Bone marker

RUSSELL G (2001) Introduction bone metabolism and its regulation. / . Eastell, R, Baumann, M, Hoyle, N R, Wieczorek, L Bone Markers Biochemical and Clinical Perspectives, London, Martin Dunitz Ltd, 1-26. 

Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S (1996) Time dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats effects of raloxifene HC1, tamoxifen, estrogen and alendronate. Bone 18 621-627... 

Increased concentrations in plasma of markers such as P1NP or cross-linked C-terminal telopeptides (CTx), or urinary excretion of DPD, indicate increased bone turnover but are generally not useful for initial diagnosis of osteoporosis. Changes in plasma concentrations or urinary excretion of bone markers may be useful for monitoring patients response to therapy. 

Four short-term (six months) human studies have been performed on the effects of different isoflavone preparations on bone mineral density (Alekel et ah, 2000 Potter et al., 1998, Clifton-Bligh et al., 2001 Hsu et al., 2001) and one on bone markers (Wagen et al., 2000). 

Hughes JA, Corny BG, Male SM, Eastell R. One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density. Thorax 1999 54(3) 223-9. 

Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Parathyroid hormone as a therapy for idiopathic osteoporosis in men effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000 85(9) 3069-76. 

Kaskani E, Lyritis GP, Kosmidis C, et al. Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1 alpha(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis a pilot study. Clin Rheumatol. 2005 24 232-238. 

Markers of bone resorption can be measured in serum or urine, whereas bone formation markers, such as bone-specific alkaline phosphatase, are usually measured in serum. Measurement of bone markers allows for real-time assessment of bone resorption or formation and can be used to monitor therapy (Ravn et al., 2003). The pyridonolines (deoxypyridinoline and pyridinoline) and the N- and C-teleopep-tides are the most frequently measured markers of bone resorption. Pyridinoline and teleopep-tides (NTx and CTx) are increased in individuals with metabolic bone diseases associated... 

Bisphosphonates are currently in clinical use for the following indications As bone markers in nuclear medicine (as technetium complexes) for the diagnosis of bone metastases and other bone lesions. This... 

General Variability of the Results of Measurements of Bone Markers. 280... 

General Potential of Bone Markers in the Diagnosis and Treatment of Bone Diseases... 

Results of the measuring of bone markers can provide us with more or less straight answers for the following questions (B4, W2) ... 

Electrophoretic separation is preceded by adjustment of the sample, usually by enzymatic cleaving with neuraminidase. Separation can be further combined with use of lectin, or with thermoinactivation. Excellent analytical selectivity of the method can be achieved by electrophoretic separation, but for routine use it provides only barely reproducible results in connection with its analytical robustness. An example of a successful application of the electrophoretic separation of BALP as a bone marker are the studies of VanHoof (V3). Currently, the need for an immunoanalytical measuring as a method of choice clearly dominates. 

Probably the most important source of variability in the measurement of bone markers is biological variability. The consequences of the combination of analytical and biological variability are the values of critical differences of two consequent measurements. Only the changes in the concentration of the analyte higher than the value of the critical difference can be with certainty assigned to the condition of the disease, or the effectiveness or ineffectiveness of treatment. The values of critical differences can be calculated by the equation ... 

Are Bone Markers Useful in the Diagnosis of Osteopenia and Osteoporosis ... 

Can Bone Markers Predict the Speed of Loss of Bone Tissue in the Future Can They Distinguish Fast Losers and Slow Losers of Bone Tissue ... 

Several publications exist that consider bone markers capable of this differentiation. An example is the report of Moss et al. (M9) concerning the serum markers BALP and osteocalcine, and urinary markers DPD and PYD. Major prospective studies—PEPI (Postmenopausal Estrogen-Progestin Intervention) (M3), Fracture Intervention Trial (B2), and the alendronate study (H6)—have not found a causal relationship between the bone markers and change in BMD, or found a relatively weak one. 

Follow-up represents the most common and the most important application for measuring bone markers in routine clinical practice. Because the results are loaded with high variability, and the patient s response to treatment is very individual, in agreement with the formulations of Blumsohn and Eastell (B4) it... 

