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Osteoporosis International

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01-02-2015 | Original Article

Lower P1NP serum levels: a predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients

Authors: L. P. C. Seguro, C. B. Casella, V. F. Caparbo, R. M. Oliveira, A. Bonfa, E. Bonfa, R. M. R. Pereira

Published in: Osteoporosis International | Issue 2/2015

Abstract

Summary

Predictors of bone mineral density (BMD) loss are additional tools in the management of osteoporosis in premenopausal women with systemic lupus erythematosus (SLE). This study provides original evidence that N-terminal propeptide of type 1 collagen (P1NP), the most specific bone formation marker, is a predictor of BMD loss in this group of women.

Introduction

SLE is associated with a high risk of low bone mass/fractures but this risk is still controversial in premenopausal women. Our aim was to determine the 1 year incidence of BMD loss in premenopausal SLE women and the value of bone turnover markers as predictors of this complication.

Methods

This study enrolled a convenience sample of 63 premenopausal SLE patients. BMD was evaluated by dual X-ray absorptiometry at lumbar spine and hip at baseline and after 12 months. BMD changes above the least significant change were considered significant. Serum levels of P1NP and CTX (electrochemiluminescence), OPG, and RANKL (ELISA) were determined at baseline.

Results

Mean age was 31.1 ± 6.8 years, and disease duration was 5.25 ± 3.8 years. 36.5 % of patients presented BMD loss and 17.5 % BMD gain at lumbar spine and/or hip. Patients were divided in three groups: BMD loss (BL), no BMD change (NC), and BMD gain (BG). Patients with BL and NC received similar cumulative/mean/maximum glucocorticoid doses during the study, but patients with BG received lower doses (p < 0.05). Baseline P1NP levels were different in the groups (BL: 36.95 ± 23.37 vs. NC: 54.63 ± 30.82 vs. BG: 84.09 ± 43.85 ng/mL; p = 0.031 BL vs. NC, p < 0.001 BL vs. BG, and p = 0.039 NC vs. BG). There was no difference in CTX, OPG, or RANKL levels. After multivariate analysis, P1NP remained as an independent risk factor for BMD loss (p < 0.03).

Conclusions

This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of BMD loss over 12 months in premenopausal SLE patients.

Pereira RM, Carvalho JF, Canalis E (2010) Glucocorticoid-induced osteoporosis in rheumatic diseases. Clinics (Sao Paulo) 65:1197–1205CrossRef

Casella CB, Seguro LP, Takayama L, Medeiros D, Bonfa E, Pereira RM (2012) Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health. Lupus 21:1335–1342PubMedCrossRef

Lane NE (2006) Therapy insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol 2:562–569PubMedCrossRef

Bhalla AK (2010) Management of osteoporosis in a pre-menopausal woman. Best Pract Res Clin Rheumatol 24:313–327PubMedCrossRef

Pereira RM, Carvalho JF, Paula AP, Zerbini C, Domiciano DS, Gonçalves H et al (2012) Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology; Brazilian Medical Association; Brazilian Association of Physical Medicine and Rehabilitation. Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis. Rev Bras Reumatol 52:580–593PubMedCrossRef

Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W et al (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (hoboken) 62:1515–1526CrossRef

Lekamwasam S, Adachi JD, Agnusdei D, Bilezikian J, Boonen S, Borgström F et al (2012) Joint IOF-ECTS GIO Guidelines Working Group. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 23:2257–2276PubMedCrossRef

Franchimont N, Canalis E (2003) Management of glucocorticoid-induced osteoporosis in premenopausal women with autoimmune disease. Autoimmun Rev 2:224–228PubMedCrossRef

Levy S, Fayez I, Taguchi N, Han JY, Aiello J, Matsui D et al (2009) Joint IOF-ECTS GIO Guidelines Working Group. Pregnancy outcome following in utero exposure to bisphosphonates. Bone 44:428–430PubMedCrossRef

10.

Kalla AA, Fataar AB, Jessop SJ, Bewerunge L (1993) Loss of trabecular bone mineral density in systemic lupus erythematosus. Arthritis Rheum 36:1726–1734PubMedCrossRef

11.

Regio P, Bonfá E, Takayama L, Pereira R (2008) The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus. Lupus 17:787–792PubMedCrossRef

12.

Sinigaglia L, Varenna M, Binelli L, Zucchi F, Ghiringhella D, Gallazzi M et al (1999) Determinants of bone mass in systemic lupus erythematosus: a cross-sectional study on premenopausal women. J Rheumatol 26:1280–1284PubMed

13.

Yeap SS, Fauzi AR, Kong NC, Halim AG, Soehardy Z, Rahimah S et al (2009) Influences on bone mineral density in Malaysian premenopausal systemic lupus erythematosus patients on corticosteroids. Lupus 18:178–181PubMedCrossRef

14.

Souto MI, Coelho A, Guo C, Mendonça LM, Pinheiro MF, Papi JÁ et al (2012) The prevalence of low bone mineral density in Brazilian patients with systemic lupus erythematosus and its relationship with the disease damage index and other associated factors. J Clin Densitom 15:320–327PubMedCrossRef

15.

Pons F, Peris P, Guañabens N, Font J, Huguet M, Espinosa G et al (1995) The effect of systemic lupus erythematosus and long-term steroid therapy on bone mass in pre-menopausal women. Br J Rheumatol 34:742–746PubMedCrossRef

16.

Hansen M, Halberg P, Kollerup G, Pedersen-Zbinden B, Hørslev-Petersen K, Hyldstrup L et al (1998) Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment. Scand J Rheumatol 27:197–206PubMedCrossRef

17.

