Skip to main content
Top
Published in: Osteoporosis International 7/2006

01-07-2006 | Original Article

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study

Authors: M. Iki, A. Morita, Y. Ikeda, Y. Sato, T. Akiba, T. Matsumoto, H. Nishino, S. Kagamimori, Y. Kagawa, H. Yoneshima ·, For the JPOS Study Group

Published in: Osteoporosis International | Issue 7/2006

Login to get access

Abstract

Introduction

The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established.

Methods

We followed 1,283 women aged 15–79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine.

Results

Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association.

Conclusion

Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.
Literature
1.
go back to reference Christiansen C, Riis BJ, Rodbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet 1:1105–1108PubMedCrossRef Christiansen C, Riis BJ, Rodbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet 1:1105–1108PubMedCrossRef
2.
go back to reference Christiansen C, Riis BJ, Rodbro P (1990) Screening procedure for women at risk of developing postmenopausal osteoporosis. Osteoporos Int 1:35–40PubMedCrossRef Christiansen C, Riis BJ, Rodbro P (1990) Screening procedure for women at risk of developing postmenopausal osteoporosis. Osteoporos Int 1:35–40PubMedCrossRef
3.
go back to reference Slemenda C, Hui SL, Longcopy C, Johnston CC (1987) Sex steroids and bone mass: a study of change about the time of menopause. J Clin Invest 80:1261–1269PubMedCrossRef Slemenda C, Hui SL, Longcopy C, Johnston CC (1987) Sex steroids and bone mass: a study of change about the time of menopause. J Clin Invest 80:1261–1269PubMedCrossRef
4.
go back to reference Johansen JS, Riis BJ, Delmas PD, Christiansen C (1988) Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. Eur J Clin Invest 18:191–195PubMed Johansen JS, Riis BJ, Delmas PD, Christiansen C (1988) Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. Eur J Clin Invest 18:191–195PubMed
5.
go back to reference Uebelhart D, Schlemmer A, Johansen JS, Gineyts E, Christiansen C, Delmas PD (1991) Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab 72:367–373PubMedCrossRef Uebelhart D, Schlemmer A, Johansen JS, Gineyts E, Christiansen C, Delmas PD (1991) Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab 72:367–373PubMedCrossRef
6.
go back to reference Slemenda C, Longcope C, Peacock M, Hui S, Johnston CC (1996) Sex steroids, bone mass and bone loss: a prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21PubMed Slemenda C, Longcope C, Peacock M, Hui S, Johnston CC (1996) Sex steroids, bone mass and bone loss: a prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21PubMed
7.
go back to reference Garnero P, Sornay-rendu E, Duboeuf F, Delmas PD (1999) Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14:1614–1621PubMedCrossRef Garnero P, Sornay-rendu E, Duboeuf F, Delmas PD (1999) Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14:1614–1621PubMedCrossRef
8.
go back to reference Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R (1996) Bone density change and biochemical indices of skeletal turnover. Cacif Tis Int 58:236–243 Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R (1996) Bone density change and biochemical indices of skeletal turnover. Cacif Tis Int 58:236–243
9.
go back to reference Iki M, Kajita E, Dohi Y, Nishino H, Kusaka Y Tsuchida C, Yamamoto K, Ishii Y (1996) Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women. Maturitas 25:59–67PubMedCrossRef Iki M, Kajita E, Dohi Y, Nishino H, Kusaka Y Tsuchida C, Yamamoto K, Ishii Y (1996) Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women. Maturitas 25:59–67PubMedCrossRef
10.
go back to reference Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C, Kelaghan J (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. J Bone Miner Res 14:1583–1595PubMedCrossRef Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C, Kelaghan J (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. J Bone Miner Res 14:1583–1595PubMedCrossRef
11.
go back to reference Roggers A, Hannon RA, Eastell R (2000) Biochemical markers as predictors of rates of bone loss after menopause. J Bone Miner Re 15:1398–1404CrossRef Roggers A, Hannon RA, Eastell R (2000) Biochemical markers as predictors of rates of bone loss after menopause. J Bone Miner Re 15:1398–1404CrossRef
12.
go back to reference Chaki, O, Yoshikata I, Kikuchi R, Nakayama M, Uchiyama Y, Hirahara F, Gorai I (2000) The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. J Bone Miner Res 15:1537–1544PubMedCrossRef Chaki, O, Yoshikata I, Kikuchi R, Nakayama M, Uchiyama Y, Hirahara F, Gorai I (2000) The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. J Bone Miner Res 15:1537–1544PubMedCrossRef
13.
