Skip to main content
Erschienen in: Osteoporosis International 6/2012

01.06.2012 | Original Article

Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study

verfasst von: M.-S. M. Ardawi, A. M. Al-Sibiany, T. M. Bakhsh, A. A. Rouzi, M. H. Qari

Erschienen in: Osteoporosis International | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Summary

Decreased serum sclerostin was evident in patients with primary hyperparathyroidism and was inversely related to parathyroid hormone (PTH). Sclerostin normalized earlier than biochemical bone turnover markers (BTMs) following parathyroidectomy.

Introduction

There is limited information on the changes of serum sclerostin in conditions with chronic PTH excess in humans. The main objectives of the present study were to: (1) examine cross-sectionally the changes of serum sclerostin levels in patients with primary hyperparathyroidism (PHPT), (2) study the time course changes in serum sclerostin in PHPT patients following parathyroidectomy (PTX) followed up longitudinally for 12 months, and (3) compare the changes in serum sclerostin to that of BTMs.

Methods

We studied 60 PHPT patients and compared them with 74 PTX patients together with 268 age- and sex-matched healthy controls. Also, we followed 27 PTX patients longitudinally at 2, 4, 6, 10, 30, 60, 180, and 360 days postoperatively. Serum sclerostin, BTMs, and minerals were measured. Also, bone mineral density was determined by dual energy X-ray absorptiometry.

Results

Patients with PHPT exhibited significantly lower mean serum sclerostin [mean, in picomoles per liter; 95% confidence interval (CI)] (28.98; 27.94–30.03) than that obtained for PTX patients (37.01; 35.75–38.27) and healthy controls (46.22; 45.13–47.31) (P < 0.0001, for each case), respectively. Serum PTH inversely correlated with serum sclerostin (r = −0.651, P < 0.0001). Serum sclerostin was normalized in PTX patients by the tenth day postoperatively and remained within the expected reference range thereafter.

