Rickets, edited by Francis H. Glorieux.
Nestle Nutrition Workshop Series, Vol. 21.
Nestec Ltd.. Vevey/Raven Press, Ltd..
New York© 1991.
Homeostasis of Inorganic Phosphate
and the Kidney
Jean-Philippe Bonjour, Joseph Caverzasio, and Rene Rizzoli
Division of Clinical Pathophysiology, Department of Medicine, University Hospital, 24
Rue Micheli-du-Crest, CH-1211 Geneva 4, Switzerland
DISTRIBUTION OF PHOSPHATE IN THE BODY
In most mammalian species, 80% to 90% of body phosphate is present in bone
mineral as a major component of hydroxyapatite. The rest is in soft tissue, blood
cells, and in the extracellular fluid. In soft tissues, phosphorus represents about 0.2%
of the wet weight. In cells it is present in the form of inorganic and organic phosphate
as bound to sugars, lipids, proteins, nucleic acids, and various nucleotides. In
plasma, one-fourth of total phosphate is present in the form of the inorganic anion,
the major fraction being the phospholipids.
PLASMA INORGANIC PHOSPHATE
The concentration of inorganic phosphate (Pi) in plasma is not set at a steady level
like that of calcium. It varies among animal species, being the highest in some fishes
and the lowest in the adult human. The plasma level of Pi also varies in relation with
age or growth of the organism. Thus, in humans plasma Pi ranges between 1.4 and
2.7 mmol/1 in newborn babies, between 1.3 and 2.0 mmol/1 in children, and between
0.7 and 1.4 mmol/1 in adult individuals.
HOMEOSTASIS OF PLASMA Pi
The mass of Pi contained in the plasma and extracellular fluid amounts to about
15 mmol in the adult human. This amount represents less than 0.1% of the total
phosphorus present in the body. Plasma Pi level is influenced by the various Pi fluxes
entering and leaving the extracellular compartment (Fig. 1). Pi enters the extracellular
compartment from the intestine, from various soft tissues, and from bone. It leaves
the extracellular compartment through the urine, as the result of the difference between glomerular filtration and net tubular reabsorption, by back flux into the in35
36
PHOSPHATE AND THE KIDNEY
EXOGENOUS SUPPLY —
GUT-
ENDOGENOUS SUPPLY
(body stores)
Renal controlling systems:
IC
controlled (?)
pool
EC
pool
•
DEMAND
Mineralization
Growth
Anabolism
Metabolism
©
TUBULAR Pi
TRANSPORT
FIG. 1 . Possible schema of Pi homeostasis. A putative intracellular (IC) pool of Pi is considered
to be the critical controlling variable in Pi homeostasis. This pool is influenced by variations in both
the Pi supply and demand imposed by body needs. The two renal controlling systems receive signals
from the IC pool of Pi. By modulating Pi fluxes at the intestinal, skeletal, and renal levels, and from
the extracellular (EC) to the IC compartment, both 1,25(OH)2D and the adaptive tubular Pi transport
system tend to correct variations in the controlled pool of Pi. In X-linked hypophosphatemia the
efferent limb (
• ) connecting the IC controlled Pi pool to the two renal controlling systems
appears to be disturbed (see text for further details). From Bonjour JP, et al. (28).
testinal lumen, and by transfer into the soft tissue and bone for the process of matrix
mineralization.
IMPORTANCE OF RENAL Pi REABSORPTION IN PLASMA Pi
HOMEOSTASIS
Among these various Pi transfers, the renal fluxes appear to be particularly important with respect to the setting of the plasma Pi level (1). In an adult human with
a plasma concentration of 1.2 mmol/1 and a glomerular filtration rate of 120 ml/min,
the daily amount of Pi filtered will be about 210 mmol. If 20% of the filtered load is
excreted in the urine the mass of Pi reabsorbed will be 168 mmol/day. This renal net
reabsorptive flux is about ten times larger than the net intestinal absorptive flux that
can be observed in adult individuals with a dietary supply of Pi amounting to 25
mmol/day and an intestinal fractional absorption of 70%. More importantly, this renal
reabsorptive flux can vary tremendously according to the dietary supply and the
utilization of Pi by the organism (2,3). Indeed, the range of the fractional reabsorption
extends from virtually 0 to 100%. Therefore, because of such an enoimous flexibility
the tubular reabsorption of Pi probably plays the central role in the regulation of the
plasma Pi level. We will therefore concentrate in this chapter on the mechanisms
that control the rate of Pi flux across the renal epithelium. Furthermore, since this
volume is devoted to rickets a special emphasis will be given to the regulatory mechanisms that could be implicated in the renal response to variations in the dietary
supply of Pi, the growth rate of the organism, and/or that of bone mineralization.
