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1 Chin J Osteoporos November 2014 Vol 20 No. 11 Published online www. wanfangdate. com. cn doi /j. issn * 张萌萌 R681 A " " Bone metabolism biochemical markers calcium and phosphorus metabolism indicator Parathyroid hormone PTH Calcitonin CT D 3 vitamin D 3 VD D hydroxy vitamin D 3 25 OH D D dihydroxy vitamin D OH 2 D 3 calcium phosphorus bone resorption markers tartra-resistant acid phosphatase TRACP I Type I collagen carboxy- terminal peptide CTX I Type I collagen amino- terminal peptide NTX pyridinoline Pyr deoxy- pyridinoline D-Pyr I Urinary type I collagen carboxy- terminal peptide U-CTX I Urinary type I collagen amino- terminal peptide U-NTX 2 /Ca /Cr bone formation markers Alkaline phosphatase ALP Bone specific alkaline phosphatase BALP Osteocalcin OC Bone Glaprotein BGP I Type I procollagen carboxyl- terminal peptide PICP I Type I procollagen amino-terminal peptide PINP Osteoprotegerin OPG * zhmm5866@ 163. com

2 Chin J Osteoporos November 2014 Vol 20 No. 11 Expert consensus of clinical application of the bone metabolic and biochemical markers by Oste oporosis Committe e of Chine se Ge rontological Socie ty ZHANG Mengmeng Diagnosis and Treatment Center of Osteoporosis in Jilin Province the Fourth Hospital of Jilin University Changchun China Corresponding author ZHANG Mengmeng zhmm5866@ 163. com Abstract The bone metabolic and biochemical markers include calcium and phosphorus metabolic indicators bone resorption markers and bone formation markers. The bone metabolic and biochemical markers are derived from the bone cartilage soft tissue skin liver kidney small intestine blood endocrine glands etc. They are enzymes and hormones secreted by osteoblasts or osteoclasts and the metabolic products of collagen or non-collagen proteins from bone matrix. The bone metabolic and biochemical markers reflect the status of bone turnover promptly w ith high sensitivity and specificity. They have been used in osteoporosis diagnosis prediction of fracture risk curative effect observation of drug treatment and the differential diagnosis of metabolic bone disease. They have important application value in the research of the pathogenesis of osteoporosis drugs for treatment of osteoporosis and the epidemiological study. The clinical use of the bone metabolic and biochemical markers is getting popular due to the mature of the detection technology. How ever the test results vary because of different source of the specimen different methods different equipment different reagents different ages different races and different gender. So far there is no unified detection standard of bone metabolic and biochemical markers in the w orld. Therefore w e collect and summarize the biological role and clinical significance of bone metabolic and biochemical markers application technology and quality control in this paper in order to provide a readable applicable and w ell referred material to colleagues. We look forw ard to promoting the detection technology for bone metabolic and biochemical markers in clinic standardizing detection process and establishing scientific reference range through the consensus so that the bone metabolic and biochemical markers can play an important role in the standardization of osteoporosis diagnosis and treatment anti-osteoporosis drug efficacy evaluation and scientific research. 1 Bone metabolism biochemical indicators ELISA CLIA ECLIA RIA 1 IRMA HPLC Table 1 Classification of bone metabolic and biochemical markers PTH CT 25- OH D OH 2 D 3 Ca P TRACP CTX NTX Pyr D-Pyr U-CTX U-NTX 2h Ca /Cr ALP BALP BGP PINP PICP OPG

