Osteoporosis markers

Total synthesis of f-t -deoxypyiTobrine, a potential biochemical marker for diagnosis of osteoporosis, is shown in Eq 10 25 Osteoporosis is a cripphng degenerative bone disease that affects the aged populadon, particularly postmenopausff women... 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

Clinical trials on postmenopausal women with osteoporosis have demonstrated that raloxifene reduces bone turnover markers by 25-35% after 1 year of treatment and reduces the relative risk of the occurrence of new vertebral fractures by 30-50% after 3 years of treatment (Ettinger et al. 1999). A post hoc analysis in women at high risk for cardiovascular diseases also showed a reduction of 40% in the rate of new cardiovascular events (Barrett-Connor et al. 2002), with no observed reduction in the overall study population after 4 years of treatment in the MORE trial. 

Research in humans has been mainly focused either in the prevention of osteoporosis in healthy postmenopausal women or in the treatment of already osteoporotic women. Some research programs have extensively used estimates of biochemical markers of bone remodeling, while others have mostly relied on evaluations of BMD, histomorphometry, and fracture incidence. 

Johnell O, Scheele WH, Lu Y, Reginster JY, Need AG, Seeman E (2002) Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 87 985-992... 

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. 

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. 

While biochemical markers of bone metabolism may be sensitive to the effects of glucocorticoids in the short term, the relation between changes in these markers and intermediate measures, such as bone mineral density, and the more important clinical outcomes of fractures, is unknown. In a random stratified sample of 3222 women in the perimenopausal age range (47-56 years), including 119 women with asthma, bone mineral density was measured to determine whether asthma was a risk factor of osteoporosis and to investigate the effect of inhaled glucocorticoids (102). The subjects had predominantly adult-onset asthma, as the age at diagnosis was over 40 years. There were 26 patients who were treated mainly with... 

Although studies in which biochemical markers of bone turnover are measured for periods of 1-2 months do not predict the development of bone thinning, osteoporosis, or fracture, they can be useful in comparing the potential effects on bone of different glucocorticoids. Studies of bone mineral density over longer time periods relate more directly to osteoporosis and fracture risk. 

The ability of androgens to counter osteoporosis is the basis of their use as a supplement to estrogens in one version of hormone replacement therapy. Testosterone can increase markers of bone formation (66). However, the early closure of epiphyses, with an arrest of growth, is a risk if children are exposed to these substances this latter effect may be produced by the estrogen to which testosterone is metabolized. In some patients with... 

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. 

Kushida, K., Takahashi, M., Kawana, K., and Inoue, T. 1995. Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis... 

Rao, L.G., Collins, E.S., Josse, R.G., Strauss, A., and Rao, A.V. 2005. Lycopene consumption significantly decreases oxidative stress and bone resorption marker in postmenopausal women at risk of osteoporosis. Joint Meeting of the ECTS and IBMS June 25-29. Geneva, Switzerland. 

Fig. 12.3 Effects of daily teriparatide (TPTD) administration on biomarkers of bone formation (bone ALP and PICP) and bone resorption (DPD/Cr and NTx/Cr) in postmenopausal women with osteoporosis. Changes in bone formation markers at 1 month were significantly correlated with improvements in bone structure after 22 months of treatment (from [48]). 

How can biochemical markers be used to assess the therapeutic efficacy of drugs to treat osteoporosis ... 

Ravn P,Thompson DE, Ross PD, et al. Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis. Bone 33 150-158, 2003. 

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