PHOSPHA TE AND THE KIDNE Y
37
RENAL Pi TRANSPORT: THE ESSENTIALS
Overall Tubular Pi Transport
In the mammalian kidney Pi transport is a saturable process with no appreciable
simple diffusion component. Thus, it is characterized by a maximum rate at which
this ion can be transferred across the tubular epithelium from lumen to blood. This
maximum rate is not an absolute constant, since it can be set at different levels
according to the physiological or pathological conditions (1,2,4-8). The determination of the maximum Pi reabsorption rate per unit volume of glomerular filtrate
(TmPi/GFR) represents the most reliable quantitative estimate of the overall tubular
Pi transport capacity. Most, if not all, significant regulatory factors or conditions
that influence Pi homeostasis by altering the renal handling of Pi have been shown
to exert their effect on TmPi/GFR. A very tight positive correlation exists between
TmPi/GFR and fasting plasma Pi concentration (1,4,9). This finding indicates that
the capacity of the renal tubule to transport Pi is very likely a major determinant of
extracellular Pi homeostasis. Therefore, understanding of the mechanisms that underlie changes in TmPi/GFR is essential for the comprehension of Pi homeostasis in
health and diseases. The fact that the renal Pi transport is exclusively a saturable
process implies that for any given TmPi/GFR the fraction of the Pi filtered which is
reabsorbed will vary as a function of the load and/or concentration of Pi reaching
the tubular transport sites. Therefore, the fractional Pi reabsorption (FRPi) or excretion (FEPi) cannot be taken as a physiological index of the transport capacity of
the renal tubule. Unfortunately, such a misleading index has been extensively used
in both experimental and clinical investigations. It should be definitively given up
in order to avoid useless controversies regarding the renal handling of Pi.
Tubular Localization Along the Nephron
In most conditions the largest portion of the filtered load of Pi is reabsorbed along
the proximal tubule. However, the distal and terminal parts of the nephron are also
sites of net Pi reabsorption. This component could be important in the determination
of the final urinary output of Pi (4,6,10).
Mechanism of Pi Transport
The reabsorption of Pi starts with the crossing of the luminal or apical membrane
of the renal epithelial cell. In the proximal tubule this membrane is endowed with
microvilli that form a brush border lining the tubular lumen. The transfer of Pi from
the luminal to the intracellular compartment is carried out against an electrochemical
gradient by a sodium cotransport system (4-7). The fate of Pi when it reaches the
intracellular compartment is not well understood. The cellular exit of Pi across the
38
PHOSPHA TE AND THE KIDNE Y
basolateral membrane could be a passive process along a favorable electrochemical
gradient.
The essential or rate-limiting step in the overall transepithelial Pi translocation is
the sodium-coupled Pi cotransport (NaPiT) across the luminal membrane. Most regulating factors that affect TmPi/GFR have been shown to influence the NaPiT rate
across brush-border membranes isolated from renal cortical tubules (4,7,11-14).
They exert their effect by altering the capacity (VmaA) of the NaPiT system. They
do not influence the apparent affinity of Pi for the transport system. The effect of
the regulators on the capacity or \max of the NaPiT system could correspond to
variations in either the number or the activity of the transporters within the luminal
membrane. This issue as well as other questions concerning the biochemical events
involved in the regulation of Pi transport can be now better approached by using
renal epithelial cell cultures (15,16).
REGULATION OF RENAL Pi TRANSPORT IN RELATION WITH Pi
SUPPLY AND DEMAND
Does PTH Play the Key Role in Pi Homeostasis?
For many years parathyroid hormone (PTH) has been considered as the main
controller of the tubular reabsorption of Pi. This belief was based on the fact that
PTH has the property of acting directly on the renal epithelium in reducing the tubular
transport of Pi. Furthermore, the secretion rate of PTH, at least in some experimental
and clinical conditions, appears to be adjusted in such a way that the hormone would
be able to maintain Pi homeostasis through its renal action. Thus, there is a direct
relationship between Pi supply and PTH secretion. Furthermore, hypo- and hyperparathyroidism are pathophysiological conditions accompanied by changes in tubular
Pi transport capacity and thereby in plasma Pi concentration. At first glance, these
uncontested facts appear to sustain the notion that PTH plays a key role in Pi homeostasis. However, there is an important link missing in this contention. The rate
of PTH production and secretion is not regulated by extracellular Pi concentration.
