Prolonged Treatments With Antiresorptive Agents and PTH Have Different Effects on Bone Strength and the Degree of Mineralization in Old Estrogen-Deficient Osteoporotic Rats

Journal Article · Fri Dec 04 00:00:00 EST 2009 · Journal of Bone and Mineral Research

DOI:https://doi.org/10.1359/jbmr.81005· OSTI ID:1627117

Cheng, Zhiqiang ^[1]; Yao, Wei ^[1]; Zimmermann, Elizabeth A. ^[2]; Busse, Cheryl ^[1]; Ritchie, Robert O. ^[2]; Lane, Nancy E. ^[1]

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1. Univ. of California, Davis, Sacramento, CA (United States)
2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. In this work, 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 mg/kg, IV), zoledronic acid (100 mg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1-34) (25 mg/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 mCT 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.

• Research Organization: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); Procter and Gamble Pharmaceuticals; USDOE Laboratory Directed Research and Development (LDRD) Program
• DOE Contract Number: AC02-05CH11231; R01 AR043052-07; 1K12HD05195801
• OSTI ID: 1627117
• Journal Information: Journal of Bone and Mineral Research, Vol. 24, Issue 2; ISSN 0884-0431
• Publisher: Wiley
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Endocrinology &amp; Metabolism
PTH(1-34)
intravenous bisphosphonates
bone mineralization
compression and bending strengths
bone mineral homogeneity