Formiga F, Nolla JM, Moga I, Roig-Escofet D (1996) Sequential study of bone mineral density in patients with systemic lupus erythematosus. Ann Rheum Dis 55:857PubMedCentralPubMedCrossRef

18.

Kipen Y, Briganti EM, Strauss B, Will R, Littlejohn G, Morand E (1999) Three year follow-up of bone mineral density change in premenopausal women with systemic lupus erythematosus. J Rheumatol 26:310–317PubMed

19.

Jardinet D, Lefebvre C, Depresseux G, Lambert M, Devogelaer JP, Houssiau FA (2000) Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine. Rheumatology (Oxford) 39:389–392CrossRef

20.

Boyanov M, Robeva R, Popivanov P (2003) Bone mineral density changes in women with systemic lupus erythematosus. Clin Rheumatol 22:318–323PubMedCrossRef

21.

Uaratanawong S, Deesomchok U, Hiransuttikul N, Uaratanawong S (2004) Four years follow-up of bone mineral density change in premenopausal women with systemic lupus erythematosus. J Med Assoc Thai 87:1374–1379PubMed

22.

Jacobs J, Korswagen LA, Schilder AM, van Tuyl LH, Dijkmans BA, Lems WF et al (2013) Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus. Osteoporos Int 24:1827–1833PubMedCrossRef

23.

Baim S, Wilson CR, Lewiecki EM, Luckey MM, Downs RW Jr, Lentle BC (2005) Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry. J Clin Densitom 8:371–378PubMedCrossRef

24.

Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A et al (2011) IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420PubMedCrossRef

25.

Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS et al (2009) Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 42:929–942PubMedCrossRef

26.

Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P, Bernecker P et al (2000) Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis 59:308–310PubMedCentralPubMedCrossRef

27.

Teichmann J, Lange U, Stracke H, Federlin K, Bretzel RG (1999) Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis. Rheumatol Int 18:137–140PubMedCrossRef

28.

Borba VZ, Vieira JG, Kasamatsu T, Radominski SC, Sato EI, Lazaretti-Castro M (2009) Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporos Int 20:427–433PubMedCrossRef

29.

Becker A, Fischer R, Scherbaum WA, Schneider M (2001) Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. Lupus 10:809–814PubMedCrossRef

30.

Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 9:Suppl 1–S1CrossRef

31.

Carmona-Fernandes D, Santos MJ, Perpétuo IP, Fonseca JE, Canhão H (2011) Soluble receptor activator of nuclear factor κB ligand/osteoprotegerin ratio is increased in systemic lupus erythematosus patients. Arthritis Res Ther 13:R175PubMedCentralPubMedCrossRef

32.

Long L, Liu Y, Wang S, Zhao Y, Guo J, Yu P et al (2010) Dickkopf-1 as potential biomarker to evaluate bone erosion in systemic lupus erythematosus. J Clin Immunol 30:669–675PubMedCrossRef

33.

Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef

34.

Fuchs SC, Guimarães SM, Sortica C, Wainberg F, Dias KO, Ughini M et al (2002) Reliability of race assessment based on the race of the ascendants: a cross-sectional study. BMC Public Health 2:1–5PubMedCentralPubMedCrossRef

35.

Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640PubMedCrossRef

36.

Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369PubMedCrossRef

37.

Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML et al (2008) International Society for Clinical Densitometry 2007 adult and pediatric official positions. Bone 43:1115–1121PubMedCrossRef

38.

El Maghraoui A, Achemlal L, Bezza A (2006) Monitoring of dual-energy X-ray absorptiometry measurement in clinical practice. J Clin Densitom 9:281–286PubMedCrossRef

39.

Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedCrossRef

40.

Domiciano DS, Figueiredo CP, Lopes JB, Kuroishi ME, Takayama L, Caparbo VF et al (2013) Vertebral fracture assessment by dual X-ray absorptiometry: a valid tool to detect vertebral fractures in community-dwelling older adults in a population-based survey. Arthritis Care Res (Hoboken) 65:809–815CrossRef

41.

Compston J (2010) Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol 6:82–88PubMedCrossRef

42.

Gifre L, Ruiz-Gaspà S, Monegal A, Nomdedeu B, Filella X, Guañabens N et al (2013) Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone 57:272–276PubMedCrossRef

43.

Conti A, Sartorio A, Ferrero S, Ferrario S, Ambrosi B (1996) Modifications of biochemical markers of bone and collagen turnover during corticosteroid therapy. J Endocrinol Invest 19:127–130PubMedCrossRef

44.

Haskelberg H, Hoy JF, Amin J, Ebeling PR, Emery S, Carr A et al (2012) Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One 7:e38377PubMedCentralPubMedCrossRef

45.

Parfitt AM (1994) Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286PubMedCrossRef

46.

Yamamoto T, Tsujimoto M, Hamaya E, Sowa H (2013) Assessing the effect of baseline status of serum bone turnover markers and vitamin D levels on efficacy of teriparatide 20 μg/day administered subcutaneously in Japanese patients with osteoporosis. J Bone Miner Metab 31:199–205PubMedCrossRef

47.

Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Risteli J (1993) Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res 8:127–132PubMedCrossRef

48.

Tudor-Locke C, McColl RS (2000) Factors related to variation in premenopausal bone mineral status: a health promotion approach. Osteoporos Int 11:1–24PubMedCrossRef

49.

Krølner B, Pors NS (1982) Bone mineral content of the lumbar spine in normal and osteoporotic women: cross-sectional and longitudinal studies. Clin Sci (Lond) 62:329–336

Title: Lower P1NP serum levels: a predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients
Authors: L. P. C. Seguro
C. B. Casella
V. F. Caparbo
R. M. Oliveira
A. Bonfa
E. Bonfa
R. M. R. Pereira
Publication date: 01-02-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2860-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lower P1NP serum levels: a predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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