title: 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.
authors.affiliation: Department of Clinical Sciences, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523, USA. jmacleay@colostate.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Macleay
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Olson
authors.forename: A Simon
authors.initials: AS
authors.lastname: Turner
mesh_terms: D000138:Acidosis / Q000097:blood / Q000209:etiology* / Q000652:urine; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000652:urine; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000652:urine; D010052:Ovariectomy; D010758:Phosphorus / Q000652:urine; D012756:Sheep
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D010758:Phosphorus; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D002118:Calcium