[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol]

Rev Invest Clin. Jan-Feb 2013;65(1):39-51.
[Article in Spanish]

Abstract

Introduction: Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution.

Objective: To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Material and methods: Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups.

Results: Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05).

Conclusion: These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Animals
  • Biomarkers
  • Body Weight / drug effects
  • Bone Diseases, Developmental / blood
  • Bone Diseases, Developmental / etiology
  • Bone Diseases, Developmental / pathology
  • Bone Diseases, Developmental / prevention & control*
  • Bone Remodeling / drug effects
  • Collagen Type I / blood
  • Elastic Modulus / drug effects
  • Femur / drug effects
  • Femur / pathology
  • Food Deprivation / physiology*
  • Growth Disorders / blood
  • Growth Disorders / etiology
  • Growth Disorders / pathology
  • Growth Disorders / prevention & control*
  • Male
  • Malnutrition / drug therapy
  • Malnutrition / physiopathology*
  • Minerals / blood
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • Organ Size / drug effects
  • Parathyroid Hormone / blood
  • Peptides / blood
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Proteins / analysis
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Weight-Bearing

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Collagen Type I
  • Minerals
  • Parathyroid Hormone
  • Peptides
  • Proteins
  • collagen type I trimeric cross-linked peptide
  • Propranolol