Bone Metabolism

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

 

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.

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

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
Osteoporosis

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.

Measuring Bone Formation:
Osteocalcin

Measuring Bone Resorption:
Crosslinks Desoxypyridinoline

  • A protein found in the bone and dentin manufactured by the osteoblasts that binds to calcium
  • A highly specific marker of late stage osteoblastic activity
  • Elevated serum levels may occur in ostemalacia, Paget’s disease of the bone, hyperthyroidism, primary hyperparathyroidism and renal osteodystrophy
  • Depressed levels have been reported in hypothyroidism and during long-term corticosteroid therapy

  • A urine test that helps establish baseline bone turnover
  • Significantly elevated in post-menopausal women with osteoporosis than normal post-menopausal women
  • It monitors changes in urinary (deoxyopyridinoline) DPD excretion associated with aminobiphosphonate antiresorptive therapy
  • DPD is excreted unmetabolized in urine and is unaffected by diet, making it suitable for assessing resorption

Assay Menu

 

Siemens 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.

Systems

ADVIA
Centaur CP

ADVIA
Centaur XP

IMMULITE / IMMULITE 1000

IMMULITE 2000/2000 XPi

Dimension EXL

 

Intact PTH

Intact PTH

Intact PTH

Intact PTH

Intact PTHc

 

 

 

Turbo Intact PTHa

 

Vitamin D Totalc

 

 

 

Osteocalcinb

Osteocalcinb

 

 

 

 

Pyrilinks-D

Pyrilinks-D

 

 

Vitamin D Totalc

Vitamin D Total

 

 

 

a) Cleared for intraoperative use
b) Not available for sale in the U.S.
c) Under development. Not available for sale. Due to local regulations, not all products will become available in all countries

 

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 D
8

  • 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


Osteocalcin
9

  • 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-D
10

  • 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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