Furthermore, in the absence of PTH the kidney is perfectly able to adjust its tubular
Pi reabsorption to the needs of the organism for this element.
The Adaptive System of Tubular Pi Transport
It has been known for many years that Pi can disappear from the urine in response
to dietary Pi restriction. This phenomenon is associated with an increase in the
overall tubular capacity to reabsorb Pi. PTH appears to play a minor role in this
adaptation (3,17,18). A PTH-independent increase in TmPi/GFR in response to Pi
restriction has been demonstrated in several mammalian species (3,4). In human,
reports strongly suggest that the increased TmPi/GFR in response to Pi restriction
is present not only in euparathyroid but also in hypoparathyroid patients (3,4).
PHOSPHATE AND THE KIDNEY
39
Importance of the Adaptive System in Pi Homeostasis
The existence of the adaptive system implies that plasma Pi concentration will be
less dependent upon variations in the amount of Pi supplied in the diet. Another
homeostatic consequence of the adaptive response concerns the conservation of the
mass of Pi mobilized from body stores during the daily phase of fasting. Indeed, in
Pi-deprived animals the adaptive enhancement of the tubular Pi transport capacity
explain why fasting is accompanied by an increase in the extracellular concentration
of Pi (19). As mentioned above, the tubular adaptation to Pi restriction is a PTHindependent phenomenon. PTH is essentially a calcium-regulating hormone. Since
PTH stimulates the tubular reabsorption of calcium whereas it decreases that of Pi,
it is obvious that this hormone cannot cope with a situation where the availability
of both calcium and Pi from the environment would vary in the same direction.
Experimentally, one can demonstrate that decreasing both dietary Pi and calcium
in the diet can be followed by an increase in the plasma level of PTH and in the
excretion of nephrogenic cAMP, whereas the tubular capacity to reabsorb Pi is adequately enhanced. This finding is probably directly related to the fact that the adaptation to a low-Pi diet is accompanied by an inhibition of the phosphaturic action
of PTH (20). It further emphasizes that PTH cannot be the unique and final controller
of the tubular reabsorption of Pi. Finally, a deficiency in the adaptive mechanism
could have dramatic consequences for Pi homeostasis, as strongly suggested by data
obtained in murine and human X-linked hypophosphatemia (see chapter by F. Glorieux). This disease is characterized by a decrease in the tubular reabsorption of Pi
associated with a defect in skeletal mineralization (21,22). In X-linked hypophosphatemia the rise in overall renal TmPi/GFR which normally takes place in response
to Pi restriction is markedly attenuated (23,24), despite the presence of an appreciable
adaptation in the brush-border membrane of cortical tubules (25).
Localization and Mechanism of Renal Adaptation
The adaptive response to variations in the dietary Pi intake is expressed in the
proximal tubule (4-7,26). The distal tubule and the collecting duct are probably also
involved. In the proximal epithelium, it is associated with an alteration in the Wmax
of the luminal membrane sodium-dependent Pi transport system (4,5,14). In renal
epithelial cell culture lowering the environmental Pi leads to an increase in \max of
the apical NaPiT system. This response requires the de novo synthesis of protein
(15). This suggests that the Pi deprivation signal induces the synthesis of new transport carrier units which are rapidly inserted within the apical membrane allowing
the maximal extraction of the small amount of Pi available in the extracellular
environment.
Adaptation to Pi Demand
We postulated that the adaptive system that reacts to changes in the Pi supply
would also respond to variations in the Pi demand (2,27). A series of clinical and
40
PHOSPHATE AND THE KIDNEY
experimental data supports this notion. Thus, in several situations where the Pi
demand can be expected to be reduced, a PTH-independent decrease in the tubular
Pi reabsorptive capacity is observed. This is the case at the end of the growth period
(11,28) or after hypophysectomy (29). Interestingly, a decreased tubular reabsorptive
Pi capacity is also observed after inducing a blockage of bone mineralization (27).
Conversely, the growth related stimulation of TmPi/GFR (9,30) could be considered
as an adaptive response to an increase Pi demand. This PTH-independent response
could be mediated by growth hormone itself or growth factors such as IGF-I (somatomedin C).
