J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://www.jofem.org

Original Article

Volume 13, Number 1, February 2023, pages 1-12

The Effect of Microgravity on Parathyroid Hormone Secretion: A Meta-Analysis

Figure 1. Flowchart showing screening and selection process for studies along with numbers of studies excluded at each step.

Figure 2. Tukey HSD plot of confidence intervals, inclusive of all studies. Red points indicate outlier data. HSD: honestly significant difference.

Figure 3. Forest plot for in-flight levels of PTH, inclusive of all studies. Squares with lines show 95% confidence intervals for a single study. Diamonds at the bottom indicate weighted average confidence interval computed from all studies. PTH: parathyroid hormone.

Figure 4. Tukey HSD plot showing 95% confidence intervals for real microgravity studies for each timepoint. Red points indicate outlier data. HSD: honestly significant difference.

Figure 5. Tukey HSD plot showing 95% confidence intervals for simulated microgravity studies for each timepoint. Red points indicate outlier data. HSD: honestly significant difference.

Figure 6. Funnel plot with standard error of studies on the y-axis plotted against standardized mean difference on the x-axis. Yellow circles represent single studies.

**Table 1.** Keywords Used to Search Individual Databases Until July 19, 2022 With Records Identified From Each Source
Database	Terms	No. of records identified
Embase, Scopus	parathyroid* AND (microgravity OR hypogravity OR “low gravity” OR weightless*)	Embase: 18; Scopus: 16
PubMed	parathyroid* AND (microgravity OR hypogravity OR “low gravity” OR weightless*) (all fields)	9
Google Scholar	parathyroid AND (microgravity OR hypogravity OR “low gravity” OR weightlessness OR weightless)	979
JAMA Network	parathyroid AND (microgravity OR hypogravity OR “low gravity” OR weightlessness)	0

Table 1. Keywords Used to Search Individual Databases Until July 19, 2022 With Records Identified From Each Source

Database

Terms

No. of records identified

Embase, Scopus

parathyroid* AND (microgravity OR hypogravity OR “low gravity” OR weightless*)

Embase: 18; Scopus: 16

PubMed

parathyroid* AND (microgravity OR hypogravity OR “low gravity” OR weightless*) (all fields)

Google Scholar

parathyroid AND (microgravity OR hypogravity OR “low gravity” OR weightlessness OR weightless)

979

JAMA Network

parathyroid AND (microgravity OR hypogravity OR “low gravity” OR weightlessness)

**Table 2.** Data Extracted for Each of the 12 Studies That Passed the Screening Process, Including Year, Name of First Author, Sample Size (n), Microgravity Condition (Real Versus Simulated), Time Points Collected, and Databases Where the Article Is Indexed
Ref.	Year	First author	n	Real/simulated	Timepoints	Database
*Smith et al report data from two separate studies, one with a sample size of six and another with 16 subjects.
[37]	2022	Linossier	9	Simulated	In-flight, R+2-7	Embase, Scopus, Google Scholar
[38]	2015	Smith	7	Real	In-flight	Scopus, Google Scholar
[39]	2012	Morgan	12	Simulated	In-flight, R+2-7	Embase
[27]	2012	Smith	6	Real	In-flight, R+0, > R+7	Scopus, PubMed, Google Scholar
[40]	2010	Armbrecht	10	Simulated	In-flight, R+1, R+2-7, >R+7	Embase, Scopus
[41]	2007	Zerwekh	10	Simulated	In-flight	Embase, Scopus, PubMed
[42]	2007	Zwart	7	Simulated	In-flight, R+0, R+1, R+2-7, >R+7	Scopus, PubMed
[28]	2005	Smith	6, 16*	Real	In-flight, R+0, R+2-7, >R+7	Embase, Scopus, Google Scholar
[43]	2005	Rittweger	25	Simulated	In-flight, R+1, R+2-7, >R+7	Google Scholar (grey)
[44]	2005	Morukov	9	Real	R+1, R+2-7, >R+7	Scopus
[45]	2004	Shackelford	18	Simulated	In-flight	Embase, Scopus, PubMed
[46]	2003	Smith	8	Simulated	In-flight, R+1, R+2-7	Scopus, PubMed

Table 2. Data Extracted for Each of the 12 Studies That Passed the Screening Process, Including Year, Name of First Author, Sample Size (n), Microgravity Condition (Real Versus Simulated), Time Points Collected, and Databases Where the Article Is Indexed

Ref.

Year

First author

Real/simulated

Timepoints

Database

*Smith et al report data from two separate studies, one with a sample size of six and another with 16 subjects.

[37]

2022

Linossier

Simulated

In-flight, R+2-7

Embase, Scopus, Google Scholar

[38]

2015

Smith

Real

In-flight

Scopus, Google Scholar

[39]

2012

Morgan

Simulated

In-flight, R+2-7

Embase

[27]

2012

Smith

Real

In-flight, R+0, > R+7

Scopus, PubMed, Google Scholar

[40]

2010

Armbrecht

Simulated

In-flight, R+1, R+2-7, >R+7

Embase, Scopus

[41]

2007

Zerwekh

Simulated

In-flight

Embase, Scopus, PubMed

[42]

2007

Zwart

Simulated

In-flight, R+0, R+1, R+2-7, >R+7

Scopus, PubMed

[28]

2005

Smith

6, 16*

Real

In-flight, R+0, R+2-7, >R+7

Embase, Scopus, Google Scholar

[43]

