Bone remodeling is a process by which old bone is resorbed and formed, resulting in the replacement of approximately 10% of the skeleton every year. If the balance between bone resorption and bone formation is affected, the rate at which each process takes place changes which can have a large impact on the remodeling of the bones. This imbalance may result in weak, brittle or deformities of affected bones.
Changes in the rate at which bone is formed and resorbed can be measured by the evaluation of specific markers of bone turnover. Bone Alkaline Phosphatase (BAP) and Osteocalcin are considered markers of bone formation while Type I collagen telopeptides (NTx and CTx) are released during bone resorption.
The role of Vitamin D in regulating circulating levels of Calcium and Phosphorous to ensure normal bone mineralization is well known. Emerging evidence correlates insufficient levels of Vitamin D to an increased risk of developing non skeletal pathologies such as cardiovascular disease, cancer, diabetes, autoimmune diseases and infectious diseases.
The diverse effects of Vitamin D are mediated by receptors that regulate hundreds of genes. Thus maintaining sufficient Vitamin D levels is key to maintaining good health. Although Vitamin D3 (cholecalciferol) can be synthesized in the skin upon exposure to ultraviolet-B (UVB) radiation, Vitamin D deficiency is common throughout the world with an estimated one billion people affected.
Parathyroid hormone (PTH), an 84 amino acid polypeptide, plays a critical role in the regulation of mineral homeostasis and bone metabolism. The measurement of PTH is used in conjunction with calcium determinations to assess disorders in calcium metabolism. PTH affects mineral homeostasis by regulating the rate of kidney mediated reabsorption of calcium and phosphorus and by stimulating the synthesis of calcitriol in the kidney. The direct effect of PTH on bone is to stimulate osteoclastic bone resorption, which is coupled with an increase in bone formation. PTH is an important regulator of calcium homeostasis.
The measurement of PTH has proven to be difficult due to the heterogeneity of peptides that occur in both the gland and circulation. In addition to the formation of fragments within the gland, there is further proteolytic breakdown of PTH once it is released into the circulation. Parathyroid hormone and its fragments are cleared from the circulation by both the kidneys and liver. The clearance of C-terminal fragments is slower than the clearance of the intact hormone and is more dependent upon renal mechanisms.
Primary and secondary hyperparathyroidism, kidney insufficiency, malabsorption-syndrome and pseudo-hypoparathyroidism result in elevated concentrations of PTH. Decreased concentrations of PTH coincide with high doses of vitamin-D fortified milk, milk-alkali-syndrome, Morbus Boeck (sarcoidosis), hyperthyreosis, ingestion of thiazide and hypercalcemia of malignancy.
PTH concentration is also decreased with absorptive hypercalciuria and hypoparathyroidism.