SHORT-TERM CHANGES IN HISTOMORPHOMETRIC AND BIOCHEMICAL TURNOVER MARKERS AND BONE-MINERAL DENSITY IN ESTROGEN AND OR DIETARY CALCIUM-DEFICIENT RATS/

Both estrogen and dietary calcium deficiencies are important risk fact ors in the pathogenesis of osteoporosis. We used an animal model of po stmenopausal osteoporosis to study histomorphometric and bone turnover markers and bone mineral changes induced by short-term (1 month) estr ogen 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, S ham-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-de ficient diet with estrogen replacement (Ovx-LoCa-Est); and 7) ovx, on a regular-calcium diet with estrogen replacement (Ovx-RCa-Est). When c ompared 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 calciu m deficiency induced bone loss in both cancellous-rich and cortical-ab undant bone sites, whereas estrogen deficiency affected cancellous-ric h 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 replacem ent can prevent bone loss from both types of deficiencies; and 3) comb ined estrogen and dietary calcium deficiencies imposed on rats may ser ve as an effective model to study the mechanism of bone loss occurring in both cancellous and cortical bone.