Markers osteocalcin

In bone, three proteins have been described which are vitamin K-dependent, osteocalcin (bone Gla protein), matrix Gla protein (MGP), and protein S. Osteocalcin is synthetized by osteoclasts, regulated by the active form of vitamin D, calcitriol. Its capacity to bind calcium needs a vitamin K-dependent y-carboxylation of three glutamic acid residues. The calcium binding capacity of osteocalcin indicates a possible role in bone mineralization, but its exact function is still unclear. However, it is widely used as a serum marker for bone mineralization. Protein S, mainly a coagulant, is also vitamin-K dependent and synthesized in the liver. Children with... 

Supplementation with high doses of vitamin K1 (1 mg/day for 14 days) or MK-4 (45 mg/day) resulted in decreased levels of undercarboxylated osteocalcin and increase of bone formation markers and in a significant reduction in bone loss, respectively. Using such high doses, any kind of effects besides vitamin K can not yet be ruled out and have to be further elucidated by long term studies. An overview can be found in a review by Palacios [4]. 

As markers of osteogenie differentiation, high activity of alkaline phosphatase, production of collagen 1 and non-collagenous calcium-binding ECM glycoproteins osteocalcin and osteopontin are currently evaluated [14-17,24-27,37,47],... 

Kanbur, N. O., Derman, O., and Kinik, E. (2002). Osteocalcin. A biochemical marker of bone turnover during puberty. Int.. Adolesc. Med. Health 14,235-244. 

Consumption of soy foods (providing 60mg/day isoflavones) for 12 weeks by postmenopausal women has been found to significantly decrease clinical risk factors for osteoporosis (short-term markers of bone turnover) including decreased urinary M-telopeptide excretion (bone resorption marker) and increased serum osteocalcin (bone formation marker). Furthermore, consumption of a soy isoflavone supplement containing 61.8 mg of isoflavones for 4 weeks by postmenopausal Japanese women significantly decreased excretion of bone resorption markers. ... 

Glucocorticoids can even cause osteoporosis when they are used for long-term replacement therapy in the Addison s disease, as has been shown by a study of 91 patients who had taken glucocorticoids for a mean of 10.6 years, in whom bone mineral density was reduced by 32% compared with age-matched controls (SEDA-19, 377 198). However, these results contrasted with the results of a Spanish study in patients with Addison s disease, in which no direct relation was found between replacement therapy and either bone density or biochemical markers of bone turnover of calcium metabolism (alkaline phosphatase, osteocalcin, procollagen I type, parathormone, and 1,25-dihydroxycolecalciferol) (SEDA-19, 377 199). 

Measurement of serum osteocalcin is a useful marker for glucocorticoid-induced osteoporosis, and can be used alongside other measures noted below. 

Serum osteocalcin determinations appear to be a helpful marker to evaluate the effects of glucocorticoids on growth in children. 

Treatment with beclomethasone dipropionate 1500 micrograms/day for 6 weeks significantly reduced markers of bone formation (osteocalcin and PICP), whereas fluticasone propionate 750 micrograms/day had no effect. Neither drug affected biochemical markers of bone resorption. There was no significant change in bone density (SEDA-22,183). 

A 2-year randomized controlled study in 90 women compared the effects of oral tibolone doses of 1.25 mg/day and 2.5 mg/day on bone loss in the early postmenopausal period all took calcium 1000 mg/day. Vertebral and femoral bone density rose in both treated groups but fell in the control group, and bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin concentrations) were similarly affected favorably in the treated groups, as was the incidence of hot flushes/ flashes (5). Studies such as this still leave open the question of the advisability of continuing tibolone treatment over a longer period. While tibolone has indeed been shown to benefit mineral bone density, few data are available to show whether it lowers fracture incidence nor is it clear whether there is a link between tibolone and breast cancer (6). 

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. 

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. 

It is the most abundant of the noncollagen proteins of bone matrix, accounting for 1% to 2% of total bone protein, or 15% of noncollagen bone protein. Osteocalcin synthesis is induced by physiological concenUations of calcitriol, and the release of osteocalcin into the circulation provides a sensitive marker of vitamin D action and metabolic bone disease (Section 3.5). 

The pathogenesis of hepatic osteopathy is primarily characterized by disturbed bone formation due to (7.) reduced osteoblast surface (with the number of osteoblasts being in the normal range) and (2.) reduction in osteocalcin. The latter substance is a bone-matrix protein formed by the osteoblasts. Therefore, the serum value is considered to be a marker of osteogenesis. There is no increase in osteoclasis. The causes and risk factors of disturbed bone metabolism are manifold and not totally understood as yet. (73)... 

The use of glucocorticoids is associated with reduced bone mineral density, bone loss, osteoporosis, and fractures. This has been described during the long-term use of glucocorticoid by any route of administration (SEDA-19, 377) (SEDA-20, 374). The effects of glucocorticoids on bone have been reviewed (SEDA-21, 417) (165). Biochemical markers of bone mineral density are listed in Table 4. In patients with secondary hypoadrenaUsm, hydrocortisone 30 mg/day for replacement produced a significant fall in osteocalcin, indicating bone loss. Lower doses of hydrocortisone (10 mg and 20 mg) produced similar efficacy in terms of quality of life but smaller effects on osteocalcin concentrations and therefore a reduction in bone loss (166). 

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