Calcium and Bone Metabolism Indices

Adv Clin Chem. 2017:82:1-46. doi: 10.1016/bs.acc.2017.06.005. Epub 2017 Aug 7.


Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) control calcium homeostasis, whereas PTH, 1,25(OH)2D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic origins, and clinical utilities of BTMs. This review will briefly discuss the regulations of calcium and phosphate homeostasis, laboratory's role in the diagnosis, and monitoring of bone and calcium metabolism, as well as the usefulness and controversies of the utilities of BTMs in the diagnosis and monitoring of metabolic bone diseases.

Keywords: 1,25-Dihydroxyvitamin D; 25-Hydroxyvitamin D; Bone alkaline phosphatase; Bone formation markers; Bone resorption markers; CTX; Calcium homeostasis; FGF23; Hormones regulating calcium homeostasis; Hypercalcemia; Hyperparathyroidism; Hyperphosphatemia; Hypocalcemia; Hypoparathyroidism; Hypophosphatemia; Measurement of 25-hydroxyvitamin D; Measurement of PTH; Measurement of calcium; Measurement of free calcium; Metabolic bone diseases; NTX; Osteocalcin; Osteomalacia; Osteoporosis; P1NP; PTH; Paget disease; Phosphate homeostasis; Regulation of phosphate homeostasis; Renal osteodystrophy; Rickets.

Publication types

  • Review

MeSH terms

  • Bone Diseases, Metabolic / metabolism*
  • Calcium / metabolism*
  • Fibroblast Growth Factor-23
  • Homeostasis*
  • Humans


  • FGF23 protein, human
  • Fibroblast Growth Factor-23
  • Calcium