Sequential Treatment of Estrogen Deficient, Osteopenic Rats with Alendronate, Parathyroid Hormone (1–34), or Raloxifene Alters Cortical Bone Mineral and Matrix Composition

Erik A. Taylor, Eve Donnelly, Xiaomei Yao, Mark L. Johnson, Sarah K. Amugongo, Donald B. Kimmel, Nancy E. Lane

Research output: Contribution to journalArticlepeer-review


Anti-resorptive and anabolic treatments can be used sequentially to treat osteoporosis, but their effects on bone composition are incompletely understood. Osteocytes may influence bone tissue composition with sequential therapies because bisphosphonates diffuse into the canalicular network and anabolic treatments increase osteocyte lacunar size. Cortical bone composition of osteopenic, ovariectomized (OVX) rats was compared to that of Sham-operated rats and OVX rats given monotherapy or sequential regimens of single approved anti-osteoporosis medications. Adult female Sprague–Dawley rats were OVX (N = 37) or Sham–OVXd (N = 6). After 2 months, seven groups of OVX rats were given three consecutive 3-month periods of treatment with vehicle (V), h-PTH (1–34) (P), alendronate (A), or raloxifene (R), using the following orders: VVV, PVV, RRR, RPR, AAA, AVA, and APA. Compositional properties around osteocyte lacunae of the left tibial cortex were assessed from Raman spectra in perilacunar and non-perilacunar bone matrix regions. Sequential treatments involving parathyroid hormone (PTH) caused lower mean collagen maturity relative to monotherapies. Mean mineral:matrix ratio was 2.2% greater, mean collagen maturity was 1.4% greater, and mean carbonate:phosphate ratio was 2.2% lower in the perilacunar than in the non-perilacunar bone matrix region (all P < 0.05). These data demonstrate cortical bone tissue composition differences around osteocytes caused by sequential treatment with anti-osteoporosis medications. We speculate that the region-specific differences demonstrate the ability of osteocytes to alter bone tissue composition adjacent to lacunae.

Original languageEnglish (US)
Pages (from-to)303-314
Number of pages12
JournalCalcified Tissue International
Issue number3
StatePublished - Mar 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge Lynn Johnson, PhD, of the Cornell Statistical Consulting Unit for assistance with statistical analysis. This work was funded by National Institutes of Health Grants #?s R01 AR043052-07, 1 P50 AR03043, P50 AR060752NIH to NEL; The Endowment for Aging Research at UC Davis to NEL; and the Center for Musculoskeletal Health at UC Davis.

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.


  • Carbonate:phosphate
  • Collagen maturity
  • Crystallinity
  • Mineral:matrix
  • Osteocyte
  • Perilacunar
  • Raman spectroscopy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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