Biomarkers of Bone Regulation

Maintaining strong and healthy bones is crucial for overall well-being. Bones not only provide structural support for the body but also protect vital organs and serve as reservoirs for essential minerals like calcium and phosphorus. Key aspects of bone health include bone density and bone strength.

Osteoporosis is a condition characterized by weakened and fragile bones. It is the most prevalent metabolic bone disorder worldwide and can affect people of all ages, though it is more commonly associated with aging (1). Both men (2) and women can develop osteoporosis, but postmenopausal women are at a higher risk due to declining estrogen levels, which normally help protect bone health (3). Prevention strategies include maintaining a balanced diet and engaging in regular exercise.

Bone remodeling is a continuous, tightly regulated process involving the resorption of old or damaged bone and the formation of new bone tissue. Various hormones and factors influence bone metabolism. The bone cycle encompasses different phases, and markers of bone metabolism can be classified into markers of bone formation, markers of bone resorption, and markers involved in the regulation of bone metabolism.

Biomarkers of bone regulation

Protein biomarkers are frequently utilized in clinical research and practice to evaluate bone health and monitor the effectiveness of osteoporosis treatments. Some of these biomarkers offer insights into the regulatory processes governing bone metabolism and turnover. Measuring these markers can help assess overall bone health. Key regulatory biomarkers include:

Sclerostin (SOST): Produced by osteocytes, the bone cells embedded within bone tissue, sclerostin is a bone-specific inhibitor of the Wnt signaling pathway. It negatively influences bone formation by promoting osteoclastogenesis and increasing bone resorption. Elevated levels of sclerostin may indicate reduced bone formation.

Dickkopf-1 (DKK-1): Similar to sclerostin, DKK-1 inhibits Wnt signaling, which is essential for bone formation. Increased serum DKK-1 levels can promote bone resorption, potentially signaling suppressed bone formation.

The Wnt signaling pathway is one of the most vital mechanisms regulating bone metabolism. Sclerostin and Dickkopf-1 function as inhibitors of Wnt signaling and are essential in the regulation of bone formation and resorption.

 

Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL): A critical regulator of osteoclast development and activation, RANKL promotes bone resorption by stimulating osteoclast activity. It is secreted by osteocytes and plays a central role in osteoclast formation.

Osteoprotegerin (OPG): Serving as a decoy receptor for RANKL, OPG modulates bone resorption. The ratio of OPG to RANKL influences bone remodeling processes, with alterations potentially impacting bone strength.

Fibroblast Growth Factor 23 (FGF23): This hormone regulates phosphate balance and vitamin D metabolism. Abnormal FGF23 levels are linked to bone disorders such as hypophosphatemic rickets, which can impair bone health.

 

These biomarkers can easily be measured in human blood samples with an ELISA assay

 

Sclerostin (SOST) ELISA  (BI-20492)

• • Most internationally referenced Sclerostin ELISA with more than 320 citations
  • Low sample volume – 20µl / well
  • Full validation package

 

Bioactive Sclerostin ELISA (BI-20472)

• • Targets the receptor binding region
  • Full validation package
  • Low sample volume – 20 µl of serum/plasma per well 

 

Dickkopf-1 (DKK-1) ELISA  (BI-20413)

• • Widely cited +180 publications
  • Direct measurement
  • Validated following international quality guidelines

 

Osteoprotegerin (OPG) ELISA (BI-20403)

• • most referenced human OPG ELISA in +280 citations
  • day test, ready to use color coded reagents
  • controls included

 

Free soluble RANKL ELISA (BI-20462)

• • Highly sensitive  – measurable concentrations in healthy subjects
  • Only assay measuring free, uncomplexed soluble RANKL
  • Cited in over +320 citations 

 

FGF23 c-terminal multi-matrix ELISA (BI-20702)

• • for serum and plasma samples
  • full validation package 
  • cited in +60 publications

 

FGF23 intact ELISA (BI-20700)

• • for serum and plasma samples
  • full validation package
  • one-step ELISA

 

Literature 

1. Bone Health and Osteoporosis Prevention and Treatment. Muñoz M, Robinson K, Shibli-Rahhal A.Clin Obstet Gynecol. 2020 Dec;63(4):770-787. doi: 10.1097/GRF.0000000000000572. PMID: 33017332.
2. Osteoporosis in men. Lancet Diabetes Endocrinol. Vilaca T, Eastell R, Schini M. 2022 Apr;10(4):273-283. doi: 10.1016/S2213-8587(22)00012-2. Epub 2022 Mar 2. PMID: 35247315.
3. Postmenopausal Osteoporosis: A Review of Latest Guidelines. Subarajan P, Arceo-Mendoza RM, Camacho PM. Endocrinol Metab Clin North Am. 2024 Dec;53(4):497-512. doi: 10.1016/j.ecl.2024.08.008. Epub 2024 Oct 5. PMID: 39448132.