British Journal of Rheumatology 1998;37:27±33
EFFECT OF LOW-DOSE PREDNISONE (WITH CALCIUM AND
CALCITRIOL SUPPLEMENTATION) ON CALCIUM AND BONE
METABOLISM IN HEALTHY VOLUNTEERS
W. F. LEMS, G. J. M. VAN VEEN,$ M. I. GERRITS,* J. W. G. JACOBS,
H. H. M. L. HOUBEN,$ H. J. M. VAN RIJN* and J. W. J. BIJLSMA
Department of Rheumatology and Clinical Immunology and *Department of Clinical Chemistry, Utrecht
University Hospital and $Department of Rheumatology, Hospital `de Wever', Heerlen, The Netherlands
SUMMARY
The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the
uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the e€ect of low-dose
(10 mg/day) prednisone (LDP) and the possible mitigating e€ects of calcium and 1,25 (OH)2 vitamin D (calcitriol) on calcium
and bone metabolism in eight healthy, young male volunteers. The study consisted of four observation periods: in the ®rst
period, LDP was prescribed during 1 week; in the second, third and fourth periods, calcium (500 mg/day), calcitriol (0.5 mg
b.i.d.) and calcium in combination with calcitriol, respectively, were added to LDP. Bone formation was measured by means
of serum osteocalcin, carboxy-terminal propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone resorption
by means of urinary excretion of calcium, hydroxyproline, (free and total) pyridinoline, (free and total) deoxypyridinoline
and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP). Dietary calcium and sodium intake were
maintained at a stable level during the entire study period. Treatment with LDP led to a decrease in osteocalcin, P1CP and
alkaline phosphatase (all P < 0.01). Urinary excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase,
but remained unchanged or slightly reduced (P < 0.05), depending on the time of measurement and the marker of bone
resorption. Parathyroid hormone (PTH) (insigni®cantly) increased during LDP (+19%) and LDP plus calcium (+14%), but
decreased during supplementation with calcitriol (ÿ16%) and calcium/calcitriol (ÿ44%; P < 0.01). Urinary excretion of
calcium increased during treatment with LDP and calcitriol (P < 0.05) and calcium/calcitriol (P < 0.05). It is concluded
that LDP has a negative e€ect on bone metabolism, since bone formation decreased while bone resorption remained
unchanged or decreased slightly. The increase in PTH during LDP could be prevented by calcitriol combined with calcium
supplementation.
KEY WORDS: Corticosteroids, Low-dose prednisone, Osteoporosis, Osteocalcin, Pyridinolines.
AN intriguing question is whether low-dose prednisone (LDP) leads to bone loss. Long-term administration of high-dose corticosteroids (Cs) is associated
with bone loss [1, 2], which may lead to fractures
[1, 3, 4]. High-dose Cs have a direct negative e€ect
on bone formation [5±8]. In addition, moderate to
high-dose Cs have an indirect e€ect on bone resorption: during Cs treatment, intestinal calcium absorption is decreased [9, 10] and urinary calcium
excretion increased [11], which may lead to a hypocalcaemia-mediated increase in parathyroid hormone
(PTH) and subsequently (relatively or absolutely)
increased bone resorption [6±8].
Although some earlier studies could not demonstrate an e€ect of LDP on bone mass [12, 13], in
other more recent studies bone loss was found for
patients treated with Cs, even when prescribed in low
dosages [14±16]. These last three studies, predominantly involving elderly postmenopausal women
with rheumatoid arthritis (RA), suggest that the
administration of 7.5 mg prednisone/day is associated
with bone loss. Unfortunately, interpretation of
calcium and bone metabolism in patients treated with
Cs is dicult, because these processes are in¯uenced
not only by Cs, but also by the underlying disease
for which the prednisone was prescribed [17, 18].
Therefore, we examined the e€ect of LDP on calcium
and bone metabolism in healthy volunteers. We
chose a slightly higher dosage of Cs because we
believe that the bioavailability of prednisone is higher
in elderly postmenopausal women with RA than in
healthy, young male volunteers, because of di€erences in kidney function and serum albumin (low
serum albumin is accompanied by a high free fraction
of cortisol).
In addition, we also examined the e€ect of calcium
and/or calcitriol supplementation during LDP treatment. Theoretically, both calcium and calcitriol could
enhance intestinal calcium absorption and (thus)
counteract Cs-induced hypocalcaemia, which may
lead to hyperparathyroidism. Calcitriol probably also
has a direct positive e€ect on bone formation [19, 20],
which may be important for Cs-treated patients
because Cs induce a decrease in bone formation.
