Biochemical markers are a fundamental tool that can be used in all study types, from early proof-of-concept studies to long term chronic toxicology or pharmacology studies, in all standard species. Biomarkers are often used alone or in conjunction with imaging techniques to allow more insight into mechanisms of action. They are an invaluable tool to provide pharmacokinetic/pharmacodynamic profiling and/or to assess the potential impact of anti-drug antibody development. In conjunction with in vivo imaging measures, these data are used to determine if additional end-points are needed to further characterize the effects of a drug on the skeleton.

Experience with various panels of markers:

• Bone turnover: markers of bone formation, bone resorption
• Cartilage turnover
• Muscle injury
• Kidney injury
• Metabolism: Lipid profile
• Hormones: sex steroid hormones, calciotropic hormones (PTH, vitamin D calcitonin, FGF23), metabolism (adiponenctin, growth hormone)
• Cytokines and growth factors

Selected Publications:

Biochemical Markers of Bone Turnover, Chapter 5 in Bone Toxicology. 2017 Smith SY and Samadfam R. Eds: SY Smith, A Varela, R Samadfam, Springer: Molecular and Integrative Toxicology series.

One year of abaloparatide, a selective activator of the PTH1 receptor, increased bone formation and bone mass in osteopenic ovariectomized rats without increasing bone resorption.  Varela A, Chouinard L, Lesage E, Smith SY, Hattersley G.  J Bone Miner Res. 2017 Jan 32(1):24-33.

Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys.  Kostenuik PJ, Smith SY, Samadfam R, Jolette J, Zhou L, Ominsky MS. J Bone Miner Res. 2015 Apr;30(4):657-69.

Long-term treatment with eldecalcitol (1α, 25-dihydroxy-2β- (3-hydroxypropyloxy) vitamin D3) suppresses bone turnover and leads to prevention of bone loss and bone fragility in ovariectomized rats.  Takeda S, Smith SY, Tamura T, Saito H, Takahashi F, Samadfam R, Haile S, Doyle N, Endo K. Calcif Tissue Int. 2015 Jan;96(1):45-55.

Eldecalcitol, a vitamin D analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.  SY Smith, N Doyle, M Boyer, L Chouinard, H Saito. Bone. 2013 57:116–22.

The effect of rosiglitazone on bone mass and fragility is reversible and can be attenuated with alendronate.  Kumar S, Hoffman SJ, Samadfam R, Mansell P, Jolette J, Smith SY, Guldberg RE, Fitzpatrick LA. J Bone Miner Res. 2013 Jul;28(7):1653–65.

Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovaroectimized rats.  Samadfam R, Awori M, Benardeau A, Bauss F, Sebokova E, Wright M, Smith SY, J Endocrinol. 2012 Feb;212(2):179-86.

Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.  Ominsky MS, Stouch B, Schroeder J, Pyrah I, Stolina M, Smith SY, Kostenuik PJ.  Bone. 2011 49:162-73.

Two Doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength.  Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C.  J Bone Miner Res. 2010 May;25(5):948-59.

Evaluation of cartilage and bone degradation in a murine collagen antibody-induced arthritis model.  Oestergaard S, Rasmussen KE, Doyle N, Varela A, Chouinard L, Smith SY, Qvist P, Karsdal MA.  Scand J Immunol. 2008 Mar;67(3):304-12.

Early elevation in circulating levels of C-telopeptides of type II Collagen Predicts structural damage in articular cartilage in the rodent model of Collagen-induced Arthritis. Oestergaard S, Chouinard L, Doyle N, Smith SY, Tanko LB, Qvist P.   Arthritis Rheum. 2006 54(9): 2886-90.

The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases.  Oestergaard S, Chouinard L, Doyle N, Karsdal MA, Smith SY, Qvist P, Tankó LB. Osteoarthritis Cartilage. 2006 Jul;14(7):670-9.

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