Skip to main content
Top
Published in: Osteoporosis International 3/2013

01-03-2013 | Short Communication

The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis

Authors: L. Zhang, L. Li, M. Yang, K. Xu, G. Boden, G. Yang

Published in: Osteoporosis International | Issue 3/2013

Login to get access

Abstract

Summary

The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2–L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation.

Introduction

rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis.

Methods

Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 μg, N = 89) or once-weekly intramuscular injection of elcatonin (200 U, N = 35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment.

Results

At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients (r = 0.45, p = 0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels (p = 0.008 and p = 0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2–L4 (r = 0.47, p = 0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group.

Conclusion

The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Meunier PJ, Vignot E, Garnero P, Confavreux E, Paris E, Liu-Leage S, Sarkar S, Liu T, Wong M, Draper MW (1999) Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group. Osteoporos Int 10:330–336PubMedCrossRef Meunier PJ, Vignot E, Garnero P, Confavreux E, Paris E, Liu-Leage S, Sarkar S, Liu T, Wong M, Draper MW (1999) Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group. Osteoporos Int 10:330–336PubMedCrossRef
2.
go back to reference Riggs BL, Melton LJ III (1995) The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 17:505S–511SPubMedCrossRef Riggs BL, Melton LJ III (1995) The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 17:505S–511SPubMedCrossRef
3.
go back to reference Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRef Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRef
4.
go back to reference Reeve J, Bradbeer JN, Arlot M et al (1991) hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses. Osteoporos Int 1:162–170PubMedCrossRef Reeve J, Bradbeer JN, Arlot M et al (1991) hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses. Osteoporos Int 1:162–170PubMedCrossRef
5.
go back to reference Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550–555PubMedCrossRef Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550–555PubMedCrossRef
6.
go back to reference Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL (2003) Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 18:539–543PubMedCrossRef Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL (2003) Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res 18:539–543PubMedCrossRef
7.
go back to reference Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, Lindsay R (2001) Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 16:925–931PubMedCrossRef Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, Lindsay R (2001) Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 16:925–931PubMedCrossRef
8.
go back to reference Pettway GJ, Meganck JA, Koh AJ, Keller ET, Goldstein SA, McCauley LK (2008) Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation. Bone 42:806–818PubMedCrossRef Pettway GJ, Meganck JA, Koh AJ, Keller ET, Goldstein SA, McCauley LK (2008) Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation. Bone 42:806–818PubMedCrossRef
9.
go back to reference Bikle DD, Sakata T, Leary C, Elalieh H, Ginzinger D, Rosen CJ, Beamer W, Majumdar S, Halloran BP (2002) Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. J Bone Miner Res 17:1570–1578PubMedCrossRef Bikle DD, Sakata T, Leary C, Elalieh H, Ginzinger D, Rosen CJ, Beamer W, Majumdar S, Halloran BP (2002) Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. J Bone Miner Res 17:1570–1578PubMedCrossRef
10.
go back to reference 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
11.
go back to reference Brixen KT, Christensen PM, Ejersted C, Langdahl BL (2004) Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis. Basic Clin Pharmacol Toxicol 94:260–270PubMed Brixen KT, Christensen PM, Ejersted C, Langdahl BL (2004) Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis. Basic Clin Pharmacol Toxicol 94:260–270PubMed
12.
go back to reference Bradshaw AD, Sage EH (2001) SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 107:1049–1054PubMedCrossRef Bradshaw AD, Sage EH (2001) SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 107:1049–1054PubMedCrossRef
13.
go back to reference Delany AM, Kalajzic I, Bradshaw AD, Sage EH, Canalis E (2003) Osteonectin-null mutation compromises osteoblast formation, maturation, and survival. Endocrinology 144:2588–2596PubMedCrossRef Delany AM, Kalajzic I, Bradshaw AD, Sage EH, Canalis E (2003) Osteonectin-null mutation compromises osteoblast formation, maturation, and survival. Endocrinology 144:2588–2596PubMedCrossRef
14.
go back to reference Delany AM, Amling M, Priemel M, Howe C, Baron R, Canalis E (2000) Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest 105:915–923PubMedCrossRef Delany AM, Amling M, Priemel M, Howe C, Baron R, Canalis E (2000) Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest 105:915–923PubMedCrossRef
15.
go back to reference Boskey AL, Moore DJ, Amling M, Canalis E, Delany AM (2003) Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wild-type controls. J Bone Miner Res 18:1005–1011PubMedCrossRef Boskey AL, Moore DJ, Amling M, Canalis E, Delany AM (2003) Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wild-type controls. J Bone Miner Res 18:1005–1011PubMedCrossRef
16.
go back to reference Machado do Reis L, Kessler CB, Adams DJ, Lorenzo J, Jorgetti V, Delany AM (2008) Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice. Bone 43:264–273PubMedCrossRef Machado do Reis L, Kessler CB, Adams DJ, Lorenzo J, Jorgetti V, Delany AM (2008) Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice. Bone 43:264–273PubMedCrossRef
17.
go back to reference Hwang JS, Tu ST, Yang TS, Chen JF, Wang CJ, Tsai KS (2006) Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis. Osteoporos Int 17:373–378PubMedCrossRef Hwang JS, Tu ST, Yang TS, Chen JF, Wang CJ, Tsai KS (2006) Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis. Osteoporos Int 17:373–378PubMedCrossRef
18.
go back to reference Zhang XZ, Wang B, Yang J et al (2009) A randomized, multicenter controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with elcatonin in postmenopausal women with osteoporosis in China. Chin Med J (Engl) 122:2933–2938 Zhang XZ, Wang B, Yang J et al (2009) A randomized, multicenter controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with elcatonin in postmenopausal women with osteoporosis in China. Chin Med J (Engl) 122:2933–2938
19.
go back to reference Lindsay R, Miller P, Pohl G, Glass EV, Chen P, Krege JH (2009) Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20:943-948 Lindsay R, Miller P, Pohl G, Glass EV, Chen P, Krege JH (2009) Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20:943-948
20.
go back to reference Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S (2008) A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 23:205–214PubMedCrossRef Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S (2008) A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 23:205–214PubMedCrossRef
Metadata
Title
The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis
Authors
L. Zhang
L. Li
M. Yang
K. Xu
G. Boden
G. Yang
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 3/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-1956-3

Other articles of this Issue 3/2013

Osteoporosis International 3/2013 Go to the issue