Journal of Hainan Medical University. Wei Li. 1. Introduction. 28 Journal of Hainan Medical University 2016; 22(21): 28-32

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1 28 Journal of Hainan Medical University 2016; 22(21): Journal of Hainan Medical University Dual-energy X-ray absorptiometry assessment of postmenopausal women with vertebral fragility fracture and its relationship with serum bone turnover and bone metabolism indexes Wei Li Department of Nuclear Medicine, the Fifth People s Hospital of Shanghai, Fudan University, Shanghai, , China ARTICLE INFO Article history: Received Received in revised form Accepted Available online Keywords: Postmenopausal osteoporosis Bone mineral density Vertebral fragility fracture Bone turnover Bone metabolism ABSTRACT Objective: To study the relationship between dual-energy X-ray bone mass density measurement results of postmenopausal women with vertebral fragility fracture and the serum bone turnover as well as bone metabolism indexes. Methods: A total of 158 postmenopausal women who received DXA tests in our hospital between April 2012 and December 2015 were selected, were divided into osteoporosis group, osteopenia group and normal bone mass group according to the bone mineral density measurement results, and were divided into no vertebral fracture group, thoracic vertebral fracture group, lumbar vertebral fracture group and thoracolumbar vertebral fracture group according to the thoracolumbar vertebral anterioposterior and lateral film results, and serum was collected to determine bone turnover and bone metabolism indexes. Results: Femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with thoracic vertebral fracture and thoracolumbar vertebral fracture were significantly lower than those of the subjects without vertebral fracture, and femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with lumbar vertebral fracture were not significantly different from those of the subjects without vertebral fracture; serum PINP, ICTP, CTX, TRACP-5b, MMP13, OPG and OPN content of osteoporosis group and osteopenia group were significantly higher than those of normal bone mass group while 25(OH)D, BGP and ON content were significantly lower than those of normal bone mass group; serum PINP, ICTP, CTX, TRACP-5b, MMP13, OPG and OPN content of osteoporosis group were significantly higher than those of osteopenia group while 25(OH)D, BGP and ON content were significantly lower than those of osteopenia group. Conclusions: Dual-energy X-ray bone densitometry has clear prediction value for postmenopausal women with thoracic vertebral fragility fracture and thoracolumbar vertebral fragility fracture, and is closely related to the changes of bone turnover and bone metabolism. 1. Introduction Postmenopausal osteoporosis (PMOP) is a kind of systemic metabolic bone disease caused by postmenopausal ovarian function decline and decreased estrogen levels, and it is characterized by osteopenia and bone microstructure damage[1,2]. The women Corresponding author: Wei Li, No. 128, Ruili Road, Minhang District, Shanghai, , China. Tel: ; Fund project: Research Project of the Fifth People s Hospital of Shanghai No: 2013WYQJ05. with postmenopausal osteoporosis are affected by increased bone fragility, and the risk of fractures in various areas of the body significantly increases. Epidemiological data shows that the risk of fragility fracture in women's life is more than the total risk of breast, ovarian and cervical cancer, and fragility fracture is gradually becoming one of the important diseases threatening the health of postmenopausal women[3,4]. Dual-energy X-ray absorptiometry (Lunar Prodigy, DXA) is the preferred method in the diagnosis of osteoporosis, and the close relationship between low bone mineral density measured by DXA and vertebral fragility fracture has been accepted by more and more scholars[5,6]. However, the changes of

