Short-term changes in histomorphometric and biochemical turnover markers and bone mineral density in estrogen- and/or dietary calcium-deficient rats

Abstract

Both estrogen and dietary calcium deficiencies are important risk factors in the pathogenesis of osteoporosis. We used an animal model of postmenopausal osteoporosis to study histomorphometric and bone turnover markers and bone mineral changes induced by short-term (1 month) estrogen and/or dietary calcium deficiency in the mature rat. Seven groups of rats were studied: 1) basal; 2) sham, fed a calcium-deficient diet (0.1% Ca, Sham-LoCa); 3) sham, fed a regular-calcium diet (1.0% Ca, Sham-RCa); 4) ovariectomy (ovx), on a calcium-deficient diet (Ovx-LoCa); 5) ovx, on a regular-calcium diet (Ovx-RCa); 6) ovx, on a calcium-deficient diet with estrogen replacement (Ovx-LoCa-Est); and 7) ovx, on a regular-calcium diet with estrogen replacement (Ovx-RCa-Est). When compared with sham-operated animals on a regular calcium diet (Sham-RCa), either deficiency alone elevated the turnover markers osteocalcin (BGP) (Sham-LoCa 24.5%; Ovx-RCa 54.7%) and pyridinoline (Sham-LoCa 48.3%, Ovx-RCa 112.3%). Reductions in cancellous bone mass (Cn-BV/TV, Sham-LoCa −26.5%, Ovx-RCa −41.1%) and trabecular connectivity (Node.Node, Sham-LoCa −54.5%, Ovx-RCa −62.6%) were observed. Combined deficiencies (Ovx-LoCa) showed a greater change (BGP, +66.0%; pyridinoline +117.7%; Cn-BV/TV −64.4%; Nd.Nd −95.6%). Estrogen treatment was effective in preventing bone loss from both estrogen and calcium deficiencies. From bone mineral density (BMD) measurements, we found that dietary calcium deficiency induced bone loss in both cancellous-rich and cortical-abundant bone sites, whereas estrogen deficiency affected cancellous-rich bone sites only (BMD, distal femur; Sham-LoCa −9.7%, Ovx-RCa −8.3%; femur diaphysis: Sham-LoCa −5.1%, Ovx-RCa +0.0%). Our results suggest the following: 1) levels of serum BGP and urinary pyridinoline can be used as markers to monitor bone turnover in rats; 2) estrogen replacement can prevent bone loss from both types of deficiencies; and 3) combined estrogen and dietary calcium deficiencies imposed on rats may serve as an effective model to study the mechanism of bone loss occurring in both cancellous and cortical bone.