Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study
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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.
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.
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.
Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.
KeywordsBone mineral density Bone turnover markers Japanese women Longitudinal study Population-based epidemiologic study Random sample
This study was conducted by the JPOS Study Group, comprising Fumiaki Marumo (Chairman of the Study Group, Professor Emeritus, Tokyo Medical and Dental University), Toshihisa Matsuzaki (Co-chairman of the Study Group, Institute of Comprehensive Community Care), Etsuko Kajita (Nagoya University School of Health Sciences), Tomoharu Matsukura (Kanazawa University), and Takashi Yamagami (Hokuriku Health Service Association), along with the authors. Financial support for the baseline survey was provided by the Japan Milk Promotion Board and the Japan Dairy Council. The follow-up surveys were financially supported by a Grant-in-aid for Scientific Research (B #10470114, 1998–2000, and B #1437017, 2002–2003) from the Japanese Society for the Promotion of Science and a grant in 2000–2002 from the Research Society for Metabolic Bone Diseases, Japan. The authors wish to express special thanks to the personnel of the health departments of Hirara City, Sanuki City, and Nishi-Aizu Town for their excellent support of the study, and to those from SRL, Tokyo, Japan; Toyo Medic, Osaka, Japan; and Toyukai Medical Corporation, Tokyo, Japan, for their technical assistance with the surveys.
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