Clinical and Technical Review - Tecomedical

More documents

Recommendations

Info

2 Bone turnover Biomarker in Osteoporosis Diagnosis of metabolic bone diseases can be established by measuring bone mineral density (BMD) at the hips or spine. However, BMD is a static measure of bone composition, reflecting its history. A baseline BMD value does not offer any prediction of future bone loss or response to therapy. Moreover, since biochemical bone marker reflect the wholebody rates of bone turnover, the combined measurement of bone marker and BMD provides more information on the overall bone loss than BMD measurement at specific skeletal sites alone. The increasing number of drugs available for treatment of osteoporosis and other bone diseases requires the use of more rapid and predictive methods to assess therapy efficacy. While detectable and significant changes in BMD take 18 to 24 months to develop, bone turnover marker have been shown to detect changes in bone tissue within 3-6 months after starting anti-resorptive therapy. Therefore, measurement of bone turnover marker is increasingly recommended as a key component of therapy management: to rapidly identify therapy responders and non-responders, to assess therapy efficacy and to determine the optimal therapy and dose of treatment. Bone marker are intended for use as an aid in: • management of postmenopausal osteoporosis and Paget’s disease; • monitoring of postmenopausal women on hormonal or bisphosphonate therapy; • prediction of skeletal response to hormonal therapy in postmenopausal women. • Detection and monitoring of Bone metastasis. Biomarker and Cartilage Destruction Degenerative joint disease such as osteoarthritis (OA) and rheumatoid arthritis (RA) are major causes of disability and impaired quality of life among the elderly. Despite better understanding of the underlying pathomechanisms, current clinical practice for diagnosing these diseases mainly relies on symptom assessment, which has limited sensitivity and specificity. By the time radiological techniques can reveal specific sign, the disease has advanced to a late phase with pronounced structural damage, when the only therapeutical option remaining is joint replacement. As marker provide a dynamic measure of current degradation rate in contrast to radiological investigations, they allow a rapid determination of the therapeutic effects, and they may also be used for selecting the therapies and drug dose, which are most efficient. In the lack of established diagnostic methods allowing the detection of cartilage degradation, early diagnosis and disease monitoring remain a major challenge of health care professionals. Therefore Biochemical marker for Cartilage degradation and synthesis are helpful for the management of Rheumatoid Arthritis and Osteoarthritis. Biomarker for diagnosing skeletal metastases Cancers have the ability to metastasize to organs distant from the site of the primary tumor. Breast, prostate, and lung cancer are primary tumors that most frequently metastasize to the skeleton. The chronic presence of bone metastasis often results in complete pathologic remodeling of the affected bone compartment, making affected bones vulnerable to several complications. Such complications include pathologic fractures, spinal cord compression, hypocalcemia, and severe bone pain. All reducing quality of life and worsening prognosis. Therefore, early diagnosis and adequate treatment of bone metastasis is critically important for the clinical management of cancer patients. Emerging evidence suggests that biomarker of bone turnover carry notable potentials to become useful diagnostic tools for the diagnosis of bone metastases. The study by Leeming et al was sought to assess the relative use of eight biomarker for the detection of bone metastases in cancer forms frequently spreading to the skeleton. Participants were 161 patients with either breast, prostate, or lung cancer. The presence and extent of bone metastases was assessed by imaging techniques (computer tomography and/or magnetic resonance imaging) and Technetium-99m scintigraphy. Number of bone metastases was recorded, and the skeletal load was graded, as previously proposed by Soloway. The Serum or urinary level of the bone resorption marker (alpha-CTX, beta-CTX, NTX, and ICTP), formation marker (BSAP), and osteoclastogenesis marker (osteoprotegerin, RANKL, and TRAP5b) was measured by commercially available immunoassays. There was a uniform pattern of significantly increased levels of the resorption marker in patients with bone metastases compared with those without. The relative responsiveness of marker was calculated to obtain insights into the relative sensitivity of the different marker to signal skeletal involvement. The plot demonstrates a trend toward greater relative increases in the level of the urine alpha-CTX and serum BSAP marker compared with other marker; differences becoming more evident with increasing Soloway score.