Conclusions

Significantly decreased serum sclerostin was evidenced in PHPT patients as compared with PTX and euparathyroid controls. The inverse PTH and sclerostin relationship suggests that sclerostin is downregulated by PTH in humans. Serum sclerostin normalized earlier than BTMs following parathyroidectomy.
Literatur
1.
Zurück zum Zitat Silvestrini G, Ballanti P, Leopizzi M, Sebastiani M, Berni S, DiVitro M, Bonucci E (2007) Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone. J Molecu Histol 38:261CrossRef Silvestrini G, Ballanti P, Leopizzi M, Sebastiani M, Berni S, DiVitro M, Bonucci E (2007) Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone. J Molecu Histol 38:261CrossRef
2.
Zurück zum Zitat Kneissel M (2009) The promise of sclerostin inhibition for the treatment of osteoporosis. IBM S BoneKEy 6:259–264CrossRef Kneissel M (2009) The promise of sclerostin inhibition for the treatment of osteoporosis. IBM S BoneKEy 6:259–264CrossRef
3.
Zurück zum Zitat Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887PubMedCrossRef Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887PubMedCrossRef
4.
Zurück zum Zitat Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R (2006) Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 21:1738–1749 Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R (2006) Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 21:1738–1749
5.
Zurück zum Zitat Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589PubMedCrossRef Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589PubMedCrossRef
6.
Zurück zum Zitat Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmely P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME (2002) A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12–q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110:144–152PubMedCrossRef Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmely P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME (2002) A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12–q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110:144–152PubMedCrossRef
7.
Zurück zum Zitat Balemans W, Patel N, Ebeling M, van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, van Hul W (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91–97PubMedCrossRef Balemans W, Patel N, Ebeling M, van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, van Hul W (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91–97PubMedCrossRef
8.
Zurück zum Zitat Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997PubMedCrossRef Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997PubMedCrossRef
9.
Zurück zum Zitat Li X, Ominsky MS, Niu Q-T, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23(6):860–869PubMedCrossRef Li X, Ominsky MS, Niu Q-T, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23(6):860–869PubMedCrossRef
10.
Zurück zum Zitat Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel of BMP antagonist. EMBO J 22:6267–6276PubMedCrossRef Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel of BMP antagonist. EMBO J 22:6267–6276PubMedCrossRef
11.
Zurück zum Zitat Bellido T, Ali AA, Gubrij I, Plotkin LI, Iu Q, O'brien CA, Manolagas SC, Jilka RL (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577–4583PubMedCrossRef Bellido T, Ali AA, Gubrij I, Plotkin LI, Iu Q, O'brien CA, Manolagas SC, Jilka RL (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577–4583PubMedCrossRef
12.
Zurück zum Zitat Li X, Omnisky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shlhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C (2009) Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24(4):578–588PubMedCrossRef Li X, Omnisky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shlhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C (2009) Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24(4):578–588PubMedCrossRef
13.
Zurück zum Zitat Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25(5):948–959PubMedCrossRef Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25(5):948–959PubMedCrossRef
14.
Zurück zum Zitat Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG785, a sclerostin monoclonal antibody. J Bone Miner Res 26(1):19–26PubMedCrossRef Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG785, a sclerostin monoclonal antibody. J Bone Miner Res 26(1):19–26PubMedCrossRef
15.
Zurück zum Zitat van Lierop AH, Witteveen JE, Hamdy NAT, Papapoulos SE (2010) Patients with primary hyperparathyroidism have lower circulating levels than euparathyroid controls. Eur J Endocrinol 163:833–837PubMedCrossRef van Lierop AH, Witteveen JE, Hamdy NAT, Papapoulos SE (2010) Patients with primary hyperparathyroidism have lower circulating levels than euparathyroid controls. Eur J Endocrinol 163:833–837PubMedCrossRef
16.
Zurück zum Zitat Ardawi M-SM, Qari MH, Rouzi AA, Maimani AA, Radaddi RM (2010) Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women. Osteoporos Int 22:462–475 Ardawi M-SM, Qari MH, Rouzi AA, Maimani AA, Radaddi RM (2010) Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women. Osteoporos Int 22:462–475
17.
Zurück zum Zitat Christiansen P, Steiniche T, Brixen K, Hessov I, Melsen F, Heickendroff L, Mosekilde LE (1999) Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy. Bone 25(2):237–244PubMedCrossRef Christiansen P, Steiniche T, Brixen K, Hessov I, Melsen F, Heickendroff L, Mosekilde LE (1999) Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy. Bone 25(2):237–244PubMedCrossRef
18.
