Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats
Authors: John F Aloia
Maria Sarah N Guevarra
James K Yeh
Mariano Castro Magana
Journal: Hormone research in paediatrics (2010)
Discipline: CLINICAL MEDICINE
Keywords: Growth hormone; Parathyroid hormone; Bone growth; Bone formation; Bone mineral density
Affiliations: Department of Pediatric Endocrinology, Winthrop University Hospital, Mineola, NY 11501, USA. 

Abstract:  Background/aims: Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Methods: Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. Results: GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. Conclusion: The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. 

Retracted: No

PubPeer comments:
 There are serious concerns about the integrity of this publication, which overlap with 2 other papers by the same research group. On May 19 2021, the following email was sent to editors and publishers of the relevant journals: Re: Chaudhry AA, Castro-Magana M, Aloia JF, Yeh JK. Differential effects of growth hormone and alpha calcidol on trabecular and cortical bones in hypophysectomized rats. Pediatr Res. 2009;65(4):403-408. [submitted 17 6 08; accepted 3 11 08] Referenced as YA1 in previous correspondence Guevarra MS, Yeh JK, Castro Magana M, Aloia JF. Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats. Horm Res Paediatr. 2010;73(4):248-257. [submitted 15 1 09; accepted 12 6 09] Referenced as YA2 in previous correspondence Iglesias L, Yeh JK, Castro-Magana M, Aloia JF. Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study. J Bone Miner Metab 2011;29(2):159-167. [submitted 18 03 10; accepted 11 6 10] Referenced as YA3 in previous correspondence We write to notify you of ongoing concerns about the integrity of these publications. These concerns have now been peer-reviewed and published at the Journal of Clinical Epidemiology, https: doi.org 10.1016 j.jclinepi.2021.05.002. A pdf of that paper is attached with relevant text and analyses highlighted. It was stated by the authors, in correspondence to the editors of JBMM, that the work reported in YA1 and YA2 was from the same study, but the work reported in YA3 was from an independent study. It also transpires that no raw data are available for independent review. Two things indicate that the authorsu2019 claim that there were 2 independent studies cannot be correct: 1.tStatistical analyses indicate that the amount of identical summary data reported in YA3 and YA1 YA2 is essentially impossible. This is reported in the highlighted text and Results in the JCE paper 2.tIn YA3, the authors acknowledge that the photomicrographs for the Intact, Hx and HX + GH animals in Figure 2 were reproduced from Figure 1 in YA1 u2013 clearly this means that independent studies were not conducted. These issues are not addressed or assuaged in the correction notices published for each paper. Additional concerns are requests by the authors to add authors to YA1 and YA2 (see correction notices), fully 10 years after publication, and numerous methodological discrepancies, which the authors claim to confidently correct despite not having any raw data from the experiments to hand. Is it suggested that experimental protocols were retained but not results? Thus, which of the papers, YA1 YA2 or YA3, report reliable data? Both cannot be correct. Consequently, readers cannot trust either set of results. In this situation, the only way the integrity of the literature can be preserved is for the authors to provide a detailed public explanation of the impossibly identical data, explain the eccentric authorship problems, and then properly correct the numerous errors and discrepancies in the 3 papers. Otherwise, all 3 papers should be retracted because they are unreliable. Without individual raw data for the experiments, this seems unlikely to occur and therefore the concerns, in their entirety, will not able to be adequately addressed. Presumably each of the journals would agree that unreliable papers should be either fixed so they are reliable, or retracted. We would be grateful to receive an acknowledgement of receipt of this email, and to then receive a detailed response to the concerns raised. , 
 Each of these 3 papers now has an expression of concern (Chaudhry et al, Iglesias et al) or a u2018publisheru2019s noteu2019 (Guevarra et al). Each notice indicates that the original data are not available and that the authors have failed to respond to correspondence about the concerns leading to the expressions of concern. The publisheru2019s note reports that the authorsu2019 institution u2018did not have access tou2019 the study authors. It seems unlikely that original data are not available. The papers were submitted between 2008 and 2010. All the analyses were done using GraphPad Prism, and so there would be electronic datasets available for those analyses or the raw data. The concerns about integrity of papers by this group were first raised with Winthrop University in 2017, and specific concerns were raised about these 3 papers in 2018, only 7-8y after the last paper was submitted. In this digital age, it seems highly unlikely that electronic datasets would not be available only 7y after publication. Even if the original data are not available, there are mathematically impossible data in the papers. That doesnu2019t appear to be in dispute, nor would it change were the original data available. How can the reader be assured the data are valid when the authors themselves presumably donu2019t have any data to check confirm they are valid? The failure of the authors and their institution to adequately address these concerns is very disappointing, and exacerbates concerns about the integrity of these papers. It would be most helpful to journal readers and fellow scientists if they would comment publicly about this matter. ,