Key words
parathyroid hormone 1–34 - calcitriol - calcium - bone mineral density
Introduction
Hypoparathyroidism is a rare disorder associated with low or absent production of
parathyroid hormone (PTH). PTH deficiency results in abnormal mineral homeostasis
and is characterized by hypocalcemia, hyperphosphatemia, and hypomagnesemia [1]. In the kidneys, PTH promotes calcium reabsorption, phosphate excretion, and conversion
of 25(OH)D by 1α-hydroxylase to 1,25(OH)2D. In the intestines, 1,25(OH)2D enhances the absorption of calcium and, to a lesser degree, phosphate [1]. PTH deficiency disrupts normal mineral homeostasis by lowering intestinal and renal
calcium absorption due to reduced renal conversion of 25-hydroxyvitamin D to active
1,25-dihydroxyvitamin D [2]
[3]
[4]. Lack of PTH also decreases bone turnover. A reduction or absence of circulating
PTH leads initially to a decrease in bone resorption and then to a coupled reduction
in bone formation [2]
[3]
[4]
[5]. In adults, the cause of hypoparathyroidism is typically the result of a complication
of neck surgery or radiation [2]
[3]
[6]. Hypoparathyroidism can also result from a number of genetic or autoimmune disorders
including familial isolated hypoparathyroidism, DiGeorge syndrome, autoimmune polyendocrine
insufficiency type 1 with immune-mediated destruction of the parathyroid glands, and
autosomal dominant hypocalcemia resulting from activating mutations in the calcium-sensing
receptor [5]
[7]
[8]
[9]
[10].
The current conventional treatment for hypoparathyroidism is large doses of oral calcium
and active vitamin D metabolites or analogues to relieve the symptoms caused by hypocalcemia
[11]
[12]. However, this approach is not always successful in controlling the disease and
precisely controlling serum calcium levels [1]
[13]
[14]. Short- and long-term complications include large swings in serum calcium levels
(hypo or hypercalcemia) and risk of calcification of the brain, kidney, and other
tissues [1]
[15].
Several studies have evaluated the use of hormone replacement therapy in treating
hypoparathyroidism using either full-length hormone PTH (1–84) or the biologically
active fragment PTH (1–34). Both PTH (1–34) and PTH (1–84) are commercially produced
by recombinant DNA technology and are on the market as Forteo® and Natpara®, respectively. All of the clinical studies of PTH (1–34) included in this analysis,
however, were performed at the NIH where they used synthetic human PTH (1–34) formulated
by the NIH pharmacy [6]. Overall, prior studies investigating the use of PTH-replacement therapy for hypoparathyroidism
found that PTH-replacement therapy can maintain normal serum calcium and phosphate
levels or reduce the levels of concurrent treatment with calcium and active vitamin
D analogues by improving PTH-dependent renal calcium reabsorption or correct diminished
bone turnover [1]
[5]
[6].
In January 2015, PTH (1–84) was approved in the United States by the Federal Drug
Administration (FDA) as adjunct therapy to calcium and vitamin D therapy for the control
of hypocalcemia in patients with hypoparathyroidism [1]. Therefore, PTH (1–84) (Natpara®) is recently available as an adjunct to conventional therapy for patients who are
refractory to calcium and calcitriol alone [1]. Recombinant PTH (1–34) (Forteo®) was approved in 2002 for treatment of severe osteoporosis in adults and, over the
past decade, has been used extensively both in Europe and in the US as an off-label
replacement therapy for hypoparathyroidism [16]. Toxicology studies in rats found both PTH (1–34) and PTH (1–84) led to dose dependent
osteosarcomas in rats [17]. Consequently, both drugs are contraindicated for use in children and the FDA issued
a black box warning against use in children [6].
To date, most of the previous studies have been small, which limits the interpretation
of some of the findings [6]
[18]. In addition, the results for renal calcium excretion and phosphate levels have
been variable [6]. This study investigated the effect of human parathyroid hormone replacement therapy
on specific disease-related outcomes, including serum and urine calcium levels, serum
phosphate levels, and levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in
patients with hypoparathyroidism.
