title: Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment.
abstract: The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU + ALEN), SRT (HU + SRT), or a combination of ALEN and SRT (HU + SRT/ALEN) for 28 days. HU + SRT and HU + SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000 ms isometric + 1000 ms eccentric). Additionally, HU + ALEN and HU + SRT/ALEN rats received 10 µg/kg of body weight of ALEN three times per week. HU reduced cancellous bone-formation rate (BFR) by 80%, with no effect of ALEN treatment (-85% versus CC). SRT during HU significantly increased cancellous BFR by 123% versus CC, whereas HU + SRT/ALEN inhibited the anabolic effect of SRT (-70% versus HU + SRT). SRT increased bone volume and trabecular thickness by 19% and 9%, respectively, compared with CC. Additionally, osteoid surface (OS/BS) was significantly greater in HU + SRT rats versus CC (+32%). Adding ALEN to SRT during HU reduced Oc.S/BS (-75%), Ob.S/BS (-72%), OS/BS (-61%), and serum TRACP5b (-36%) versus CC. SRT and ALEN each independently suppressed a nearly twofold increase in adipocyte number evidenced with HU and inhibited increases in osteocyte apoptosis. These results demonstrate the anabolic effect of a low volume of high-intensity muscle contractions during disuse and suggest that both bone resorption and bone formation are suppressed when SRT is combined with bisphosphonate treatment.
authors.affiliation: Departments of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Swift
authors.forename: Sibyl N
authors.initials: SN
authors.lastname: Swift
authors.forename: Mats I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: Harry A
authors.initials: HA
authors.lastname: Hogan
authors.forename: Scott D
authors.initials: SD
authors.lastname: Bouse
authors.forename: Susan A
authors.initials: SA
authors.lastname: Bloomfield
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D019386:Alendronate / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D019417:Hindlimb Suspension; D007527:Isoenzymes / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D020966:Muscular Disorders, Atrophic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D010011:Osteocytes / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055070:Resistance Training; D013643:Tarsus, Animal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate