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Journal of Endocrinological Investigation

Erschienen in:

01.06.2017 | Original Article

The effect of parathyroid hormone (1–84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis

verfasst von: J. Pepe, C. Cipriani, F. P. Cantatore, A. Fabbri, E. Pola, V. Vinicola, O. Raimo, F. Biamonte, R. Pascone, C. Ferrara, S. Minisola

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 6/2017

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Abstract

Purpose

To investigate the effect of 18 months’ parathyroid hormone 1–84 (PTH 1–84) treatment on serum levels of bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF), in postmenopausal women with established osteoporosis.

Methods

Thirty-seven postmenopausal women with osteoporosis (mean age 72.9 ± 8.1 years old) and 23 healthy controls (mean age 68.9 ± 9.9 years old) were enrolled. Patients were treated with daily subcutaneous injections of PTH (1–84) 100 mcg for 18 months, plus calcium 1 gr and vitamin D 800 IU per os daily. Blood samples were taken every 6 months during the study.

Results

At baseline, there were no differences considering anthropometric parameters, co-morbidities, current medications used between patients and controls. Mean serum VEGF levels were significantly higher in osteoporotic patients compared to controls (436.7 ± 259.7 vs. 260.3 ± 184.3 pg/ml, p = 0.006), while there were no differences in mean serum values of BMP4 (5.3 ± 1.7 vs. 5.7 ± 1.6 pg/ml, p = 0.40). Serum VEGF levels increased by approximately 20% after 12 months of PTH (1–84) treatment compared to baseline (p = 0.03) and by 22% after 18 months (p = 0.01). A significant increase of 10% in mean serum BMP4 levels was observed after 18 months of PTH (1–84) treatment compared to baseline (p = 0.02). In the control group we found no differences after 18 months compared to baseline in BMP4 (5.7 ± 1.6 vs. 6.0 ± 1.5 pg/ml, p = 0.53) and VEGF (260.3 ± 184.3 vs. 257.4 ± 107.1 pg/ml, p = 0.94).

Conclusions

PTH (1–84) treatment increased serum levels of VEGF and BMP4 in postmenopausal women with severe osteoporosis.

Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, Blosch CM, Mathisen AL, Morris SA, Marriott TB, Treatment of Osteoporosis with Parathyroid Hormone Study Group (2007) Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 146:326–339CrossRefPubMed

Adler RA (2016) Osteoporosis treatment: complexities and challenges. J Endocrinol Invest 39(7):719–720CrossRefPubMed

Lewiecki EM, Binkley N (2016) What we don’t know about osteoporosis. J Endocrinol Invest 39:491–493CrossRefPubMed

Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446CrossRefPubMedPubMedCentral

Biver E, Hardouin P, Caverzasio J (2013) The “bone morphogenic proteins” pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets. Cytokine Growth Factor Rev 24:69–78CrossRefPubMed

Suzawa M, Takeuchi Y, Fukumoto S, Kato S, Ueno N, Miyazono K, Matsumoto T, Fujita T (1999) Extracellular matrix-associated bone morphogenetic proteins are essential for differentiation of murine osteoblastic cells in vitro. Endocrinology 140:2125–2133CrossRefPubMed

Matsumoto Y, Otsuka F, Takano-Narazaki M, Katsuyama T, Nakamura E, Tsukamoto N, Inagaki K, Sada KE, Makino H (2013) Estrogen facilitates osteoblast differentiation by upregulating bone morphogenetic protein-4 signaling. Steroids 78:513–520CrossRefPubMed

Peng H, Wright V, Usas A, Gearhart B, Shen HC, Cummins J, Huard J (2002) Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 110:751–759CrossRefPubMedPubMedCentral

Street J, Lenehan B (2009) Vascular endothelial growth factor regulates osteoblast survival evidence for an autocrine feedback mechanism. J Orthop Surg Res 16:4–19

10.

Prisby R, Menezes T, Campbell J (2013) Vasodilation to PTH (1–84) in bone arteries is dependent upon the vascular endothelium and is mediated partially via VEGF signaling. Bone 54:68–75CrossRefPubMed

11.

Senel K, Baykal T, Seferoglu B, Altas EU, Baygutalp F, Ugur M, Kiziltunc A (2013) Circulating vascular endothelial growth factor concentrations in patients with postmenopausal osteoporosis. Arch Med Sci 9:709–712CrossRefPubMedPubMedCentral

12.

Cebi H, Aksahin E, Yuksel HY, Celebi L, Aktekin CN, Ha Pa O (2010) Plasma vascular endothelial growth factor levels are similar in subjects with and without osteoporosis. Eklem Hastalik Cerrahisi 21:91–97PubMed

13.