Materials and Methods
Search strategy
This meta-analysis was performed in accordance with PRISMA guidelines. Medline, Cochrane,
EMBASE, and Google Scholar databases were searched until January 13, 2015 using the
following search terms: hypoparathyroidism, parathyroid hormone/PTH, hormone replacement
therapy, vitamin D, calcitriol, and calcium. Randomized controlled trials (RCTs) and
2 arm, nonrandomized prospective studies, which investigated treatment in patients
who had chronic hypoparathyroidism≥18 months were included. All included studies had
to quantitatively report the outcomes of interest. Retrospective studies, cohort studies;
letters, comments, editorials, case report; proceeding, and personal communications
were excluded. The lists of potential studies were hand searched by 2 independent
reviewers, and if necessary, a third reviewer was consulted to resolve any discrepancies
regarding study eligibility.
Data extraction
The following information/data was extracted from studies that met the inclusion criteria:
the name of the first author, year of publication, study design, number of participants
in each group, participants’ age and gender, intervention, and outcomes (e. g., serum
calcium levels, 24-h urine calcium level, serum phosphate level, and serum 25-dihydroxyvitamin
D and 1,25-dihydroxyvitamin D levels).
Quality assessment
The quality of each included study was assessed using the Cochrane Collaboration’s
tool for assessing risk to assess the included studies [19]. Two reviewers assessed the quality of the studies and a third was consulted for
solving any discrepancies.
Statistical analysis
The primary outcome was serum calcium levels and 24-h urine calcium levels. Secondary
outcomes were levels of serum phosphorous, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin
D.
Standardized difference in means (or so called standard mean difference) was used
as the index of effect size that represented the effect of PTH-replacement therapy
in the treatment of hypoparathyroidism. Heterogeneity was assessed by Cochran’s Q
statistic and I2. Cochran’s Q statistic was defined as the weighted sum of the squared deviations
of the estimates of all studies and I2 indicated the percentage of the observed between-study variability caused by heterogeneity.
Either the Q statistic with p<0.1 or I2>50% was considered indicative of heterogeneity. If heterogeneity existed, standardized
difference in means of selected studies was pooled under random effect model using
the DerSimonian-Laird approach. Otherwise, the fixed-effects model (Mantel-Haenszel
approach) was used. Sensitivity analysis was performed by the leave-one-out approach.
A 2-sided p-value<0.05 was considered statistically significant. Publication bias
was not evaluated as at least 5 studies are necessary for this analysis [20]. All statistical analyses were performed using Comprehensive Meta-Analysis, version
2.0 (Biostat, Englewood, NJ, USA).
Results
The initial search identified 181 potential studies of which 161 were excluded for
not being relevant ([Fig. 1]). After a complete full-text review of the remaining 20 studies, 15 were eliminated
for not reporting the outcomes of interest quantitatively (n=12), being single-arm
studies (n=2), and being a repeated study of an included RCT (n=1) .
Fig. 1 Flow chart for study selection.
Five studies were included finally in the meta-analysis [13]
[14]
[16]
[19]
[20]. Winer et al. [18] reported the findings from a 3-year long-term randomized, parallel group, open-label
study, of which a number of the participants (21/27) were recruited from previous
RCTs from the same research group [21]
[22]. In the study of Winer et al. (2003) [18], only 6 subjects had not been exposed to PTH therapy.
Four studies were randomized controlled studies [13]
[14]
[16]
[18] and one study was a randomized crossover trial [20] ([Table 1]). Two of the 4 studies investigated the effect of PTH (1–84) compared with placebo
[13]
[14], and the other 3 studies evaluated the effect of PTH (1–34) compared with calcitriol
(1,25-dihydroxyvitamin D) [16]
[18]
[21]. All subjects also received calcium, vitamin D, or α-calcidol/calcitriol/ergocalciferol
as dietary supplement ([Table 1]). Together the 5 studies included 245 subjects. Across the studies, the mean duration
of disease ranged from 8–17 years, and the mean follow-up time was from 10 weeks to
3 years. The mean age of participants ranged from 8.8 to 53 years of age. One long-term
randomized, parallel group, open-label study was specifically designed for pediatric
patients (age 5–14 years) [16]. The studies of Winer et al. (2010) [16] and Winer et al. (1996) [21] consisted mostly of males (60–71%), while those of Sikjaer et al. (2011) [14], Winer et al. (2003) [18], and Mannstadt et al. (2013) [13] primarily recruited females (71–90%).
