title: Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.
abstract: Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, Ulm, 89081, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Haffner-Luntzer
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, Ulm, 89081, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Heilmann
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, Ulm, 89081, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Heidler
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, Ulm, 89081, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Liedert
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
authors.forename: Timur Alexander
authors.initials: TA
authors.lastname: Yorgan
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Vom Scheidt
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, Ulm, 89081, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
mesh_terms: D000126:Achlorhydria / Q000150:complications*; D000818:Animals; D001862:Bone Resorption / Q000209:etiology*; D002118:Calcium / Q000378:metabolism / Q000627:therapeutic use; D002128:Calcium Metabolism Disorders / Q000150:complications / Q000503:physiopathology*; D019587:Dietary Supplements; D005260:Female; D005264:Femoral Fractures / Q000150:complications* / Q000378:metabolism; D017102:Fracture Healing; D051379:Mice; D011897:Random Allocation; D043887:Receptor, Cholecystokinin B / Q000235:genetics
chemical_list: D043887:Receptor, Cholecystokinin B; D002118:Calcium
keywords: calcium malabsorption; calcium supplementation; fracture healing; hypochlorhydria; post-traumatic bone loss