Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice

• Published in: Bone (New York, N.Y.) Vol. 87; pp. 27 - 36
• Main Authors: Wendelboe, Mette Høegh, Thomsen, Jesper Skovhus, Henriksen, Kim, Vegger, Jens Bay, Brüel, Annemarie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2016
• Subjects: Absorptiometry, Photon; Alkaline Phosphatase - blood; Animals; Bisphosphonate; Body Weight - drug effects; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - pathology; Bone Density - drug effects; Bone formation; Bone resorption; Bone Resorption - blood; Bone Resorption - drug therapy; Bone Resorption - prevention & control; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Female; Femur - diagnostic imaging; Femur - drug effects; Femur - pathology; Fractures, Bone - pathology; Imidazoles - pharmacology; Imidazoles - therapeutic use; Lactation; Lactation - drug effects; Mice; Organ Size - drug effects; Orthopedics; Osteogenesis - drug effects; Tartrate-Resistant Acid Phosphatase - blood; Weaning; X-Ray Microtomography; Bone resorption; Bisphosphonate; Mice; Bone formation; Lactation
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2016.03.012

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 12 days, then the pups were removed, and thereafter recovery took place for 28 days. Zln, 100 μg/kg, was given s.c. on the day of delivery, and again 4 and 8 days 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 28 days 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.