Adjustment of TmPi/GFR to Renal Mass Reduction
In chronic renal failure or after experimental reduction in the renal mass there is
a decrease of TmPi/GFR of the remaining nephrons. This change has been shown
to be PTH-independent (31-34) and could be considered as an adaptive response
aimed at maintaining Pi homeostasis.
Effect of IGF-I on Renal Pi Transport
Recently we obtained evidence that IGF-I can stimulate TmPi/GFR in hypophysectomized rats (35). This response could be due to a direct effect of IGF-I on the
renal tubule. Indeed, in vitro IGF-I stimulates selectively the Vmax of the NaPiT
system present in the apical membrane of cultured renal epithelial cells (35).
Controlled and Controlling Elements
The nature of the controlled and controlling components of the homeostatic system
which determine the adaptation of the tubular Pi transport to the Pi needs of the
organism remains quite obscure. Whether IGF-I, or other growth factors could be
involved remains an intriguing possibility. Nevertheless the presence of growth hormone is not a prerequisite for observing a stimulation of Pi reabsorption in response
to a low-Pi diet (29). Some speculative predictions can be made about the homeostatic
Pi system. Unlike the system responsible for the homeostasis of calcium, that of Pi
does not seem to operate for maintenance of the extracellular level of Pi at a fixed
value which would be an absolute constant, whatever might be the Pi needs of the
organism. Indeed, for a given Pi supply it appears that the tubular Pi transport capacity, and thereby the plasma Pi concentration, is set at different levels according
to the growth and the Pi needs of the organism. Thus, some intracellular pool(s) of
Pi might represent the controlled variable rather than merely the extracellular or
plasma concentration of Pi per se (31). The identification of this (or these) pool(s)
will be crucial for understanding the homeostasis of Pi in relation to the adaptive
response of the renal Pi transport system. If these controlled Pi pools are localized
PHOSPHATE AND THE KIDNEY
41
outside the kidney the existence of a hormonal factor can be envisaged. Such a factor
would connect this unknown controlled pool of Pi with the kidney, thereby forming
an essential component of the efferent limb responsible for the adaptive response
of the tubular transport of Pi (Fig. 1). Of the various candidates considered, parathyroid hormone, calcitonin, vitamin D metabolites, thyroxine, growth hormone,
and other factors secreted by the pituitary gland have been excluded (17,28,29,36).
The nature of the molecular mechanism responsible for the adaptive response at the
renal cellular and plasma membrane level also remains unclear at the present time.
Pathophysiological Implications
Alterations in the renal handling of Pi and thereby in the phosphatemia observed
in various diseases are not necessarily accompanied by pathological phenomena specific of disturbances in the Pi status of the organism. For example, in diseases such
as hyper- and hypoparathyroidism, hyper- and hypothyroidism, and hyper- or hyposecretion of growth hormone, the changes in the renal handling and plasma concentration of Pi do not in themselves appear to have any physiological consequences.
Indeed, in these conditions hypophosphatemia is not accompanied by signs of Pi
depletion, or hyperphosphatemia associated with signs of Pi intoxication. Consequently, the change in the renal handling and plasma levels of Pi observed in these
diseases cannot be considered as pathological phenomena requiring therapeutic correction. In fact, they may well represent an adaptive readjustment of the tubular Pi
transport system to extrarenal alterations in the utilization and/or metabolism of Pi
(36). Thus in chronic hypoparathyroidism, the increase in the tubular Pi reabsorptive
capacity and subsequent rise in phosphatemia could be compensatory for the reduced
extrarenal clearance of Pi (36).
Tubular Pi Adaptation and 1,25(OH)2D3
The renal 1,25(OH)2D3-producing system is certainly another very important controlling element of Pi homeostasis. In many physiological and physiopathological
circumstances, variations in TmPi/GFR are associated with parallel changes in the
renal production and plasma level of 1,25(OH)2D3. The increase in 1,25(OH)2D3 in
response to Pi restriction is also a PTH-independent phenomenon. It has been clearly
demonstrated that the increased production of 1,25(OH)2D3 is not responsible for
the stimulation of the tubular Pi transport. Furthermore, there is no experimental
evidence demonstrating that the stimulation of Pi transport could be directly responsible for the increase in 1,25(OH)2D3 production. Therefore, it remains tempting
to speculate that the 1,25(OH)2D-producing and the adaptive tubular Pi transport
systems, two major controlling elements of Pi homeostasis, might be regulated by
one single mechanism (37). Both 1,25(OH)2D3 production and the adaptive tubular
Pi transport system appear to act in concert for maintaining Pi homeostasis (Fig. 1).
