Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome

Jay R. Shapiro, Adele L. Boskey, Stephen B. Doty, Lyudmila Lukashova, Mary E. Blue

Research output: Contribution to journalArticle

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder predominately affecting young females, caused by deficiency of the global transcriptional protein methyl CpG binding protein 2 (MeCP2). Osteoblasts express MeCP2 and girls with RTT experience early onset osteoporosis, decreased bone mass and an increased fracture risk. There is no defined treatment for osteoporosis associated with RTT. The present study evaluated the effects of zoledronic acid (ZA), a third generation nitrogen-containing bisphosphonate with primarily anti-osteoclastic activity, in a mouse model of MeCP2 deficiency. Mice received weekly injections of 20 μg/kg ZA for six weeks. Due to the shortened lifespan of hemizygous male (Mecp2-null) mice, treatment began at 3 weeks of age for this group and corresponding wildtype (WT) male mice. Treatment for heterozygous (HET) and WT female mice began at 8 weeks of age. Micro-computed tomography (micro-CT) and dynamic analyses of bone turnover were performed. ZA treatment led to significant increases in bone volume fraction, number, connectivity density and apparent density of trabecular bone in all genotypes of mice. In contrast, cortical bone generally was unaffected by ZA injections. Parameters of bone turnover, including mineral apposition rate, labeled bone surface and bone formation rate decreased after treatment with ZA. Mecp2-null mice had reduced labeled bone surface and bone formation rate compared to WT male mice. The results indicate that ZA treatment significantly improved trabecular bone mass in a murine model of RTT with little effect on cortical bone.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBone
Volume99
DOIs
StatePublished - Jun 1 2017

Fingerprint

Rett Syndrome
Bone and Bones
Acids
Methyl-CpG-Binding Protein 2
Osteogenesis
Osteoporosis
Protein Deficiency
Diphosphonates
Osteoblasts
Bone Density
Minerals
Nitrogen
Age Groups
Genotype
Tomography
Proteins

Keywords

  • Bone histomorphometry
  • Bone turnover
  • MeCP2
  • Micro-CT
  • Mouse model
  • Rett syndrome
  • Zoledronic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

Cite this

Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome. / Shapiro, Jay R.; Boskey, Adele L.; Doty, Stephen B.; Lukashova, Lyudmila; Blue, Mary E.

In: Bone, Vol. 99, 01.06.2017, p. 1-7.

Research output: Contribution to journalArticle

Shapiro, Jay R.; Boskey, Adele L.; Doty, Stephen B.; Lukashova, Lyudmila; Blue, Mary E. / Zoledronic acid improves bone histomorphometry in a murine model of Rett syndrome.

In: Bone, Vol. 99, 01.06.2017, p. 1-7.

Research output: Contribution to journalArticle

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