Mineral Biomarkers: Serum Calcium to Phosphorus Ratio

Optimal Takeaways

The blood calcium to phosphorus ratio (Ca/P) offers valuable information on parathyroid function, with deviations pointing to conditions like primary hyperparathyroidism, hypoparathyroidism, or hypophosphatemia. Higher ratios often signify hyperparathyroidism or low phosphorus levels, while lower ratios hint at hypoparathyroidism or diseases like rheumatoid arthritis. A low Ca/P ratio has been notably observed in rheumatoid arthritis patients, indicating increased oxidative stress and disruptions in joint lubrication. Moreover, diets with insufficient calcium and excess phosphorus can lead to detrimental changes in the Ca/P balance, affecting bone health, vascular calcification, and overall morbidity. Further studies are required to understand the relationship between dietary Ca/P ratio, serum Ca/P ratio, and parathyroid function.

Standard Range: 1.90 - 4.20 Ratio (1.47 - 3.25 Ratio (SI))  

The ODX Range: 2.30 - 3.20 Ratio (1.78 - 2.48 Ratio (SI))

Low calcium:phosphorus ratio may be associated with hyperphosphatemia, hypoparathyroidism (Madeo 2020), and rheumatoid arthritis (Walwadkar 2006).

High calcium:phosphorus ratio may be associated with primary hyperparathyroidism and hypophosphatemia (Madeo 2018, 2019).

Overview

The parathyroid gland maintains the ratio of serum calcium to phosphorus (Ca/P) and can be used to identify disorders such as primary hyperparathyroidism (PHPT), hypoparathyroidism, and hypophosphatemia. One retrospective case-control study involving 150 patients with PHPT, 306 patients with hypophosphatemia, and 150 controls found that a Ca/P ratio above 3.56 (2.75 SI) was highly accurate for identifying PHPT and hypophosphatemia (Madeo 2019).

A smaller study of 97 PHPT patients and 96 controls found a Ca/P ratio of 3.5 (2.71 SI) successfully identified 84 out of the 97 with PHPT. The same cut-off was determined using corrected and uncorrected calcium (Madeo 2018). A large study of 432 PHPT patients, 217 hypoparathyroidism patients, and 389 controls found that a Ca/P ratio above 3.29 (2.55 SI) accurately identified those with PHPT. In contrast, a Ca/P ratio below 2.30 (1.78 SI) identified those with hypoparathyroidism (Madeo 2020).

A low Ca/P ratio is also observed in rheumatoid arthritis (RA), as demonstrated in a study of 50 RA patients and 50 controls. Those with RA had a significantly lower mean Ca/P ratio of 1.79 (1.39 SI) versus 3.52 (2.72 SI) in controls and significantly lower serum calcium and significantly higher serum phosphorus. Those with RA also exhibited signs of oxidative stress, including elevated lipid peroxides, nitric oxide, and significantly lower vitamin E levels. Researchers suggest that increased oxidative stress and exposure to superoxide, hydrogen peroxide, and peroxynitrite radical from nitric oxide contribute to the depolymerization of hyaluronic acid and loss of joint lubrication (Walwadkar (2006).

Unhealthy diets often contain an insufficiency of calcium and an excess of phosphorus, which can have adverse effects on bone, vascular calcification, and morbidity and may detrimentally alter the balance of calcium and phosphorus in the body (Gutiérrez 2020, Adatorwovor 2015, Spiegel 2012). Future research exploring the association between dietary Ca/P ratio, serum Ca/P ratio, and parathyroid function would help to better define this relationship, especially with evidence suggesting that insufficient calcium intake can increase serum parathyroid hormone (Kemi 2010).

References

Adatorwovor, Reuben et al. “Intakes of Calcium and Phosphorus and Calculated Calcium-to-Phosphorus Ratios of Older Adults: NHANES 2005-2006 Data.” Nutrients vol. 7,11 9633-9. 19 Nov. 2015, doi:10.3390/nu7115492

Kemi, Virpi E et al. “Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake.” The British journal of nutrition vol. 103,4 (2010): 561-8. doi:10.1017/S0007114509992121

Gutiérrez, Orlando M et al. “Effects of phosphorus and calcium to phosphorus consumption ratio on mineral metabolism and cardiometabolic health.” The Journal of nutritional biochemistry vol. 80 (2020): 108374. doi:10.1016/j.jnutbio.2020.108374

Madeo, Bruno, et al. "Serum calcium to phosphorous (Ca/P) ratio is a simple, inexpensive, and accurate tool in the diagnosis of primary hyperparathyroidism." JBMR plus 2.2 (2018): 109-117.

Madeo, B et al. “Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders.” Journal of endocrinological investigation vol. 42,9 (2019): 1041-1049. doi:10.1007/s40618-019-01025-6

Madeo, Bruno et al. “The calcium-to-phosphorous (Ca/P) ratio in the diagnosis of primary hyperparathyroidism and hypoparathyroidism: a multicentric study.” Endocrine vol. 68,3 (2020): 679-687. doi:10.1007/s12020-020-02276-7

Spiegel, David M, and Kate Brady. “Calcium balance in normal individuals and in patients with chronic kidney disease on low- and high-calcium diets.” Kidney international vol. 81,11 (2012): 1116-22. doi:10.1038/ki.2011.490

Walwadkar, S D et al. “Oxidative stress and calcium-phosphorus levels in Rheumatoid arthritis.” Indian journal of clinical biochemistry : IJCB vol. 21,2 (2006): 134-7. doi:10.1007/BF02912928