2005

Rittweger

Simulated

In-flight, R+1, R+2-7, >R+7

Google Scholar (grey)

[44]

2005

Morukov

Real

R+1, R+2-7, >R+7

Scopus

[45]

2004

Shackelford

Simulated

In-flight

Embase, Scopus, PubMed

[46]

2003

Smith

Simulated

In-flight, R+1, R+2-7

Scopus, PubMed

**Table 3.** Summary of Results From Two-Way ANOVA for a Relationship Between PTH Level and Timepoint, Experimental Condition, and the Combination of These Factors
Source	Sum of squares	DF	Mean square	F	P
ANOVA: analysis of variance; DF: degrees of freedom; PTH: parathyroid hormone.
Time	202.825	4	50.706	92.602	< 0.01
Condition	51.013	1	51.013	93.162	< 0.01
Time × condition	40.502	4	10.125	18.491	< 0.05
Residual	215.197	144	1.4944

Table 3. Summary of Results From Two-Way ANOVA for a Relationship Between PTH Level and Timepoint, Experimental Condition, and the Combination of These Factors

Source

Sum of squares

Mean square

ANOVA: analysis of variance; DF: degrees of freedom; PTH: parathyroid hormone.

Time

202.825

50.706

92.602

< 0.01

Condition

51.013

93.162

< 0.01

Time × condition

40.502

10.125

18.491

< 0.05

Residual

215.197

144

1.4944

**Table 4.** Tukey HSD Testing With 95% Confidence Intervals for Each Timepoint, Separated by Experimental Condition
Time	Condition	n	Mean	Standard error	95% confidence interval
*Timepoints differ significantly (P < 0.05) by experimental condition. HSD: honestly significant difference.
In-flight	Real	19	-1.5195	0.1698	-1.8532 to -1.1857
	Simulated	99	-1.4803	0.07437	-1.6265 to -1.3341
R+0*	Real	28	0.1207	0.1398	-0.1542 to 0.3956
	Simulated	8	-1.1400	0.2616	-1.6544 to -0.6256
R+1*	Real	25	1.1176	0.1480	0.8266 to 1.4086
	Simulated	50	-0.7226	0.1046	-0.9283 to -0.5169
R+2-7*	Real	31	0.8897	0.1329	0.6284 to 1.1510
	Simulated	71	-0.3001	0.08782	-0.4728 to -0.1275
>R+7	Real	37	0.8681	0.1217	0.6289 to 1.1073
	Simulated	35	0.6857	0.1251	0.4398 to 0.9316

Table 4. Tukey HSD Testing With 95% Confidence Intervals for Each Timepoint, Separated by Experimental Condition

Time

Condition

Mean

Standard error

95% confidence interval

*Timepoints differ significantly (P < 0.05) by experimental condition. HSD: honestly significant difference.

In-flight

Real

-1.5195

0.1698

-1.8532 to -1.1857

Simulated

-1.4803

0.07437

-1.6265 to -1.3341

R+0*

Real

0.1207

0.1398

-0.1542 to 0.3956

Simulated

-1.1400

0.2616

-1.6544 to -0.6256

R+1*

Real

1.1176

0.1480

0.8266 to 1.4086

Simulated

-0.7226

0.1046

-0.9283 to -0.5169

R+2-7*

Real

0.8897

0.1329

0.6284 to 1.1510

Simulated

-0.3001

0.08782

-0.4728 to -0.1275

>R+7

Real

0.8681

0.1217

0.6289 to 1.1073

Simulated

0.6857

0.1251

0.4398 to 0.9316

**Table 5.** Summary Data for In-Flight Serum and Urinary Calcium Levels
Serum calcium	Urinary calcium
Results are included from all studies as well as separated by microgravity condition. Data include the weighted average x of Cohen’s d and number of studies reporting significant change. Ionized calcium is not included due to a lack of data.
All (11)	3	0.300	All (6)	6	0.803
Real (3)	0	-0.460	Real (2)	2	0.797
Simulated (8)	3	0.589	Simulated (4)	4	0.806

Table 5. Summary Data for In-Flight Serum and Urinary Calcium Levels

Serum calcium

Urinary calcium

Cond. (n)

# significant

In-flight x

Cond. (n)

# significant

In-flight x

Results are included from all studies as well as separated by microgravity condition. Data include the weighted average x of Cohen’s d and number of studies reporting significant change. Ionized calcium is not included due to a lack of data.

All (11)

0.300

All (6)

0.803

Real (3)

-0.460

Real (2)

0.797

Simulated (8)

0.589

Simulated (4)

0.806

**Table 6.** Summary Data for In-Flight Calcifediol and Calcitriol Levels
Calcifediol	Calcitriol
Results are included from all studies as well as separated by microgravity condition. Data include the weighted average x of Cohen’s d and number of studies reporting significant change.
All (8)	1	0.411	All (9)	6	-0.960
Real (4)	0	-0.313	Real (4)	1	-0.208
Simulated (4)	1	0.738	Simulated (5)	5	-1.220

Table 6. Summary Data for In-Flight Calcifediol and Calcitriol Levels

Calcifediol

Calcitriol

Cond. (n)

# significant

In-flight x

Cond. (n)

# significant

In-flight x

Results are included from all studies as well as separated by microgravity condition. Data include the weighted average x of Cohen’s d and number of studies reporting significant change.

All (8)

0.411

All (9)

-0.960

Real (4)

-0.313

Real (4)

-0.208

Simulated (4)

0.738

Simulated (5)

-1.220