Submitted 19 November 1996; revised version accepted 22 May
1997.
Correspondence to: W. F. Lems, Department of Rheumatology
and Clinical Immunology F02.223, University Hospital Utrecht,
PO Box 85500, 3508 CA Utrecht, The Netherlands.
PATIENTS AND METHODS
The study group consisted of eight healthy, male
volunteers: mean age 26 yr (range 20±36), mean
# 1998 British Society for Rheumatology
27
28
BRITISH JOURNAL OF RHEUMATOLOGY VOL. 37 NO. 1
height 181 cm (range 169±187), mean weight 72 kg
(range 60±82). None of them took any medication,
and none had a disorder which might interfere with
calcium or bone metabolism. For each volunteer, the
individual calcium and sodium intakes were maintained at a stable level during the whole study period
with the help of a dietician. The mean daily calcium
intake was 1394 mg (range 1000±1950); the mean
daily sodium intake was 3400 mg (range 2600±4000);
the estimated daily energy intake was 2599 kcal
(range 1988±4000). The volunteers were seen every
week by a physician (GV) who assessed possible sidee€ects; serum glucose, body weight and blood
pressure were measured. The study, which lasted 4
months, consisted of four observation periods of 1
month each. Medication was taken by the volunteers
for 1 week from day 0 to day 7. Blood and urine
samples were collected on days ÿ3 and 0 (the mean
of these two measurements is the baseline value),
during treatment (days 2, 4 and 7) and after treatment (days 9 and 11). Between each treatment period,
there was a 3-week wash-out period. The volunteers
came at 9.00 a.m to the metabolic ward of the
hospital (`de Wever', Heerlen). At that time, blood
samples were taken and urine samples were collected
in the fasting state (second void urine collections).
In the ®rst period, the volunteers took 10 mg
prednisone/day (LDP) early in the morning after the
blood samples were collected, in the second period
LDP with 500 mg elementary calcium (Calcium
Sandoz Forte) in the evening, in the third period
LDP together with calcitriol 0.5 mg b.i.d., and in the
fourth period LDP, calcium and calcitriol (same
dosages).
The samples were divided for the di€erent
determinations and frozen at ÿ208C until assay. All
measurements were performed twice. Total osteocalcin (OC) was determined using a new human
speci®c immunoradiometric assay (ELSA-OSTEO;
Cis Biointernational, Bagnols, France) which recognizes a large N-terminal mid-fragment in addition to
the intact molecule. The normal value for postmenopausal women is 24.4 ng/ml (range 12.9±55.9),
according to the manufacturer. Intra-assay and interassay coecients of variation are 3.1 and 1.8%, respectively [21]. In vitro measurement of carboxyterminal propeptide of type 1 procollagen (P1CP;
[22]) and carboxy-terminal cross-linked telopeptide
of type 1 collagen (1CTP; [23]) was obtained by a
radioimmunoassay (Orion Diagnostica, Finland).
According to the manufacturer, normal values are
50±220 mg/l for P1CP and 1.7±5.0 mg/l for 1CTP,
and the intra-assay and inter-assay coecients of
variation are 3 and 5% for P1CP, and 4 and 6% for
1CTP, respectively. Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were determined as the free fraction as well as the total Pyr and Dpyr. To obtain the
total fraction, urine was hydrolysed in 6 N HCl
at 1108C for 18 h. Extraction was performed by
cellulose CF1 column chromatography. The extraction product was freeze±dried before separation on a
reverse-phase C18 column by HPLC and identi®cation by spectro¯uorometry [24]. In our laboratory,
normal values for healthy persons aged 22±64 yr are
free Pyr 11.3 mmol/mol creat (range 5.9±36.2), free
Dpyr 3.6 mmol/mol creat (range 1.0±13.5), total Pyr
24.2 mmol/mol creat (range 13.5±53.2) and total Dpyr
7.1 mmol/mol creat (range 2.2±27.6). These values are
comparable with data from the literature [25]. In our
laboratory, the intra-assay coecients of variation
for pyridinolines were <10%, and the inter-assay
coecients of variation were <12.5% [24].
