Exp Clin Endocrinol Diabetes 2011; 119(7): 440-444
DOI: 10.1055/s-0031-1275661
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Comparisons of Serum Sclerostin Levels among Patients with Postmenopausal Osteoporosis, Primary Hyperparathyroidism and Osteomalacia

H. Kaji1 , 2 , Y. Imanishi3 , T. Sugimoto4 , S. Seino1 , 2
  • 1Division of Diabetes and Endocrinology, Department of Internal Medicine
  • 2Division of Cellular and Molecular Medicine, Department of Physiology and Cellular Biology, Kobe University Graduate School of Medicine
  • 3Department of Metabolism, Endocrinology & Molecular Medicine, Osaka City University Graduate School of Medicine
  • 4Internal Medicine 1, Shimane University Faculty of Medicine
Weitere Informationen

Publikationsverlauf

received 22.06.2010 first decision 17.08.2010

accepted 01.10.2010

Publikationsdatum:
10. Juni 2011 (online)

Abstract

Wnt-β-catenin signaling is important for bone formation. Sclerostin inhibits bone formation mainly by suppressing this signal, and several studies suggest that the suppression of sclerostin expression contributes to the bone anabolic action of parathyroid hormone (PTH). We therefore examined serum sclerostin levels using enzyme-linked immunosolvent assay in 18 patients with postmenopausal osteoporosis, 9 postmenopausal women with primary hyperparathyroidism (pHPT) and 7 patients with osteomalacia. Serum levels of sclerostin were significantly lower in the group with pHPT, compared with those with postmenopausal osteoporosis. Moreover, serum sclerostin levels were significantly lower in the group with tumor-induced osteomalacia, but not in the group with osteomalacia without tumor, compared with those with postmenopausal osteoporosis. In patients with pHPT, serum sclerostin levels were significantly and negatively correlated to serum calcium and PTH levels. In patients with postmenopausal osteoporosis, serum levels of sclerostin levels were significantly and positively related to serum calcium and creatinine levels. In conclusion, we showed that serum sclerostin levels are decreased presumably through endogenous PTH elevation in postmenopausal women with pHPT, compared with the patients with postmenopausal osteoporosis.

