which include
parathyroid hormone, vitamin D metabolites, and calcito-
nin, are highly implicated in the regulation of both bone
remodeling and calcium homeostasis. In addition to their
direct action on bone cell activity, these hormones act on
various target tissues such as kidney and intestine. This
article describes the acute and long-term effects of exercise
on both calcium homeostasis and calciotropic hormones in
various populations. It clearly shows that exercise modifies
calcium homeostasis and calciotropic hormone levels and
that the variations in response are modulated by parameters
related to exercise, including duration and intensity, as well
as by individual characteristics such as age, sex, and
training status.
L. Maı̈moun (&)
C. Sultan
Service d’Hormonologie, Hôpital Lapeyronie, Centre Hospitalier
Universitaire Montpellier UM1, 191 avenue Doyen Gaston
Giraud, 34295 Montpellier Cedex 5, France
e-mail: l-maimoun@chu-montpellier.fr;
laurent.maimoun@laposte.net
C. Sultan
Unité d’Endocrinologie Pédiatrique, Hôpital Arnaud de
Villeneuve, Centre Hospitalier Universitaire Montpellier UM1,
34295 Montpellier Cedex 5, France
Keywords Physical activity
Calciotropic hormone

Calcium homeostasis
Parathyroid hormone

Vitamin D metabolite
Athlete
Introduction
Physical activity is known to induce modifications in bone
mineral density (BMD) [1] and bone turnover [2, 3]. The
specific mechanisms by which bone metabolism is influ-
enced by physical activity are still not thoroughly under-
stood. It appears, however, that bone mass adaptations may
result principally from increased mechanical strain, as
demonstrated by the higher BMD observed in athletes
practicing sports that generate high weight bearing or
impact loading in comparison with sedentary controls and
athletes practicing sports like swimming, which has lower
mechanical constraints [1, 4]. Nevertheless, endocrine
changes related to physical activity and the modification of
bone metabolism, including alterations in testosterone [5],
IGF-I, and leptin [6] secretion, have also been reported.
Other hormonal parameters may also be implicated,
such as the calciotropic hormones, which include para-
thyroid hormone (PTH), vitamin D metabolites, and cal-
citonin. They are highly implicated in the regulation of
bone remodeling and calcium homeostasis [7–9].
The aim of this review was to focus on the effects of
various types of physical activity on both calcium
homeostasis and calciotropic hormones in different popu-
lations. Moreover, the potentially additional osteogenic
effect of an exercise-related variation in PTH and calcitriol
was also studied.
The MEDLINE database was searched (from 1966 to
January 2009) using the following systematic search terms:
‘‘exercise,’’ ‘‘physical activity,’’ ‘‘training,’’ and ‘‘athletes’’
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278 L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis

combined with ‘‘calcium homeostasis,’’ ‘‘parathyroid hor-
mone,’’ and ‘‘vitamin D.’’ The studies resulting from this
search were examined in detail, and when the data were
relevant (population characteristics, training data, exercise
evaluated, timing analysis, basal values of hormones and
mineral), the studies were included in this review. No
review articles or animal studies were included, except
those that contributed to explaining a physiological
mechanism of adaptation.
Calcium Homeostasis, Calciotropic Hormones,
and Physical Activity
Basal Values in Athletes
Few studies have evaluated the effects of prolonged phys-
ical activity on calcium homeostasis and basal calciotropic
hormones [3, 7, 9–11] (Table 1). Generally, whatever the
age, intense training seems to have no [7, 12–14] or only a
limited [2, 10, 15] effect on basal serum phosphate (P), total
Ca, ionized Ca (iCa), or urinary Ca. Only moderately higher
values of basal iCa [10], total Ca [2, 15], and 24-hour uri-
nary Ca [11] have been reported in active subjects in
comparison with controls. Concerning calciotropic hor-
mones, Bell et al. [7] reported higher 25-(OH) and
1,25(OH)2D concentrations in subjects with regular muscle-
building activity in comparison with age-matched controls.
Higher values of vitamin D metabolites were also reported
in male triathetes, track and field athletes, decathletes [9,
11], and postmenopausal endurance-trained women [10] but
not in male cyclists, triathletes, or swimmers [3]. Certain
factors known to be altered by physical exercise may be
implicated in the variation in vitamin D status. These
include (1) a fall in serum P levels [16, 17]; (2) a transient
decrease in iCa during exercise [12, 17–22] that may tran-
siently stimulate PTH secretion [12, 18–28] and thereby
activate renal calcitriol synthesis; (3) a rise in growth hor-
mone secretion during exercise [10, 29] that is exacerbated
in athletes in comparison with less active subjects [10] and,
as suggested by the concomitant increase in 25(OH)D, a
precursor metabolite; (4) an increase in sunlight exposure