Serum alkaline phosphatase (AP), calcium, creatinine and inorganic phosphorus were measured with
a Hitachi 717 autoanalyser using BoehringerMannheim Reagents (Germany). Intact PTH was
measured with IRMA from Nichols Institute (San
Juan Capistrano, CA, USA). Calcium in urine was
measured colorometrically with a Technicon RA1000 Autoanalyzer. Hydroxyproline in urine was
measured using Hypronosticon (Organon, The
Netherlands). All data obtained from urinary assays
were corrected for the creatinine concentration
measured by a standard colorimetric method.
Statistics
Statistical analysis was carried out with the
Number Cruncher Statistical System (NCSS), Version
5.1. For comparison of data with a normal distribution, paired T-tests were used, and for an irregular
distribution the Wilcoxon rank sum test was used.
All statistical tests were two-sided; a P value of
<0.05 was considered to be statistically signi®cant.
Data were analysed in two ways: data were compared with baseline, as described above, and the
mean for the treatment period (days 2, 4 and 7) was
compared with baseline; the di€erence was given as a
percentage of baseline. No adjustment for multiple
testing was made.
RESULTS
First period: LDP alone
The results of the ®rst week (only LDP) are shown
in Table I. During LDP treatment, there was a
decrease in the serum OC level (P < 0.01) which
rapidly returned to baseline after discontinuation of
LDP. P1CP and AP were decreased inconsistently
either during or after treatment with LDP (both
P < 0.01). Serum calcium was increased only on day
2 of LDP treatment (P < 0.05). Serum 1CTP was
decreased (P < 0.05) at the end of the treatment
period and 2 days thereafter. During LDP intake,
Dpyr (tot), Pyr (free) and Dpyr (free) were decreased
at di€erent times: Dpyr (total) only on the second
day of LDP treatment (P < 0.05), Pyr (free) only on
the fourth day of LDP treatment (P < 0.05) and
Dpyr (free) only 2 days after discontinuation of
LDP. Pyr (tot) and urinary excretion of calcium
remained unchanged. All markers of bone resorption,
except total Dpyr, showed a consistent pattern of
decrease during LDP treatment in comparison to
baseline, and a (tendency of) return to baseline on
29
LEMS ET AL.: EFFECT OF LOW-DOSE PREDNISONE
TABLE I
E€ect of low-dose prednisone on markers of bone metabolism in healthy volunteers. First period: e€ect of prednisone 10 mg/day. Baseline:
mean of values on days ÿ3 and 0; days 0±7: 10 mg prednisone/day; days 8±11: no treatment. Di€erence: percentage change during LDP with
respect to baseline
Mean (S.D.)
Baseline
Osteocalcin
30 (11)
P1CP
188.8 (82.1)
Alkaline phosphatase 78.3 (15.7)
Calcium (serum)
2.41 (0.07)
UCal/Cr
0.14 (0.06)
UHydr/Cr
24.3 (6.7)
PTH
2.45 (0.9)
1CTP
5.6 (2.1)
Pyr (free)
15 (5.6)
Pyr (total)
37.2 (11.9)
Dpyr (free)
3.6 (1.3)
Dpyr (total)
10.9 (2.9)
Day 2
23.4** (8.5)
172.2 (69.9)
74** (15.9)
2.46* (0.04)
0.17 (0.07)
19.9* (7.4)
2.36 (0.8)
5.6 (2.2)
13.5 (3.8)
33.2 (6.3)
2.9 (0.9)
9.1* (1.6)
Day 4
23.9* (9.4)
163.1** (72.3)
73.1* (15.4)
2.41 (0.09)
0.14 (0.06)
19.4* (6.5)
3.3 (1.2)
5.0 (1.4)
12.2* (3.0)
32.6 (11.1)
2.9 (0.7)
9.5 (3.3)
Day 7
22.6** (9.5)
173.9 (94.6)
72.9 (16.1)
2.38 (0.08)
0.17 (0.09)
21.5 (5.8)
3.1 (1)
4.8* (1.3)
12.5 (4.0)
34.6 (10.8)
2.9 (1.0)
11.1 (2.9)
Day 9
28.2 (8.4)
164.8** (69.4)
72.5* (15.1)
2.42 (0.17)
0.15 (0.08)
18.8 (7.3)
3.1 (1.8)
4.8* (1.6)
12 (3.6)
31.2 (7.7)
2.7* (1.0)
9.2 (2.2)
Day 11
30.1 (10.1)
168.1* (74.5)
73.6 (14.3)
2.39 (0.04)
0.15 (0.13)
20.5 (7.0)
2.8 (0.9)
5.0 (1.5)
14.9 (5.3)
34.2 (14.9)
3.3 (1.5)
9.6 (4.2)
Di€erence
ÿ22% (P < 0.01)
ÿ10% (P < 0.05)
ÿ7% (P < 0.05)
+2%
+14%
ÿ17% (P < 0.05)
+19%
ÿ9% (P < 0.05)
ÿ15%
ÿ10%
ÿ16%
ÿ9%
*P < 0.05; **P < 0.01 in comparison to baseline.
day 11 (= 4 days after stopping the LDP treatment).