Costa N, Paramanathan S, Mac Donald D, Wierzbicki AS, Hampson C (2009) Factors regulating circulating vascular endothelial growth factor (VEGF): association with bone mineral density (BMD) in post-menopausal osteoporosis. Cytokine 46:376–381CrossRefPubMed

14.

Dincel VE, Sepici-Dincel A (2014) The importance and the differences of bone morphogenetic proteins for osteoporotic hip fractures. Acta Orthop Belg 80:216–221PubMed

15.

Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. JBMR 9:1137–1148.

16.

Russo S, Carlucci L, Cipriani C, Ragno A, Piemonte S, Fiacco Rd, Pepe J, Fassino V, Arima S, Romagnoli E, Minisola S (2011) Metabolic changes following 500 μg monthly administration of calcidiol: a study in normal females. Calcif Tissue Int 89:252–257CrossRefPubMed

17.

Paglia F, Dionisi S, De Geronimo S, Rosso R, Romagnoli E, Raejntroph N, Ragno A, Celi M, Pepe J, D’Erasmo E, Minisola S (2001) Biomarkers of bone turnover after a short period of steroid therapy in elderly men. Clin Chem 47:1314–1316PubMed

18.

Brunner S, Theiss HD, Murr A, Negele T, Franz WM (2007) Primary hyperparathyroidism is associated with increased circulating bonemarrow-derived progenitor cells. Am J Physiol Endocrinol Metab 293:E1670–E1675CrossRefPubMed

19.

Cusano NE, Rubin MR, Zhang C, Anderson L, Levy E, Costa AG, Irani D, Bilezikian JP (2014) Parathyroid hormone 1–84 alters circulating vascular endothelial growth factor levels in hypoparathyroidism. J Clin Endocrinol Metab 99:E2025–E2028CrossRefPubMedPubMedCentral

20.

Christodoulakos G, Lambrinoudaki I, Panoulis C, Papadias C, Sarandakou A, Liakakos T, Alexandrou A, Creatsas G (2004) Effect of hormone therapy, tibolone and raloxifene on circulating vascular endothelial growth factor in Greek postmenopausal women. Eur J Endocrinol 151:187–192CrossRefPubMed

21.

Kamiya N, Kobayashi T, Mochida Y, Yu PB, Yamauchi M, Kronenberg HM, Mishina YJ (2010) Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. JBMR 25:200–210.CrossRef

22.

Gatti D, Viapiana O, Idolazzi L, Fracassi E, Rossini M, Adami S (2011) The waning of teriparatide effect on bone formation markers in postmenopausal osteoporosis is associated with increasing serum levels of DKK1. J Clin Endocrinol Metab 96:1555–1559CrossRefPubMed

23.

Piemonte S, Romagnoli E, Bratengeier C, Woloszczuk W, Tancredi A, Pepe J, Cipriani C, Minisola S (2012) Serum sclerostin levels decline in postmenopausal women with osteoporosis following treatment with intermittent PTH. J Endocrinol Invest 35:866–868PubMed

24.

Drake MT, Srinivasan B, Mödder UI, Peterson JM, McCready LK, Riggs BL, Dwyer D, Stolina M, Kostenuik P, Khosla S (2010) Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab 95:5056–5062CrossRefPubMedPubMedCentral

25.

Lasco A, Catalano A, Morabito N, Gaudio A, Basile G, Trifiletti A, Atteritano M (2011) Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis. Osteoporos Int 22:299–303CrossRefPubMed

26.

Luppen CA, Chandler RL, Noh T, Mortlock DP, Frenkel B (2008) BMP-2 versus BMP-4 expression and activity in glucocorticoid-arrested MC3T3-E1 osteoblasts: Smad signaling, not alkaline phosphatase activity, predicts rescue of mineralization. Growth Factors 26:226–237CrossRefPubMedPubMedCentral

27.

Pufe T, Scholz-Ahrens KE, Franke AT, Petersen W, Mentlein R, Varoga D, Tillmann B, Schrezenmeir J, Glüer CC (2003) The role of vascular endothelial growth factor in glucocorticoid-induced bone loss: evaluation in a minipig model. Bone 33:869–876CrossRefPubMed

Titel: The effect of parathyroid hormone (1–84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis
verfasst von: J. Pepe
C. Cipriani
F. P. Cantatore
A. Fabbri
E. Pola
V. Vinicola
O. Raimo
F. Biamonte
R. Pascone
C. Ferrara
S. Minisola
Publikationsdatum: 01.06.2017
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 6/2017
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-017-0636-8

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The effect of parathyroid hormone (1–84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis