Reference intervals of biochemical bone turnover markers for Saudi Arabian women: A cross-sectional study
Introduction
Bone is a dynamic tissue consistently undergoing remodeling through a cycle that includes formation and resorption. Biochemical bone turnover markers (BTMs) are specific bone-derived molecules categorized as bone formation or resorption markers: these markers are present in serum or urine and are reliable, non-invasive, and relatively inexpensive methods for assessing bone turnover [1], [2]. Over the past two decades, specific assays of biochemical BTMs have been developed and were used with other parameters in the diagnosis, monitoring and management of metabolic bone diseases including osteoporosis [3]. Several biochemical BTMs have been used to: predict bone density changes; predict future fracture risk [4], [5]; identify patients with metabolic bone diseases [6]; assess the efficiency of antiresorptive and/or anabolic therapies, as well as monitoring the response or the compliance of patients to such therapies [7], [8], [9], [10]. In addition, monitoring acute changes in bone turnover is very difficult to follow with bone mineral density (BMD) measurements, since the changes in BMD values are very small and take more than a year to detect, unlike the changes seen in biochemical BTMs which are rapid (within 3 months) and sufficiently sensitive to effectively monitor acute changes in bone turnover [6], [7], [8]. These potential clinical applications may increase the accuracy of prediction according to the use of BTMs and help the preventive modalities in the management of patients at high risk for metabolic bone diseases including osteoporosis or patients with osteoporotic fractures [6]. In addition, in the last decade, several biochemical BTMs are now commercially available on autoanalyzers which will improve on the potential and technical variabilities of the markers and will facilitate their wider use in routine clinical practice for the assessment of bone remodeling activity [11].
It is very important to establish reference intervals of biochemical BTMs before using them in a clinical setting. Therefore, much effort has been made to establish reference interval values of biochemical BTMs in various populations [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. However, there are no information or studies on the reference interval values for biochemical BTMs in Saudi or for any other Arabian populations. Accordingly, the present study provides the first report on the reference interval values for biochemical BTMs in Saudi women of different age groups, taking into consideration the known determinants of BTMs such as age, body mass index (BMI) and menopausal status. Thus, the main objectives of the present study are to: (1) establish age-specific reference interval values of biochemical BTMs [namely: serum osteocalcin (s-OC); serum bone-specific alkaline phosphatase (s-bone ALP); serum procollagen type 1 N-terminal propeptide (s-PINP); serum crosslinked C-terminal telopeptide of Type 1 collagen (s-CTX); urinary CTX (u-CTX); urinary N-telopeptide of type 1 collagen (u-NTX); urinary pyridinoline (u-PYD); urinary deoxypyridinoline (u-DPD) and serum tartarate-resistant acid phosphatase isoform-5b (s-TRACP-5b)] in randomly selected Saudi pre-menopausal women; (2) study the changes in biochemical BTMs in relation to age in pre- and post-menopausal women; and factors reported to influence bone turnover and (3) determine the effect of menopausal status on BTMs.
Section snippets
Study design
Over a period of 50 months (October 2005–November 2009), a total of 5850 Saudi women were prospectively recruited at random during a health survey from 40 primary health care centers (PHCCs) scattered around the city of Jeddah (divided into 7 geographical areas) to ensure that the average health status of the studied group will reflect a randomly selected adult population. The sample size was calculated using the sample size determination option in Epi-Info Statistical Package (version 6) [USD,
Anthropometric and other characteristics of the studied Saudi women
Table 1 shows the basic anthropometric characteristics of the studied Saudi healthy pre- (n = 1557), and post-menopausal (n = 568) women aged 20–79 years. Post-menopausal women exhibited higher parity (P < 0.001); BMI (P < 0.001) and WHR (P < 0.000) values as compared with pre-menopausal women (Table 1). All women exhibited normal BMD values according to the age group and WHO criteria [26] with pre-menopausal women showing significantly higher BMD values (at both lumbar spine (L1–L4) and femoral neck
Discussion
It is important to establish reference intervals for each biochemical BTMs from a representative sample of the healthy adult population in order to correctly assess bone turnover according to such markers in subjects of varying ages and health conditions. A population-based database including a wide range of age groups would demonstrate the changes in bone metabolism over a period of time and provide an opportunity to use such markers for comparisons of bone turnover among various populations
Acknowledgments
We are grateful to the Ministry of Higher Education for the financial support to the Center of Excellence for Osteoporosis Research (CEOR) at King Abdulaziz University, (Grant# CEOR/001-08) Jeddah, Saudi Arabia. We thank all the subjects who participated in the present study, and we thank all the staff and colleagues at the CEOR, King Abdulaziz University Hospital, and the Primary Care Health Centers for their invaluable assistance during the execution of the present study. Special thanks are
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