2 29 bone mineral density are unclear in PMOP women with vertebral fragility fractures of different parts, and the relationship of bone mineral density with bone turnover and bone metabolism in different parts is also yet to be elucidated. In the following study, dual-energy X-ray absorptiometry assessment of vertebral fragility fracture in PMOP and its relationship with serum bone turnover and bone metabolism indexes were analyzed. Thoracolumbar vertebral anterioposterior and lateral film examination was conducted, vertebral anterior and posterior height was measured, vertebral height change (Hx) was calculated to determine whether there was vertebral compression fracture, and the judgment method was as follows: (1) normal: Hx<20%; (2) mild fracture: 20% 曑 Hx 曑 25%; (3) moderate fracture: 25%<Hx 曑 40%; (4)severe fracture: Hx>40%. 2. Materials and methods 2.1. Research subjects A total of 158 postmenopausal women who received DXA tests in our hospital between April 2012 and December 2015 were selected as the research subjects, and the following people were excluded: (1) patients with severe liver and kidney disease, thyroid and parathyroid dysfunction, bone tumors and osteoarticular disease; (2) patients complicated with secondary osteoporosis; (3) patients who took the drugs that affected bone metabolism for a long time; (4) patients with previous history of severe trauma and vertebral fractures. According to the DXA test results and the WHO-recommended criteria for the diagnosis of osteoporosis, the included subjects were divided into osteoporosis group, osteopenia group and normal bone mass group. Osteoporosis group included 57 cases, they were (58.9±7.2) years old and the BMI was (23.5±3.6) kg/m 2 ; osteopenia group included 38 cases, they were (58.9±7.8) years old and the BMI was (23.8±3.1) kg/m 2 ; normal bone mass group included 63 cases, they were (59.4±7.8) years old and the BMI was (23.2±3.5) kg/m 2. The three groups of subjects showed no significant difference in general information Bone mineral density test and judgment methods DXA was used for testing, the instrument accuracy was 1%, error of replication was <1%, and the femoral neck, hip and lumbar vertebra L1-4 bone mineral density (BMD) were measured. WHOrecommended criteria were referred to judge bone mineral density test results: (1) normal: measured BMD value was lower than the peak bone mass of the same gender and race of healthy adults by not more than 1 standard deviation, T value 曒 -1.0 SD; (2) decreased BMD: measured BMD value was lower than the peak bone mass of the same gender and race of healthy adults by more than 1 standard deviation but not more than 2.5 standard deviations, -2.5 SD<T value<-1.0 SD; (3) osteoporosis: measured BMD value was lower than the peak bone mass of the same gender and race of healthy adults by more than 2.5 standard deviations, T value 曑 -2.5 SD Thoracolumbar vertebral X-ray test and judgment methods 2.4. Serum index detection methods Before bone mineral density test, 6-8 ml of peripheral blood sample was collected from the subjects and centrifuged to get serum, enzyme-linked immunosorbent assay kits were used to determine N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptides of type I collagen (CTX), pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), tartrateresistant acid phosphatase (TRACP), matrix metalloproteinase-13 (MMP13), osteocalcin (BGP), osteopontin (OPN), osteoprotegerin (OPG) and osteonectin (ON) content, and full-automatic electrochemical luminescence kits were used to determine calcium (Ca) and phosphorus (P) content Statistical methods SPSS20.0 software was used to input and analyze data, measurement data analysis between two groups was performed by t test, measurement data analysis among three groups was by variance analysis and P<0.05 indicated statistical significant differences. 3. Results 3.1. X-ray images of vertebral fragility fractures of different parts in postmenopausal women X-ray images of typical cases in postmenopausal women with vertebral fragility fractures of different parts were shown as follows, Figure 1a was for lumbar vertebral wedge fracture, Figure 1b was for thoracic vertebral wedge fracture and Figure 1c was for thoracolumbar vertebral wedge fracture. a b c Figure 1. X-ray images of vertebral fragility fractures of different parts in postmenopausal women. a: lumbar vertebral wedge fracture; b: thoracic vertebral wedge fracture; c: thoracolumbar vertebral wedge fracture

