Calcium isotope determination for diagnosis and monitoring of osteoporosis

Logo_osteolabs_Osteoporose_frueh_erkennem_mit_RandGerman version

Introduction

The diagnosis of osteoporosis is usually made radiologically using the bone density measurement (DXA), which measures the radiopacity of the bones. Unfortunately this commonly used method has the disadvantage of late diagnosis when bone substance has already decreased. Therapy assessment can be done even later. The radiation exposure of the patient represents an additional disadvantage.

Measurement of the bone metabolism represents a better method. It provides us the ability to detect early appearance of osteoporosis. This is possible by measuring the calcium mineral balance instead of the commonly used DXA-method. Our new method provides several advantages

  • the diagnosis can be made years earlier
  • a short-term (about 2-3 weeks) therapy monitoring is possible
  • the estimated calcium loss per day is determinable
  • all bones (DXA: only femoral neck + lumbar body) are detected
  • no radiation exposure

Method

Bones are the calcium reservoir of humans. Calcium Ca2+ is found in food in different heavy isotopes, e.g. 42Ca or 44Ca. These isotopes have the same chemical reaction, are stable and not radioactive but they are different in weight. In the human body Ca2+ is reabsorbed in the renal tubules and stored in the bone. Light Ca isotopes are reacting faster than the heavy ones in chemical reactions and accumulate in human bones at the end of the process.

During the bone formation, mainly light Ca isotopes (42Ca) are used. This leads to higher concentrations of heavy Ca isotopes (44Ca) left in blood and urine. During bone loss or osteoporosis, the light Ca isotopes are increasingly excreted. They are detectable in blood and urine.

The ratio 42Ca /44Ca (δ44/42Ca) allows a prediction about bone formation or bone resorbtion. The measurement reflects the calcium buildup or loss, which can be converted to grams per day (more details at http://www.labor-krause.de/osteolabs).

Calcium is reabsorbed in the renal tubules. By measuring in urine and blood, an additional statement can be made about the rate of kidney resorption. There is reason to believe that the procedure will also detect early stages of renal insufficiency.

 

Diagramm_Ca-Isotopenverhaeltnisse_bei_Osteop_in_diff_Material

Fig 1: Mean Ca isotope values in women with (n=14) and without osteoporosis (n=66). Ca isotope values in blood and serum are plotted with their corresponding mean values for the diet, feces and calculated mean value for the bone (see details in the text). There is no statistical difference in Ca isotope values between the two groups concerning the diet (p=0.3) or the feces (p=0.6). However, women suffering from DXA diagnosed osteoporosis showed significantly lower δ44/42CaBlood (p<0.001) and δ44/42CaUrine (p=0.004) values than those not suffering from osteoporosis. With the kind permission of Prof. Eisenhauer, Kiel, Germany

Limitations:

  • Calcium is reabsorbed in the renal tubules. This also leads to an increased reabsorption of light calcium isotopes. In the case of renal insufficiency, this reabsorption is lower. There is a decrease in (δ44 / 42Ca) in blood and an increase in urine. For this reason, renal insufficiency is routinely excluded during the measurement. The tubular resorption has a direct influence. Further studies aiming to contribute.
  • Vegan or vegetarian diet has little influence.
  • The influence of fractures is unknown. Three months interval is recommended.
  • Greater physical activity leads to temporary fluctuations. The determination must take place after several hours rest or after sleep.
  • The new method measures the change in the calcium mineral balance. A statement about the current density is only possible by DXA.

Studies:

In collaboration with UKSH and CRC Kiel, OSTEOGEO (100 postmenopausal women) and peak bone (30 healthy pre-menopausal women) clinical trials were performed. Additional osteoporotic women were found. This was to be expected by the detection of calcium loss already in earlier stages and the consideration of the entire skeleton. More details on our website. Results above the threshold indicate an even calcium balance and no osteoporosis. On values below the indicated threshold of osteoporosis, a DXA measurement can be recommended to determine the current bone density (Rangarajan et al. 2018, J.Skulan et al 2007).

Recommended materials:

Composition and δ44/42 of calcium varies with the daytime, the physical activity (e.g. marathons) and ingestion. Therefore blood and urine samples must be taken after several hours of rest or after sleep.

  • 2 ml serum
  • 10 ml first morning urine (stabilized with boronic acid)
  • self disclosure and a statement of agreement

Costs:

The cost of the entire laboratory diagnostics amounts to 424,31€.

Miscellaneous

Information leaflets and patient flyers (in German) for laying out in the waiting room can be obtained from us. We are asked the more frequent of patients who has the examination done. For this we need partner doctors. To register as a partner doctor please click here.

Since the procedure is still very expensive, we ask the patient to clarify that he must wait for the result at least two weeks.

Dr. med. Thomas Lorentz