Bone Turnover Biochemical Markers

With estimates that one out of two white women in North America will suffer from an osteoporotic fracture sometime in their life, prevention of osteoporosis should be a major health objective for all women (and men). In addition, especially in post-menopausal women it is useful to predict the rate of bone loss and to further monitor how bone therapies are assisting over time.

Biochemical markers for bone turnover have improved over the last few years (1) and may help with prediction of rate of bone loss. Serum bone alkaline phosphatase, total osteocalcin and procollagen type 1 N-terminal propetide assays are best markers for bone formation (1). N- and C-terminal crosslinked telopeptides in urine and C-terminal telopeptides in serum are sensitive for bone resorption (1). Deoxypiridinoline in urine is another measurement of bone resorption, primarily useful during treatment (2).

Monitoring these biochemical markers can be useful for predicting rate of bone loss thereby can be supportive of recognizing osteoporosis or how effective antiresorptive or hormone-replacement therapies are on a patient. Depending on the rate status, a clinician can decide what therapies are most useful and make adjustments as seen fit.

A disadvantage is that biomarkers may not be as specific as needed to adequately detect rates of bone turnover, because any significant increase in resorption or formation results in increases in all biochemical markers (3). The markers are also not indicative of any certain disease, only reflecting on bone metabolism despite reason for changes (3).

Reference List

1. Eastell R, Hannon RA. Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc 2008;67:157-62.
2. Kitatani K, Nakatsuka K, Naka H, Miki T, Morii H, Nishizawa Y. Clinical usefulness of measurements of urinary deoxypyridinoline (DPD) in patients with postmenopausal osteoporosis receiving intermittent cyclical etidronate: advantage of free form of DPD over total DPD in predicting treatment efficacy. J Bone Miner Metab 2003;21:217-24.
3. Srivastava AK, Vliet EL, Lewiecki ML, Abdelmalek A, Gluck O, Baylink DJ. Clinical Use of Serum and Urine Bone Markers in the Management of Osteoporosis [Abstract and Introduction]. Curr Med Res Opin 2005;21(7):1015-1026. Available at: http://www.medscape.com/viewarticle/508542_print. Accessed on 22 Jan 2010.

Detecting Levels of Iron Storage

Ferritin is the body's major iron-storage protein and its levels in serum are parallel to iron stores. Normally, 1 ng/mL of serum ferritin is related to about 8 mg  of iron in storage. It rises somewhat in males and post-menopausal females. Any rise or decrease in levels of serum ferritin indicates available iron stores in the body. 

As a diagnostic tool, serum ferritin is the most sensitive test of iron-deficiency anemia in a patient. In presence of iron deficiency, ferritin is generally the first sign followed by decreased iron levels and changes noted in red blood cells such as size, color and number. Low levels of ferritin indicate reduced iron stores or, rarely, malnutrition due to protein depletion. A decrease can also result from hemodialysis. Levels below 10 mg/100 mL is a diagnosis of iron-deficiency anemia. 

Higher levels, in contrast, indicate hemochromatosis, hemosiderosis, iron poisoning, or a recent blood transfusion. A higher level of ferritin can also be found in patients with megaloblastic anemia, hemolytic anemia and chronic hepatitis. It is also elevated in those with chronic disease states such as chronic liver disease, uremia, alcoholism, collagen diseases or neoplasm. 

The serum ferritin study is limited because ferritin may act as an acute-phase reactant protein such as in states of inflammatory diseases, infections, metastatic cancer and lymphomas. In these cases, ferritin levels may increase one or two days after onset and peak at three to five days. To classify anemias, tests of serum ferritin should be accompanied with serum iron levels and total iron-binding capacity. 

There are also interfering factors with serum ferritin, mainly blood transfusions, recent dietary intake of red meat, hemolytic diseases, iron storage disorders like hemochromatosis, menstruation (women will have decreased ferritin levels after menstruation), and drugs that increase ferritin levels.

Summarized from

Pagana, K.D., Pagana, T.J. Mosby's Manual of Diagnostic and Laboratory Tests, 3rd ed. Mosby Elsvier, 2006, pp 249-50.