Alendronate administration and skeletal response during chronic alcohol intake in the adolescent male rat

Alendronate is an aminobisphosphonate that inhibits bone resorption in oste oporotic humans and rats but does not induce osteomalacia. Several bisphosp honates, including alendronate, also have direct positive actions on osteob lasts, bone formation, and mineralization. We studied the effects of alendr onate on skeletal development in adolescent male rats during chronic alcoho l intake. Four groups of age- and weight-matched male Sprague-Dawley rats ( 35 days of age) were fed the Lieber-DeCarli diet containing 36% of calories as MOH (E), the EtOH diet plus 60 mg/kg alendronate (EA) every other day i ntraperitoneally (ip), an isocaloric diet (I), or the isocaloric diet plus 60 mg/kg alendronate (IA) every other day ip. Body weight, femur length, se rum levels of osteocalcin (OC), insulin-like growth factor 1 (IGF-1), testo sterone, and luteinizing hormone (LH); femur distal metaphyseal and middiap hyseal bone mineral density (BMD) and tibial metaphyseal gene expression fo r alpha-1-type I collagen (Col I), OC, and bone alkaline phosphatase (AP); and femur strength by four-point bending to failure were measured after 28 days of feeding and alendronate injections. Serum alcohol levels at death w ere 156 +/- 13 mg/dl (E) and 203 +/- 40 mg/dl (EA). Alendronate given to al cohol-fed rats increased metaphyseal BMD by more than 3-fold over rats fed alcohol alone. Alendronate given to isocaloric pair-fed rats increased meta physeal BMD by more than 2.5-fold over rats fed the isocaloric diet alone. Cortical BMD was reduced by alcohol but was increased by alendronate. Alcoh ol consumption reduced serum IGF-1 levels, and alendronate increased IGF-1 levels in alcohol-fed rats. Serum OC, testosterone, and LH were unaffected by alcohol and alendronate. Quantitative dot blot hybridization using rat c omplementary DNA (cDNA) probes and normalization against 18S submit ribosom al RNA (rRNA) levels revealed no changes in tibial metaphyseal gene express ion for type I collagen, osteocalcin, or alkaline phosphatase. Alcohol sign ificantly reduced the biomechanical properties of the femurs that were part ially compensated by alendronate. Chronic alcohol consumption uncouples for mation from ongoing resorption, and resorption is inhibited by alendronate, However, alendronate's positive effects on osteoblast-mediated mineralizat ion during chronic alcohol consumption point to the potential use of bispho sphonates in the treatment of decreased bone formation secondary to alcohol -induced diminished osteoblast function.