Bone Metabolism Assay Menu

In the past decades, the global incidence of osteoporosis has increased dramatically with rising life expectancy, and over 200 million people suffer from osteoporosis worldwide. By 2050, the global cost of osteoporosis is expected to exceed $130 billion and the annual hip fracture incidence is expected to increase to 6.3 million.^1,2 The highest risk of hip fractures are currently found in Norway, Sweden, Iceland, Denmark, and the United States, but by 2050 Asia is expected to account for almost one-half of all global fractures.^3,4

Calcium Homeostasis

Building Strong Bones

Calcium and phosphorous are the most abundant minerals found in the body, and the majority of both minerals are found in the skeletal system. Calcium regulation is required for many basic body functions, such as cell function, bone structure, blood clotting, and neural transmission. Insufficient calcium or loss of calcium is called hypocalcemia, whereas too much calcium in the blood, often a result of malignancy or primary hyperthyroidism, is called hypercalcemia. The body regulates calcium through the parathyroid hormone (PTH) and vitamin D, and, to a lesser extent, calcitonin.

Enhancing Calcium Absorption with PTH and Vitamin D

PTH	Vitamin D
Enhances calcium absorption in the intestines by stimulating the renal synthesis of 1.25(OH)2D Increases the amount of calcium in the blood through the release of PTH and the removal of calcium from the bone Decreases the amount of calcium by releasing less PTH	Helps to form and maintain strong and healthy bones by increasing the amount of dietary calcium absorbed by the intestines Stops the parathyroid gland from secreting parathyroid hormone, which would increase levels of calcium in the blood Protects against osteoporosis, cancer, and hypertension

Clinical Utility of Calcium and PTH for Differential Diagnosis

Physicians use the combination of calcium and PTH measurements to aid in the differential diagnosis of several diseases.

Disease	Calcium Level	PTH Level	Description
Hyperparathyroidism	High	High	Usually caused by a benign tumor on the parathyroid gland. Surgical removal of tumor is confirmed using intraoperative PTH^.5
Hypoparathyroidism	Normal	Low	Cause of hypocalcemia since the thyroid gland is sometimes damaged during surgery and unable to produce PTH^.6
Hypercalcemia of malignancy	High	Low	High levels of calcium caused by bone metastasis that destroy the bone and release calcium into the bloodstream.⁷
Secondary hyperparathyroidism in renal disease	Low	High	Renal patients often have low circulating calcium levels which cause PTH levels to rise. Dietary calcium supplements help the PTH levels return to normal. Persistently elevated PTH levels in renal patients can lead to bone disease, causing muscle pain, bone deformity and increased incidence of fracture^.5

Bone Turnover

Osteoporosis (“porous bone”) is a bone disease that increases the risk for fracture. It is caused by the loss of bone density from losing too much, not making enough, or a combination of both. Bone metabolism is the constant process of the body removing old bone (“bone turnover”) and replacing it (“bone resorption”). These processes take place in the osteoblasts, which form new bone, and osteoclasts, which break down old bone. As long as these processes are in balance, bone mass remains on a constant level.

At mid-life, individuals begin to lose bone quicker than they are able to replace it due to calcium metabolism, calcium and vitamin D deficiency, and hormonal factors, such as changes of estrogen level. Measuring proteins produced by the osteoblasts and osteoclasts provides a real-time evaluation of bone turnover, especially in the management of post-menopausal osteoporosis. Bone resorption markers can monitor progress of therapeutic interventions within a few weeks or months, whereas bone formation markers can take 6 to 12 months. This is still an improvement over bone mineral density (BMD), which can take as long as one to two years to determine the effectiveness of treatment.

Bone Turnover Measurement: Osteocalcin and Crosslinks Desoxypyridinoline

Assay Menu

Siemens Healthineers is dedicated to providing quality bone metabolism assays that improve patient care and allow laboratories of any size to consolidate testing on the ADVIA Centaur®, IMMULITE®, and Dimension® Systems.

	ADVIA Centaur® CP System	ADVIA Centaur® XP/XPT Systems	Atellica® Solution	Dimension® EXL™ Systems	IMMULITE® / IMMULITE 1000® Systems	IMMULITE® 2000/2000 XPi® Systems
Intact PTH	√^a	√^a	√		√	√
Osteocalcin					√^†	√^†
Pyrilinks-D					√	√
Turbo Intact PTH					√^a
Vitamin D Total	√^*	√	√	√

a) Cleared for intraoperative use*Under development. Not commercially available. Future availability cannot be guaranteed† Not available for sale in the U.S.The products featured here may not be commercially available in all countries. Due to regulatory reasons their future availability cannot be guaranteed. Please contact your local Siemens Healthineers organization for further details.

Siemens offers calcium measurement on all of its clinical chemistry and integrated systems, including the ADVIA® Chemistry, Dimension® and Dimension Vista® systems.

PTH⁸

Enhances calcium absorption in the intestines by stimulating the renal synthesis of 1,25(OH)2vitamin D
Increases the amount of calcium in the blood through the release of PTH and the removal of calcium from the bone
Decreases the amount of calcium by releasing less PTH

Vitamin D⁸

Helps to form and maintain strong and healthy bones by increasing the amount of dietary calcium absorbed by the intestines
Stops the parathyroid gland from secreting parathyroid hormone, which would increase levels of calcium in the blood
Protects against osteoporosis, cancer, and hypertension

Osteocalcin⁹

Protein that binds to calcium; it is manufactured by the osteoblasts in bone and dentin
A highly specific marker of late stage osteoblastic activity
Higher serum-osteocalcin levels are relatively well correlated with increases in bone mineral density

Pyrilinks-D¹⁰

Excreted in urine and is a specific marker of bone resorption and osteoclastic activity.
Used along with other bone markers to diagnose bone diseases such as osteoporosis, bone metastatis, and Paget's disease
Useful in monitoring treatments that contain bone-active agents such as estrogens and bisphosphonates.

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Reginster JY, Burlet N. Osteoporosis: A still increasing prevalence. Bone. 2006 Feb;38(2 Suppl 1):S4-9.

Johnell O. The socioeconomic burden of fractures: today and in the 21st century. Am J Med. 1997 Aug 18;103(2A):20S-25S; discussion 25S-26S.

Kanis JA, Johnell O, De Laet C, Jonsson B, Oden A, Ogelsby AK. International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res. 2002 Jul;17(7):1237-44.

Gullberg B, Johnell O, Kanis JA World-wide projections for hip fracture. Osteoporosis Int. 1997;7(5):407-13.

National Endocrine and Metabolic Disease Information Service, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH

Medline Plus, U.S. National Library of Medicine and the National Institute of Health

National Cancer Institute

Prim Care Clin Office Pract 2008;35:215-37

http://en.wikipedia.org/wiki/Osteocalcin

http://en.wikipedia.org/wiki/Deoxypyridinoline