There is a consistent, although not statistically signi®cant, increase in PTH during (day 4 and 7) and
shortly after (day 11) the treatment period, followed
by a decrease to baseline on day 11.
The decrease in serum OC during 7 days of
treatment with LDP (ÿ22%; P < 0.01) was greater
than that found for P1CP (ÿ10%; P < 0.05) and AP
(ÿ7%; P < 0.05). PTH was increased (+19%) during LDP (not statistically signi®cant).
The second (LDP plus calcium), third (LDP plus
calcitriol) and fourth (LDP plus calcium/calcitriol)
periods
During the second, third and fourth periods, the
decrease in OC (ÿ22%, ÿ24%, ÿ16%, ÿ27%; data
shown in Fig. 1), P1CP (ÿ10%, ÿ15%, ÿ7%, ÿ9%)
and AP (ÿ7%, ÿ4%, 0%, ÿ7%) was roughly the
same as in the ®rst period. The changes in OC during
the four treatment periods are shown in Fig. 1.
PTH increased in the second period (+14%; not
signi®cant) and decreased in the third (ÿ16%; not
FIG. 1.Ð E€ect of low-dose prednisone (LDP; 10 mg/day) on
serum osteocalcin (mean, S.D.) in healthy volunteers (=®rst period).
Second period: LDP and calcium (500 mg/day). Third period: LDP
and calcitriol 0.5 mg b.i.d. Fourth period: LDP and calcium plus
calcitriol. **P < 0.01 in comparison to baseline.
signi®cant) and fourth (ÿ44%; P < 0.01) periods.
The changes in PTH during the four treatment
periods are shown in Fig. 2.
The changes in levels of Pyr/Dpyr were also
roughly the same as in the ®rst period, although the
decrease in bone resorption was slightly less for all
measured pyridinolines: Pyr (free): ÿ15%, +5%,
ÿ8% and ÿ3%, in the ®rst, second, third and fourth
periods, respectively; Pyr (total): ÿ10%, ÿ5%, ÿ5%
and ÿ5%; DPyr (free): ÿ16%, +9%, ÿ4% and
ÿ6%; DPyr (tot): ÿ9%, ÿ4%, 0% and ÿ6% (data
not shown).
Urinary calcium excretion increased in the third
(+40%; P < 0.05) and fourth (+61%; P < 0.05)
periods. Changes in the urinary excretion of hydroxyproline (Hydr) were not signi®cant in the second
(ÿ17%), third (ÿ11%) and fourth periods (ÿ0%).
Hypercalcaemia was not observed in any of the
volunteers in the present study.
One volunteer withdraw because of gastrointestinal
FIG. 2.ÐE€ect of low-dose prednisone (LDP; 10 mg/day) on
serum parathyroid hormone (mean, S.D.) in healthy volunteers
(=®rst period). Second period: LDP and calcium (500 mg/day).
Third period: LDP and calcitriol 0.5 mg b.i.d. Fourth period: LDP
and calcium plus calcitriol. Di€erence between baseline and treatment period: ®rst period: +19%, second period: +14%, third
period: ÿ16%, fourth period: ÿ44% (P < 0.01).
30
BRITISH JOURNAL OF RHEUMATOLOGY VOL. 37 NO. 1
complaints after the third period. During all periods,
no (other) side-e€ects of therapy were observed; in
particular, neither hypertension nor hyperglycaemia
occurred.
DISCUSSION
E€ect of low-dose prednisone
During LDP treatment, AP, P1CP and OC all
decreased, indicating that bone formation is
depressed not only during treatment with high-dose
Cs [6±8], but also when low dosages of Cs are
administered. In the present study, we observed a
decrease of 22% in serum OC during treatment with
LDP, which is comparable with the decrease of 17
and 33% found in earlier studies [26, 27]. Changes in
OC were consistent: OC had decreased during LDP
therapy and returned to baseline 2 days after discontinuation of LDP. Changes in AP and P1CP were
less consistent, not only during but also after LDP
treatment. Earlier data had also indicated that a
decrease in OC could be observed within 24 h of
initiating Cs [27], while P1CP decreased 2±4 days
after starting Cs [28]. This suggests that Cs-induced
changes in bone formation are re¯ected most
accurately by OC.
