Start Date
Expiration Date
CPT Codes
Reference Test
ATLAS Test Code

Specimen Information


Red, Plain


0.5 ml

Transport Info

Centrifuge and immediately transfer serum to separate plastic tube

Fasting Required?
Patient Instructions

Reference Range

Adult Male: 5.4-24.2 nM BCE
Premenopausal, Adult Female: 6.2-19.0 nM BCE


Enzyme-Linked Immunosorbent Assay (ELISA)

Clinical Significance

Monitor antiresorptive therapy with estrogen and calcium supplementation as well as drug therapy.

Bone is continuously being turned over by the coupled process of osteoclast- mediated bone resorption, followed by osteoblast-mediated bone formation. This process is necessary for the normal development and maintenance of the skeleton. An imbalance in these two processes leads to changes in skeletal structure and bone mass. Through the early twenties, formation occurs at a faster rate than resorption. In the thirties, an equilibrium is reached where formation and resorption occur at about the same rate. After this period, there is a progressive decline in bone density. Osteoporosis is a disease characterized by low bone mass and deterioration of bone tissue due to increased bone resorption or decreased bone formation, resulting in weak bones that are prone to fracture. Osteoporosis is a leading cause of disability, affecting more than 20 million postmenopausal women in the U.S. Over one million fractures are associated with osteoporosis annually. Also, approximately 50% of patients with osteoporosis-related hip fractures become partially or permanently disabled. While osteoporosis is typically associated with postmenopausal women, it is by no means gender specific. Age-related bone loss occurs in both men and women beginning around age 40. Early diagnosis of osteoporosis is imperative to allow intervention to decrease risk fracture. Patients determined to be at high risk may then be treated with hormone replacement therapy (HRT) or bisphosphonates to reduce bone resorption, thereby reducing bone fracture. Several non-invasive methods are available to evaluate bone tissue quality, such as dual-energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). However, these methods cannot detect small changes, limiting frequency and feasibility of testing. Currently, ARUP offers two types of bone markers: 1) osteocalcin or bone specific alkaline phosphatase for measurement of bone formation and 2) N- telopeptide (NTx), deoxypyridinoline, or total pyridinoline for measurement of bone resorption. Biochemical markers of bone turnover exhibit significant changes during bone formation and resorption. These markers are useful in the management of patients with metabolic bone disease, allow earlier evaluation of treatment, and are predictors of the risk of osteopetrosic fractures. ARUP offers four biochemical markers for the evaluation of bone turnover: 1) Bone Specific Alkaline Phosphatase (BSAP) for bone formation, 2) Osteocalcin (Bone G1a Protein) for bone formation 3) Cross-Linked N-Telopeptides of Type 1 Collagen (NTx) for bone resorption , and 4) Deoxypyridinoline Crosslinks (Dpd) for bone resorption . Bone Formation: BSAP: The isoenzyme of alkaline phosphatase found in bone is a tetrameric glycoprotein localized on the cell membrane of osteoblasts. The function of bone alkaline phosphatase is not clearly understood, but it is possibly involved in the mineralization of bone. The level of BSAP in serum is considered to indicate the metabolic status of osteoblasts. The measurement of BSAP in serum provides information useful in the evaluation and treatment of patients with Paget's disease, osteomalacia, primary hyperparathyroidism, osteodystrophy, osteoporosis, and metastases to bone. The procedure employs a solid phase two-site immunoradiometric assay (IRMA). The sensitivity of the assay is 2.0 µg/L. Bone Formation: Osteocalcin: Osteocalcin, or bone gla protein, is a noncollagenous protein in mature bone. It is synthesized by osteoblasts and incorporated into bone matrix, although a fraction of the newly synthesized osteocalcin is released into the circulation. Metabolized mainly in the kidney and to a lesser extent in the liver, the half-life in the circulation is about 5 minutes. Osteocalcin production is dependent on 1,25 Dihydroxy Vitamin D; Vitamin K; and Vitamin C. Serum osteocalcin correlates with bone formation. It is increased in conditions characterized by increased bone turnover such as: • Hyperparathyroidism • Hyperthyroidism • Acromegaly • Paget's disease of bone. It is decreased in states such as: • Hypoparathyroidism • Hypothyroidism • Patients on glucocorticoid therapy. Osteocalcin, in conjunction with other biochemical markers such as bone specific alkaline phosphatase and amino-terminal telopeptide of the crosslinks of collagen, has been shown to reflect and predict the rate of bone loss in postmenopausal women. Although predominantly synthesized by osteoblasts, osteocalcin enters the circulation during bone resorption as well as formation, indicating rate of bone turnover. Osteocalcin levels and other markers may assist in choosing the most effective treatment for this disease and in monitoring the effectiveness of the treatment. Bone Resoprtion: NTx: Approximately 90% of organic bone is made up of type I collagen. Type I collagen is a helical protein that is cross-linked at the N-terminal and C-terminal ends of the molecule and forms the basic fabric and tensile strength of bone tissue. These cross-links are released during bone remodeling by osteoclasts. Cross-linked N-telopeptides of type I collagen (NTx), found in serum and urine as a stable end-product of bone resorption, offer a valuable tool to monitor bone metabolism. The procedure is a competitive-inhibition enzyme-linked immunosorbent assay (ELISA). Assay values are reported as nanomoles bone collagen equivalents per liter (nM BCE). In N-Telopeptide, Cross-Linked, Urine, final values are corrected for urinary dilution using urinary creatinine analysis and are expressed as nM BCE per millimole creatinine per liter (mM creatinine). Serum NTx, in comparison, provides a quantitative measurement of NTx in serum as an indicator of bone resorption. A baseline NTx level is determined prior to initiating HRT or antiresorptive therapy. The patient is tested quarterly until the desired reduction in NTx level is achieved. Bone Resorption: Pyridinium Crosslinks: Approximately 90% of the matrix of bone is type I collagen. The collagen crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpd) are formed during maturation of collagen fibrils. During bone resorption, these pyridinium crosslinks are released into circulation. Dpd and Pyd are then excreted in free and peptide-bound forms into the urine. The free forms of the pyridinium crosslinks can be measured by immunoassay. While Pyd can be found in bone, cartilage, and many soft tissues, Dpd is located primarily in bone. Noninvasive radiologic techniques such as dual-energy x-ray absorptiometry (DXA) allow for early diagnosis of osteoporotic patients. Once diagnosed, patients can be treated with estrogen replacement therapy or antiresorptive medications. While DXA can also be used to accurately monitor therapy response, many months to years may be needed to detect measurable changes in bone density. In contrast, biochemical markers, such as pyridinium crosslinks, can mark changes in a relatively short amount of time (2-3 months). Biochemical markers are a valid alternative method for monitoring osteoporosis therapy.


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