With the increased use of bone density measurements, osteoporosis can now be more easily diagnosed and treated. This has prompted the scientific community's strong interest in the biochemical markers of bone metabolism. The bones are constantly recycled, absorbed, and reshaped. Bone is absorbed by osteoclasts and bone is produced by osteoblasts. Osteoporosis is a common disease of postmenopausal women and is associated with increased bone resorption and reduced bone formation. The result is the creation of thin and weak bones that are prone to fractures. Osteoporosis is now increasingly recognized in older men. Early diagnosis allows therapeutic intervention and prevention of bone fractures.
Bone density measurement is a valuable tool in the determination of osteoporosis, but it cannot detect small changes in bone metabolism. Although bone density measurements can be used to monitor the effectiveness of treatment, it may take years to be able to detect measurable changes in bone density. Biochemical Bone Turnover Markers (BTMs), however, can identify any changes within a few months of applying a successful treatment. In addition, the cost of measuring BTMs is generally lower than the corresponding cost of measuring bone density.
Because levels of Biochemical Bone Turnover Markers vary with time of day and bone volume, their measurements are not used as routine tests to detect osteoporosis. Their use is very helpful in evaluating the efficacy of treatment by comparing them with the corresponding values before treatment is applied. BTMs levels are reduced by the use of anti-absorption drugs (eg estrogens, bisphosphonates, calcitonin, raloxifene). Biochemical Bone Turnover Markers have been shown to accurately predict bone density and treatment efficacy while also being useful in documenting patients' compliance with treatment.
N-Telopeptides and C-Telopeptides (NTx and CTx) are protein fragments of type 1 collagen, a substance that makes up nearly 90% of the organic portion of bone. The C- and N-terminals of these proteins are crosslinked to provide the bone strength needed. When bone is absorbed, CTx and NTx are released into the bloodstream and then excreted in the urine. The serum levels of these fragments have been shown to correlate very well with their corresponding urine measurements, of course, when creatinine clearance is co-evaluated. The measurement of these fragments can be used to evaluate treatment response (within 3 to 6 months) and are good indicators of bone resorption.
The Amino-terminal Propeptide of Procollagen 1 (P1NP), like NTx, is directly proportional to the amount of new collagen produced by osteoblasts. Its concentration is increased in patients with various bone diseases characterized by increased osteoblast activity. Measurement of P1NP is the most effective indicator of new bone formation and is particularly useful in monitoring bone formation and anti-absorptive therapies.
Osteocalcin, or Bone Protein G1a (BGP), is a non-collagenic bone protein and is synthesized by osteoblasts. It enters the bloodstream during bone resorption and bone formation and is a good indicator of bone metabolism. Serum Osteocalcin levels are associated with bone destruction and formation (bone recycling). Elevated levels are associated with increased bone loss. Osteocalcin is a protein dependent on vitamin K. Decreased intake of vitamin K is associated with reduced levels of Osteocalcin. This may also explain the pathophysiology of osteoporosis dependent on vitamin K deficiency.
Deoxypyridinoline (DPD, D-Pyrilinks) is formed during the maturation of type 1 collagen during the formation of new bone. During bone resorption, these molecules are released into the bloodstream and then excreted in the urine without further metabolism.
Bone Fraction of Alkaline Phosphatase or otherwise Ostase (BSAP) is an alkaline phosphatase isoenzyme and is found in the osteoblast cell membrane. It is therefore an indicator of osteoblast metabolic status and bone formation.
All these Biochemical Bone Turnover Markers cannot estimate the risk of bone fracture in the way that bone density can do. Their essential help lies in evaluating the effectiveness of osteoporosis treatment.
Biochemical Bone Turnover Markers can also be used to monitor the activity and treatment of bone Paget's disease, hyperparathyroidism and bone metastases. Biochemical Bone Turnover Markers are usually high in children because of the increased bone resorption associated with the development and remodeling of the long bones. Their levels peak around the age of 14 and then gradually decline to adult values. Because estrogens are a potent inhibitor of osteoclast activity (bone resorption), bone loss begins shortly after menopause begins. Therefore, the levels of biochemical markers increase after menopause.
What Do Pathological Values Mean?
- Increase: Osteoporosis, bone Paget's disease, advanced bone tumors (primary or metastatic), acromegaly, hyperparathyroidism, hyperthyroidism.
- Decrease: Hypoparathyroidism, hypothyroidism, cortisone therapy, effective osteoporosis treatment
Laboratory test results are the most important parameter for the diagnosis and monitoring of all pathological conditions. 70%-80% of diagnostic decisions are based on laboratory tests. Correct interpretation of laboratory results allows a doctor to distinguish "healthy" from "diseased".
Laboratory test results should not be interpreted from the numerical result of a single analysis. Test results should be interpreted in relation to each individual case and family history, clinical findings and the results of other laboratory tests and information. Your personal physician should explain the importance of your test results.
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