Data in the literature on bone resorption during
Cs treatment are inconsistent. Urinary excretion of
Hydr was increased in patients receiving 20 mg
prednisone/day [29], but remained unchanged in
healthy volunteers taking LDP [27] and (euthyroid)
patients with Graves' ophthalmopathy treated with
60 mg prednisone/day [30]. Previous studies on the
e€ect of Cs on bone resorption were hampered by
the fact that (a) bone resorption is also in¯uenced by
the underlying disease for which the Cs were prescribed [17, 18], and (b) previously used markers of
bone resorption were probably less reliable than
recently developed markers, such as the pyridinolines
[31]. Urinary excretion of Hydr is not a reliable
marker of bone resorption [31] since (a) it is also produced by breakdown of the C1q fraction of complement, (b) it is metabolized by the liver and (c)
measurement is in¯uenced by diet. Recently, new
markers of bone resorption have been developed:
1CTP [23] and the pyridinolines. An advantage of
1CTP is that it is a serum marker of bone resorption;
a disadvantage is that it probably is not very sensitive
to changes in bone resorption [32]. At present, Pyr
and Dpyr are regarded as the most reliable markers
of bone resorption [33, 34]. In comparison with the
conventional method of measurement of bone resorption by means of Hydr, two important advantages of
the pyridinolines are that they are not metabolized
and diet does not in¯uence measurement [35].
This is the ®rst study of the e€ect of LDP on
1CTP, Pyr (free and total fraction) and Dpyr (free
and total fraction) in healthy volunteers. In our
opinion, the observation, in the present study, that
all ®ve markers of bone resorption (1CTP, Pyr free/
total, Dpyr free/total) were not increased, but
unchanged or decreased during treatment with
LDP (although the changes were only incidentally
signi®cant), is intriguing. Moreover, for all markers,
except total Dpyr, we observed a clear pattern of
decrease during LDP treatment in comparison to
baseline and a (tendency of) return to baseline on
day 11 (= 4 days after stopping the LDP treatment).
Thus, the unchanged or increased bone resorption
found for patients treated with moderate to high
doses of Cs in other studies [27, 29, 30] was not
con®rmed in the present study. In fact, bone resorption showed a tendency to decrease during treatment
with LDP. The combination of decreased bone
resorption and the negative in¯uence of LDP on
bone mass [14±16] is only possible if bone formation
is inhibited more than bone resorption; this is
suggested in the present study, in which OC seems to
decrease more than the pyridinolines. These results
con®rm recent ®ndings that intra-articular injections
of Cs have predominantly an inhibiting e€ect on
bone formation and lead to only a slight (insigni®cant) decrease in bone resorption in patients with RA
[36]. It could be that this uncoupling is responsible
for bone loss during long-term treatment with LDP.
E€ect of calcium supplementation
In an earlier study, we found no decrease in
bone formation, as indicated by the serum OC
concentration, during combined treatment with LDP
and calcium, while serum OC decreased during treatment with LPD alone [27]. This result was dicult
to interpret because of the relatively short wash-out
period (1 week) between treatments. In the present
study with longer wash-out periods (3 weeks), we
observed that during combined treatment with LDP
and calcium (second observation period), serum OC
decreased, like when LDP was given alone; moreover,
AP and P1CP also decreased. We conclude that
a positive e€ect of calcium supplementation on
(markers of ) bone formation was not observed
during LDP treatment.
In the present study, we observed an (insigni®cant)
increase in PTH during treatment with LDP (+19%)
and LDP plus calcium (+14%), which suggests that
calcium supplementation alone does not prevent
secondary hyperparathyroidism. The discrete changes
in urinary excretion of calcium and the pyridinolines
and serum 1CTP were roughly the same as during
treatment with LDP alone.
E€ect of calcitriol
Theoretically, treatment with calcitriol is attractive
for Cs-treated patients, because it not only increases
intestinal calcium absorption [9, 10], but probably
also has a direct stimulatory e€ect on osteoblasts and
bone formation [19, 20]. In rats, high-dose Cs caused
a reduction in serum OC and histomorphometrically
measured bone formation, which was counteracted 1
week later with (high-dose) 1,25 vitamin D [19].