3 Bone mineral density of vertebral fragility fractures of different parts in postmenopausal women 25(OH)D, BGP and ON content were significantly lower than those of osteopenia group (P<0.05) (Table 3). Femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with thoracic vertebral fracture and thoracolumbar vertebral fracture were significantly lower than those of the subjects without vertebral fracture (P<0.05), and femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with lumbar vertebral fracture were not significantly different from those of the subjects without vertebral fracture (P>0.05) (Table 1) Serum bone turnover indexes in postmenopausal women Serum PINP, ICTP, CTX, TRACP-5b and MMP13 content were significantly different among three groups. Serum PINP, ICTP, CTX, TRACP-5b and MMP13 content of osteoporosis group and osteopenia group were significantly higher than those of normal bone mass group (P<0.05); serum PINP, ICTP, CTX, TRACP-5b and MMP13 content of osteoporosis group were significantly higher than those of osteopenia group (P<0.05) (Table 2) Serum bone metabolism indexes in postmenopausal women Serum Ca and P content were not significantly different among three groups while 25(OH)D, BGP, OPN, OPG and ON content were significantly different. Serum OPG and OPN content of osteoporosis group and osteopenia group were significantly higher than those of normal bone mass group while 25(OH)D, BGP and ON content were significantly lower than those of normal bone mass group (P<0.05); serum OPG and OPN content of osteoporosis group were significantly higher than those of osteopenia group while 4. Discussion Bone mass is decided by bone microstructure, bone metabolism, bone turnover, bone mineralization degree, bone matrix components and other characteristics, and the abnormal bone metabolism and bone turnover will affect bone microstructure, bone mineralization degree and bone matrix components. Ovarian function declines and the estrogen levels significantly reduce in postmenopausal women, and they affect the osteoblast and osteoclast activity to cause the change of bone metabolism and bone turnover, ultimately leading to systemic bone disease characterized by osteopenia and bone microstructure damage[7,8]. That the bone mass loss reaches the criteria for osteoporosis can be diagnosed with PMOP. The bone fragility increases obviously in patients with PMOP, and the risk of fragility fracture in multiple parts of the body obvious increases[9,10]. Vertebral fragility fracture is the most common type of fragility fracture in patients with PMOP, and vertebral fragility fracture not only affects the living quality of patients themselves, but can also increase the economic burden of the families and society[11,12]. DXA is the gold standard for clinical diagnosis of osteoporosis, and the close relationship between low bone mineral density measured by DXA and vertebral fragility fracture has been accepted by more and more scholars. With the development of DXA technology in recent years, DXA imaging can be used to measure the bone mineral density of the femoral neck, hip, spine and many other parts, and can provide more comprehensive reference for the diagnosis of osteoporosis and the prediction of the occurrence risk of vertebral compression fractures[13,14]. However, it is unclear at present about the changes in bone Table 1 Comparison of bone mineral density among postmenopausal women with vertebral fragility fractures of different parts. Groups Case No. Measured BMD value (g/m 2 ) BMD T value (SD) Femoral neck Hip Lumbar vertebra Femoral neck Hip Lumbar vertebra No vertebral fracture ± ± ± ± ± ±0.32 Thoracic vertebral fracture ±0.08 * 0.63±0.07 * 0.70±0.09 * -2.64±0.32 * -2.03±0.26 * -3.29±0.72 * Thoracolumbar vertebral fracture ±0.07 * 0.54±0.06 * 0.66±0.08 * -3.29±0.39 * -2.89±0.35 * -3.82±0.84 * Lumbar vertebral fracture ± ± ± ± ± ±0.47 * : compared with subjects without vertebral fracture, differences were statistically significant, P<0.05. Table 2 Comparison of serum bone turnover indexes among postmenopausal women (ng/ml). Groups Case No. PINP ICTP CTX TRACP-5 b MMP13 Osteoporosis ±6.35 ab 52.48±6.72 ab 0.68±0.09 ab 3.69±0.52 ab 48.66±6.71 ab Osteopenia ±5.63 a 39.14±5.28 a 0.59±0.07 a 2.78±0.36 a 35.61±5.69 a Normal bone mass ± ± ± ± ±4.28 F P <0.05 <0.05 <0.05 <0.05 <0.05 a: compared with normal bone mass group, P<0.05; b: compared with osteopenia group, P<0.05.