Zurück zum Zitat Ardawi M-SM, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Radaddi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a crosssectional study. Bone 47:804–814PubMedCrossRef Ardawi M-SM, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Radaddi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a crosssectional study. Bone 47:804–814PubMedCrossRef
19.
Zurück zum Zitat Christianser P, Steiniche T, Brixen K, Hessov I, Melsen F, Heickendroff L, Mosekilde LE (1999) Primary hyperparathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year follow-up study. Bone 25(5):589–595CrossRef Christianser P, Steiniche T, Brixen K, Hessov I, Melsen F, Heickendroff L, Mosekilde LE (1999) Primary hyperparathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year follow-up study. Bone 25(5):589–595CrossRef
20.
Zurück zum Zitat World Health Organization (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Report Series. WHO, Geneva, No. 843 World Health Organization (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Report Series. WHO, Geneva, No. 843
21.
Zurück zum Zitat Gaudio A, Pennisi P, Bratengeir C, Torrisi V, Linder B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiorce CE (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253PubMedCrossRef Gaudio A, Pennisi P, Bratengeir C, Torrisi V, Linder B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiorce CE (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253PubMedCrossRef
22.
Zurück zum Zitat Modder UIL, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and men. J Bone Miner Res 26(1):27–34PubMedCrossRef Modder UIL, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and men. J Bone Miner Res 26(1):27–34PubMedCrossRef
23.
Zurück zum Zitat Modder UI, Hoey KA, Amin S, McCready LK, Chenbach SJ A, Riggs BL, Melton LJ III, Khosla S (2011) Relation of age, gender and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26(2):373–379PubMedCrossRef Modder UI, Hoey KA, Amin S, McCready LK, Chenbach SJ A, Riggs BL, Melton LJ III, Khosla S (2011) Relation of age, gender and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26(2):373–379PubMedCrossRef
24.
Zurück zum Zitat McNulty M, Singh RJ, Li X, Bergstralh EJ, Kumar R (2011) Determination of serum and plasma sclerostin concentrations by enzyme-linked immunoassays. J Clin Endocrinol Metab 96:E1159–E1162PubMedCrossRef McNulty M, Singh RJ, Li X, Bergstralh EJ, Kumar R (2011) Determination of serum and plasma sclerostin concentrations by enzyme-linked immunoassays. J Clin Endocrinol Metab 96:E1159–E1162PubMedCrossRef
25.
Zurück zum Zitat Guo CY, Thomas WE, AlDehaimi AW, Assiri AM, Eastell R (1996) Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 81:3487–3491PubMedCrossRef Guo CY, Thomas WE, AlDehaimi AW, Assiri AM, Eastell R (1996) Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 81:3487–3491PubMedCrossRef
26.
Zurück zum Zitat Osterode W, Winker R, Bieglmayer C, Vierhapper H (2004) Effects of parathyroidectomy on lead mobilization from bone in patients with primary hyperparathyroidism. Bone 35:942–947PubMedCrossRef Osterode W, Winker R, Bieglmayer C, Vierhapper H (2004) Effects of parathyroidectomy on lead mobilization from bone in patients with primary hyperparathyroidism. Bone 35:942–947PubMedCrossRef
27.
Zurück zum Zitat Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL (2003) Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278:50259–50272PubMedCrossRef Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL (2003) Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278:50259–50272PubMedCrossRef
28.
29.
Zurück zum Zitat Aubin JE, Heersche JNM (2001) Cellular actions of parathyroid hormone on osteoblast and osteoclast differentiation. In: Bilezikian JP, Marcus R, Levine MA (eds) The parathyroids. Basic and clinical concepts. Academic, San Diego, pp 199–211 Aubin JE, Heersche JNM (2001) Cellular actions of parathyroid hormone on osteoblast and osteoclast differentiation. In: Bilezikian JP, Marcus R, Levine MA (eds) The parathyroids. Basic and clinical concepts. Academic, San Diego, pp 199–211
30.
Zurück zum Zitat Pfeilschifter J, Munday GR (1987) Modulation of type β transforming growth factor activity in bone cultures by osteoporotic hormones. Proc Natl Acad Sci USA 84:2024–2028PubMedCrossRef Pfeilschifter J, Munday GR (1987) Modulation of type β transforming growth factor activity in bone cultures by osteoporotic hormones. Proc Natl Acad Sci USA 84:2024–2028PubMedCrossRef
31.
Zurück zum Zitat Drake MT, Srinivasan B, Modder 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. Bone Miner Res 95(11):5056–5062 Drake MT, Srinivasan B, Modder 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. Bone Miner Res 95(11):5056–5062
32.
Zurück zum Zitat Datta NS, Abou-Samra AB (2009) PTH and PTHrP signaling in osteoblasts. Cell Signal 21:1245–1254PubMedCrossRef Datta NS, Abou-Samra AB (2009) PTH and PTHrP signaling in osteoblasts. Cell Signal 21:1245–1254PubMedCrossRef
33.
Zurück zum Zitat Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446PubMedCrossRef Jilka RL (2007) Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 40:1434–1446PubMedCrossRef
Metadaten
Titel
Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study
verfasst von
M.-S. M. Ardawi
A. M. Al-Sibiany
T. M. Bakhsh
A. A. Rouzi
M. H. Qari
Publikationsdatum
01.06.2012
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 6/2012
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-011-1806-8

Weitere Artikel der Ausgabe 6/2012

Osteoporosis International 6/2012 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.