Administration of 2 mg 1,25 vitamin D/day for 2
weeks to postmenopausal women led to a rise in
LEMS ET AL.: EFFECT OF LOW-DOSE PREDNISONE
serum OC, which was accompanied by a rise in
serum and urinary calcium [37]. It is thought that
calcitriol may counteract the Cs-induced suppression
of serum OC by interference with the OC gene [38].
In the present study, a mitigating e€ect on OC during
LDP plus calcitriol in contrast to LDP alone was not
observed. In other studies, calcitriol was administered
in a higher dosage [20, 37] and for a longer period
[37]. We chose a dosage of calcitriol of 1 mg/day,
because higher dosages of calcitriol are associated
with hypercalcaemia.
The discrete changes in the urinary excretion of
calcium and the pyridinolines and serum 1CTP were
roughly the same as found during treatment with
LDP alone.
When LDP and calcitriol (with and without calcium) were combined, urinary excretion of calcium
was increased. Although renal calcium excretion is
not a very sensitive way to measure intestinal calcium
absorption, this ®nding may suggest that calcitriol
increases the intestinal absorption of calcium during
LDP treatment. During combined treatment of
LDP with calcitriol, PTH decreased (ÿ16%). PTH
decreased even more (ÿ44%, P < 0.01) when both
calcium and calcitriol were given together with LDP.
These data indicate that the combination of calcitriol
and calcium is the best way to counteract secondary
hyperparathyroidism.
Clinical consequences
Extrapolation of these results for healthy volunteers to patients may be dicult. In patients, the risk
of side-e€ects of treatment with LDP has to be
weighed against the positive e€ect of reduction of
disease activity [39]. On the one hand, Cs may have
many side-e€ects, even at low dosages [40]. On the
other hand, bone loss in patients with RA is closely
related to the in¯ammatory process [41]. Recently,
Kirwan et al. [42] suggested that adjuvant treatment
with LDP of patients with early RA may lead to a
decrease in the number of newly formed erosions.
Whether LDP will have a positive e€ect on bone
mass in RA patients by reducing the in¯ammatory
process needs to be investigated.
Should Cs-treated patients be supplemented with
calcium and/or calcitriol?
Earlier, Reid and Ibbertson [43] showed a decrease
in urinary Hydr excretion during calcium supplementation in Cs-treated patients (prednisone 15 mg/
day). We have demonstrated that calcium (500 mg/
day), supplemented during 2 yr in patients with
various rheumatic diseases on chronic prednisone
treatment (mean dosage 14 mg/day), has a positive
e€ect on the prevention of progressive bone loss [44].
Because of the decreased intestinal calcium absorption [9, 10] and increased renal calcium excretion
[11], as well as the above-mentioned data, we think
that calcium supplementation is useful for Cs-treated
patients; it appears to be a safe and logical approach
to the prevention, at least partly, of (relatively)
31
increased bone resorption in patients receiving moderate to high-dose Cs. However, the positive e€ect of
calcium supplementation was modest in the present
study, probably due to the low dosage of Cs.
Data on the e€ect of vitamin D on bone mass
during Cs treatment are con¯icting: some studies
[45, 46] found no e€ect of vitamin D treatment, while
others report positive results [9, 47, 48]. A disadvantage of calcitriol is the increase in hypercalcaemia
[49]. Hypercalcaemia was not observed in the present
study, but the number of volunteers was small. The
observation that the combination of calcitriol and
calcium prevents secondary hyperparathyroidism
during LDP treatment is a strong argument in favour
of calcitriol and calcium for Cs-treated patients.
However, because of con¯icting data on the e€ect of
vitamin D on bone mass and the risk of hypercalcaemia, this approach must be investigated
further.
In summary, bone formation and bone resorption
both decrease during LDP treatment. Because bone
formation is more strongly inhibited than bone
resorption, the net e€ect of LDP on bone is negative.
PTH increased during LDP therapy. This increase
was prevented by combined supplementation of
calcium and calcitriol, but not by supplementation of
calcium alone. This suggests that combined administration of calcium and calcitriol to Cs-treated patients
may counteract secondary hyperparathyroidism.
ACKNOWLEDGEMENTS
WFL received a grant from the Dutch League
Against Rheumatism: Het Nationaal Reumafonds.
This study was also supported by a grant from
Hofmann-La Roche, The Netherlands.
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