Table 1 Basal values of calcitropic hormones in athletes and controls

Study Subjects Training characteristics Basal values of calciotropic hormones

Bell et al. [7] M muscle-building (n = 14, Muscle-building 25(OH)D (?43.7%), 1,25(OH)2D (?37.9%) in
24 ± 1 years) 45 minutes, 3/week; exercisers [ CO
M CO (n = 14, 26 ± 1 years) No regular training sCa, iCa, PTH (NS)
Zittermann et al. [11] M athletes (n = 31, 25.4 years) 15 ± 6.6 hours/week 25(OH)D (?53.8%), 1,25(OH)2D (?34.6%),
M with low activity (n = 26, 25 years) Sedentary lifestyle urCa (?23.4%) in athletes [ low active
Lima et al. [13] M athletes (n = 18, 15.6 ± 1.7 years) 17.8 hours/week sCa, urCa/Cr (NS)
with weight-bearing activities
M athletes (n = 27, 14.9 ± 1.6 years) 16.4 hours/week
with low impact
M CO (n = 24, 15.2 ± 2.0 years) 2–3 hours/week
Maimoun et al. [3] M cyclists (n = 11, 27.4 ± 5.8 years) 10.6 hours/week sCa, iPTH, 1,25(OH)2D (NS)
M swimmers (n = 13, 25.5 ± 6.5 years) 10.2 hours/week
M triathletes (n = 14, 25.7 ± 6.6 years) 10.9 hours/week
M CO (n = 10, 27.5 ± 4.3 years) No regular training
Nelson et al. [10] W endurance-trained (n = 15, 22.6 ± 2.4 miles run/ 1,25(OH)2D (?24%); iCa (?2.3%) in
62.2 years) week exercisers [ CO
W CO (n = 18, 61.4 years) No regular training PTH (–54.4%) in exercisers \ CO
CT, 25(OH)D, sCa, urCa (NS)
Maimoun et al. [9] M decathletes (n = 13, 15.5 hours/week 1,25(OH)2D (?37.1%) in decathletes [ CO
22.4 ± 2.9 years)
M CO (n = 13, 25.8 ± 3.3 years) No regular training iPTH (=)
Brahm et al. [15] Endurance athletes (23 M, 7 W; 7 hours/week iPTH (–23.2%) in athletes \ CO
32 years)
CO (23 M, 7 W; 32 years) No regular training sCa (?3%) in athletes [ CO
M, men; W, women; CO, control; NS, difference not statistically significant between trained and CO; sCa, total serum calcium; iCa, ionized
calcium; urCa, urinary calcium; 25(OH)D, 25-hydroxyvitamin; 1,25(OH)2D, 1,25-dihydroxyvitamin D; CT, calcitonin; iPTH, intact parathyroid
hormone

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L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis 279

Table 2 Long-term effects of physical activity on calcium metabolism–related hormones

Study Study population Training Exercise evaluated Timing analysis Variation in
characteristics calciotropic
hormones

