title: Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.
abstract: In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss.
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark. Electronic address: mette.hoeegh.wendelboe@post.au.dk.
authors.forename: Mette Høegh
authors.initials: MH
authors.lastname: Wendelboe
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark. Electronic address: jst@biomed.au.dk.
authors.forename: Jesper Skovhus
authors.initials: JS
authors.lastname: Thomsen
authors.affiliation: Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. Electronic address: kh@nordicbioscience.com.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark. Electronic address: jbve@biomed.au.dk.
authors.forename: Jens Bay
authors.initials: JB
authors.lastname: Vegger
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 3, DK-8000 Aarhus C, Denmark. Electronic address: mb@biomed.au.dk.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Brüel
mesh_terms: D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D050723:Fractures, Bone / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007774:Lactation / Q000187:drug effects*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase / Q000097:blood; D014886:Weaning; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Bisphosphonate; Bone formation; Bone resorption; Lactation; Mice