As mentioned above in response to Pi deprivation, the stimulation of the tubular
42
PHOSPHATE AND THE KIDNEY
reabsorptive capacity will tend to attenuate the decrement in the extracellular Pi
concentration. The action of 1,25(OH)2D3 of stimulating the mobilization of Pi from
the intestinal lumen and from the bone will also tend to counteract the fall in extracellular Pi concentration entailed by Pi restriction. In addition, 1,25(OH)2D3 appears to favor the entry of Pi into some internal pool(s) (36). Such an action could
explain why the chronic administration of 1,25(OH)2D3 in physiological doses to
thyroparathyroidectomized animals leads to an apparent paradoxical decrease in the
tubular Pi reabsorptive capacity (28). Assuming that an important action of
1,25(OH)2D3 would be to increase the availability of extracellular Pi for internal
pool(s) of Pi, which might require a strict regulation, one could expect that this
extrarenal effect would entail a decrease in the tubular Pi reabsorptive capacity as
long as the Pi intake remains constant.
CONCLUSION
The plasma concentration of Pi is set at different levels according to Pi availability
and disposal. The kidney is a key determinant in the setting of the plasma Pi level.
A large body of evidences has been accumulated indicating that the adaptive system
of the tubular Pi transport probably plays a major role in the homeostasis of Pi. This
system responds to variations in both the Pi supply and demand. It operates independently of PTH and, moreover, controls very tightly the phosphaturic action of
this hormone. It appears to act in concert with the renal l,25(OH)2D3-producing
system for adjusting renal and extrarenal Pi fluxes to the body needs of the organism.
ACKNOWLEDGMENTS
We thank Mrs. Marie-Christine Brandt for her most efficacious secretarial
assistance.
Recent quoted works from the authors of this review were supported by the Swiss
National Science Foundation (Grants 3.954-0.85 and 3200.025.535).
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16. Caverzasio J, Rizzoli R, Bonjour JP. Sodium-dependent phosphate transport inhibited by parathyroid
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17. Steele TH, DeLuca HF. Influence of dietary phosphorus on renal phosphate reabsorption in the
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19. Troehler U, Bonjour JP, Fleisch H. Plasma level and renal handling of Pi: effect of overnight fasting
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DISCUSSION
Dr. Pettifor: What factors are involved in the regulation and sensing of inorganic phosphate
(Pi) deprivation? If dietary phosphate intake is decreased there is a dramatic response within
one to two hours—how does this control take place? Another question concerns oncogenic
rickets where a bone related factor may be important. Is there any tie-up between the two?
Dr. Bonjour: The adaptive response to Pi deprivation may involve two regulatory pathways.
First, a rather "primitive" regulatory loop that would directly connect the concentration of
Pi in the environment of the renal tubular cells to the activity of the luminal Na-dependent
Pi transport system. This type of regulation would be similar to that observed in renal epithelial
cell cultures. However, this rather simple system could not explain the kind of adaptation
observed in relation with changes in the Pi demand. As, for instance, during growth where
an increase in TmPi/GFR is maintained despite high plasma and filtered load of Pi. This type
of situation could better be explained by a second regulatory pathway involving a putative
hormone that would connect the actual controlled Pi pool of the organism to the tubular Pi
transport system. Whether this putative Pi hormone could be a molecule similar to IGF-1
remains an intriguing possibility.
Dr. Glorieux: To expand on a point you made which is probably pertinent to rickets, what
is the possible importance of phosphate transport in bone cells?
Dr. Bonjour: We have recently studied the handling of Pi by osteoblast-like cells originating
from two rat osteosarcoma cell lines, ROS 17/2.8 and UMR 106. A sodium-dependent Pi
transport system in the plasma membrane of these cells (1) was identified, and interestingly,
this system is selectively stimulated by parathyroid hormone (2). This effect remains to be
confirmed in nontumoral osteoblastic cell lines, particularly in human osteoblasts. We intend
to understand better the mechanism regulating the transfer of Pi from the systemic to the
bone extracellular compartment, in relation with the process of bone matrix formation and
mineralization.
Dr. Pettifor: You said that if you give a low phosphate diet you get a fairly rapid response
in phosphate handling by the kidney, but if you starve the animal, that does not take place.
How do the animals differentiate between a low phosphate diet and starvation?