Table 1 Summary of basic characteristics of selected studies for meta-analysis.
|
Study
|
Study design
|
Interventions
|
Supplement treatment
|
Number of patients
|
Age (years) a
|
Male (%)
|
Duration of disease a (years)
|
Follow-up time
|
|
Sikjaer et al. 2011 [14]
|
RCT
|
PTH (1–84)
|
Oral calcium, vitamin D analogues †
|
32
|
53 (38–78) b
|
19
|
9.5 (2–33) b
|
24 weeks
|
|
|
Placebo
|
|
30
|
51 (31–73) b
|
10
|
8 (1–37) b
|
|
Winer et al. 2010 [16]
|
RCT
|
PTH (1–34)
|
Combined calcium and cholecalciferol
|
7
|
10.2 (2.3)
|
60
|
n/a*
|
3 years
|
|
|
Calcitriol
|
|
5
|
8.8 (2.9)
|
71
|
|
Winer et al. 2003 [18]
|
RCT
|
PTH (1–34)
|
Calcium
|
14
|
38 (18–70)
|
29
|
12 (1–35)
|
3 years
|
|
|
Calcitriol
|
|
13
|
43 (18–64)
|
46
|
18 (1–36)
|
|
Winer et al. 1996 [21]
|
Randomized Crossover Trial
|
PTH (1–34)
|
none
|
10
|
45.5 (14.5)
|
60
|
17 (2, 41) b
|
10 weeks
|
|
|
Calcitriol
|
Calcium carbonate
|
|
|
|
|
|
|
Mannstadt et al. 2013 [13]
|
RCT
|
rhPTH (1–84)
|
Oral calcium, vitamin D analogue ‡
|
90
|
47.0 (12.2)
|
23
|
14.1 (11.14)
|
24 weeks
|
|
|
Placebo
|
|
44
|
48.5 (13.7)
|
18
|
11.0 (7.98)
|
a Data were shown by mean (SD)
b Shown by median (range)
*n/a: Not available; † Vitamin D analogues included alfacalcidol, ergocalciferol, or cholecalcifero; ‡ Vitamin D analogue was calcitriol
RCT: Randomized controlled trial; PTH: Parathyroid hormone
Meta-analysis
Analysis of the data for serum calcium level indicated the presence of heterogeneity
across studies; therefore, a random effects model was used to generate pooled estimates
[Q=5.03, p=0.081, I2=60.2% for PTH (1–34); Q=3.35, p=0.067, I2=70.1% for PTH (1–84)] ([Fig. 2a]). Analysis of the data for urine calcium level indicated no heterogeneity across
studies; therefore, a fixed-effects model was used to generate pooled estimates [Q=0.92,
p=0.633, I2=0% for PTH (1–34); Q=0, p=1.00, I2=0% for PTH (1–84)] ([Fig. 2b]). Analysis of the data for serum phosphate level indicated no heterogeneity across
studies; therefore, a fixed-effects model was used to generate pooled estimates (Q=0.54,
p=0.764, I2=0% for PTH (1–34); Q=44, p=0.506, I2=0% for PTH (1–84)) ([Fig. 2c]).
Fig. 2 Forest plots for treatment effect on a serum calcium levels, b 24-h urine calcium level, and c serum phosphate level in patients with hypoparathyroidism.
The pooled standardized difference in mean serum calcium level between PTH-treated
and calcitriol/placebo-treated subjects was 0.349 (95% CI=− 0.383–1.082, p=0.350)
for PTH (1–34) and 0.414 (95% CI=− 0.238–1.066, p=0.214) for PTH (1–84), indicating
no significant increase in serum calcium level in the PTH-treatment groups relative
to the calcitriol/placebo (control) group ([Fig. 2a]). In contrast, the 24-h urine calcium levels significantly decrease in the PTH (1–34)-treated
group compared with the control group (standardized difference in means=− 0.696, 95%
CI=− 1.225 to−0.167, p=0.010) ([Fig. 2b]). No change in urine calcium level relative to control was observed in the PTH (1–84)-treatment
group. PTH (1–34) therapy did not change serum phosphate levels compared with control
(p=0.053), but PTH (1–84) treatment resulted in a significant decrease in phosphate
levels compared with control (standardized difference in means=− 0.592, 95% CI=− 0.890
to −0.294, p=0.000) ([Fig. 2c]).