References

  • 1 Almqvist EG, Becker C, Bondeson AG. et al . Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.  Clin Endocrinol. 2006;  65 760-766
  • 2 Balemans W, Ebeling M, Patel N. et al . Increased bone density in sclerostosis is due to the deficiency of a novel secreted protein (SOST).  Hum Mol Genet. 2001;  10 537-543
  • 3 Bando H, Hashimoto N, Hirota Y. et al . Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.  Inter Med. 2009;  48 353-358
  • 4 Bellido T, Ali AA, Gubrij I. et al . Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastgenesis.  Endocrinology. 2005;  146 4577-4583
  • 5 van Bezooijen RL, Roelen BAJ, Visser A. et al . Sclerostin is an osteocyteexpressed negative regulator of bone formation, but not a classical BMP antagonist.  J Exp Med. 2004;  6 805-814
  • 6 Canalis E. Update in new anabolic therapies for osteoporosis.  J Clin Endocrinol Metab. 2010;  95 1496-1504
  • 7 Choi HY, Dieckmann M, Herz J. et al . Lrp4, a novel receptor for dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turn over in vivo.  Plos One 4. 2009;  4 e7930
  • 8 Delfini E, Petramala L, Caliiumi C. et al . Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism.  Clin Exp Metab. 2007;  56 30-36
  • 9 Drezner MK. Hypophosphatemic rickets.  Endocr Dev. 2003;  6 126-155
  • 10 Endo I, Fukumoto S, Ozono K. et al . Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement.  Bone. 2008;  42 1235-1239
  • 11 Gaudion A, Pennisi P, Bratengeier C. et al . Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss.  J Clin Endocrinol Metab. 2010;  95 2248-2253
  • 12 Grey A, Mitnick MA, Shapses S. et al . Circulating levels of interleukin-6 and tumor necrosis factor-a are elevated in primary hyperparathyroidism and correlate with markers of bone resorption – a clinical research center study.  J Clin Endocrinol Metab. 1996;  81 3450-3454
  • 13 Hisa I, Kaji H, Inoue Y. et al . Fasting plasma glucose levels are related to bone mineral density in postmenopausal women with primary hyperparathyroidism.  Int J Clin Exp Med. 2008;  1 319-326
  • 14 Hodsman AB, Bauer DC, Dempster DW. et al . Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use.  Endocr Rev. 2005;  26 688-703
  • 15 Inokuchi G, Tanimoto H, Ishida H. et al . A paranasal tumor associated with tumorinduced osteomalacia.  Laryngoscope. 2006;  116 1930-1933
  • 16 Inoue Y, Canaff L, Hendy GN. et al . Role of Smad3, acting independently of transforming growth factor-β, in the early induction of Wnt-β-catenin signaling by parathyroid hormone in mouse osteoblastic cells.  J Cell Biochem. 2009;  108 285-294
  • 17 Inoue Y, Kaji H, Hisa I. et al . Vitamin D status affects osteopenia in postmenopausal patients with primary hyperparathyrodism.  Endocr J. 2008;  55 57-65
  • 18 Kaji H, Hisa I, Inoue Y. et al . Low density lipoprotein-cholesterol levels affect vertebral fracture risk in female patients with primary hyperparathyroidism.  Exp Clin Endocrinol Diabet. 2010;  118 371-376
  • 19 Keller H, Kneissel M. SOST is a target gene for PTH in bone.  Bone. 2005;  37 148-158
  • 20 Kramer I, Loots GG, Studer A. et al . Parathyroid hormone (PTH) – induced bone gain is blunted in SOST overexpression and deficient mice.  J Bone Miner Res. 2010;  25 178-189
  • 21 Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling.  J Clin Invest. 2006;  116 1202-1209
  • 22 Li X, Ominsky MS, Niu QT. et al . Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength.  J Bone Miner Res. 2008;  23 860-869
  • 23 Li X, Ominsky MS, Warmington KS. et al . Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.  J Bone Miner Res. 2009;  24 578-588
  • 24 Li X, Zhang Y, Kang H. et al . Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling.  J Biol Chem. 2005;  280 19883-19887
  • 25 Loots GG, Kneissel M, Keller H. et al . Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease.  Genomic Res. 2005;  15 928-935
  • 26 Mirza FS, Padhi D, Raisz LG. et al . Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women.  J Clin Endocrinol Metab. 2010;  95 1991-1997
  • 27 Nakchbandi IA, Lang R, Kinder B. et al . The role of the receptor activator of nuclear factor-kB ligand/osteoprotegerin cytokine system in primary hyperparathyroidism.  J Clin Endocrinol Metab. 2008;  93 967-973
  • 28 Oka M, Kamo T, Sasaki E. et al . A case of phophateuric mesenchymal tumor (mixed connective tissue variant) that developed in the subcutaneous tissue of a patient with oncogenic osteomalaica and produced fibroblast growth factor 23.  Br J Dermatol. 2007;  157 198-200
  • 29 Orimo H, Hayashi Y, Fukunaga H. et al . Diagnostic criteria of primary osteoporosis (2000 revision).  Jpan J Bone Miner Res. 2001;  18 76-82
  • 30 Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.  J Biol Chem. 2005;  280 26770-26775
  • 31 Swarthout JT, D’Alonzo RC, Selvamurugan N. et al . Parathyroid hormonedependent signaling pathways regulating genes in bone cells.  Gene. 2002;  282 1-17
  • 32 Tobimatsu T, Kaji H, Sowa H. et al . Parathyroid hormone increases β-catenin levels through Smad3 in mouse osteoblastic cells.  Endocrinology. 2006;  147 2583-2590
  • 33 White KE, Larsson TE, Econs MJ. The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23.  Endocr Rev. 2006;  27 221-241
  • 34 Winkler DG, Sutherland MK, Geoghegan JC. et al . Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.  EMBO J. 2003;  22 6267-6276

Correspondence

H. Kaji

Division of Diabetes and

Endocrinology

Department of Internal

Medicine

Kobe University Graduate

School of Medicine 7–5–2

Chuo-ku Kobe 650-0017

Kusunoki-cho

Japan

Telefon: + 81/72/382 5861

Fax: + 81/72/382 2080

eMail: hiroshik@med.kobe-u.ac.jp