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Erschienen in: Osteoporosis International 8/2019

01.05.2019 | Original Article

High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis

verfasst von: T. Rupp, S. Butscheidt, E. Vettorazzi, R. Oheim, F. Barvencik, M. Amling, T. Rolvien

Erschienen in: Osteoporosis International | Ausgabe 8/2019

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Abstract

Summary

This cross-sectional study examined the associations between c-terminal FGF23 levels, laboratory markers of bone metabolism and bone microarchitecture in 82 patients with osteoporosis. Higher FGF23 levels were associated with impaired trabecular but not cortical bone microarchitecture, and this was confirmed after adjusting for confounding variables such as age or BMI.

Introduction

Fibroblast growth factor 23 (FGF23) is an endocrine hormone-regulating phosphate and vitamin D metabolism. While its mode of action is well understood in diseases such as hereditary forms of rickets or tumor-induced osteomalacia, the interpretation of FGF23 levels in patients with osteoporosis with regard to bone microarchitecture is less clear.

Methods

C-terminal FGF23 levels and bone turnover markers were assessed in 82 patients with osteoporosis (i.e., DXA T-score ≤ − 2.5 at the lumbar spine or total hip). Bone microarchitecture was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia. Data were analyzed in a cross-sectional design using correlation and regression models.

Results

We found a significant negative logarithmic correlation between FGF23 levels and trabecular but not cortical bone microarchitecture at both skeletal sites. Furthermore, using a multiple linear regression model, we confirmed FGF23 as a predictor for reduced trabecular parameters even when adjusting for confounding factors such as age, BMI, phosphate, bone-specific alkaline phosphatase, vitamin D3, and PTH.