go back to reference Chapurlat RD, Garnero P, Sorney-Rendu E, Arlot ME, Claustrat B, Delmas PD (2000) Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women. Osteoporos Int 11:493–498PubMedCrossRef Chapurlat RD, Garnero P, Sorney-Rendu E, Arlot ME, Claustrat B, Delmas PD (2000) Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women. Osteoporos Int 11:493–498PubMedCrossRef
14.
go back to reference Dennison E, Eastel R, Fall CHD, Kellingray S, Wood PJ, Cooper C (1999) Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10:384–391PubMedCrossRef Dennison E, Eastel R, Fall CHD, Kellingray S, Wood PJ, Cooper C (1999) Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10:384–391PubMedCrossRef
15.
go back to reference Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL (2000) Determinants of bone loss from the femoral neck in women of different ages. J Bone Miner Res 15:24–31PubMedCrossRef Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL (2000) Determinants of bone loss from the femoral neck in women of different ages. J Bone Miner Res 15:24–31PubMedCrossRef
16.
go back to reference Delmas PD, Estell R, Garnero P, Seibel MJ, Stapan J (2000) A position paper on the use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11(Suppl 6):S2–S17PubMedCrossRef Delmas PD, Estell R, Garnero P, Seibel MJ, Stapan J (2000) A position paper on the use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11(Suppl 6):S2–S17PubMedCrossRef
17.
go back to reference Stepan JJ (2000) Prediction of bone loss in postmenopausal women. Osteoporos Int 11(Suppl 6):S45–S54PubMedCrossRef Stepan JJ (2000) Prediction of bone loss in postmenopausal women. Osteoporos Int 11(Suppl 6):S45–S54PubMedCrossRef
18.
go back to reference Iki M, Kagamimori S, Kagawa Y, Matsuzaki T, Yoneshima H, Marumo F (2001) Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study. Osteoporos Int 12:529–537PubMedCrossRef Iki M, Kagamimori S, Kagawa Y, Matsuzaki T, Yoneshima H, Marumo F (2001) Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study. Osteoporos Int 12:529–537PubMedCrossRef
19.
go back to reference Iki M, Akiba T, Matsumoto T, Nishino H, Kagamimori S, Kagawa Y, Yoneshima H (2004) Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-Based Osteoporosis (JPOS) Study. Osteoporos Int 15:981–991PubMedCrossRef Iki M, Akiba T, Matsumoto T, Nishino H, Kagamimori S, Kagawa Y, Yoneshima H (2004) Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-Based Osteoporosis (JPOS) Study. Osteoporos Int 15:981–991PubMedCrossRef
20.
go back to reference Kawaguchi H, Matsumoto T, Kurokawa T, Orimo H, Mizunashi K, Takuwa Y, Niimi H, Shiraki M, Ohara T, Shishiba Y, Tsuchiya Y, Takahshi H, Takatsuki K, Seino Y, Morii H, Fujita T, Okamoto S, Ogata E (1990) Serum levels of BGP determined by two-site immunoradiometric assay (IRMA) using monoclonal antibodies. Clin Endocrinol 38:1291–1296 (in Japanese) Kawaguchi H, Matsumoto T, Kurokawa T, Orimo H, Mizunashi K, Takuwa Y, Niimi H, Shiraki M, Ohara T, Shishiba Y, Tsuchiya Y, Takahshi H, Takatsuki K, Seino Y, Morii H, Fujita T, Okamoto S, Ogata E (1990) Serum levels of BGP determined by two-site immunoradiometric assay (IRMA) using monoclonal antibodies. Clin Endocrinol 38:1291–1296 (in Japanese)
21.
go back to reference Garnero P, Delmas PD (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab 77:1046–1053PubMedCrossRef Garnero P, Delmas PD (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab 77:1046–1053PubMedCrossRef
22.
go back to reference Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C (1994) Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem 40:2022–2025PubMed Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C (1994) Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem 40:2022–2025PubMed
23.
go back to reference Robins SP, Woitge H, Hesley R, Ju J, Seyedin S, Seibel MJ (1994) Direct enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J Bone Miner Res 9:1643–1649PubMed Robins SP, Woitge H, Hesley R, Ju J, Seyedin S, Seibel MJ (1994) Direct enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J Bone Miner Res 9:1643–1649PubMed
24.
go back to reference Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, Keutmann HT, Wang CA, Potts JT jr, Segre GV (1987) Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 33:1364–1367PubMed Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, Keutmann HT, Wang CA, Potts JT jr, Segre GV (1987) Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 33:1364–1367PubMed
25.
go back to reference Suzumura E, Watanabe Y, Suzuki T, Yonezawa M, Yamauchi S, Ishigami T, Takezawa J, Ichikawa M, Seino Y (1992) Study of 1,25(OH)2D RPA kit using bovine mammary gland receptor and non-HPLC purification. Clin Endocrinol 40:1211–1218 (in Japanese) Suzumura E, Watanabe Y, Suzuki T, Yonezawa M, Yamauchi S, Ishigami T, Takezawa J, Ichikawa M, Seino Y (1992) Study of 1,25(OH)2D RPA kit using bovine mammary gland receptor and non-HPLC purification. Clin Endocrinol 40:1211–1218 (in Japanese)