Maimoun et al. M triathletes (n = 7, 15 hours/week Habitual training Basal and after 1,25(OH)2D :
[30] 19.2 years) 32 weeks (?18.4%)
Ca, P, iPTH (=)
Jurimae et al. [6] M rowers (n = 12, Rest period: Basal value Before and after sCa, 1,25(OH)2D
20.8 ± 3.0 years) 11.6 hours/week 6 months (=)
Training period:
16.8 hours/week
Casez et al. [60] 140 M military recruits Good physical 15 weeks of military Before and after PTH (=)
(n = 140, 20-22 years) condition training 15 weeks
Dressendorfer M cyclists (n = 9, Good physical 6 weeks: endurance After each phase sCa (?5.1%) in
et al. [14] 24.7 ± 2.1 years) condition exercise 5/week, 50– U[I
75 minutes/session; 87% urCa (?12.5%)
of HRmax: (V) in I [ U and
18 days: very high power baseline
intermittent exercise 4/
week at 100% of HRmax:
(I)
10 days unloading taper, 2/
week (U)
M, men; W, women; CO, control; NS, difference not statistically significant between trained and CO; HRmax, maximal heart rate; sCa, total
serum calcium; urCa, urinary calcium; 25(OH)D, 25-hydroxyvitamin; 1,25(OH)2D, 1,25-dihydroxyvitamin D; iPTH, intact parathyroid hormone

due to outdoor sports activities. This last hypothesis was not
confirmed by Nelson et al. [10]. It is probable that the
increase in skeletal mass related to physical activity such as
muscle-building is induced by the enhanced Ca absorption
rates mediated by the circulating 1,25(OH)2D [10], the
major mediator of calcium absorption [11]. Moreover,
athletes also present normal [10] or relatively higher fasting
urinary Ca excretion, but this is still rather low compared
with the higher Ca intake and the enhanced absorption rate
[11]. Thus, calcium retention may be favored [10].
The higher concentration of 1,25(OH)2D found in
muscle-builders and decathletes [7, 9] contrasts with the
normal levels [10, 15] found in endurance athletes. The
lower PTH in association with the higher total Ca or iCa
concentrations in runners [10, 15] may indicate that
endurance exercise induces a permanent suppression of
PTH or a new set point in the calcium regulation of PTH
release [15].
Last, physical exercise seems to have no noticeable
effect on basal calcitonin (CT) levels [10, 12].
Long-Term Effects of Physical Activity
In Athletes
No noticeable variation in Ca, P, or other mineral (Mg, Fe,
Zn, Cu) concentrations was observed in male athletes after
a triathlon season [30] or relatively high-intensity, high-
volume cycling training [14] (Table 2). It can be con-
cluded, therefore, that oral mineral supplementation is not
indicated for performance enhancement [14]. In contrast,
24-hour urinary Ca excretion was elevated after a high-
intensity interval phase [14], suggesting that high physical
training may increase the amount of daily urinary Ca that is
lost [14, 31]. However, high dietary Ca intake and an
improvement in gastrointestinal Ca absorption might
counterbalance the Ca lost in urine and sweat [31].
After 7 months of training, an increase in 1,25(OH)2D3
and IGF-I was observed in triathletes, while intact PTH
(iPTH) concentrations were unchanged [30]. In contrast,
after 6 months of training, no significant increase in
1,25(OH)2D3 was observed in young male rowers [6]. Both
these periods were long enough to assume that a new mineral
and hormonal steady state had been reached. When shorter
periods were investigated, certain transitory variations were
reported. In nine male marathon runners, 4 weeks of training
induced parallel changes within normal ranges of CT, Ca,
and albumin and significant correlations between these
parameters. This was partially attributed to transient plasma
hypervolemia during training [32]. In the same study, an
increase in PTH values and a decrease in 1,25(OH)2D3 with
an unchanged ratio of 1,25(OH)2D3 to 25(OH)D3 were also
observed during the training period and 3 weeks of training
break. The results concerning the increase in PTH are in
accordance with those of Ljunghall et al. [23, 24]. One
explanation is a reduction in iCa concentration generated by