Conclusions

Taken together, high FGF23 levels are associated with impaired trabecular bone microarchitecture in osteoporosis patients, and this association seems to occur after adjustment of confounding variables including phosphate and vitamin D. Future longitudinal studies are now needed to validate our findings and investigate FGF23 in relation to fracture risk.
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Literatur
1.
Zurück zum Zitat Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2004) FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem Biophys Res Commun 314:409–414CrossRefPubMed Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2004) FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem Biophys Res Commun 314:409–414CrossRefPubMed
2.
Zurück zum Zitat Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T (2004) Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568CrossRefPubMedPubMedCentral Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T (2004) Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat White KE, Evans WE, O'Riordan JL, Speer MC, Econs MJ, Lorenz-Depiereux B, Grabowski M, Meitinger T, Strom TM (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348CrossRef White KE, Evans WE, O'Riordan JL, Speer MC, Econs MJ, Lorenz-Depiereux B, Grabowski M, Meitinger T, Strom TM (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348CrossRef
4.
Zurück zum Zitat Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2001) Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 98:6500–6505CrossRefPubMedPubMedCentral Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2001) Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 98:6500–6505CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Rolvien T, Kornak U, Schinke T, Amling M, Oheim R (2018) A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee. Osteoporos Int 30:685-689 Rolvien T, Kornak U, Schinke T, Amling M, Oheim R (2018) A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee. Osteoporos Int 30:685-689
6.
Zurück zum Zitat Ferrari SL, Bonjour JP, Rizzoli R (2005) Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. J Clin Endocrinol Metab 90:1519–1524CrossRefPubMed Ferrari SL, Bonjour JP, Rizzoli R (2005) Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. J Clin Endocrinol Metab 90:1519–1524CrossRefPubMed
7.
Zurück zum Zitat Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie HL, Appleby D, Nessel L, Bellovich K, Chen J, Hamm L, Gadegbeku C, Horwitz E, Townsend RR, Anderson CAM, Lash JP, Hsu CY, Leonard MB, Wolf M, Grp CS (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79:1370–1378CrossRefPubMedPubMedCentral Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie HL, Appleby D, Nessel L, Bellovich K, Chen J, Hamm L, Gadegbeku C, Horwitz E, Townsend RR, Anderson CAM, Lash JP, Hsu CY, Leonard MB, Wolf M, Grp CS (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79:1370–1378CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Marsell R, Mirza MA, Mallmin H, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Jonsson KB, Ljunggren O, Larsson TE (2009) Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int 20:1167–1173CrossRefPubMed Marsell R, Mirza MA, Mallmin H, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Jonsson KB, Ljunggren O, Larsson TE (2009) Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int 20:1167–1173CrossRefPubMed
9.
Zurück zum Zitat Isakova T, Cai X, Lee J, Katz R, Cauley JA, Fried LF, Hoofnagle AN, Satterfield S, Harris TB, Shlipak MG, Sarnak MJ, Ix JH, Health ABCS (2016) Associations of FGF23 with change in bone mineral density and fracture risk in older individuals. J Bone Miner Res 31:742–748CrossRefPubMed Isakova T, Cai X, Lee J, Katz R, Cauley JA, Fried LF, Hoofnagle AN, Satterfield S, Harris TB, Shlipak MG, Sarnak MJ, Ix JH, Health ABCS (2016) Associations of FGF23 with change in bone mineral density and fracture risk in older individuals. J Bone Miner Res 31:742–748CrossRefPubMed
10.
Zurück zum Zitat Lane NE, Parimi N, Corr M, Yao W, Cauley JA, Nielson CM, Ix JH, Kado D, Orwoll E, Osteoporotic Fractures in Men Study G (2013) Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the osteoporotic fractures in men (MrOS) study. J Bone Miner Res 28:2325–2332CrossRefPubMedPubMedCentral Lane NE, Parimi N, Corr M, Yao W, Cauley JA, Nielson CM, Ix JH, Kado D, Orwoll E, Osteoporotic Fractures in Men Study G (2013) Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the osteoporotic fractures in men (MrOS) study. J Bone Miner Res 28:2325–2332CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Mirza MA, Karlsson MK, Mellstrom D, Orwoll E, Ohlsson C, Ljunggren O, Larsson TE (2011) Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 26:857–864CrossRefPubMed Mirza MA, Karlsson MK, Mellstrom D, Orwoll E, Ohlsson C, Ljunggren O, Larsson TE (2011) Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 26:857–864CrossRefPubMed
12.
Zurück zum Zitat Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 22:425–433CrossRefPubMed Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 22:425–433CrossRefPubMed
13.
