Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset

Abstract

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

Figure 1. Serum albumin and body weight are decreased in marmosets with BGS.

(A) Serum albumin and (B) body weight of marmosets diagnosed with BGS or no disease at necropsy. Solid horizontal lines represent median values for each group of data points, dotted horizontal lines denote cutoff values suitable to identify animals with BGS. (C) Correlation between body weight and albumin levels in individual animals. Solid black line represents best-fit line of the data points. Red data points denote animals with headcaps, gold data points denote animals on restricted diets.

Figure 2. Bone and/or GI disease can be predicted by weight trends.

Percent of peak body weight of five unaffected (A) and five marmosets with GI +/– bone disease (B) for the year prior to death. Colors represent data points from individual animals, black lines represent best-fit line of the data points.

Figure 3. Skeletal system-specific tests can identify bone disease in marmosets.

(A) Example of the initial radiographic image (left panel) and analyzed image (right panel) of an animal with bone disease, with BRF calculated from the distal quarter of each femur (white arrows). (B) BRF values in marmosets diagnosed with bone disease or with no bone disease at necropsy. (C) PTH levels in marmosets diagnosed with bone disease or with no bone disease at necropsy. BRF  =  bone radiodensity fraction, PTH  =  parathyroid hormone. Solid horizontal lines represent median values for each group of data points, dotted horizontal lines denote cutoff values to distinguish animals with bone disease.