Analysis of the data indicated heterogeneity among the studies for the serum levels
of 1,25-dihydroxyvitamin D [Q=11.18, p=0.001, I2=91.1% for PTH (1–34); Q=6.94, p=0.008, I2=85.6% for PTH (1–84)] and in 25-dihydroxyvitamin D levels for PTH (1–34) (Q=4.35,
p=0.037, I2=77.0%); therefore, a random effects model was used to generate the pooled estimates
([Fig. 3a, b]). The subgroup of PTH (1–84) indicated no heterogeneity among the studies for 25-dihydroxyvitamin
D level (Q=0.24, p=0.623, I2=0%); therefore, a fixed-effects model was used to generate the pooled estimates ([Fig. 3b]).
Fig. 3 Forest plots for treatment effect on a 1,25-dihydroxyvitamin D and b 25-hydroxyvitamin D in patients with hypoparathyroidism.
The results showed that there was no difference in 1,25-dihydroxyvitamin D levels
between PTH-replacement and calcitriol/placebo treatment groups regardless of types
of PTH agent used (PTH (1–34): pooled standardized difference in means=1.060, 95%
CI=− 0.428–2.547, p=0.163; PTH (1–84): pooled standardized difference in means=0.326,
95% CI=− 0.912–1.565, p=0.606) ([Fig. 3a]). However, both PTH (1–34) (standardized difference in means=− 0.954, 95% CI=− 1.863
to−0.044, p=0.040) and PTH (1–84) (standardized difference in means=− 0.639, 95% CI=− 1.207
to − 0.071, p=0.028) treatments were associated with a significant decrease in serum
25-dihydroxyvitamin D levels ([Fig. 3b]).
Sensitivity analysis, in which each study was left out in turn, indicated that the
study of Winer et al. (2003) [18] had a mild influence over the pooled estimates for serum calcium levels (standardized
difference in means=0.493, 95% CI=0.003–0.983, p=0.049); pooled results became significant
when Winer et al. (2003) [18] was removed ([Fig. 4a]). In addition, the study of Mannstadt et al. (2013) [13] may have overly impacted the result of the 24-h urine calcium level (standardized
difference in means=− 0.696, 95% CI=− 1.225 to − 0.167, p=0.010); pooled results became
statistically significant when Mannstadt et al. (2013) [13] was removed ([Fig. 4b]).
Fig. 4 Sensitivity-analysis for a serum calcium levels, b 24 h-urine calcium level, and c serum phosphate level.
To assess whether the age of patients may have influenced our pooled results for the
treatment of PTH (1–34) on both primary outcomes, subgroup analyses that evaluated
the adult patient results were conducted ([Fig. 5]). Two studies with adult patients for each PTH (1–34) treatment were included in
the analysis. The results showed that there was no association between serum calcium
level and treatment of PTH (1–34) (standardized difference in means=0.518, 95% CI=− 0.795–1.831,
p=0.440). On the other hand, a significantly decrease in urine calcium level was found
the PTH (1–34)-treated group compared with the control group (standardized difference
in means=− 0.803, 95% CI=− 1.399 to −0.208, p=0.008) ([Fig. 5]).
Fig. 5 Forest plot for treatment effect of PTH (1–34) on primary outcomes in studies recruiting
adult participants only.
Quality assessment
Quality assessment indicated that all the studies were of good quality. All 4 of the
studies were randomized controlled studies minimizing selection bias. There was low
risk of attrition or reporting bias, and for the studies reported the necessary information,
there was low risk of performance or detection bias. Three of the 5 studies had intention-to-treat
analysis.
Discussion
The purpose of this study was to evaluate the efficacy of human PTH-replacement therapy
in adults and children with hypoparathyroidism. This meta-analysis found PTH-replacement
therapy, regardless if it was with PTH (1–34) or PTH (1–84), was not associated with
a greater increase in levels of serum calcium compared with placebo/calcitriol control.
The analysis also found that PTH (1–34) resulted in a significant decrease in urine
calcium levels relative to placebo/calcitriol (p=0.01), but there was no significant
difference with regard to phosphorous compared with placebo/calcitriol control (p=0.053).
Serum phosphorus levels in children are normally higher compared with adult levels.