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 Table 3 Short-term effects of physical activity on calcium metabolism–related hormones
280

Study Study population Training characteristics Exercise evaluated Timing analysis Variation in calcitropic hormones

123
Nishiyama et al. [12] M volleyball players 10 hours/week 30 minutes running at Initial, just after exercise and iCa and sCa ; just after exercise
(n = 9, 21.5 years) No regular physical 50% of capacity max 60 min of recovery PTH : just after exercise
M CO (n = 10, training CT (=)
21.5 years)
Salvesen et al. [18] M runners (n = 9, 6.2 running sessions/ Constant running (CR) For CR: before test and after CR for runners: PTH : after
32 years) week velocity; 4.2 m.s-1 for 4 min (warm-up) and each 10–50 min
M fire-fighters (n = 6, 3.6 running sessions/ 50 minutes and 10 min during test sCa : after 20, 40, and 50 min
age 30 years) week incremental exercise (IE)
For IE: before test and after IE for runners: PTH : after 32
for 40 minutes
4 minutes (warm-up) and and 40 minutes of exercise
CR velocity; 3.3 m.s-1 for each 8 min during the test sCa : after 8, 24, 32, and 40 minutes
50 minutes
of exercise
CR for fire-fighters: PTH (=)
sCa : after 4, 10, 20, 30, 40, and
50 minutes
Kristoffersson et al. M ice hockey players Highly trained Modified Wingate test: Before test and after 5, 60 min ICa (?5.7%) : after 5 minutes,
[38] (n = 7, 22 years) duration 30 seconds of recovery (=) after 60 minutes of recovery
sCa, PTH (=)
Ashizawa et al. [46] M (n = 10, No regular physical 3 sets of 10 repetitions for 60 min before, just after test, UrCa excretion : after 45 and
24.3 ± 0.9 years) training 7 resistance exercises: after 15, 45, 105 and 105 minutes of recovery
(60% to 80% of 1 RM) 165 minutes of recovery iCa ; just after exercise and : after
45 minutes
sCa ; just after exercise
PTH ; after 105 minutes of recovery
Thorsen et al. [20] W (n = 14, No regular physical 45 minutes running at 15 minutes before test and iCa ; after 1 and 72 hours of recovery
25.2 years) training 50% of VO2max after 1, 24, 72 hours of PTH : after 24 and 72 hours of recovery
recovery
Malm et al. [61] M (n = 8, 29.9 years) M: 44 km/week Marathon running Day –10, just after marathon urCa ; after marathon in M (–82%) and
runners W: 52 km/week and 1, 3, 5 days of recovery in W (–75%)
W (n = 15,
40.3 years) runners
Crespo et al. [39] M marathon runners 150–210 km/week Marathon (42 km running) 5 minutes before, just after sCa uncorrected for proteins : just after
(n = 11, 26 years) marathon and after 24 hours and after 24 hours
W marathon runners 100–150 km/week of recovery sCa corrected for proteins : after
(n = 7, 28.2 years) 24 hours
Zitterrmann et al. M athletes (n = 18, 15.7 ± 1.7 h 60 minutes run at 70% of 1 hour before exercise and 1,25(OH)2D : during exercise
[31] 25.2 ± 0.6 years) maximal speed after 3 hours of recovery
Or 60 minutes rest sCa adjusted to albumin (=)
and PTH (=)
L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis
 Table 3 continued
Study Study population Training characteristics Exercise evaluated Timing analysis Variation in calcitropic hormones

