Histomorphometry is a specialized technique which provides a quantitative study of the micro-organization and structure of a tissue using computer-assisted analysis of microscope images. This technique is applied to characterize effects of drug treatments primarily on bone, although methods have been adapted to provide similar assessments of muscle and adipose tissue. Histomorphometry is often combined with other histology procedures including special stains or immunohistochemistry assays.

Histomorphometry is one of the primary bone end-points providing important architectural and dynamic parameters to better understand how the bone machinery, the osteoblasts and osteoclasts, are working. These data are then integrated with other primary end-points, including biomarkers, bone densitometry and biomechanics, to provide a comprehensive assessment of treatment effects on bone.

Bone structure is typically measured at specific sites representative of the trabecular and cortical bone compartments, such as the proximal tibia, femur and a vertebra. Standardization of site selection and slide preparation is key to ensure appropriate data collection to compare control with drug-treated specimens. To minimize experimental error, rigorous quality control procedures are needed to ensure the adequacy of the slide preparation and accuracy of slide evaluations.

Dynamic parameters require the use of bone-seeking fluorochrome labels such as calcein green, tetracycline, alizarine complexone or xylenol orange. Labels are injected in vivo to become incorporated at sites where new bone is actively forming. When the bone tissue is processed, the labels become visible when exposed to fluorescent light. Using a double labelling technique, with injections given on consecutive occasions, the inter-label distances can be measured and used to derive indices of bone formation and mineralization at cancellous and cortical bone sites. These indices reflect the activity of the bone cells at the time the labels were given. Use of different labels at intervals during a study can provide valuable information on the chronology of events.

I have +20 years of experience interpreting and integrating histomorphometry data in pharmacology, efficacy and safety studies, so I can help you to focus on which parameters will be important to measure in your study, and what they mean with respect to mechanism of action and bone health.

Selected Publications:

Application of Histopathology and Bone Histomorphometry for Understanding Test Article-Related Bone Changes and Assessing Potential Bone Liabilities. Chapter 8 in Bone Toxicology. 2017 Erben RG, Jolette J, Chouinard L, Boyce R. Eds: SY Smith, A Varela, R Samadfam, Springer: Molecular and Integrative Toxicology series.

Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in ovariectomized cynomolgus monkeys by increasing bone formation without increasing bone resorption. Doyle N, Varela A, Haile S, Guldberg R, Kostenuik PJ, Ominsky MS, Smith SY, Hattersley G. Osteoporos Int. 2018 Mar;29(3):685-69.

One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats. Varela A, Chouinard L, Lesage E, Guldberg R, Smith SY, Kostenuik PJ, Hattersley G. Bone. 2017 Feb;95:143-150.

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 pioglitazone and fenofibrate co-administration on bone biomechanics and histomorphometry in ovariectomized rats.  Smith SY, Samadfam R, Chouinard L, Awori M, Bénardeau A, Bauss F, Guldberg RE, Sebokova E, Wright MB. J Bone Miner Metab. 2015 Nov;33(6):625-41.

The effects of bazedoxifene in the ovariectomized aged cynomolgus monkey.  Smith SY, Jolette J, Chouinard L, Komm BS. J Bone Miner Metab. 2015 Mar;33(2):161-72.

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.

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.

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.

Skeletal health: primate model of postmenopausal osteoporosis. Smith SY, Jolette J, Turner CH. Am J Primatol. 2009 Sep;71(9):752-65.

Intratrabecular tunneling increases trabecular number throughout the skeleton of ovariectomized rhesus monkeys treated with parathyroid hormone 1-84. Miller MA, Bare SP, Recker RR, Smith SY, Fox J. Bone. 2008 Jun;42(6):1175-83.

Treatment of postmenopausal osteoporotic women with parathyroid hormone 1-84 for 18 months increases cancellous bone formation and improves cancellous architecture: a study of iliac crest biopsies using histomorphometry and micro computed tomography. Fox J, Miller MA, Recker RR, Bare SP, Smith SY, Moreau I. J Musculoskelet Neuronal Interact. 2005 Oct-Dec; 5(4):356-7.

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