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Common biochemical markers of bone turnover predict future bone loss: A 5-year follow-up study
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
2005 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 356, no 1-2, 67-75 p.Article in journal (Refereed) Published
Abstract [en]


Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss.


We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21–79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss.


A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=−0.14 to −0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=−0.23 to −0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%).


These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.

Place, publisher, year, edition, pages
2005. Vol. 356, no 1-2, 67-75 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-29375DOI: 10.1016/j.cccn.2004.12.014Local ID: 14707OAI: diva2:250189

On the day of the defence day the status of this article was a manuscript.

Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-12Bibliographically approved
In thesis
1. Osteoporosis in women: Epidemiological and diagnostic perspectives
Open this publication in new window or tab >>Osteoporosis in women: Epidemiological and diagnostic perspectives
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

An epidemiological study of 15.462 hip fractures in Östergötland 1940-86 showed a large incidence increase mainly due to an increase in age-specific incidence of trochanteric fractures. A trendforecast assuming the same increase in incidence as over the study period and a population forecast according to the official prognosis, predicted 70% more hip fractures in the year 2000 compared to 1985. The different forecasts models were validated for the year 1995 and showed a good correlation between estimated and observed number of fractures, but varied dependent on which fracture and prognosis model that were evaluated.

A follow-up investigation of 11.517 hip fractures 1982-96 showed a downturn in incidence of female fractures and a continous increase for males, particularly of trochanteric fractures. A trend brake was thus seen and this continues up to 2010 according to our trendforecasts but may be counteracted by the increasing number of elderly after 2020. Gender ratio changed over time with increasing number of male fractures, more trochanteric fractures relative to cervical (c/t-ratio) and an increasing mean age of the fracture patient.

Age specific reference values were established for bone mineral density (BMD) in forearm, lumbar spine and hip after investigation of 429 women 20-80 years, randomly sampled from the general population. Bone density was assessed from cross-sectional data for the various skeletal sites over an almost complete adult life period and these were then compared to values obtained from other studies, densitometry technologies and reference materials. Large discordances were found between the different technologies and reference materials.

The outcome of using the T-score proposed by a WHO study group 1994 as a diagnostic cutoff principle for the diagnosis of osteoporosis (T<-2.5) and osteopenia (T<-1 - -2.5) was evaluated by calculating the resulting prevalence in a cohort of 210 women, 70 years of age. The use of different approaches in calculation of T -score and different reference samples, yielded unacceptable disparities in disease prevalence of between 9 and 72%. The differences were also heavely dependent of which and how many sites that were included in the diagnostic decision.

We studied biochemical markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline and calcium excretion in the urine) in relation to age, menopause and BMD, and their ability to predict bone loss in a 5-year follow-up perspective. Markers varied inversely to BMD, increased markedly at menopause and predicted bone loss over the next 5 years up to 75% at individual level, (AUC of an ROC analysis).

A case. finding strategy using low-energy index fractures in forearm, spine, hip or humerus was performed to detect subjects with osteoporosis. 303 consecutive women 55-75 years with a recent fracture were examined with densitometry and a risk profile questionnaire. The lowest BMD was found in spine and hip fracture patients. Odds ratio for osteoporosis was at least 8 for a patient with a prior hip fracture. The number of previous fractures correlated inversely with bone density (Z-score). Despite 92% of the fracture patients (many with a multiple fracture history) had a low bone mass (t-score<1), only 15% had been treated for osteoporosis before the index fracture.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 129 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 737
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-25686 (URN)10062 (Local ID)91-7373-531-0 (ISBN)10062 (Archive number)10062 (OAI)
Public defence
2002-06-05, Folkhälsovetenskapligt Centrums Aula, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-12Bibliographically approved

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