Prolonged treatments with antiresorptive agents and PTH have different effects on bone strength and the degree of mineralization in old estrogen-deficient osteoporotic rats

Zhiqiang Cheng, Wei Yao, Elizabeth A. Zimmermann, Cheryl Busse, Robert O. Ritchie, Nancy E Lane

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. We hypothesize that bone active agents improve bone strength in osteoporotic bone by altering different material properties of the bone. Eighteen-month-old female Fischer rats were ovariectomized (OVX) or sham-operated and left untreated for 60 days to induce osteopenia before they were treated with single doses of either risedronate (500 μg/kg, IV), zoledronic acid (100 μg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1-34) (25 μg/kg, SC, three times per week), or vehicle (NS; 1 ml/kg, three times per week). Groups of animals were killed after days 60 and 180 of treatment, and either the proximal tibial metaphysis or lumbar vertebral body were studied. Bone volume and architecture were assessed by μCT and histomorphometry. Measurements of bone quality included the degree of bone mineralization (DBM), localized elastic modulus, bone turnover by histomorphometry, compression testing of the LVB, and three-point bending testing of the femur. The trabecular bone volume, DBM, elastic modulus, and compressive bone strength were all significantly lower at day 60 post-OVX (pretreatment, day 0 study) than at baseline. After 60 days of all of the bone active treatments, bone mass and material measurements agent were restored. However, after 180 days of treatment, the OVX + PTH group further increased BV/TV (+30% from day 60, p < 0.05 within group and between groups). In addition, after 180 days of treatment, there was more highly mineralized cortical and trabecular bone and increased cortical bone size and whole bone strength in OVX + PTH compared with other OVX + antiresorptives. Treatment of estrogen-deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength. However, prolonged treatment for 180 days with PTH resulted in additional gains in bone quality and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalJournal of Bone and Mineral Research
Volume24
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Bone Density Conservation Agents
Estrogens
Bone and Bones
Physiologic Calcification
Therapeutics
zoledronic acid
Bone Remodeling
Elastic Modulus
Teriparatide
Compressive Strength
Postmenopausal Osteoporosis
Metabolic Bone Diseases
Inbred F344 Rats

Keywords

  • Bone mineral homogeneity
  • Bone mineralization
  • Compression and bending strengths
  • Intravenous bisphosphonates
  • PTH(1-34)

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Prolonged treatments with antiresorptive agents and PTH have different effects on bone strength and the degree of mineralization in old estrogen-deficient osteoporotic rats. / Cheng, Zhiqiang; Yao, Wei; Zimmermann, Elizabeth A.; Busse, Cheryl; Ritchie, Robert O.; Lane, Nancy E.

In: Journal of Bone and Mineral Research, Vol. 24, No. 2, 02.2009, p. 209-220.

Research output: Contribution to journalArticle

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