In a similar experiment (D3) with a follow-up of the response to alendronate therapy (10 mg a day for a period of 25 weeks), the best-answering marker was U-NTx/Cr (100% of responders) DPD, BALP, PICP, and osteocalcine reacted very similarly (81-88% of responders). In this case, the response to the treatment also provided the measurement of BMD, although not as effectively as the bone markers (maximum response was provided by the values of lumber BMD, in 44% of responders. Kyd et al. (K7) achieved, in practically identically organized followup of the effectiveness of alendronate therapy in months, 66% of responders with the help of U-NTx, but only 23% of responders for U-DPD. As well, they used establishing the CTx in serum, with a 66% response to treatment. Kress et al. (K5) watched the course of therapeutic intervention with application of 10 mg of alendronate per day for a period of 6 months with the help of BALP, and obtained 85% of responders. Hannon et al. had in the above-mentioned study (H2) only 45% of responders to the same therapy when BALP was used for evaluation. 

Only the answer to these and other questions may bring the decisive facts about the possibilities that the establishing of bone markers in serum and in urine brings for diagnostics and follow-up of the therapeutic response in patients with osteoporosis. 

D12. Di Somma, C., Colao, A., Di Sarno, A., Klain, M., Landi, M. L., et al., Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males. J. Clin. Endocrinol. Metab. 83, 807-813 (1998). 

Zittermann, A. Geppert, J. Baier, S. Zehn, N. Gouni-Berthold, I. Berthold, H.K. Reinsberg, J. Stehle, P. Short-term effects of high soy supplementation on sex hormones, bone markers, and lipid parameters in young female adults. Eur. J. Nutr. 2004, 43 (2), 100-108. 

Contradictory results have been published about the prophylactic use of two other bisphosphonates in patients treated with glucocorticoids. There were no bone losses after therapy, and no differences in bone density or biochemical bone markers between placebo and clodronate (SEDA-22, 447) (217). 

Bone markers are used to assess bone turnover (resorption or formation) in patients with osteoporosis. This testing is useful for identifying osteoporotic individuals with elevated bone resorption and for predicting and assessing the response to therapy. Markers of bone resorption include collagen cross-finks (N telopeptide, deoxypyridinoline, or C-telopeptide). Because bone resorption and formation are coupled, markers of bone formation (BAP and serum osteo-... 

Biochemical markers of bone resorption and. formation have a number of potential uses" including (1) monitoring the effectiveness of therapy, (2) selection of patients for therapy, (3) prediction of bone loss, and (4) prediction of fracture risk. Of these, bone markers are currently most used for monitoring the effectiveness of therapy. Effective anti-resorptive therapy is followed by a significant reduction in resorption markers within few weeks, normally reaching a plateau within 3 to 6 months. Markers of bone formation respond more slowly, usually reaching a plateau at 6 to 12 months. Depending on the antiresorptive therapy and the bone marker, effective therapy is associated with a bone marker reduction of 20% to 80%. 

In contrast to many bone diseases, osteoporosis is often characterized by modest alterations in bone turnover, and thus only small changes may occur during therapy. A period of 1 to 3 years must pass before measurements of bone mass (for example, dual energy x-ray absorptiometry) can identify statistically significant changes in bone mass during therapy. Measurements of bone markers provide earlier assessments of bone resorption and/or formation. Because most current therapies are antiresorptive and resorption markers respond more quickly to these therapies, resorption markers have received the greatest attention. 

In addition to their use m metabohc bone disease, markers of bone turnover are potentially useful tools in diagnosing and monitoring metastatic bone disease. As with metabolic bone disease, there is more evidence supporting the use of resorption markers m monitoring therapy. Additional studies are required to determine the ultimate clinical utility of bone markers in metastatic bone disease. 

Bone marker concentrations in urine and serum vary with the time of day because of the diurnal variation of bone resorption and formation. Because of the nocturnal peak in bone turnover, most bone markers peak in the early morning hours (4 am to 8 am) and reach their nadir in the afternoon (1 pm to 11 pm). The amplitude of this variation is greatest for resorption markers, with nadir values averaging 70% of peak values. Consequently, speci-... 

Within-subject biological variation of bone markers has been reported to be (coefficients of variation) 5% to 60%... 

Delmas PD, Hardy P, Garnero P, Dain M. Monitoring individual response to hormone replacement therapy with bone markers. Bone 2000 26 553-60. 

Demers LM. Bone markers in the management of patients with skeletal disease. Cancer 2003 97 ... 

Gundberg CM. Osteocalcin. In Eastell R, Baumann M, Hoyle NR, Wieczorek L., eds. Bone markers biochemical and clinical perspectives. London Martin Dunitz, 2001 65-72. 

---