Effect of dietary-induced metabolic acidosis and ovariectomy on bone mineral density and markers of bone turnover

Abstract

Dietary-induced metabolic acidosis (DIMA) has been implicated as a significant confounder in the development of osteoporosis. Twenty-four mature ewes were randomly assigned to four groups of six sheep. Group 1 consumed a control diet (ND); group 2 consumed a normal diet (ND) and had ovariectomy (OVX), group 3 consumed a diet that induced metabolic acidosis (MA), without OVX, and group 4 consumed a diet that induced MA, with OVX. The study was conducted over 180 days and the sheep were maintained on the assigned diet throughout. Sheep were weighed and bone mineral density (BMD) was measured, using dual-energy X-ray absorptiometry (DEXA), on days 0 and 180. Serum bone alkaline phosphatase (BAP), urine deoxypyridinoline (DPD), and fractional excretions (FE) of Ca and P were determined on days 0, 90, and 180. Arterial blood pH was determined on day 180. Analysis consisted of a two-way analysis of variance for repeated measures with significance set at P < or = 0.05. Body weights, serum BAP, and urine DPD were not influenced by either diet or OVX status. DIMA did significantly increase urinary FE of Ca and P and significantly decreased lumbar BMD and arterial pH. Arterial pH remained within physiologic normal limits. DIMA was a more potent cause of calcium wasting than OVX over the time frame of this study. Sheep appear to be sensitive to DIMA and will therefore be a useful animal model to study the influence of diet on the development of osteoporosis. The specific mechanisms through which DIMA exerts its influence are still unknown and are the subject of ongoing studies.

Bone turnover markers in sheep and goat: A review of the scientific literature

“…Ding et al (2010) and Andreasen et al (2015) stated that the induction by glucocorticoids in sheep is similar to the change in the microstructure of human bone also induced by long-term glucocorticoid treatment, therefore being a useful model. MacLeay et al (2004b) though not knowing what the true mechanism is involved in diets that induce metabolic acidosis in bone loss, concluded that the sheep model is useful for studies of osteoporosis induced by diet.…”

Long-term effects of ovariectomy on the properties of bone in goats

“…In previous studies, rats (5), large osteopenic animal models, such as nonhuman primates and sheep, have been used as models (6,7). However, the time required to establish an accurate osteoporosis model is unknown (8)(9)(10)(11)(12). Therefore, the aim of the present study was to use locally available Chinese goats to establish a large osteopenic animal model through application of an ovariectomy (OVX), with a follow-up period of 24 months.…”

Serum total and bone alkaline phosphatase levels and their correlation with serum minerals over the lifespan of sheep

“…For preclinical studies of post-menopausal osteoporosis, usually 8 to 10 years old ewes are used after ovariectomy (Turner et al, 1995) or after a corticoid administration protocol (Chavassieux et al, 1997). Also, adult sheep subjected to an induction regimen consisting of ovariectomy, to promote oestrogen deficiency, associated with a specific calcium-/vitamin Drestricted diet and/or a glucocorticoid medication protocol have been used (MacLeay et al, 2004;Ding et al, 2010). Furthermore, in animal science studies on sheep, bone markers have already been used for monitoring alterations in bone turnover during growth or due to different physiological demands during the female reproductive cycle, where high calcium requirements occur and mineral homeostasis and bone metabolism could overcome significant changes (Allen, 2003;Liesegang et al, 2006), or even to evaluate the diurnal and circadian variations of these biomarkers (Liesegang et al, 2003).…”