4 31 mineral density in PMOP women with vertebral fragility fracture of different parts. Vertebral fragility fracture trends to occur in the thoracic vertebra and lumbar vertebra, and according to the different involved parts, it can be divided into thoracic vertebral fragility fracture, lumbar vertebral fragility fracture and thoracolumbar vertebral fragility fracture[15]. In the study, the bone mineral density in postmenopausal women with vertebral fragility fracture of different parts was measured and analyzed, and the result showed that femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with thoracic vertebral fracture and thoracolumbar vertebral fracture were significantly lower than those of the subjects without vertebral fracture, and femoral neck, hip and lumbar vertebra L1-4 bone mineral density of subjects with lumbar vertebral fracture were not significantly different from those of the subjects without vertebral fracture. This means that when thoracic vertebral fragility fracture and thoracolumbar vertebral fragility fracture occur in postmenopausal women, the bone mineral density of each monitoring site decreases significantly; and when simple vertebral lumbar fragility fracture occurs, the bone mineral density of each monitoring site is without obvious changes. Analysis of the study believes that lumbar vertebra will show relatively obvious hyperplasia and hardening as well as the surrounding tissue calcification with growing age, and simple determination of bone mineral density cannot really reflect the local lumbar vertebral bone strength, which affects the value assessment of bone mineral density measurement for lumbar vertebral fragility fracture. So it is speculated that measurement of bone mineral density in multiple parts of the body can better predict the risk of thoracic vertebral fragility fracture and thoracolumbar vertebral fragility fracture, but the prediction value for the risk of simple lumbar vertebral fragility fracture remains to be further studied. Postmenopausal osteoporosis is characterized by enhanced bone turnover, and both osteoclast-mediated bone resorption process and osteoblast-mediated bone formation process are enhanced, and the bone resorption process is more than bone formation process. A variety of bone turnover marker molecules in serum could reflect the status of bone resorption and bone formation. Type I collagen is produced by type I procollagen splitting, is mainly from the osteoblasts, and is the most important collagen composition in bone tissue; the content of by-product PINP produced during splitting can reflect the amount of ossein formation, and also reflect the osteoblast activity and bone formation process[16]; type I collagen is degraded under the action of osteoclasts and related proteases, ICTP and CTX are its degradation products, and they can reflect the osteoclast activity and bone resorption process. TRACP and MMP13 are the new marker molecules of bone resorption process discovered in recent years[17]. TRACP includes two subsets: TRACP-5a and TRACP-5b, TRACP-5b is from osteoclasts, has the activity to degrade calcium phosphate mineralization materials in the bone matrix, is involved in the bone resorption process and could reflect the osteoclast viability; MMP13, also known as collagenase 3, has degradation effect on type I, type II and type III collagen and can preferentially degrade the characteristic type II collagen in hyaline cartilage, and decreased amount of type II collagen will result in lowered speed of transforming into type I collagen and correspondingly reduced amount of type I collagen[18]. In the study, the DXA-measured bone mineral density was referred to divide the postmenopausal women into osteoporosis group, osteopenia group and normal bone mass group, and the analysis of the content of bone turnover marker molecules showed that the lower the bone mineral density, the higher the serum PINP, ICTP, CTX, TRACP-5b and MMP13 content. This means that the DXA-measured bone mineral density is closely related to the bone turnover process, the lower the bone mineral density, the stronger the bone turnover process. In the course of osteoporosis, the change of bone turnover process is mostly associated with abnormal bone metabolism, and the content of a variety of bone metabolism-regulating molecules changes. OPG is a member of the tumor necrosis factor receptor superfamily that can compete with RANKL to be combine with RANK and inhibit the bone destruction effect mediated by RANKL; OPN is a kind of secretory phosphoglycoprotein that has promoting effect on osteoclast differentiation and maturation as well as bone resorption[19]; Vitamin D is an important fat-soluble vitamin in the body that regulates calcium phosphate metabolism, and 25(OH)D3 is its active form and has promoting effect on osteogenic precursor cell differentiation and maturation as well as osteoblast activity; BPG is the most abundant non-collagen composition in bone tissue, and it is mainly secreted by osteoblasts and participates in the maintenance of bone mineralization rate and the regulation of bone reconstruction; ON is a kind of extracellular matrix non-collagen, it can form nonsoluble compounds with type I collagen in the bone tissue and then induce calcium and phosphorus deposition and promote the formation and reconstruction of bone microstructure[20]. In the study, serum levels of bone metabolism molecules in postmenopausal women with different BMD were analyzed, and the result showed that the lower the bone mineral density, the higher the serum OPG and OPN content and the lower the 25(OH)D3, BGP and ON content. This means that DXA-measured bone mineral density is closely related to bone metabolism, and the lower the bone mineral density, the lower the content of related molecules promoting bone destruction and the higher the content of related molecules promoting osteogenesis. To sum up, dual-energy X-ray bone densitometry has clear prediction value for postmenopausal women with thoracic vertebral fragility fracture and thoracolumbar vertebral fragility fracture, and is closely related to the changes of bone turnover and bone metabolism.

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