Rudberg et al. [25] W (n = 8, 57 years) Recreational activity Maximal exercise test on
W (n = 7, 23 years) ergometer cycling
(24 minutes’ duration)
Jogging for 30–40 minutes
at moderate level
Rong et al. [41] M (n = 8, Noncompetitive Endurance exercise at 55%
23 ± 3 years) physical of VO2max on cycle
training \ 2 hours/ ergometer for
week 45 minutes (E55%)
Similar exercise at 85%
of VO2max (E85%)
for 15 minutes
Strength exercise at 85%
of 3 RM (STR)
Same schedule without
exercise (CO)
Ashizawa et al. [46] M (n = 14, 24.5 years) No regular physical 3 sets of 10 repetitions for
training 7 resistance exercises
Just before, just after, and
after 20 minutes of recovery
Just before, during the last
minute of exercise and CO,
and after 1, 4, 24 hours of
recovery
Before exercise, just after, 1
and 3 days after exercise
sCa (?14.3%), iCa (?4.5%) :
PTH(=)
PTH (?43.3%) :
sCa, iCa (=)
PTH : only during STR and (=) after
1 hour of recovery
PH corrected iCa : after E55% and ;
after STR
urCa : (?48%) 1 day (=) 3 days of
recovery
L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis

(60–80% of 1 RM)
Bouassida et al. [21] M (n = 12, 23.6 years) Physically active Exercise 1: (E1) Running
at 70% of VO2max
during 21 min following
by 21 min at 80% of
VO2max
Exercise 2: (E2)
Similar exercise but with
a 40-minute passive
recovery between the 2
periods
Brahm et al. [19] M (n = 10, 30 years) VO2max 46.7 in W; 35 minutes incremental
W (n = 10, 28 years) 56.2 ml/kg/minute in running exercise at 30%,
M 47%, 76%, and 100%
of VO2max
Ljunghall et al. [24] M military recruits Training program for 7-day field exercise
(n = 17, 5 months maneuver
20 ± 0.4 years)
M, men; W, women; CO, control; NS, difference not statistically significant between trained subjects and CO; VO2max, maximal O2 uptake; VT, ventilatory threshold; sCa, total serum calcium;
iCa, ionized calcium; urCa, urinary calcium; 25(OH)D, 25-hydroxyvitamin; 1,25(OH)2D, 1,25-dihydroxyvitamin D; CT, calcitonin; iPTH, intact parathyroid hormone
Just before; during exercise at
7, 21, and 42 or 82 minutes;
and after 24 hours of
recovery
At rest after each load, after
30 min and 24 hours of
recovery
Before, just after training, and
1, 3, 5 days of recovery
For E1: PTH : at 7–42 minutes of
exercise and after 24 hours of recovery
iCa ; at 7–42 minutes of exercise and
(=) after 24 hours of recovery
sCa (=)
For E2: PTH : at 7–82 minutes of
exercise and (=) 24 hours of recovery
iCa ; at 7–82 minutes of exercise and
(=) 24 hours of recovery Total Ca (=)
PTH : after exercise (?36%) and in
recovery (?40%)
Ca adjusted to albumin : (?3%) just
after exercise
PTH : (? 25%) just after training; 1, 3,
5 days of recovery (=)
sCa (=)
281