In the study designed for children with chronic hypoparathyroidism, serum phosphorus
was consistently above normal in both treatment groups [16]. PTH (1–84) treatment resulted in no change in urine calcium relative to placebo/calcitriol
control (p=0.689), but there was a significant decrease in serum phosphate levels
(p<0.001). There was no difference between either type of PTH therapy and placebo/calcitriol
(p≥0.163) Both PTH (1–34) and PTH (1–84) caused a significant decrease in serum 25-dihydroxyvitamin
D levels (p≤0.04) but not in 1,25-dihyrdoxyvitamin D. The differences in findings
between the 2 therapies may reflect differences in the study designs or possible differences
in biological activity between the molecules. We also performed subgroup analysis
that evaluated only adults which found that in adults PTH (1–34) therapy did not result
in a significant difference in serum calcium levels compared with placebo/calcitriol
control (p=0.440) but did significantly reduce urine calcium levels (p=0.008). These
findings are similar to those of the entire populations. The importance of this meta-analysis
study is that by evaluating the pooled data for PTH (1–34) and PTH (1–84) treatments,
it gives additional insight into the benefit and the activity of the different PTH
therapies in treating hypoparathyroidism.
Analysis of the efficacy of PTH (1–34) and PTH (1–84) separately found that mean serum
calcium was maintained within or slightly below normal range (nonsignificant difference)
but urine calcium was significantly decreased after the PTH (1–34) treatment. PTH
(1–34) did reduce the urine calcium level to the normal range (1.25–6.25 mmol/24 h).
These findings may suggest that PTH (1–34) maintains the serum calcium level by increasing
renal calcium reabsorption and decreasing urine calcium excretion.
In the RCTs included in this study, patients received oral calcium and vitamin D analogue(s)
as supplement treatment. However, as above mentioned, short- and long-term complications
indicate that large swings in serum calcium levels (hypo- or hypercalcemia) may occur
after the treatment. Furthermore, studies with PTH (1–84) did not achieve this important
goal of reducing urine calcium possibly because patients received large, fixed, single
daily doses. Mean serum 1,25-dihydroxyvitamin D concentrations were maintained in
the normal range but mean serum concentration of 25-hydroxyvitamin D decreased in
both PTH (1–34) and PTH (1–84) groups. A decrease in serum level of 25-hydroxyvitamin
D implied that PTH therapy maintained the serum level of 1,25-hydroxyvitamin D by
improving conversion of 25(OH)D by 1α-hydroxylase to 1,25(OH)2D. In an RCT reported by Mannstadt et al. (2013) [13], 1,25-dihydroxyvitamin D concentrations patients treated with PTH (1–84) were maintained
in the normal range despite reductions in oral calcium and active vitamin D [13].
Potential advantages of PTH-replacement therapy is that it may result in improved
maintenance of serum calcium levels and reduce the need for treating with calcium
and active vitamin D or vitamin D analogues [6]. PTH-replacement therapy may also lower urinary calcium, improve bone quality, reduce
ectopic tissue calcification, and improved quality of life [23]
[24]. In addition, there is evidence that hypoparathyroidism is associated with elevated
cholesterol levels, a risk factor for cardiovascular disease [25]. It is unclear if PTH-replacement therapy would affect cholesterol levels.
This meta-analysis suggests that PTH-replacement therapy can simultaneously maintain
normal serum and urine calcium. Several prior studies found PTH-replacement therapy
reduced the need for additional calcium or vitamin D and improved bone mineral density
[14]. We did not analyze if the use of PTH-replacement therapy resulted in a reduction
in the need for calcium supplementation or vitamin D or its analogues. We also did
not evaluate the impact of PTH-replacement therapy on bone mineral density.
Currently, PTH is marketed for the treatment of osteoporosis and is only available
at a fixed dose of 20 μg (teriparatide; Forteo®, Eli Lilly and Company, Indianapolis, IN, USA) [28]. PTH (1–84) is available in the U.S. at a once daily dosage of 50 μg (Natpara®, NPS Pharmaceuticals, Inc, Bedminster, NJ, USA) [26]. However, due to the occurrence of osteosarcomas and death in rat toxicology studies
of rhPTH (1–34) [27], the FDA does not permit administration of PTH (1–34) to children or adults younger
than 24 years of age, and PTH is not approved by the FDA for use in hypoparathyroidism
[12]
[27]. PTH (1–84) was only recently approved in 2015 in the US for the treatment of osteoporosis
and because of the potential risk of osteosarcoma, it is recommended only for patients
who cannot be well-controlled on calcium supplements and active forms of vitamin D
alone. The available preparations of PTH can only be used once daily, as twice daily
administration will cause hypercalcemia in most patients [26]
[28].