Figure 1: Soloway 0 = Patients without bone metastasis Soloway 1 = Patients with < 6 bone metastases Soloway 2 = Patients with < 20 bone metastases Soloway 3 = Patients with > 20 bone metastases but less than a “super scan” Soloway 4 = Patients with “super scan” that is defined by a > 75 % involvement of the ribs, vertebrae and pelvic bones Relative increases in bone resorption, bone formation, and osteoclastogenesis marker as a function of the extent of skeletal involvement assessed in 132 breast and prostate cancer patients. Relative increases are expressed as percentage of levels in patients with Soloway score 0 (1) . Currently, the diagnosis of bone metastasis in cancer patients relies predominantly on imaging techniques, such as plain radiography or Technetium-99 scintigraphy. Although scintigraphy is more sensitive than plain radiography and even can give quantitative information regarding skeletal involvement, this examination is also more expensive, invasive, time-consuming and exposes cancer patients to irradiation, limiting its use for monitoring purposes. Thus, these weaknesses of current methodologies point out an unmet need for establishing supplementary diagnostic tools like biochemical marker. Regulators of bone turnover Bone remodeling is an ongoing dynamic process consisting of bone resorption (due to osteoclasts digesting type I collagen) and bone formation (due to osteoblasts). Normally, these processes are balanced, resulting in 10 % replacement of the skeleton, each year. However, due to aging, disease or other conditions, bone turnover may become imbalanced where bone resorption and formation occur at different rates. OPG (Osteoprotegerin), also known as osteoclast inhibiting factor (OCIF), inhibits the differentiation and activation of osteoclasts. On the other hand, sRANKL (soluble receptor activator of nuclear factor (NF)-κB ligand) is the main stimulator for the formation of mature osteoclasts. Stimulation occurs through binding of sRANKL to the osteoclastic membrane receptor RANK. OPG inhibits the binding of sRANKL to RANK and thus the activation of osteoclasts. The OPG/sRANKL system is therefore a key regulator of bone resorption. Abnormalities in the balance of the OPG/sRANKL system may be the cause of bone loss in many metabolic bone diseases as osteoporosis, Paget’s disease, metastatic cancers and rheumatic bone degradation. In normal healthy people, sRANKL levels are generally low because the majority is bound by OPG. Decreased levels of OPG and/or increased levels of sRANKL may indicate an imbalance of the OPG/sRANKL system. OPG and/or sRANKL measurements can be used as an aid in determining the cause of bone loss by assessing imbalances in the OPG/sRANKL system in: • Post menopausal osteoporosis • Paget’s disease • Metastatic cancer • Diseases with locally increased resorption activity • Indicating bone loss in rheumatoid arthritis • Therapy monitoring after treatment with OPG • Determining an imbalance in vascular calcification (high OPG was associated with cardiovascular- and all-cause mortality in hemodialysis patients; Morena et al. 2006). • Metastatic Renal Cell Carcinoma (OPG) 3
Page 1: Author: Peter Haima, Ph Clinical an
Page 5 and 6: Bone Resorption Osteoclast: Large m
Page 7 and 8: Bone Turnover - Biochemical Marker
Page 9 and 10: Bone marker and their behavior in v
Page 11 and 12: Biomarker according to NIH Osteoart
Page 13 and 14: Cartilage Synthesis - Biochemical M
Page 15 and 16: Cartilage Biomarker and their behav
Page 17 and 18: Bonemarker normal values for childr
Page 19 and 20: Specific recommendations BAP Osteoc
Page 21 and 22: Bone marker - Reference values in a
Page 23 and 24: Cross reactivity - different specie

Clinical and Technical Review - Tecomedical

Create successful ePaper yourself

Delete template?

Save as template?