123
282
a rise during prolonged exercise in free fatty acids that form a
complex binding, rather than a change in total serum Ca [23].
The decrease in 1,25(OH)2D3 values suggests some inhibi-
tion of 1-hydroxylation of 25(OH)D3, which may occur in
periods of intensified training under the effect of hormones
(testosterone–estrogen balance or growth hormone) or kid-
ney malfunction [32]. Nevertheless, these results contrast
with those obtained from cross-sectional studies discussed
above [7, 9–11].
In Sedentary Individuals
One month of weight training induced a nonsignificant
increase (P = 0.10) in 1,25(OH)2D3 in young subjects
between 18 and 31 years [33]. However, it appeared that
the model of variation was related to the vitamin D
receptor polymorphism [33].
In the Elderly
An endurance training program consisting of 6 weeks of
bicycle ergometer exercise for 1 hour per day, 4 days per
week, did not modify the levels of total Ca, albumin-cor-
rected total Ca, P, 1,25(OH)2D3, or PTH in healthy elderly
male subjects [34]. In contrast, in subjects of both sexes
with a mean age of 74 years, an 8-week progressive aerobic
training program associated with antioxidant supplementa-
tion induced an increase in 25(OH)2D3 and 1,25(OH)2D3
and a reduction in iPTH levels. These hormonal modifica-
tions were not related to a variation in iCa [35].
Short-Term Effects of Physical Activity
The effects of physical exercise on serum Ca have been
extensively studied, but the results remain controversial.
Some authors observed a drop in total Ca or iCa [12, 20–
22, 36], whereas others found either no alteration [26, 27,
31] or a rise [18, 37–40] associated with a concomitant
increase in PTH [12, 18, 20–22, 27] or no variation [38]
(Table 3). These divergent results may be attributed to
whether or not calcium was adjusted to hemoconcentration
[39, 40], the type of exercise, whether characteristics such
as intensity and duration were evaluated [27], training level
[34], and physical fitness [19]. In contrast, whatever the
type of exercise, fitness level, or age of the subjects, PTH-
related peptide [41] or CT levels did not seem to be
affected by physical exercise [12, 20, 28, 41–44].
In Athletes
Very homogenous results, highlighting the increase in
PTH, were reported in studies evaluating exercise that did
not exceed 60 minutes. Bouassida et al. [21] reported a
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L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis
decrease in iCa and an increase in PTH during and after
two high-intensity continuous or intermittent protocols
performed at 75–85% of VO2max for 42 minutes in heal-
thy young males. PTH concentrations appeared greater
after the continuous protocol than the intermittent protocol
and remained elevated for 24 hours only in the continuous
protocol. Similar findings were observed by Nishiyama
et al. [12] in both athletic and nonathletic groups of young
men after 30 minutes of moderate-intensity exercise.
Salvesen et al. [18] reported that running at high and low
intensities increased PTH levels in long-distance runners
but similar exercise did not show any variation in PTH
levels in fire-fighters. This difference was partially attrib-
uted to the specific mode of training in the two populations.
Guillemant et al. [26] reported stimulation of PTH secre-
tion (maximal increase 270% of initial values) in 12 well-
trained male triathletes after 60 minutes of ergometer
cycling at 80% of VO2max, while total Ca levels decreased
during the recovery period. Elevated PTH during and after
prolonged endurance exercise was also observed and did
not seem related to the decrease in total Ca during and after
exercise [23, 24].
The results concerning prolonged activity that exceeds
60 minutes are less abundant but confirm the increase in
PTH after exercise [40]. These findings were observed in
road cyclists after 2 hours of cycle ergometry at a moderate
intensity of 60–75% of the ventilatory threshold [40].
Very brief and intense exercise (Wingate test), on the
other hand, does not seem to modify the concentrations of
PTH or total Ca, although an increase in iCa was observed
[38]. Similar data concerning total Ca were previously
reported by Ljunghall et al. [45], and this was associated
with an increase in iCa when the workload was increased.
During moderate-endurance exercise, a notable increase in
total Ca and albumin and a decline in iCa were observed,
while PTH levels increased during the last 5 hours of the
test. These data highlight the impact of exercise duration