PTH-replacement therapy may work best using flexible dosing to adjust to the needs
of different patients [13]. One study evaluated the efficacy and safety of PTH (1–34) in adults with hypoparathyroidism
who received titrated PTH dosing aimed at normalizing calcium levels in the blood
and urine [13]. In the study, the doses of the PTH (1–34) or calcitriol were adjusted to achieve
serum calcium levels within the normal, or just below the normal, range [13]. The study found that, during a 3-year follow-up, serum calcium levels and urine
calcium excretion were essentially within the normal range in the PTH (1–34) treated
patients [20]. In contrast, only the serum calcium levels were within the normal range for the
calcitriol treated patients. The bone mineral content and bone mineral density also
improved to a greater extent with the PTH (1–34) compared with the calcitriol treatment
[13]. In general, the findings were similar to the study of Winer et al. (2010) [16] that also used flexible dosing in children aged 5–14 years except there was no difference
in the serum calcium levels between PTH (1–34) and calcitriol [16]. In contrast to PTH (1–34), studies with PTH (1–84) have only assessed fixed doses
of PTH. Currently due to the fixed daily dosing of commercially available PTH-replacement
therapy, the use of these drugs should be as an experimental treatment in patients
in which calcium levels cannot be maintained using conventional methods [6]. Further, well designed studies that use similar dosing strategies are required
to better understand the long-term efficacy and safety of treating hypoparathyroidism
with PTH-replacement therapy.
All included studies were randomized trials (4 being RCTs and one being a randomized
cross-over study). However, our meta-analysis has several limitations. The overall
sample size was small, partly reflecting the rarity of this disease. The studies differed
in populations (3 enrolled primarily female adults women, and 2 studies were performed
in children) and active drug (2 studied PTH (1–84) and 3 investigated PTH (1–34).
Although, the pharmacokinetics and pharmacodynamics may differ slightly between PTH
(1–84) and PTH (1–34) [26]
[28], the published results do not indicate any apparent difference in efficacy between
the 2 molecules [6]
[23]. However to date, there has not been a head-to-head study between PTH (1–84) and
PTH (1–34) [6]. In addition, the studies with PTH (1–34) and PTH (1–84) differed in design and
purpose; PTH (1–34) studies titrated doses of the molecule to normalize both urine
and calcium levels, while studies with PTH (1–84) used a fixed dose along with calcitriol
and calcium. Calcitriol, which was co-administered with PTH in 3 of the 5 included
studies has potent calcemic and calciuric effects, which may confound the interpretation
of the “true” PTH effect. Another limitation of our analysis is that it did not evaluate
changes in symptoms resulting from PTH-replacement therapy. The follow-up time in
the 3 of the 4 the studies, which enrolled adults, was<6 months [13]
[14]
[21]. The other study evaluated PTH (1–34) therapy up to 3 years in adults and found
it was safe and effective [18]. Additional long-term studies are necessary to further determine the long-term effects
of PTH therapy. This is important as treatment of hypoparathyroidism, a life-long
disorder, requires long-term therapy [6]. Only one study investigated the twice daily administration of PTH-replacement therapy
in children (5–14 years of age) [16]. They found that, up to 3-years, treatment with PTH (1–34) was well tolerated and
was similar to calcitriol treatment in maintaining normal serum and urine calcium
levels, kidney function, bone mineral accrual, and developmental growth. Similar to
adults, longer term studies in children are required to establish the efficacy and
safety of PTH-replacement in treating hypoparathyroidism in this young patient population.
In addition, there is evidence that hyperparathyroidism may be associated with thyroid
carcinomas in about 3% of patients [29]. It would be of interest to further investigate the relationship of hyperparathyroidism
and the risk of thyroid cancer and the effect of PTH therapy on this risk.
Conclusion
In conclusion, our meta-analysis suggests that, in patients with hypoparathyroidism,
PTH (1–34), but no PTH (1–84) replacement therapy, can maintain the serum calcium
levels in normal range by reducing the levels of urine calcium. However, serum phosphate
level is reduced by PTH (1–84)-replacement therapy but not by PTH (1–34). Both PTH
(1–34) and PTH (1–84)-replacement therapy may maintain the serum level of 1,25-dihydroxyvitamin
D. It may be achieved by improving conversion of 25-dihydroxyvitamin D by 1α-hydroxylase
to 1,25-dihydroxyvitamin D, which results in a decrease in serum levels of 25-dihydroxyvitamin
D.