3 Chin J Osteoporos November 2014 Vol 20 No CT calcium and phosphorus metabolism indicator Table 2 2 Classification of calcium and phosphorus metabolic indicators parathyroid hormone PTH calcitonin CT D 3 vitamin D 3 VD 3 calcium Ca phosphorus P Parathyroid hormone PTH D dihydroxy vitamin D OH 2 D 3 D VDR OH 2 D 3 PTH 6 PTH Ca 2 + OC D OC 7 IGF-1 PTH PTH 2 PTH 25- OH D 3 21 D 3 PTH OH 2 D OH D 3 D Calcitonin CT D parafollicular cells C 32 PTH PTH Ⅰ Serum Calcium 99% 1% PTH CT CT D 3 vitamin D 3 VD hydroxy vitamin D 3 25 OH D dihydroxy vitamin D OH 2 D 3 D 3 VD 3 5 VD hydroxy vitamin D 3 25 OH D 3 1a OH 2 D 3 4 ~ 6 CT 50% D 3

4 Chin J Osteoporos November 2014 Vol 20 No Table 3 The normal reference values of calcium and ph phosphorus metabolic indicators D PTH 15 ~ 65 pg /ml ECLIA Serum phosphorus 2. 2 bone resorption markers tartra-resistant acid Na 2 HPO 4 NaH 2 PO 4 CaHPO 4 MgHPO 4 phosphatase TRACP 6 2 HPO - 4 / Gaucher H 2 PO - 4 TRACP OC TRACP 19 P13. 2 ~ ~ 40kD TRACP 85% ~ 95% D CT ~ pg /ml ~ pg /ml ECLIA ECLIA 25- OH D 3 10 ~ 30 ng /ml ECLIA Ca ~ mmol /L P ~ mmol /L PTH. Parathyroid hormone CT. Calcitonin 25- OH D dihy droxyvitamin D 3 25 D 3 Ca. calciump. phosphoruseclia. Table 4 4 Classification of bone resorption markers Tartrate resistant acid phosphatase TRACP I Type I collagen carboxy-terminal peptide CTX I Type I collagen amino-terminal peptide NTX Urinary pyridinoline Pyr Urinary deoxypyridinoline D-Pyr I Urinary type I collagen carboxy-terminal peptide U-CTX I Urinary type I collagen amino-terminal peptide U-NTX 2 / Ca /Cr TRACP TRACP-5b 8 TRACP-5b I Type I collagen Paget s carboxy-terminal peptide CTX I

5 Chin J Osteoporos November 2014 Vol 20 No % I CTX NTX α2 Ⅰ 3 α2 Ⅰ MMP CTX-MMP CTX α2 Ⅰ 8 α-ctx β- CTX CTX- Ⅰ NTX MMP Pyr D- Pyr 3 C 1 Ⅰ C α1 Ⅰ 13 1 Ⅰ C α1 Ⅰ α2 NTX 14 Ⅰ α-ctx β- CTX pyridinoline Pyr CrossLaps CTX 1000Da deoxypyridinoline D-Pyr Pyr 3- CTX CTX Hydroxylysyl pyridinoline HP D-Pyr Paget s Lysyl pyridinoline HP CTX Pyr D-Pyr I Pyr D- 12 Pyr NTX CTX I Type I collagen aminoterminal peptide NTX NTX Pyr Pyr D-Pyr Ⅰ D-Pyr Ⅰ D-Pyr NTX 3-2 N- 1 1 Pyr D-Pyr Pyr D-Pyr NTX 40% 60% NTX /Cr BMD Pyr D-Pyr 4 1 Table 5 5 The normal reference values of bone resorption makers Pyr D-Pyr CTX NTX TRACP-5b ~ nmol /mmol Cr HPLC /ELISA 1. 8 ~ nmol /mmol Cr HPLC /ELISA 3. 9 ~ 4. 9nmol /mmol Cr ± μg /L ± μg /L ± μg /L 5 ~ 65nmol BCE /mmol Cr 3 ~ 63nmol BCE /mmol Cr 6. 2 ~ 19nmol BCE 5. 4 ~ 24. 2nmol /L BCE /L 0. 5 ~ 3. 8U /L 0. 5 ~ 4. 8U /L 0. 5 ~ 3. 8U /L Crosslaps ELISA /RIA ELISA /RIA ELISA /RIA Osteomark TM Osteomark TM ELISA /RIA ELISA /RIA /RIA Pyr. D-Pyr. CTX. I NTX. I TRACP-5b. HPLC. ELISA. RIA.