and intensity on the response of calcium homeostasis [23].
In Sedentary Individuals
Physical exercise induces an immediate modification in
calcium homeostasis and calcitropic hormones in sedentary
individuals, as in athletes. In untrained young women,
45 minutes of running at 50% of VO2max induced a
reduction in iCa at 1 and 72 hours and an increase in PTH
at 24 and 72 hours after exercise [20]. In unathletic young
women, an increase in PTH was also observed after mod-
erate jogging (30–40 minutes), despite unchanged total and
ionized Ca [25], and after a single session (30 minutes) of
brisk walking with or without additional weight (5 kg)
[28]. PTH values returned to baseline after 14 minutes of
recovery [28]. In young men, PTH concentrations
L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis
increased immediately after a strength-building exercise
but not following 45 or 15 minutes of endurance cycling
exercise at 55% or 85% of VO2max [41].
In the Elderly
A brief maximal incremental exercise test increased serum
iPTH level in association with a concomitant decrease in
serum iCa level and 25(OH)D in elderly active subjects
[22]. The iPTH variation was directly related to basal iPTH
levels. Similarly, an immediate rise in PTH was reported in
men 55–73 years old by Zerath et al. [34] after a maximal
exercise test, and this change was not related to albumin-
corrected serum Ca. Moreover, the PTH rise was enhanced
by 6 weeks of training. No variation was reported for
serum PTH in postmenopausal women after a heavy
ergometer cycling exercise (mean duration 24 minutes),
although an increase in iCa, total Ca, and P values was
observed [25]. Similarly, no variation in PTH or iCa levels
was observed in postmenopausal women after 90 minutes
of brisk walking at a intensity of 50% of VO2max [44].
The apparently divergent responses of iCa, total Ca, and
PTH to exercise may be partly explained by the results of a
recent study that investigated the response of calcitropic
hormones as a function of intensity level in seven highly
trained cyclists [27]. The data demonstrated that iPTH
increased only after 50 minutes during high-intensity
exercise and that the variation in PTH values was inde-
pendent of total Ca variation or hemoconcentration. These
findings suggest an interrelationship between exercise
duration and intensity. The correlation between the rise in
lactate and the increase in serum PTH may also indicate a
general association between work intensity and the stimu-
lus to PTH secretion [18].
Various mechanisms have been proposed to explain the
modifications in iCa and PTH following exercise. In par-
ticular, the decrease in iCa may be attributed to various
factors: (1) marked elevations in serum P concentration
provoked by P release from muscle ATP and/or creatine-P
[26] that form complex binding with iCa [12, 27, 34]; (2) a
rise in free fatty acids that form a complex binding with
free Ca ions [23, 24]; (3) hypercalciuria [11, 17, 46] caused
by decreased renal Ca reabsorption related to the metabolic
acidosis induced by exercise [47] and accentuated in ath-
letes [11]; and (4) a loss of Ca in sweat [11, 26, 40], which
has been evaluated at approximately 70 mg/hour [40]. The
increase in urinary Ca excretion seems to be independent of
osteoclast activation, as demonstrated by the reduced DPD,
but can be attributed to the mechanisms involved in non-
cell-mediated physiochemical bone dissolution due to
lactic acidosis [17, 46].
The extracellular concentration of iCa is the main
determinant for PTH secretion [48], and the exercise-
283
induced increase in serum PTH levels may be directly
related to the reduction in iCa [21, 22]. Brent et al. [49]
reported an inverse sigmoidal curve between iCa and PTH,
suggesting that a slight modification in iCa concentration
induces large reciprocal changes in serum PTH. Guillemant
et al. [26] confirmed this hypothesis by showing that oral
Ca supplementation (972 mg divided into eight repeated
ingestions) during a 60-minute 80% VO2max cycle
ergometer exercise partially suppressed PTH release com-
pared with the large increase in PTH without Ca load
(ingestion of low-Ca water).
However, a decrease in total Ca or iCa is not the only
cause of the increase in PTH because PTH also increases
despite no variation [41] or an increase in serum total or
iCa concentrations [18, 45, 50]. Moreover, no direct
associations between changes in dermal Ca loss or serum
Ca and changes in PTH have been found [40]. Other
mechanisms independent of Ca variation may explain the
PTH increase related to exercise. These include (1) the