Zurück zum Zitat Boutroy S, Khosla S, Sornay-Rendu E, Zanchetta MB, McMahon DJ, Zhang CA, Chapurlat RD, Zanchetta J, Stein EM, Bogado C, Majumdar S, Burghardt AJ, Shane E (2016) Microarchitecture and peripheral BMD are impaired in postmenopausal White women with fracture independently of Total hip T-score: an international multicenter study. J Bone Miner Res 31:1158–1166CrossRefPubMedPubMedCentral Boutroy S, Khosla S, Sornay-Rendu E, Zanchetta MB, McMahon DJ, Zhang CA, Chapurlat RD, Zanchetta J, Stein EM, Bogado C, Majumdar S, Burghardt AJ, Shane E (2016) Microarchitecture and peripheral BMD are impaired in postmenopausal White women with fracture independently of Total hip T-score: an international multicenter study. J Bone Miner Res 31:1158–1166CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Butscheidt S, Rolvien T, Vettorazzi E, Frieling I (2018) Trabecular bone microarchitecture predicts fragility fractures in postmenopausal women on denosumab treatment. Bone 114:246–251CrossRefPubMed Butscheidt S, Rolvien T, Vettorazzi E, Frieling I (2018) Trabecular bone microarchitecture predicts fragility fractures in postmenopausal women on denosumab treatment. Bone 114:246–251CrossRefPubMed
16.
Zurück zum Zitat Breer S, Brunkhorst T, Beil FT, Peldschus K, Heiland M, Klutmann S, Barvencik F, Zustin J, Gratz KF, Amling M (2014) 68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT. Bone 64:222–227CrossRefPubMed Breer S, Brunkhorst T, Beil FT, Peldschus K, Heiland M, Klutmann S, Barvencik F, Zustin J, Gratz KF, Amling M (2014) 68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT. Bone 64:222–227CrossRefPubMed
17.
Zurück zum Zitat Levey AS, Stevens LA, Schmid CH, Zhang YP, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Co CKDE (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YP, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Co CKDE (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro–computed tomography. J Bone Miner Res 25:1468–1486CrossRefPubMed Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro–computed tomography. J Bone Miner Res 25:1468–1486CrossRefPubMed
19.
Zurück zum Zitat Imel EA, Liu Z, McQueen AK, Acton D, Acton A, Padgett LR, Peacock M, Econs MJ (2016) Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone 86:98–105CrossRefPubMedPubMedCentral Imel EA, Liu Z, McQueen AK, Acton D, Acton A, Padgett LR, Peacock M, Econs MJ (2016) Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone 86:98–105CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Shanbhogue VV, Hansen S, Folkestad L, Brixen K, Beck-Nielsen SS (2015) Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with hypophosphatemic rickets. J Bone Miner Res 30:176–183CrossRefPubMed Shanbhogue VV, Hansen S, Folkestad L, Brixen K, Beck-Nielsen SS (2015) Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with hypophosphatemic rickets. J Bone Miner Res 30:176–183CrossRefPubMed
21.
Zurück zum Zitat Tsuchida T, Ishimura E, Miki T, Matsumoto N, Naka H, Jono S, Inaba M, Nishizawa Y (2005) The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure. Osteoporos Int 16:172–179CrossRefPubMed Tsuchida T, Ishimura E, Miki T, Matsumoto N, Naka H, Jono S, Inaba M, Nishizawa Y (2005) The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure. Osteoporos Int 16:172–179CrossRefPubMed
22.
Zurück zum Zitat Bacchetta J, Boutroy S, Vilayphiou N, Juillard L, Guebre-Egziabher F, Rognant N, Sornay-Rendu E, Szulc P, Laville M, Delmas PD, Fouque D, Chapurlat R (2010) Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease. J Bone Miner Res 25:849–857PubMed Bacchetta J, Boutroy S, Vilayphiou N, Juillard L, Guebre-Egziabher F, Rognant N, Sornay-Rendu E, Szulc P, Laville M, Delmas PD, Fouque D, Chapurlat R (2010) Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease. J Bone Miner Res 25:849–857PubMed
23.
Zurück zum Zitat Burnett SM, Gunawardene SC, Bringhurst FR, Juppner H, Lee H, Finkelstein JS (2006) Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res 21:1187–1196CrossRefPubMed Burnett SM, Gunawardene SC, Bringhurst FR, Juppner H, Lee H, Finkelstein JS (2006) Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res 21:1187–1196CrossRefPubMed
24.
Zurück zum Zitat Carpenter TO, Whyte MP, Imel EA, Boot AM, Hogler W, Linglart A, Padidela R, Van't Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA (2018) Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med 378:1987–1998CrossRefPubMed Carpenter TO, Whyte MP, Imel EA, Boot AM, Hogler W, Linglart A, Padidela R, Van't Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA (2018) Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med 378:1987–1998CrossRefPubMed
25.
Zurück zum Zitat Kocijan R, Englbrecht M, Haschka J, Simon D, Kleyer A, Finzel S, Kraus S, Resch H, Muschitz C, Engelke K, Sticherling M, Rech J, Schett G (2015) Quantitative and qualitative changes of bone in psoriasis and psoriatic arthritis patients. J Bone Miner Res 30:1775–1783CrossRefPubMed Kocijan R, Englbrecht M, Haschka J, Simon D, Kleyer A, Finzel S, Kraus S, Resch H, Muschitz C, Engelke K, Sticherling M, Rech J, Schett G (2015) Quantitative and qualitative changes of bone in psoriasis and psoriatic arthritis patients. J Bone Miner Res 30:1775–1783CrossRefPubMed
Metadaten
Titel
High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis
verfasst von
T. Rupp
S. Butscheidt
E. Vettorazzi
R. Oheim
F. Barvencik
M. Amling
T. Rolvien
Publikationsdatum
01.05.2019
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 8/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-019-04996-7

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