26.
go back to reference McCloskey EV, Spector TD, Eyres KS, Fern ED, O’Rourke N, Vasikaran S, Kanis JA (1993) The assessment of vertebral deformity: a method for use in population studies and clinical trials. Osteoporos Int 3:138–147PubMedCrossRef McCloskey EV, Spector TD, Eyres KS, Fern ED, O’Rourke N, Vasikaran S, Kanis JA (1993) The assessment of vertebral deformity: a method for use in population studies and clinical trials. Osteoporos Int 3:138–147PubMedCrossRef
27.
go back to reference Nathan H (1962) Osteophytes of the vertebral column. J Bone Joint Surg 44-A:243–269 Nathan H (1962) Osteophytes of the vertebral column. J Bone Joint Surg 44-A:243–269
28.
go back to reference Sato Y, Tamaki J, Kitayama F, Kusaka Y, Kodera Y, Koutani A, Iki M (2005) Development of a food-frequency questionnaire to measure the dietary calcium intake of adult Japanese women. Tohoku J Exp Med 207:217–222PubMedCrossRef Sato Y, Tamaki J, Kitayama F, Kusaka Y, Kodera Y, Koutani A, Iki M (2005) Development of a food-frequency questionnaire to measure the dietary calcium intake of adult Japanese women. Tohoku J Exp Med 207:217–222PubMedCrossRef
29.
go back to reference Garnero P, Hausher E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PG, Delmas PD (1996) Markers of bone resorption predict hip fracture in elderly women: the Eidos prospective study. J Bone Miner Res 11:1531–1538PubMedCrossRef Garnero P, Hausher E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PG, Delmas PD (1996) Markers of bone resorption predict hip fracture in elderly women: the Eidos prospective study. J Bone Miner Res 11:1531–1538PubMedCrossRef
30.
go back to reference Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the Ofely study. J Bone Miner Res 15:1526–1536PubMedCrossRef Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the Ofely study. J Bone Miner Res 15:1526–1536PubMedCrossRef
31.
go back to reference Ross PD, Kress BC, Parson RE, Wasnich RD, Armour KA, Mizrahi IA (2000) Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int 11:76–82PubMedCrossRef Ross PD, Kress BC, Parson RE, Wasnich RD, Armour KA, Mizrahi IA (2000) Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int 11:76–82PubMedCrossRef
32.
go back to reference Luukinen H, Käkönen SM, Pettersson K, Koski K, Laippala P, Lövgren T, Kivelä SL, Väänänen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15:2473–2478PubMedCrossRef Luukinen H, Käkönen SM, Pettersson K, Koski K, Laippala P, Lövgren T, Kivelä SL, Väänänen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15:2473–2478PubMedCrossRef
33.
go back to reference Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C (1996) Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 19:9–12PubMedCrossRef Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C (1996) Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 19:9–12PubMedCrossRef
34.
go back to reference Komukai S, Ohta H, Makita K, Yanamoto S, Takamatsu K, Okano H, Yajima M, Nozawa S (2003) One-year spinal bone change in pre- and perimenopausal Japanese women. Hormone Res 59:79–84PubMedCrossRef Komukai S, Ohta H, Makita K, Yanamoto S, Takamatsu K, Okano H, Yajima M, Nozawa S (2003) One-year spinal bone change in pre- and perimenopausal Japanese women. Hormone Res 59:79–84PubMedCrossRef
35.
go back to reference Picard D, Imback A, Couturier R, Lepage R, Ste-Marie LG (2000) Longitudinal study of bone density and its determinants in women in peri or early menopause. Calcif Tissue Int 67:356–360PubMedCrossRef Picard D, Imback A, Couturier R, Lepage R, Ste-Marie LG (2000) Longitudinal study of bone density and its determinants in women in peri or early menopause. Calcif Tissue Int 67:356–360PubMedCrossRef
37.
go back to reference Arslan AA, Zeleniuch-Jacquotte A, Lukanova A, Rinaldi S, Kaaks R, Toniolo P (2003) Reliability of follicle-stimulating hormone measurements in serum. Reprod Biol Endocrinol 1:49PubMedCrossRef Arslan AA, Zeleniuch-Jacquotte A, Lukanova A, Rinaldi S, Kaaks R, Toniolo P (2003) Reliability of follicle-stimulating hormone measurements in serum. Reprod Biol Endocrinol 1:49PubMedCrossRef
Metadata
Title
Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study
Authors
M. Iki
A. Morita
Y. Ikeda
Y. Sato
T. Akiba
T. Matsumoto
H. Nishino
S. Kagamimori
Y. Kagawa
H. Yoneshima ·
For the JPOS Study Group
Publication date
01-07-2006
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 7/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-005-0052-3

Other articles of this Issue 7/2006

Osteoporosis International 7/2006 Go to the issue