6 Chin J Osteoporos November 2014 Vol 20 No. 11 Pyr D-Pyr D-Pyr BMD 15 D-Pyr Pyr D-Pyr Pyr D-Pyr 17 Pyr D-Pyr Pyr D-Pyr Pyr D-Pyr SLE Pyr D-Pyr Paget s Pyr D-Pyr 12 Pyr D-Pyr 5 Pyr D-Pyr Pyr D-Pyr 16 Table 6 6 Classification of bone formation markers Alkaline phosphatase ALP Bone specific alkaline phosphatase BALP Osteocalcin bone Glaprotein OC BGP I Type I procollagen carboxyl-terminal peptide PICP I Type I procollagen amino-terminal peptide PINP Osteoprotegerin OPG 2. 3 bone formation markers Alkaline phosphatase ALP Bone specific alkaline phosphatase BALP 49 OC BALP OC OC γ 4 OC OC OC BALP OC ALP BALP OC Paget s OC 4 18 BALP OC OC Osteocalcin OC Bone Glaprotein BGP γ- bone Glaprotein BGP

7 Chin J Osteoporos November 2014 Vol 20 No OC OPG OC 19 OC BMD OPG I Type I procollagen carboxyl-terminal peptide PICP I RA OPG Type I procollagen amino-terminal peptide PINP 90% I I OPG OC OPG / RANKL I α OPG N C OPG PINP PICP PICP PINP OPG OPG 20 PICP ~ 8 min PINP OPG OPG I OPG OPG P1NP OPG 29 OPG OP PINP Osteoprotegerin OPG ostoeprotegerin OPG Simonet tumor necrosis factor TNF 22 7 OPG OPG OPG 401 I OPG / κb RANK / Ⅱ I OP RANK RANKL II OPG 8q23-24 Southern OP OPG 1 27 kb bp 5 27 OPG 401 N 21 OPG 30 osteoclast OC 28 AS PICP 4 3 PICP PINP OP

8 Chin J Osteoporos November 2014 Vol 20 No. 11 Table 7 7 The normal reference values of bone formation makers BALP OC PICP PINP OPG 3. 8 ~ μg /L 3. 7 ~ μg /L 1. 0 ~ 36 μg /L 1. 0 ~ 35 μg /L 50 ~ 170 μg /L 38 ~ 202 μg /L ~ ng /ml 21 ~ 78 ng /ml /IRMA /EIA IRMA /RIA /ELISA RIA /ELISA RIA /ELISA ± ng /L ELISA BALP. Bone alkaline phosphatase OC. Osteocalcin PICP. Type I procollagen carboxyl-terminal peptide I PINP. Type I procollagen amino terminal peptide I OPG. Osteoprotegerin IRMA. immunoradiometric assay EIA. enzyme immunoassay BMD 3. 3 PINP CTX < 25% BMD PINP CTX 32 Table 8 8 Application of bone metabolic and biochemical markers in the type diagnosis and differential diagnosis of osteoporosis OP BALP TRACP E 2 IL-1 PINP PICP 25 OH D 3 OP 25 OH D OH 2 D 3 T TGF-β PINP OP GH E 2 T PICP CTX-1 PTH OH 2 D 3 25 OH D 3 OP PTH 25 OH D 3 IGF-1 E 2 BALP PICP CTX-1 Table 9 9 The monitoring indicators and time recommendation in the osteoporosis treatment E 2 CTX-1 BALP 3 6 IL-1 BALP PINP PICP BGP TRACP CTX-1 Ca CT PTH Ca P OH 2 D 3 Ca PTH 1 2 D 3 PTH CT Ca P 25 OH D 3 1 2

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