release during exercise of catecholamines, which are se-
cretalogues for PTH that can stimulate secretion despite
hypercalcemia [51], and (2) acidosis, which has a direct
effect on the increase in PTH secretion independently of Ca
level [52].
Independently of exercise-related factors like intensity
or duration [27, 41], the PTH response may also be mod-
ulated by individual training characteristics and physical
fitness since it has been shown that training enhances the
PTH response [34]. Moreover, the PTH response is also
modulated by the resting PTH level [22], which is probably
dependent on the level of physical fitness [19]. Neverthe-
less, in a very recent study, we found that the increase in
iPTH and the concomitant decrease in iCa levels after
maximal exercise were independent of sex, age, and
training status [36].
The increase in PTH secretion during exercise may have
various forms of physiological impact on bone metabolism.
PTH acts directly on osteoblasts [53], and intermittent
administration of PTH increased bone mass, improved
trabecular bone microarchitecture in rats [54], and pro-
duced the largest gain in trabecular bone mass and reduced
the risk of fracture in osteoporotic patients [55]. An
attractive hypothesis is thus that the increase in PTH
release induced by intermittent exercise is a systemic
mediator likely to promote anabolic action on the bone
tissue [22, 25, 28]. In this context, Chow et al. [8] reported
that a single administration of PTH in rats just before
mechanical stimulation significantly augmented the ensu-
ing osteogenic response. Moreover, in thyroparathyr-
oidectomized rats, no detectable response to mechanical
stimulation was observed. In any case, mechanical
responsiveness could be restored by a single administration
of PTH before stimulation. PTH thus seems to have a major
123
284
role in the mechanical responsiveness of bone by sensi-
tizing bone cells to mechanical stimulation. However, the
mechanism by which this occurs should be clarified [8]. In
an experimental study, Ryder and Duncan [56] demon-
strated that PTH potentiated the cellular responses of
osteoblasts to mechanical loading. This response may be
mediated by an increase in the activation of intracellular
Ca, a second messenger [56]. If the assumption is correct,
the most favorable effects of PTH on the skeleton are
achieved with low resting levels and large increases during
acute exercise [19]. Moreover, PTH may act on bone
through the receptor activator for nuclear factor jB ligand
(RANKL)/osteoprotegerin (OPG) pathway. While contin-
uous PTH exposure stimulates RANKL and suppresses
OPG expression [57, 58], thereby enhancing osteoclasto-
genesis, intermittent PTH exposure stimulated IGF-I
mRNA, an anabolic skeletal growth factor [57]. Of note,
subcutaneous administration of human PTH(1–38) has
been shown to induce a rapid and transient decrease in
OPG mRNA in both femur metaphyseal and diaphyseal
bone of rats [59].
In addition, iPTH stimulates kidney production of
1,25(OH)2D3, the most biologically active metabolite of
vitamin D, from the precursor 25(OH)D. Although it was
not possible to demonstrate an immediate positive effect of
exercise on 1,25(OH)2D3 [22, 31, 36], it is likely, as
mentioned above, that repeated and transient increases in
PTH induce greater synthesis of 1,25(OH)2D3 over the long
term [7, 9–11]. In contrast to the possibly favorable effect
on bone health of an intermittent increase in PTH, Gu-
illemant et al. [26] suggested that the increase in PTH may
trigger an increase in bone resorption. Moreover, the
increase in PTH after submaximal exercise only in runners
with low BMD and the inverse correlation between the
percent change in PTH and BMD may accentuate an
existing low bone density condition [26].
Conclusion
In humans, Ca homeostasis is noticeably modified after a
single bout of exercise. This modification is mainly
reflected by a decrease in iCa and an increase in iPTH.
Although the transitional increase in iPTH level would
have a potentially anabolic effect on bone, no data permit
definitive conclusions to be drawn about this hormonal
effect. It appears that the PTH response is conditioned not
only by the type of exercise, particularly its duration and
intensity, but also by individual characteristics. Exercise
generates mechanical constraints that improve BMD. It
also seems to modify the values of hormones like
1,25(OH)2D, which then potentialize its effect.
123
L. Maı̈moun, C. Sultan: Physical Activity and Calcium Homeostasis
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