Dr. Bonjour: The distinction may well be related to the fall in extracellular Pi concentration
that occurs with low Pi diet, but not with fasting (3-4). During fasting, the mobilization of
Pi from soft tissues compensates for the non-supply of Pi from the diet, so that no fall in
plasma Pi occurs unless the period of fasting is prolonged for several days. When rats are
PHOSPHA TE AND THE KIDNE Y
45
fed a low Pi meal for the first time, hypophosphatemia occurs probably because Pi is transferred into the intracellular compartment of soft tissues together with other nutrients. Insulin
could play an important role in this intracellular transfer of Pi during the feeding phase. The
fall in extracellular Pi might be the signal that is sensed by the proximal tubular cells and
leads to the stimulation of the Pi transport system present in the luminal membrane.
Dr. Marx: Most reports deal with serum phosphorus values after an overnight fast. Serum
phosphorus levels in humans show a dramatic diurnal cycle, more so than other minerals.
The cycle amplitude is greatest during adolescence with peak values during sleep (5), the
period of most rapid bone growth. Much still needs to be learned about the importance of
this striking rhythm. The mouse is really a nocturnal animal. Has anyone evaluated the 24
hour cycle of phosphorus in serum of mice or other nocturnal animals?
Dr. Bonjour: We reported a few years ago on the diurnal fluctuation of plasma Pi in rats
(3). This fluctuation depends markedly upon the prior dietary intake of Pi. Thus, in rats
previously fed a low Pi diet, plasma Pi rises after overnight fasting, whereas in rats adapted
to a high Pi intake, plasma Pi fell slightly or did not change. The mechanism of this apparent
paradoxical response was explained by showing that in normal animals, the kidney, by adapting its tubular Pi transport capacity to the prior dietary intake of Pi, accounts for the difference
in the phosphatemic response to overnight fasting, and consequently for the difference in the
diurnal fluctuation of plasma Pi observed between animals fed low or high Pi diets. Mobilization of Pi from body stores during the fasting phase leads to a rather marked increase in
plasma Pi, inasmuch as the renal tubule reabsorbs entirely the filtered load of Pi. This is the
case when the kidney adapts normally to a period of Pi deprivation. In X-linked hypophosphatemic mice, which are not able to adapt (6) to Pi restriction, the hyperphosphatemic
response to fasting is absent (7).
Dr. Schenk: In one of your diagrams, you have indicated osteoblasts among epithelial
structures, such as in the gut and in the kidney. This may be dangerous, because the type
of phosphate transport in osteoblasts seems basically different. Epithelial cells form a tight
barrier and pump phosphate through their membrane. Osteoblasts do not form an epithelium
and most likely pack phosphate into small containers, either visible or not, and deposit these
into the matrix, and their content is released near the mineralization front where the critical
final concentration is reached. Mineralization actually takes place about 10 microns away
from the cell.
Dr. Bonjour: I agree with you that Pi transport to the mineralization front could involve
a more complicated system than a simple osteoblastic transfer from the systemic extracellular
compartment to the bone extracellular compartment. We are now trying to identify what
kind of Pi transport system is present in matrix vesicles produced by osteoblastic cells or
epiphyseal chondrocytes. Nevertheless, it remains important, conceptually, to consider osteoblasts as cells having well defined polarized functions.
Dr. Guesry: What is the possible mechanism by which muscular activity may play a role
in phosphate homeostasis at the bone level? Immobilized patients, for example, have hyperphosphatemia. Does muscular activity play a role on the deposition of phosphorus into
bone through electrical stimulation?
Dr. Bonjour: Mechanical forces influence the activity of bone forming cells. Therefore,
muscle activity will indirectly affect the rate of bone matrix formation and mineralization,
and thus the amount of Pi deposited into bone. I do not know however which specific
mechanical stimuli can modify the activity of osteoblasts. Prostaglandins have been suggested
to play a role in this mechanical transduction.
46
PHOSPHA TE AND THE KIDNEY
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in osteoblast-like cells. Am J Physiol 1989:256:E93-E100.
3. Troehler U. Bonjour JP. Fleisch H. Plasma level and renal handling of Pi: effect of overnight fasting
with and without Pi supply. Am J Physiol 1981:24I:F5O9-I6.
4. Caverzasio J. Bonjour JP. Mechanism of rapid phosphate (Pi) transport adaptation to a single low Pi
meal in rat renal brush border membrane. Pflugers Arch 1985 ;404:227—31.
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adolescence. Ped Res 1984:18:456-62.
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