The Changing Roles of Bone Remodeling Biomarkers


Bones are traditionally known for their support, protection and movement properties, as well as their role in the processes of mineral balance and blood cell production. Research supports that bones do more than they were originally recognized for. Previous research investigating osteocalcin not only helped to change the scientific community’s understanding of bones, but also increased the use of bone remodeling biomarkers in other fields of study.

This diagram illustrates other fields of study where bone biomarkers are proving useful and demonstrates the changing roles of bone remodeling biomarkers.

Overview of Bone Remodeling

Bone remodeling (also known as bone metabolism) refers to the process of old bone being destroyed and then replaced with new bone. It is a continuous cycle of growth and resorption that is carefully orchestrated by bone cells, hormones, and cell signaling molecules. Multiple regulatory systems are used to keep bone remodeling balanced including the RANKL/RANK/OPG system1,2. Imbalances in bone metabolism can lead to bone diseases.

Bone Remodeling Biomarkers

The functions of bones now cover a multitude of areas. As such, traditional bone remodeling biomarkers are aiding in discoveries across various research areas.

Osteocalcin (OC)

OC is a hormone synthesized in the bones by osteoblasts, as well as a marker of bone formation.  Recent research on OC has linked the hormone to both fertility and energy homeostasis functions3-5. Previous research investigating OC not only helped to increase the use of bone remodeling biomarkers in other fields of study.


Recent research has shown both OPG and sRANKL to be more than just regulators of bone metabolism. Evidence suggests OPG and sRANKL are involved in type 2 diabetes and multiple forms of cancer6-8.


Sclerostin is produced and secreted by osteocytes within the Wnt signaling pathway, thus regulating bone formation. Research on sclerostin and diabetes has contributed toward supporting evidence of bones having endocrine functions9,10.

Dickkopf-1 (DKK-1)

DKK-1 is a known bone remodeling biomarker acting as an inhibitor of the Wnt signaling pathway and regulating bone metabolism. Recent research illustrates the involvement of DKK-1 in tumourgenetic activity among multiple cancers11,12.

Osteopontin (OPN)

OPN is a protein produced in bone and plays a vital role in the differentiation of osteoclasts, regulation of calcium deposits, and enhancement of osteoclast activity. OPN has gained interest in many other research areas including cardiovascular and cancer research13,14.

Periostin (Postn)

Postn is a protein expressed by osteoblasts required for sclerostin inhibition, making it a necessity to the overall regulation of bone metabolism15. Research has shown postn to also be involved in various diseases such as asthma16.


Previous research investigating osteocalcin not only helped to change the scientific community’s understanding of bones, but also increased the use of bone biomarkers in other fields of study. Now bone remodeling biomarkers have the potential to be used in the study of other disease areas and could even aid in the development of new disease therapies.

Download our eBook Think Outside the Bones: The Cross Functionality of Bone Metabolism Biomarkers to learn more.

Bone Remodeling Biomarkers

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  1. Walsh & Choi. (2014). Biology of the RANKL-RANK-GOP system in immunity, bone, and beyond. Front Immunol., 5, 511. PMID: 25368616.
  2. Khosla. (2001). Minireview: The OPG/RANKL/RANK system. Endocrinology, 142(12), 5050-5. PMID: 11713196.
  3. Ferron et al. (2010). Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell, 142(2), 296-308. PMID: 20655470.
  4. Oury et al. (2013). Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. Clin. Invest., 123(6), 2421-2433. PMID: 23728177.
  5. Kajimura et al. (2013). Adiponectin regulates bone mass accrual through two opposite mechanisms, one local and one central, that both rely on FoxO1. Cell Metab, 17(6), 901-915. PMC: 3679303.
  6. Clemens et al. (2011). The osteoblast: an insulin target cell controlling glucose homeostasis. J. Bone Miner. Res., 26(4), 677-680. PMID: 21433069.
  7. Lu et al. (2016). Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non-small cell lung cancer. Oncol. Lett., 11(3), 2261-2265. PMID: 26998159.
  8. Li et al. (2014). Potential role of the OPG/RANK/RANKL axis in prostate cancer invasion and bone metastasis. Oncology Reports, 32(6), 2605-2611. PMID: 25333856.
  9. Daniele et al. (2015). Sclerostin and insulin resistance in prediabetes: Evidence of a cross talk between bone and glucose metabolism. Diabetes Care, 38, 1509-1517.  DOI: 10.2337/dc14-2989.
  10. Liu & Habener. (2010). Wnt Signaling in Pancreatic Islets. The Islets of Langerhans Volume 654 of the series Advances in Experimental Medicine and Biology, 391-419.
  11. Han et al. (2015). Serum dickkopf-1 is a novel serological biomarker for the diagnosis and prognosis of pancreatic cancer. Oncotarget, 6(23). PMID: 26101916.
  12. Rachner et al. (2014). High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients. BMC Cancer, 14, 649. PMID: 25182503.
  13. Wolak. (2014). Osteopontin – A multi-modal marker and mediator in atherosclerotic vascular disease. Atherosclerosis, 236(2), 327-37. PMID: 25128758.
  14. Rodrigues et al. (2007). The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol. Biomarkers Prev., 16(6),1087-97. PMID: 17548669.
  15. Bonnet et al. (2009). The matricellular protein periostin is required for Sost inhibition and the anabolic response to mechanical loading and physical activity. J. Biol. Chem.,284(51), 35939–50. PMID: 19837663.
  16. Li et al. (2015). Periostin: Its role in asthma and its potential as a diagnostic or therapeutic target. Respir. Res., 16, 57. PMID: 25981515.


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