Bone metabolism is a continual cycle of bone growth and resorption that is carefully orchestrated by the dynamic relationship between osteoclasts, osteoblasts and an array of hormonal and regulatory influences. The relative levels of these signaling molecules dictate whether healthy, balanced bone metabolism ensues. Disturbances to this delicate equilibrium where resorption is greater than growth can weaken the skeletal architecture and put one at risk for the development of chronic and debilitating diseases such as Osteoporosis.
As we continue to gain a better understanding of the intricacies of bone metabolism and the key regulators involved, we may gain further insights into mechanisms underlying other bone-related diseases as well. ALPCO’s portfolio of bone metabolism assays serves as a powerful tool for studying bone-related pathologies and may help guide the development of new, targeted therapeutics.
- Osteoporosis
- Osteopetrosis
- Paget’s Disease
- Rheumatoid Arthritis
- Cancer & Bone Metastases
- Immobilization-induced Bone Loss
- Chronic Kidney Disease
Informational Videos
Introduction to Bone Biology
Video produced by Amgen
Role of Osteoblasts & Osteoclasts in Bone Remodeling
Video produced by Amgen
Role of OPG & sRANKL in Postmenopausal Osteoporosis
Video produced by Amgen
Sclerostin: A Novel Regulator in the Cycle of Bone Growth and Resorption
Sclerostin, a protein product of the SOST gene, inhibits osteoblast activity via antagonism of the Wnt signaling pathway and plays a key role in the cycle of bone growth and resorption. Reports show that sclerostin expression and/or circulating levels are elevated in osteoporosis, immobilization-induced bone loss, rheumatoid arthritis, multiple myeloma and bone metastases, making it a therapeutic target of great interest for the fields of bone and cancer research.1,2,3 There are indications that sclerostin levels are also elevated with chronic kidney disease, suggesting relevance in the study of renal insufficiency as well.4,5
A growing body of evidence sheds light on sclerostin’s novel role in the crosstalk between diabetes, obesity and bone metabolism. As the population continues to age, so does the prevalence of chronic diseases such as obesity, type 2 diabetes and osteoporosis. A number of recent reports have shown that sclerostin levels are increased and bone turnover markers decreased in type 2 diabetes.6,7,8,9 Type 2 diabetes is associated with increased fracture risk, and it appears that the Wnt signaling pathway may be intimately involved, potentially at the level of insulin secretion from the pancreatic beta cells.
Video produced by Amgen
Reproductive and Growth Hormones
Bone metabolism is regulated by a complex array of hormonal influences and growth factors that foster communication between osteoclasts and osteoblasts and which have profound effects on the skeleton. The key players in the Hypothalamic-Pituitary-Gonadal Axis are the reproductive hormones (estrogen, progesterone and testosterone), while the Growth Hormone/Insulin Growth Factor Axis has direct impact on cartilage expansion, bone modeling and remodeling.
References
1. Rey JP, Ellies DL. Wnt modulators in the biotech pipeline. Developmental Dynamics. Mar 2010; Vol 239 No 3: 102-114.
2. Gaudio et al. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metabolism. May 2010; Vol 95 No 5: 2248-2253.
3. Colucci S et al. Myeloma cells suppress osteoblasts through sclerostin secretion. Blood Cancer. Jun 2011; Vol 1 No 6: e27.
4. Drüeke TB & Lafage-Proust. Sclerostin: just one more player in renal bone disease? Clin J Am Soc Nephrology. Apr 2011; Vol 6, No 4: 700-703.
5. Cejka D et al. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrology. Apr 2011; Vol 6 No 4: 877-882.
6. Gaudio A, Privitera F, Battaglia K, Torrisi V, Sidoti MH, Pulvirenti I, Canzonieri E, Tringali G, Fiore CE. 2012 Sclerostin levels associated withinhibition of the Wnt/β-catenin signaling and reduced bone turnover in type 2 diabetes mellitus. J Clin Endocrinol Metab. 97(10):3744-50.
7. García-Martín A, Rozas-Moreno P, Reyes-García R, Morales-Santana S, García-Fontana B, García-Salcedo JA, Muñoz-Torres M. 2012 Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 97(1):234-41.
8. Vestergaard P. 2009 Bone metabolism in type 2 diabetes and role of thiazolidinediones. Curr Opin Endocrinol Diabetes Obes. 16(2):125-31
9. Starup-Linde J. 2013 Diabetes, biochemical markers of bone turnover, diabetes control, and bone.Front Endocrinol (Lausanne) 4(21):1-17.
